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<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Sustain. Food Syst.</journal-id>
<journal-title>Frontiers in Sustainable Food Systems</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Sustain. Food Syst.</abbrev-journal-title>
<issn pub-type="epub">2571-581X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fsufs.2025.1636177</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Sustainable Food Systems</subject>
<subj-group>
<subject>Systematic Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Cyanide in cassava: unveiling health risks in the lens of unsustainable food systems in Sub-Saharan Africa &#x02013; a systematic review</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name><surname>Osman</surname> <given-names>Gareth</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x0002A;</sup></xref>
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<contrib contrib-type="author">
<name><surname>Maleta</surname> <given-names>Wyson</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
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<contrib contrib-type="author">
<name><surname>Masamba</surname> <given-names>Kingsley</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
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<contrib contrib-type="author">
<name><surname>Ng&#x00027;ong&#x00027;ola-Manani</surname> <given-names>Tinna</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
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<name><surname>Kalimbira</surname> <given-names>Alexander A.</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<aff id="aff1"><sup>1</sup><institution>Department of Human Nutrition and Health, Bunda College, Lilongwe University of Agriculture and Natural Resources</institution>, <addr-line>Lilongwe</addr-line>, <country>Malawi</country></aff>
<aff id="aff2"><sup>2</sup><institution>Department of Monitoring and Evaluation, Soils, Food and Healthy Communities (SFHC)</institution>, <addr-line>Mzuzu</addr-line>, <country>Malawi</country></aff>
<aff id="aff3"><sup>3</sup><institution>Department of Food Science and Technology, Bunda College, Lilongwe University of Agriculture and Natural Resources</institution>, <addr-line>Lilongwe</addr-line>, <country>Malawi</country></aff>
<author-notes>
<fn fn-type="edited-by"><p>Edited by: Kwaku Gyebi Duodu, University of Pretoria, South Africa</p></fn>
<fn fn-type="edited-by"><p>Reviewed by: Antoinette Simpah Anim-Jnr, Kwame Nkrumah University of Science and Technology, Ghana</p>
<p>Samuel Tonyemevor, Kwame Nkrumah University of Science and Technology, Ghana</p></fn>
<corresp id="c001">&#x0002A;Correspondence: Gareth Osman <email>gareth.osman94&#x00040;gmail.com</email></corresp>
</author-notes>
<pub-date pub-type="epub">
<day>25</day>
<month>08</month>
<year>2025</year>
</pub-date>
<pub-date pub-type="collection">
<year>2025</year>
</pub-date>
<volume>9</volume>
<elocation-id>1636177</elocation-id>
<history>
<date date-type="received">
<day>27</day>
<month>05</month>
<year>2025</year>
</date>
<date date-type="accepted">
<day>05</day>
<month>08</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x000A9; 2025 Osman, Maleta, Masamba, Ng&#x00027;ong&#x00027;ola-Manani and Kalimbira.</copyright-statement>
<copyright-year>2025</copyright-year>
<copyright-holder>Osman, Maleta, Masamba, Ng&#x00027;ong&#x00027;ola-Manani and Kalimbira</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p></license>
</permissions>
<abstract>
<sec>
<title>Objective</title>
<p>Cassava (<italic>Manihot esculenta</italic> Crantz) remains a vital staple crop across Sub-Saharan Africa (SSA), sustaining millions of livelihoods. However, its consumption poses a significant public health concern due to the presence of cyanogenic glycosides. This systematic review synthesizes evidence on the health impacts of cyanide exposure from cassava consumption in SSA and examines how these risks are shaped by structural vulnerabilities in food systems.</p></sec>
<sec>
<title>Methods</title>
<p>A comprehensive literature search was conducted across four databases: PubMed, Scopus, JSTOR, and AJOL. Retrieved publications were organized using Mendeley Desktop. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two independent reviewers carried out the search and screening processes, with any disagreements resolved through discussion with a third reviewer. The review included human epidemiological studies&#x02014;observational, interventional, and clinical&#x02014;that examined the health impacts of dietary cassava intake among populations in SSA. The keywords used in the search included cassava, cyanide, hydrogen cyanide, linamarin, lotaustralin, cyanogenic glycosides, konzo, health risk, acute poisoning, toxicity, tropical ataxic neuropathy, and neurological disorder. The initial search was conducted in January 2025 and updated on 24th June 2025.</p></sec>
<sec>
<title>Results</title>
<p>The review identified 45 relevant studies, with the majority conducted in the Democratic Republic of Congo (<italic>n</italic> = 18), followed by Mozambique (<italic>n</italic> = 10), Tanzania (<italic>n</italic> = 7), and Nigeria (<italic>n</italic> = 6). Urinary thiocyanate levels often exceeded the World Health Organization&#x00027;s safety threshold of 350 &#x003BC;mol/L, reaching up to 1,730 &#x003BC;mol/L, particularly among individuals affected by konzo. These adverse health outcomes were often compounded by armed conflict, drought, poor infrastructure, and protein-deficient diets. Climate-related stressors, such as El Ni&#x000F1;o events and prolonged dry spells may further intensify reliance on cassava, resulting in the consumption of inadequately processed roots. Residual Hydrogen Cyanide (HCN) concentrations in cassava products varied widely depending on the processing method. Among these, the wetting method consistently achieved the greatest reductions, lowering HCN levels to as little as 4 ppm.</p></sec>
<sec>
<title>Conclusion</title>
<p>Cyanide exposure from cassava remains a significant public health concern in SSA, particularly in areas with fragile food systems and limited access to safe processing methods. Strengthening food system resilience, expanding access to safer cassava cultivars (e.g., biofortified cassava varieties), and promoting effective processing methods such as wetting, are essential strategies for reducing cassava-related health risks.</p></sec></abstract>
<kwd-group>
<kwd>cassava</kwd>
<kwd>cyanide</kwd>
<kwd>food systems</kwd>
<kwd>food safety</kwd>
<kwd>konzo</kwd>
<kwd>Sub-Saharan Africa</kwd>
</kwd-group>
<counts>
<fig-count count="3"/>
<table-count count="7"/>
<equation-count count="0"/>
<ref-count count="97"/>
<page-count count="15"/>
<word-count count="10604"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Nutrition and Sustainable Diets</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec id="s1">
<title>1 Introduction</title>
<p>Cassava (<italic>Manihot esculenta</italic> Crantz) is the world&#x00027;s fourth most important staple food, following rice, wheat, and maize, and serves as a dietary staple for over one billion people worldwide (<xref ref-type="bibr" rid="B2">Adebayo, 2023</xref>). Its resistance to drought, ability to thrive even in poor soils, and flexibility to be planted and harvested nearly year-round, underscore its critical role in food security, particularly in drought-prone and nutrient-depleted regions like Sub-Saharan Africa (SSA). Cassava occupies a pivotal role in the agricultural landscape of Africa, where it is the second most crucial staple crop after maize, with the highest per capita consumption occurring in SSA (<xref ref-type="bibr" rid="B40">Hood et al., 2023</xref>). On average, individuals in SSA consume &#x0007E;300 g of cassava daily, contributing up to 37% of the region&#x00027;s dietary energy intake (<xref ref-type="bibr" rid="B7">Bamigboye, 2023</xref>). However, beyond its contributions to food security, cassava presents complex trade-offs.</p>
<p>As a region, SSA grapples with complex challenges, including climate change, declining agricultural productivity, and increasing food insecurity. In this context, cassava has emerged as a resilient and indispensable crop that is promoted as a drought-tolerant crop [<xref ref-type="bibr" rid="B36">Food and Agriculture Organization of the United Nations (FAO), 2022</xref>] that sustains livelihoods across diverse landscapes. Recent trends, particularly between 2010 and 2023, show that cassava production in SSA is on the rise, driven by its growing significance as a food security crop amidst worsening climate variability, declining yields of traditional cereals like maize and rice, and increasing population pressures (<xref ref-type="bibr" rid="B35">FAOSTAT, 2025</xref>; <xref ref-type="bibr" rid="B77">Otekunrin, 2024</xref>).</p>
<p>Nutritionally, cassava is a source of starch, delivering 160 kcal/100 g when consumed raw, while its protein (&#x0003C;2%), fat (&#x0003C;1%), and micronutrient content (&#x0003C;1%) are minimal (<xref ref-type="bibr" rid="B82">Salvador et al., 2014</xref>). Due to its wide consumption as a staple food in SSA, where vitamin A deficiency remains a significant public health problem (<xref ref-type="bibr" rid="B92">UNICEF, 2023</xref>), biofortification programmes have successfully developed biofortified cassava varieties enriched with pro-vitamin A that have proven efficacy in improving serum retinol in school children (<xref ref-type="bibr" rid="B85">Talsma et al., 2016</xref>) and acceptable by consumers (<xref ref-type="bibr" rid="B14">Bechoff et al., 2018</xref>). As cassava broadens, it will likely continue to be promoted, increasing access and consumption in many SSA societies.</p>
<p>Despite the resilience and potential that cassava possesses, the utilization of cassava and its products is to some extent compromised by cyanide. Cyanogenic glycosides, primarily linamarin and lotaustralin which exist in the ratio 97:3 (<xref ref-type="bibr" rid="B57">Lykkesfeldt and Lindberg M&#x000F8;ller, 1994</xref>) are natural constituents of cassava that present a real threat to human health (<xref ref-type="bibr" rid="B81">Rivadeneyra-Dom&#x000ED;nguez and Rodr&#x000ED;guez-Landa, 2020</xref>). Cassava is considered bitter if its cyanide concentrations exceed 100 mg/kg, and sweet if cyanide levels are below 100 mg/kg (<xref ref-type="bibr" rid="B38">Fukushima et al., 2016</xref>). Consumption of inadequately processed bitter cassava results in enzymatic hydrolysis to release Hydrogen Cyanide (HCN), a potent toxin with deleterious effects on physiological functions. Cumulative exposure to cyanide has been linked to a range of adverse health outcomes, including acute poisoning and chronic neurological conditions such as tropical ataxic neuropathy and konzo&#x02014;a paralytic neurological disease primarily linked to cyanide exposure and commonly affecting children and women of reproductive age (<xref ref-type="bibr" rid="B83">Siddiqi et al., 2020</xref>; <xref ref-type="bibr" rid="B4">Alitubeera et al., 2019</xref>; <xref ref-type="bibr" rid="B72">Oluwole and Oludiran, 2013</xref>).</p>
<p>Importantly, the choice to grow bitter cassava is not always accidental or a result of limited knowledge. In many SSA communities, farmers intentionally cultivate bitter varieties due to their higher yield potential, better storability, and suitability for processing into flour (<xref ref-type="bibr" rid="B43">Imakumbili et al., 2019</xref>; <xref ref-type="bibr" rid="B73">Oluwole et al., 2007</xref>). Moreover, environmental factors such as soil characteristics and crop management practices&#x02014;including poor weeding, piecemeal harvesting, and the age of the plant at harvest&#x02014;can influence cassava root bitterness and subsequently increase cyanogenic glucoside production (<xref ref-type="bibr" rid="B43">Imakumbili et al., 2019</xref>). Additionally, bitter cassava serves as a natural deterrent to pests, livestock, and theft, as its toxicity discourages unwanted harvesting or consumption before proper processing (<xref ref-type="bibr" rid="B52">Kapinga et al., 1997</xref>; <xref ref-type="bibr" rid="B21">Chiwona-Karltun et al., 1998</xref>). This suggests that cyanide exposure from cassava and cassava-related products is still prevalent in SSA (<xref ref-type="bibr" rid="B37">Forkum et al., 2025</xref>). This health risk is further compounded by the fragility of food systems in the region, encompassing production, processing, storage, distribution, and consumption. These components are often fragmented, under-resourced, and vulnerable to a range of stressors, including climate variability, land degradation, socio-economic inequality, and political instability (<xref ref-type="bibr" rid="B91">Ulimwengu, 2024</xref>; <xref ref-type="bibr" rid="B15">Bjornlund et al., 2022</xref>). Such systemic weaknesses hinder the adoption of safe cassava processing practices such as adequate fermentation, wetting, drying, or soaking needed to reduce cyanide levels in cassava. Hence, populations remain at risk of chronic or acute cyanide exposure. Despite such systemic challenges, reliance on cassava continues to grow.</p>
<p>While various reviews have examined cassava toxicity and efforts to mitigate cyanide toxicity through cassava processing methods (<xref ref-type="bibr" rid="B55">Kuliahsari et al., 2021</xref>; <xref ref-type="bibr" rid="B79">Panghal et al., 2021</xref>; <xref ref-type="bibr" rid="B59">McMahon et al., 1995</xref>), specific cyanide-related health conditions such as konzo (<xref ref-type="bibr" rid="B6">Baguma et al., 2021</xref>; <xref ref-type="bibr" rid="B81">Rivadeneyra-Dom&#x000ED;nguez and Rodr&#x000ED;guez-Landa, 2020</xref>; <xref ref-type="bibr" rid="B26">Cliff et al., 2011</xref>; <xref ref-type="bibr" rid="B53">Kashala-Abotnes et al., 2019</xref>; <xref ref-type="bibr" rid="B68">Nhassico et al., 2008</xref>; <xref ref-type="bibr" rid="B5">Aregheore and Agunbiade, 1991</xref>), as well as the safety of cassava and cassava-derived products (<xref ref-type="bibr" rid="B37">Forkum et al., 2025</xref>), remain persistent public health concerns. However, there is a critical gap in understanding how these health risks are embedded within and perpetuated by the broader structural vulnerabilities of food systems in SSA. Therefore, the objective of this review was to synthesize existing evidence on the health risks associated with cyanide exposure from cassava consumption in SSA, and to examine how these risks are shaped and perpetuated by structural vulnerabilities within the region&#x00027;s food systems. The review aims to inform integrated, context-sensitive interventions that promote food safety, public health, and sustainable food systems.</p></sec>
<sec id="s2">
<title>2 Methods</title>
<p>This systematic review was conducted following guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA 2020) (<xref ref-type="bibr" rid="B78">Page et al., 2021</xref>). Given the nature of the research question and the diversity of study designs, the SPIDER framework (Sample, Phenomenon of Interest, Design, Evaluation, Research type) was employed to structure the review objectives and eligibility criteria, as it is particularly effective for synthesizing qualitative and mixed-methods research (<xref ref-type="bibr" rid="B30">Cooke et al., 2012</xref>). <xref ref-type="table" rid="T1">Table 1</xref> shows the SPIDER framework and its application to this study.</p>
<table-wrap position="float" id="T1">
<label>Table 1</label>
<caption><p>Summary of the SPIDER framework and its application to the study.</p></caption>
<table frame="box" rules="all">
<thead>
<tr style="background-color:#919498;color:#ffffff">
<th valign="top" align="left"><bold>SPIDER element</bold></th>
<th valign="top" align="left"><bold>Definition</bold></th>
<th valign="top" align="left"><bold>Application to the study</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Sample</td>
<td valign="top" align="left">Population or group of interest</td>
<td valign="top" align="left">Populations in Sub-Saharan Africa consuming cassava</td>
</tr> <tr>
<td valign="top" align="left">Phenomenon of interest</td>
<td valign="top" align="left">The behaviors, experiences, or exposures being studied</td>
<td valign="top" align="left">Cyanide toxicity from cassava consumption</td>
</tr> <tr>
<td valign="top" align="left">Design</td>
<td valign="top" align="left">Type of research design</td>
<td valign="top" align="left">Observational studies, case reports, outbreak investigations, clinical studies</td>
</tr> <tr>
<td valign="top" align="left">Evaluation</td>
<td valign="top" align="left">Outcomes or measures of interest</td>
<td valign="top" align="left">Health outcomes such as konzo, neuropathy, cognitive impairment, and acute poisoning</td>
</tr> <tr>
<td valign="top" align="left">Research type</td>
<td valign="top" align="left">Qualitative, quantitative, or mixed methods</td>
<td valign="top" align="left">Primarily quantitative studies, with some mixed methods approaches</td>
</tr></tbody>
</table>
</table-wrap>
<sec>
<title>2.1 Eligibility criteria</title>
<p>The inclusion and exclusion criteria were developed not only to ensure methodological rigor but also to align with the review&#x00027;s central theme: understanding the health risks of cassava consumption through the lens of unsustainable food systems in SSA. These criteria ensure that the selected studies reflect the human health consequences of systemic weaknesses in food systems within SSA. <xref ref-type="table" rid="T2">Table 2</xref> shows the inclusion and exclusion criteria for the review.</p>
<table-wrap position="float" id="T2">
<label>Table 2</label>
<caption><p>Inclusion and exclusion criteria.</p></caption>
<table frame="box" rules="all">
<thead>
<tr style="background-color:#919498;color:#ffffff">
<th valign="top" align="left"><bold>Inclusion criteria</bold></th>
<th valign="top" align="left"><bold>Exclusion criteria</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Human studies conducted in SSA.</td>
<td valign="top" align="left">&#x02022;Animal or laboratory experiments or <italic>in vitro</italic> studies. &#x02022;Technical focus only: studies focused solely on genetic engineering, breeding or agronomic practices.</td>
</tr> <tr>
<td valign="top" align="left">Studies investigating health outcomes associated with cassava consumption and cyanide exposure (e.g., konzo, neuropathy, acute poisoning)</td>
<td valign="top" align="left">&#x02022;Studies conducted outside SSA &#x02022;Lack of relevance to cassava as a crop</td>
</tr> <tr>
<td valign="top" align="left">Observational studies, clinical studies, case reports, and outbreak investigations</td>
<td valign="top" align="left">Articles not addressing health impacts of cassava or cyanide exposure</td>
</tr> <tr>
<td valign="top" align="left">Study reporting primary data with quantitative or mixed-methods analysis</td>
<td valign="top" align="left">Review articles, editorials, opinion pieces, or non-peer-reviewed sources</td>
</tr> <tr>
<td valign="top" align="left">Publications in English</td>
<td valign="top" align="left">Non-English publications</td>
</tr> <tr>
<td valign="top" align="left">No restriction on publication year</td>
<td/>
</tr></tbody>
</table>
</table-wrap></sec>
<sec>
<title>2.2 Information sources and search strategy</title>
<p>A comprehensive literature search was conducted in the following electronic databases: PubMed, Scopus, Journal Storage (JSTOR), and African Journals Online (AJOL). Prior to the search, an academic librarian was consulted to assist in developing comprehensive search strategies, identifying relevant databases, optimizing keywords and subject heading selection, and ensuring rigorous adherence to the PRISMA guidelines. The search strategy used a combination of relevant keywords and concepts related to cassava and cyanide. The keywords used in the search included cassava, cyanide, hydrogen cyanide, linamarin, lotaustralin, cyanogenic glycosides, konzo, health risk, acute poisoning, toxicity, tropical ataxic neuropathy, and neurological disorder. A full search index and the Boolean search strings used for each database are shown in <xref ref-type="table" rid="T3">Table 3</xref>. To ensure comprehensive search, no restrictions or filters were placed on publication year, language or country during the search of various databases. The initial search was conducted in January 2025 and updated on 24th June 2025. Two independent reviewers performed the search and screening processes and resolved any disagreements through discussion or consultation with a third reviewer. Supplementary data illustrating cassava production trends were obtained from <xref ref-type="bibr" rid="B35">FAOSTAT (2025</xref>).</p>
<table-wrap position="float" id="T3">
<label>Table 3</label>
<caption><p>Search algorithms returning publications in the database search.</p></caption>
<table frame="box" rules="all">
<thead>
<tr style="background-color:#919498;color:#ffffff">
<th valign="top" align="left"><bold>Database</bold></th>
<th valign="top" align="left"><bold>Algorithm</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">PubMed</td>
<td valign="top" align="left">((&#x0201C;Cassava&#x0201D;[All Fields] OR &#x0201C;Manihot esculenta&#x0201D;[All Fields] OR &#x0201C;Cyanogenic glycosides&#x0201D;[All Fields] OR &#x0201C;Linamarin&#x0201D;[All Fields] OR &#x0201C;Lotaustralin&#x0201D;[All Fields] OR &#x0201C;Hydrogen cyanide&#x0201D;[All Fields] OR (&#x0201C;Cyanide&#x0201D;[All Fields] AND &#x0201C;Cassava&#x0201D;[All Fields])) AND (&#x0201C;Konzo&#x0201D;[All Fields] OR &#x0201C;Tropical ataxic neuropathy&#x0201D;[All Fields] OR &#x0201C;Neurological disorder&#x0201D;[All Fields] OR &#x0201C;Acute poisoning&#x0201D;[All Fields] OR &#x0201C;Health risk&#x0201D;[All Fields] OR &#x0201C;Toxicity&#x0201D;[All Fields]))</td>
</tr> <tr>
<td valign="top" align="left">Scopus</td>
<td valign="top" align="left">(TITLE-ABS-KEY(&#x0201C;cassava&#x0201D;) OR TITLE-ABS-KEY (&#x0201C;Manihot esculenta&#x0201D;) OR TITLE-ABS-KEY (&#x0201C;cyanogenic glycoside<sup>&#x0002A;</sup>&#x0201D;) OR TITLE-ABS-KEY (&#x0201C;linamarin&#x0201D;) OR TITLE-ABS-KEY (&#x0201C;lotaustralin&#x0201D;) OR TITLE-ABS-KEY (&#x0201C;hydrogen cyanide&#x0201D;) OR (TITLE-ABS-KEY (&#x0201C;cyanide&#x0201D;) AND TITLE-ABS-KEY(&#x0201C;cassava&#x0201D;))) AND (TITLE-ABS-KEY(&#x0201C;konzo&#x0201D;) OR TITLE-ABS-KEY (&#x0201C;tropical ataxic neuropathy&#x0201D;) OR TITLE-ABS-KEY (&#x0201C;neurological disorder<sup>&#x0002A;</sup>&#x0201D;) OR TITLE-ABS-KEY (&#x0201C;acute poisoning&#x0201D;) OR TITLE-ABS-KEY (&#x0201C;health risk<sup>&#x0002A;</sup>&#x0201D;) OR TITLE-ABS-KEY (&#x0201C;toxicity&#x0201D;))</td>
</tr> <tr>
<td valign="top" align="left">JSTOR</td>
<td valign="top" align="left">((cassava) AND (&#x0201C;health risk&#x0201D;)) ((cassava) AND (toxicity)) ((cassava) AND (cyanide)) ((cassava) AND (konzo)) ((cassava) AND (&#x0201C;acute poisoning&#x0201D;)) ((cassava) AND (&#x0201C;tropical ataxic neuropathy&#x0201D;)) ((cassava) AND (&#x0201C;neurological disorder&#x0201D;)) ((Linamarin) OR (Lotaustralin))</td>
</tr> <tr>
<td valign="top" align="left">AJOL</td>
<td valign="top" align="left">cassava AND &#x0201C;health risk&#x0201D; cassava AND toxicity cassava AND cyanide cassava AND konzo cassava AND &#x0201C;acute poisoning&#x0201D; cassava AND &#x0201C;tropical ataxic neuropathy&#x0201D; cassava AND &#x0201C;neurological disorder&#x0201D; Linamarin OR Lotaustralin</td>
</tr></tbody>
</table>
</table-wrap></sec>
<sec>
<title>2.3 Study selection and data extraction</title>
<p>All database search results were collated, stored, and managed in Mendeley desktop software (version 1.19.8). Multiple folders were created in Mendeley to contain the results of each database search, and then all the results were aggregated into a single folder with duplicates removed. The study selection process was conducted in two phases: an initial screening of titles and abstracts, followed by a full-text review of potentially eligible studies. Data from the included studies were extracted using a standardized data extraction form. The extracted data included: study characteristics (i.e., authors, publication year, study location, study population); cyanide exposure assessment (i.e., thiocyanate concentrations); residual HCN concentrations and cassava processing methods; reported health outcomes or adverse effects; and potential confounding factors.</p>
<sec>
<title>2.3.1 Risk of bias and quality assessment of included studies</title>
<p>A comprehensive quality appraisal was conducted for all studies included in this review, following the PRISMA 2020 guidelines. Study quality was assessed using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies [<xref ref-type="bibr" rid="B66">National Heart, Lung, and Blood Institute (NHLBI), 2013</xref>] and the JBI Critical Appraisal Checklist for Case Series [<xref ref-type="bibr" rid="B49">Joanna Briggs Institute (JBI), 2017</xref>], depending on study design. Each study was independently evaluated by two reviewers to minimize bias. Any discrepancies were resolved through discussion and consensus. <xref ref-type="table" rid="T4">Table 4</xref> summaries the quality rating score.</p>
<table-wrap position="float" id="T4">
<label>Table 4</label>
<caption><p>Summary of the quality rating score.</p></caption>
<table frame="box" rules="all">
<thead>
<tr style="background-color:#919498;color:#ffffff">
<th valign="top" align="left"><bold>Score range</bold></th>
<th valign="top" align="center"><bold>Percentage of criteria met</bold></th>
<th valign="top" align="left"><bold>Quality rating</bold></th>
<th valign="top" align="left"><bold>Interpretation</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">0&#x02013;4 (NIH tool) / 0&#x02013;4 (JBI tool)</td>
<td valign="top" align="center">0&#x02013;49</td>
<td valign="top" align="left">Low</td>
<td valign="top" align="left">Study has significant methodological concerns; high risk of bias</td>
</tr> <tr>
<td valign="top" align="left">5&#x02013;9 (NIH tool) / 5&#x02013;7 (JBI tool)</td>
<td valign="top" align="center">50&#x02013;79</td>
<td valign="top" align="left">Moderate</td>
<td valign="top" align="left">Study meets many criteria but has some limitations; moderate risk of bias</td>
</tr> <tr>
<td valign="top" align="left">10&#x02013;14 (NIH tool) / 8&#x02013;10 (JBI tool)</td>
<td valign="top" align="center">80&#x02013;100</td>
<td valign="top" align="left">High</td>
<td valign="top" align="left">Study meets most or all criteria; low risk of bias</td>
</tr></tbody>
</table>
</table-wrap></sec></sec>
<sec>
<title>2.4 Data synthesis and analysis</title>
<p>The findings from the included studies were synthesized based on geographical distribution (country of study population), cyanide exposure levels reported (e.g., in &#x003BC;mol L<sup>&#x02212;1</sup>), reported health outcomes (e.g., konzo, tropical neuropathy, acute poisoning), and their underlying factors such as processing methods and HCN concentrations in cassava products. A geographic map and tabular summaries were used as appropriate to the data. The findings have been reported following the PRISMA statement, including a flow diagram of the study selection process, tabular summaries of study characteristics (design, population, and key findings), and narrative syntheses, highlighting patterns, contradictions and gaps, as appropriate.</p></sec></sec>
<sec id="s3">
<title>3 Results</title>
<sec>
<title>3.1 List of included publications</title>
<p>The initial database search identified a total of 4,964 records: PubMed (<italic>n</italic> = 631), Scopus (<italic>n</italic> = 1,446), JSTOR (<italic>n</italic> = 1,284), and AJOL (<italic>n</italic> = 1,603). After removing 681 duplicate records, 4,283 unique records were screened for titles and abstracts. From this pool, 472 publications were retrieved for full-text screening. Records were excluded at this stage based on irrelevance to the topic, that is, purely technical focus, use of animal or <italic>in vitro</italic> models, lack of relevance to cassava as a crop, non-English language, or unavailability of the full text. Following full-text screening, 426 publications were excluded for not addressing health impacts, being review articles or editorials, or being conducted outside SSA. Finally, 45 studies met the inclusion criteria and were included in the final review (<xref ref-type="fig" rid="F1">Figure 1</xref>).</p>
<fig position="float" id="F1">
<label>Figure 1</label>
<caption><p>Workflow for search, screening, and inclusion for databased identified publications.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fsufs-09-1636177-g0001.tif">
<alt-text>Flowchart detailing the selection process for a review. From an initial 4,964 records identified, 681 duplicates were removed. Of the remaining 4,283, 3,811 were excluded for irrelevance, including technical focus, animal studies, and language issues. This left 472 publications for full-text screening. Of these, 427 were excluded for reasons like not addressing health impacts. Ultimately, 45 publications were included in the review.</alt-text>
</graphic>
</fig>
<sec>
<title>3.1.1 Quality appraisal of included studies</title>
<p>Out of the 45 studies, 24 were appraised using the JBI Critical Appraisal Checklist for Case Series tool and 21 using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies tool (<xref ref-type="table" rid="T5">Table 5</xref>). Most studies (<italic>n</italic> = 26, 58%) were rated as having moderate quality, while 19 studies (42%) were rated as high quality. No study was rated as low quality. Among the JBI-assessed studies, quality scores ranged from 67% to 90%, with most studies meeting 8 or 9 out of 10 criteria. For the NIH-assessed studies, scores ranged from 62% to 80%, with most studies meeting 8 or 9 out of 14 criteria. Common limitations included lack of clarity in participant selection, absence of blinding, and limited reporting on confounding factors.</p>
<table-wrap position="float" id="T5">
<label>Table 5</label>
<caption><p>Quality appraisal of all included studies using JBI Critical Appraisal Checklist for Case Series and NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.</p></caption>
<table frame="box" rules="all">
<thead>
<tr style="background-color:#919498;color:#ffffff">
<th valign="top" align="left"><bold>References</bold></th>
<th valign="top" align="left"><bold>Study design</bold></th>
<th valign="top" align="left"><bold>Tool</bold></th>
<th valign="top" align="left"><bold>Criteria met (%)</bold></th>
<th valign="top" align="left"><bold>Quality rating</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B75">Osuntokun et al. 1968</xref>)</td>
<td valign="top" align="left">Clinical case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">6/9 (67%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B76">Osuntokun et al. 1969</xref>)</td>
<td valign="top" align="left">Observational cross-sectional survey</td>
<td valign="top" align="left">NIH</td>
<td valign="top" align="left">8/13 (62%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B58">Makene and Wilson 1972</xref>)</td>
<td valign="top" align="left">Clinical case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">7/10 (70%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">Ministry of Health (<xref ref-type="bibr" rid="B60">1984</xref>)</td>
<td valign="top" align="left">Observational cross-sectional</td>
<td valign="top" align="left">NIH</td>
<td valign="top" align="left">8/13 (62%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B25">Cliff et al. 1985</xref>)</td>
<td valign="top" align="left">Case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">9/10 (90%)</td>
<td valign="top" align="left">High</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B24">Cliff et al. 1986</xref>)</td>
<td valign="top" align="left">Observational cross-sectional</td>
<td valign="top" align="left">NIH</td>
<td valign="top" align="left">8/13 (62%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B42">Howlett et al. 1990</xref>)</td>
<td valign="top" align="left">Observational cross-sectional</td>
<td valign="top" align="left">NIH</td>
<td valign="top" align="left">10/14 (71%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B61">Mlingi et al. 1991</xref>)</td>
<td valign="top" align="left">Case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">8/10 (80%)</td>
<td valign="top" align="left">High</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B88">Tyllesk&#x000E4;r et al. 1991</xref>)</td>
<td valign="top" align="left">Cross-sectional epidemiological</td>
<td valign="top" align="left">NIH</td>
<td valign="top" align="left">8/13 (62%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B3">Akintonwa and Tunwashe 1992</xref>)</td>
<td valign="top" align="left">Case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">6/9 (67%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B41">Howlett et al. 1992</xref>)</td>
<td valign="top" align="left">Case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">8/10 (80%)</td>
<td valign="top" align="left">High</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B87">Tyllesk&#x000E4;r et al. 1992</xref>)</td>
<td valign="top" align="left">Cross-sectional analytical</td>
<td valign="top" align="left">NIH</td>
<td valign="top" align="left">8/13 (62%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B33">Essers et al. 1992</xref>)</td>
<td valign="top" align="left">Clinical case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">8/10 (80%)</td>
<td valign="top" align="left">High</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B62">Mlingi et al. 1992</xref>)</td>
<td valign="top" align="left">Observational study with case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">9/10 (90%)</td>
<td valign="top" align="left">High</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B90">Tyllesk&#x000E4;r et al. 1993</xref>)</td>
<td valign="top" align="left">Case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">7/9 (78%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B94">van Heijst et al. 1994</xref>)</td>
<td valign="top" align="left">Clinical case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">8/10 (80%)</td>
<td valign="top" align="left">High</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B12">Banea-Mayambu et al. 1997</xref>)</td>
<td valign="top" align="left">Observational case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">9/10 (90%)</td>
<td valign="top" align="left">High</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B27">Cliff and Nicala 1997</xref>)</td>
<td valign="top" align="left">Longitudinal clinical case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">8/9 (89%)</td>
<td valign="top" align="left">High</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B28">Cliff et al. 1997</xref>)</td>
<td valign="top" align="left">Observational case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">8/10 (80%)</td>
<td valign="top" align="left">High</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B29">Cliff et al. 1999</xref>)</td>
<td valign="top" align="left">Cross-sectional observational</td>
<td valign="top" align="left">NIH</td>
<td valign="top" align="left">9/13 (69%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B13">Banea-Mayambu et al. 2000</xref>)</td>
<td valign="top" align="left">Cross-sectional comparative observational</td>
<td valign="top" align="left">NIH</td>
<td valign="top" align="left">9/13 (69%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B22">Chiwona-Karltun et al. 2000</xref>)</td>
<td valign="top" align="left">Cross-sectional observational</td>
<td valign="top" align="left">NIH</td>
<td valign="top" align="left">9/13 (69%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B86">Tshala-Katumbay et al. 2001</xref>)</td>
<td valign="top" align="left">Case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">8/10 (80%)</td>
<td valign="top" align="left">High</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B74">Onabolu et al. 2001</xref>)</td>
<td valign="top" align="left">Cross-sectional ecological</td>
<td valign="top" align="left">NIH</td>
<td valign="top" align="left">9/13 (69%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B16">Bonmarin et al. 2002</xref>)</td>
<td valign="top" align="left">Epidemiological case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">7/10 (70%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B32">Ernesto et al. 2002</xref>)</td>
<td valign="top" align="left">Observational case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">8/10 (80%)</td>
<td valign="top" align="left">High</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B65">Mwanza et al. 2003</xref>)</td>
<td valign="top" align="left">Clinical case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">8/10 (80%)</td>
<td valign="top" align="left">High</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B19">Cardoso et al. 2004</xref>)</td>
<td valign="top" align="left">Observational case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">7/10 (70%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B71">Okafor 2004</xref>)</td>
<td valign="top" align="left">Cross-sectional biochemical exposure</td>
<td valign="top" align="left">NIH</td>
<td valign="top" align="left">8/13 (62%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B23">Ciglenecki et al. 2011</xref>)</td>
<td valign="top" align="left">Case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">8/10 (80%)</td>
<td valign="top" align="left">High</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B20">Chabwine et al. 2011</xref>)</td>
<td valign="top" align="left">Epidemiological case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">8/10 (80%)</td>
<td valign="top" align="left">High</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B31">Diasolua Ngudi et al. 2011</xref>)</td>
<td valign="top" align="left">Cross-sectional observational</td>
<td valign="top" align="left">NIH</td>
<td valign="top" align="left">9/13 (69%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B11">Banea et al. 2012</xref>)</td>
<td valign="top" align="left">Case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">9/10 (90%)</td>
<td valign="top" align="left">High</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B9">Banea et al. 2013</xref>)</td>
<td valign="top" align="left">Case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">9/10 (90%)</td>
<td valign="top" align="left">High</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B72">Oluwole and Oludiran 2013</xref>)</td>
<td valign="top" align="left">Cross-sectional geospatial ecological</td>
<td valign="top" align="left">NIH</td>
<td valign="top" align="left">8/10 (80%)</td>
<td valign="top" align="left">High</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B17">Bumoko et al. 2014</xref>)</td>
<td valign="top" align="left">Cross-sectional observational</td>
<td valign="top" align="left">NIH</td>
<td valign="top" align="left">9/13 (69%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B8">Banea et al. 2015a</xref>)</td>
<td valign="top" align="left">Case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">9/10 (90%)</td>
<td valign="top" align="left">High</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B10">Banea et al. 2015b</xref>)</td>
<td valign="top" align="left">Cross-sectional survey</td>
<td valign="top" align="left">NIH</td>
<td valign="top" align="left">9/13 (69%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B18">Bumoko et al. 2015</xref>)</td>
<td valign="top" align="left">Cross-sectional observational</td>
<td valign="top" align="left">NIH</td>
<td valign="top" align="left">9/13 (69%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B67">Nhassico et al. 2015</xref>)</td>
<td valign="top" align="left">Case series</td>
<td valign="top" align="left">JBI</td>
<td valign="top" align="left">9/10 (90%)</td>
<td valign="top" align="left">High</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B51">Kambale et al. 2017</xref>)</td>
<td valign="top" align="left">Cross-sectional observational</td>
<td valign="top" align="left">NIH</td>
<td valign="top" align="left">9/13 (69%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B54">Kashala-Abotnes et al. 2018</xref>)</td>
<td valign="top" align="left">Cross-sectional observational</td>
<td valign="top" align="left">NIH</td>
<td valign="top" align="left">9/13 (69%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B4">Alitubeera et al. 2019</xref>)</td>
<td valign="top" align="left">Cross-sectional outbreak investigation</td>
<td valign="top" align="left">NIH</td>
<td valign="top" align="left">9/13 (69%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B83">Siddiqi et al. 2020</xref>)</td>
<td valign="top" align="left">Cross-sectional outbreak investigation</td>
<td valign="top" align="left">NIH</td>
<td valign="top" align="left">9/13 (69%)</td>
<td valign="top" align="left">Moderate</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B50">Kabamba et al. 2023</xref>)</td>
<td valign="top" align="left">Cross-sectional observational</td>
<td valign="top" align="left">NIH</td>
<td valign="top" align="left">9/13 (69%)</td>
<td valign="top" align="left">Moderate</td>
</tr></tbody>
</table>
</table-wrap></sec></sec>
<sec>
<title>3.2 Geographical scope of included publications</title>
<p><xref ref-type="fig" rid="F2">Figure 2</xref> illustrates the frequency of included publications by the country where the studies were conducted. The Democratic Republic of Congo (DRC) had the highest frequency of publications (<italic>n</italic> = 18), followed by Mozambique (<italic>n</italic>= 10), Tanzania (<italic>n</italic> =7), and Nigeria (<italic>n</italic> = 6). Other countries such as Malawi, Uganda, Zambia, and Cameroon each contributed only one study. This distribution highlights a concentration of research activity in regions with a high burden of cassava-related cyanide exposure, particularly in Central and East Africa.</p>
<fig position="float" id="F2">
<label>Figure 2</label>
<caption><p>Frequency of publications included by country where studies took place.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fsufs-09-1636177-g0002.tif">
<alt-text>Map of Africa highlighting specific countries in color, each with accompanying populations in parentheses. Democratic Republic of the Congo (blue, n = 18), Mozambique (orange, n = 10), Tanzania (black, n = 7), Nigeria (green, n = 6), Cameroon (yellow, n = 1), Malawi (red, n = 1), Uganda (pink, n = 1), Zambia (purple, n = 1). Legend included.</alt-text>
</graphic>
</fig>
<sec>
<title>3.2.1 Cassava production trends</title>
<p><xref ref-type="fig" rid="F3">Figure 3</xref> illustrates increasing cassava production trends from 2000 to 2023 in selected countries. Notably, Nigeria and DRC demonstrated the most pronounced increases. Specifically, cassava production in DRC has shown a consistent and sustained rise since 2010. Although Nigeria experienced an overall substantial rise during the same period, production declined in 2013, 2019, and 2020.</p>
<fig position="float" id="F3">
<label>Figure 3</label>
<caption><p>Cassava production trends in selected countries (2000-2023). Data Source: <xref ref-type="bibr" rid="B35">FAOSTAT (2025</xref>).</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fsufs-09-1636177-g0003.tif">
<alt-text>Line graph showing production quantities from 2000 to 2023 for six countries. Nigeria leads with a significant increase, peaking around 2019. The Democratic Republic of the Congo follows a steady rise. Other countries, United Republic of Tanzania, Mozambique, Uganda, and Zambia, maintain lower, relatively stable levels. </alt-text>
</graphic>
</fig></sec></sec>
<sec>
<title>3.3 Urinary thiocyanate concentration and associated health conditions</title>
<p>Urinary thiocyanate levels, a biomarker of cyanide exposure from cassava consumption, were reported in 28 of the 45 included studies (<xref ref-type="table" rid="T6">Table 6</xref>). The levels varied widely across populations, health conditions, and intervention periods. Several studies, particularly those conducted in the DRC, Mozambique, and Tanzania, reported extremely high thiocyanate levels, far above the World Health Organization&#x00027;s safety threshold of 350 &#x003BC;mol/L for urinary thiocyanate. The highest concentrations were observed in individuals diagnosed with konzo - a neurological disorder linked to cyanide toxicity. For instance, (<xref ref-type="bibr" rid="B86">Tshala-Katumbay et al. 2001</xref>) reported concentrations of 1,128 &#x003BC;mol/L among individuals with konzo in the DRC, while (<xref ref-type="bibr" rid="B61">Mlingi et al. 1991</xref>) reported a mean value of 1,730 &#x003BC;mol/L at the onset of a konzo outbreak in Tanzania. Similarly, (<xref ref-type="bibr" rid="B87">Tyllesk&#x000E4;r et al. 1992</xref>) found levels of 757 &#x003BC;mol/L in affected children compared to 50 &#x003BC;mol/L in unaffected peers. In addition, neurological conditions (e.g., tropical ataxic neuropathy), cognitive impairment, and acute intoxication events were reported.</p>
<table-wrap position="float" id="T6">
<label>Table 6</label>
<caption><p>Urinary thiocyanate concentrations and related health conditions reported in the included studies.</p></caption>
<table frame="box" rules="all">
<thead>
<tr style="background-color:#919498;color:#ffffff">
<th valign="top" align="left"><bold>References</bold></th>
<th valign="top" align="left"><bold>Country</bold></th>
<th valign="top" align="left"><bold>Summary of study population</bold></th>
<th valign="top" align="left" colspan="2"><bold>Mean urinary thiocyanate level</bold></th>
<th valign="top" align="left"><bold>Health condition diagnosed or studied</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B75">Osuntokun et al. 1968</xref>)</td>
<td valign="top" align="left">Nigeria</td>
<td valign="top" align="left">9 patients aged 19&#x02013;61 years</td>
<td valign="top" align="left" colspan="2">N/A</td>
<td valign="top" align="left">Tropical ataxic neuropathy</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B76">Osuntokun et al. 1969</xref>)</td>
<td valign="top" align="left">Nigeria</td>
<td valign="top" align="left">384 individuals over 10 years</td>
<td valign="top" align="left" colspan="2">N/A</td>
<td valign="top" align="left">Tropical ataxic neuropathy</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B58">Makene and Wilson 1972</xref>)</td>
<td valign="top" align="left">Tanzania</td>
<td valign="top" align="left">Adults (8 patients and 19 controls)</td>
<td valign="top" align="left" colspan="2">N/A</td>
<td valign="top" align="left">Tropical ataxic neuropathy</td>
</tr> <tr>
<td valign="top" align="left">Ministry of Health (<xref ref-type="bibr" rid="B60">1984</xref>)</td>
<td valign="top" align="left">Mozambique</td>
<td valign="top" align="left">17 affected and 17 control families</td>
<td valign="top" align="left" colspan="2">N/A</td>
<td valign="top" align="left">Spastic paraparesis (Konzo)</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B25">Cliff et al. 1985</xref>)</td>
<td valign="top" align="left">Mozambique</td>
<td valign="top" align="left">1983: 31 children, 30 from neighboring area, and 28 urban children</td>
<td valign="top" align="left">Cassava (Paraparesis)</td>
<td valign="top" align="left">84 mmol/mol<sup>&#x0002A;</sup></td>
<td valign="top" align="left">Spastic paraparesis (Konzo)</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td valign="top" align="left">Control (no cassava and paraparesis)</td>
<td valign="top" align="left">9 mmol/mol<sup>&#x0002A;</sup></td>
<td/>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B24">Cliff et al. 1986</xref>)</td>
<td valign="top" align="left">Mozambique</td>
<td valign="top" align="left">375 school children</td>
<td valign="top" align="left">Children with clonus</td>
<td valign="top" align="left">125 mmol/mol<sup>&#x0002A;</sup></td>
<td valign="top" align="left">Neurological dysfunction (ankle clonus)</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td valign="top" align="left">Children without clonus</td>
<td valign="top" align="left">70 mmol/mol<sup>&#x0002A;</sup></td>
<td/>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B42">Howlett et al. 1990</xref>)</td>
<td valign="top" align="left">Tanzania</td>
<td valign="top" align="left">39 cases of affected individuals</td>
<td valign="top" align="left" colspan="2">N/A</td>
<td valign="top" align="left">Konzo</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B61">Mlingi et al. 1991</xref>)</td>
<td valign="top" align="left">Tanzania</td>
<td valign="top" align="left">2,100 inhabitants (4 individuals with konzo</td>
<td valign="top" align="left">At onset</td>
<td valign="top" align="left">1,730 &#x003BC;mol/L</td>
<td valign="top" align="left">Konzo</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td valign="top" align="left">After 1 year</td>
<td valign="top" align="left">178 &#x003BC;mol/L</td>
<td/>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B88">Tyllesk&#x000E4;r et al. 1991</xref>)</td>
<td valign="top" align="left">DRC</td>
<td valign="top" align="left">134 konzo cases; 40 households; 152 other individuals</td>
<td valign="top" align="left" colspan="2">N/A</td>
<td valign="top" align="left">Konzo</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B3">Akintonwa and Tunwashe 1992</xref>)</td>
<td valign="top" align="left">Nigeria</td>
<td valign="top" align="left">3 individuals (ages 8, 17, and 18) from the same family</td>
<td valign="top" align="left" colspan="2">0.40&#x02013;0.7 mg/L<sup>&#x00023;</sup></td>
<td valign="top" align="left">Acute intoxication</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B33">Essers et al. 1992</xref>)</td>
<td valign="top" align="left">Mozambique</td>
<td valign="top" align="left">7 individuals, aged 6-32 (women and children)</td>
<td valign="top" align="left" colspan="2">51 mmol/mol<sup>&#x0002A;</sup></td>
<td valign="top" align="left">Konzo</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B41">Howlett et al. 1992</xref>)</td>
<td valign="top" align="left">Tanzania</td>
<td valign="top" align="left">28,500 inhabitants, with 116 konzo cases</td>
<td valign="top" align="left" colspan="2">N/A</td>
<td valign="top" align="left">Konzo</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B87">Tyllesk&#x000E4;r et al. 1992</xref>)</td>
<td valign="top" align="left">DRC</td>
<td valign="top" align="left">77 adults and 31 children (affected); 46 children (unaffected)</td>
<td valign="top" align="left">Children (affected)</td>
<td valign="top" align="left">757 &#x003BC;mol/L</td>
<td valign="top" align="left">Konzo</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td valign="top" align="left">Children (unaffected)</td>
<td valign="top" align="left">50 &#x003BC;mol/L</td>
<td/>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B62">Mlingi et al. 1992</xref>)</td>
<td valign="top" align="left">Tanzania</td>
<td valign="top" align="left">95 individuals (28 men, 37 women, 30 children)</td>
<td valign="top" align="left">Drought year (1988)</td>
<td valign="top" align="left">1120 &#x003BC;mol/L</td>
<td valign="top" align="left">&#x02022;Konzo &#x02022;Acute intoxication</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td valign="top" align="left">Normal year(1989)</td>
<td valign="top" align="left">68 &#x003BC;mol/L</td>
<td/>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B90">Tyllesk&#x000E4;r et al. 1993</xref>)</td>
<td valign="top" align="left">Tanzania</td>
<td valign="top" align="left">2 male patients (age 19 and 25 years)</td>
<td valign="top" align="left" colspan="2">N/A</td>
<td valign="top" align="left">Konzo</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B94">van Heijst et al. 1994</xref>)</td>
<td valign="top" align="left">Tanzania</td>
<td valign="top" align="left">20 patients (age 11&#x02013;39 years)</td>
<td valign="top" align="left" colspan="2">N/A</td>
<td valign="top" align="left">Tropical neuropathy</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B27">Cliff and Nicala 1997</xref>)</td>
<td valign="top" align="left">Mozambique</td>
<td valign="top" align="left">9 patients (7 children and 2 adult women)</td>
<td valign="top" align="left" colspan="2">N/A</td>
<td valign="top" align="left">Konzo</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B28">Cliff et al. 1997</xref>)</td>
<td valign="top" align="left">Mozambique</td>
<td valign="top" align="left">384 total cases</td>
<td valign="top" align="left">Schoolchildren</td>
<td valign="top" align="left">207 &#x003BC;mol/L</td>
<td valign="top" align="left">Konzo</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B12">Banea-Mayambu et al. 1997</xref>)</td>
<td valign="top" align="left">DRC</td>
<td valign="top" align="left">298 individuals across 5 villages</td>
<td valign="top" align="left">Dry season (savanna)</td>
<td valign="top" align="left">593 &#x003BC;mol/L</td>
<td valign="top" align="left">Konzo</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td valign="top" align="left">Wet season (Savanna)</td>
<td valign="top" align="left">359 &#x003BC;mol/L</td>
<td/>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B29">Cliff et al. 1999</xref>)</td>
<td valign="top" align="left">Mozambique</td>
<td valign="top" align="left">397 school children</td>
<td valign="top" align="left">Children with clonus</td>
<td valign="top" align="left">244 &#x003BC;mol/L</td>
<td valign="top" align="left">&#x02022;Ankle clonus &#x02022;Konzo</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td valign="top" align="left">Children without clonus</td>
<td valign="top" align="left">154 &#x003BC;mol/L</td>
<td/>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B13">Banea-Mayambu et al. 2000</xref>)</td>
<td valign="top" align="left">DRC</td>
<td valign="top" align="left">502 children (0&#x02013;36 months)</td>
<td valign="top" align="left">North (safe processing)</td>
<td valign="top" align="left">50 &#x003BC;mol/L</td>
<td valign="top" align="left">Stunting</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td valign="top" align="left">South (short processing)</td>
<td valign="top" align="left">757 &#x003BC;mol/L</td>
<td/>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B22">Chiwona-Karltun et al. 2000</xref>)</td>
<td valign="top" align="left">Malawi</td>
<td valign="top" align="left">176 women farmers</td>
<td valign="top" align="left" colspan="2">50 &#x003BC;mol/L</td>
<td valign="top" align="left">No reported cases of konzo or intoxication</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B74">Onabolu et al. 2001</xref>)</td>
<td valign="top" align="left">Nigeria</td>
<td valign="top" align="left">1272 school children</td>
<td valign="top" align="left">Area A (TAN-edemic)</td>
<td valign="top" align="left">73 &#x003BC;mol/L</td>
<td valign="top" align="left">Tropical Ataxic Neuropathy</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td valign="top" align="left">Areas C (North-low cassava consumption)</td>
<td valign="top" align="left">17 &#x003BC;mol/L</td>
<td/>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B86">Tshala-Katumbay et al. 2001</xref>)</td>
<td valign="top" align="left">DRC</td>
<td valign="top" align="left">2,723 inhabitants, with 55 konzo cases</td>
<td valign="top" align="left" colspan="2">1128 &#x003BC;mol/L</td>
<td valign="top" align="left">Konzo</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B16">Bonmarin et al. 2002</xref>)</td>
<td valign="top" align="left">DRC</td>
<td valign="top" align="left">237 confirmed Konzo cases</td>
<td valign="top" align="left" colspan="2">N/A</td>
<td valign="top" align="left">Konzo</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B32">Ernesto et al. 2002</xref>)</td>
<td valign="top" align="left">Mozambique</td>
<td valign="top" align="left">30 schoolchildren per site from 5 communities</td>
<td valign="top" align="left">Terrene-A (sun drying</td>
<td valign="top" align="left">384 &#x003BC;mol/L</td>
<td valign="top" align="left">Konzo</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td valign="top" align="left">Mujocojo (heap fermentation)</td>
<td valign="top" align="left">225 &#x003BC;mol/L</td>
<td/>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B65">Mwanza et al. 2003</xref>)</td>
<td valign="top" align="left">DRC</td>
<td valign="top" align="left">21 Congolese patients</td>
<td valign="top" align="left" colspan="2">N/A</td>
<td valign="top" align="left">Konzo</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B19">Cardoso et al. 2004</xref>)</td>
<td valign="top" align="left">Mozambique</td>
<td valign="top" align="left">School children from four sites, 30 samples per site</td>
<td valign="top" align="left">Niboia (&#x0003E;cassava consumption)</td>
<td valign="top" align="left">351 &#x003BC;mol/L</td>
<td valign="top" align="left">Konzo</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td valign="top" align="left">Munhacuco (&#x0003C; cassava consumption)</td>
<td valign="top" align="left">58 &#x003BC;mol/L</td>
<td/>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B71">Okafor 2004</xref>)</td>
<td valign="top" align="left">Nigeria</td>
<td valign="top" align="left">85 individuals (40 Gari processors, 25 cassava consumers and 20 smokers</td>
<td valign="top" align="left">Cassava consumers</td>
<td valign="top" align="left">62 &#x003BC;mol/L</td>
<td valign="top" align="left">Acute intoxication</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td valign="top" align="left">Gari processors</td>
<td valign="top" align="left">148 &#x003BC;mol/L</td>
<td/>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B20">Chabwine et al. 2011</xref>)</td>
<td valign="top" align="left">DRC</td>
<td valign="top" align="left">61 individuals</td>
<td valign="top" align="left" colspan="2">129 &#x003BC;mol/L</td>
<td valign="top" align="left">Konzo</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B23">Ciglenecki et al. 2011</xref>)</td>
<td valign="top" align="left">Cameroon</td>
<td valign="top" align="left">469 individuals (children under 15 and women of reproductive age)</td>
<td valign="top" align="left" colspan="2">N/A</td>
<td valign="top" align="left">Konzo</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B31">Diasolua Ngudi et al. 2011</xref>)</td>
<td valign="top" align="left">DRC</td>
<td valign="top" align="left">3,015 individuals across 487 households</td>
<td valign="top" align="left" colspan="2">N/A</td>
<td valign="top" align="left">Konzo</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B11">Banea et al. 2012</xref>)</td>
<td valign="top" align="left">DRC</td>
<td valign="top" align="left">Total population of 2,206 (50 konzo cases identified)</td>
<td valign="top" align="left">Pre-intervention</td>
<td valign="top" align="left">332 &#x003BC;mol/L</td>
<td valign="top" align="left">Konzo</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td valign="top" align="left">Post-intervention</td>
<td valign="top" align="left">130 &#x003BC;mol/L</td>
<td/>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B9">Banea et al. 2013</xref>)</td>
<td valign="top" align="left">DRC</td>
<td valign="top" align="left">Total population of 1,315 (61 Konzo cases identified)</td>
<td valign="top" align="left">Pre-intervention</td>
<td valign="top" align="left">930 &#x003BC;mol/L</td>
<td valign="top" align="left">Konzo</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td valign="top" align="left">Post-intervention</td>
<td valign="top" align="left">150 &#x003BC;mol/L</td>
<td/>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B72">Oluwole and Oludiran 2013</xref>)</td>
<td valign="top" align="left">Nigeria</td>
<td valign="top" align="left">150 farmers</td>
<td valign="top" align="left" colspan="2">N/A</td>
<td valign="top" align="left">Ataxic polyneuropathy</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B17">Bumoko et al. 2014</xref>)</td>
<td valign="top" align="left">DRC</td>
<td valign="top" align="left">40 children (21 konzo, 19 non-konzo)</td>
<td valign="top" align="left">Konzo children</td>
<td valign="top" align="left">Max &#x0007E;1,032 &#x003BC;mol/L</td>
<td valign="top" align="left">&#x02022;Konzo &#x02022;Cognitive impairment</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td valign="top" align="left">Non-konzo children</td>
<td valign="top" align="left">Max&#x0007E; 688 &#x003BC;mol/L</td>
<td/>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B18">Bumoko et al. 2015</xref>)</td>
<td valign="top" align="left">DRC</td>
<td valign="top" align="left">210 children (123 konzo, 87 non-konzo)</td>
<td valign="top" align="left">Konzo children</td>
<td valign="top" align="left">519 &#x003BC;mol/L</td>
<td valign="top" align="left">Konzo</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td valign="top" align="left">Non-konzo children</td>
<td valign="top" align="left">388 &#x003BC;mol/L</td>
<td/>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B8">Banea et al. 2015a</xref>)</td>
<td valign="top" align="left">DRC</td>
<td valign="top" align="left">4,588 individuals, with 144 konzo cases</td>
<td valign="top" align="left">Pre-intervention</td>
<td valign="top" align="left">444 &#x003BC;mol/L</td>
<td valign="top" align="left">Konzo</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td valign="top" align="left">Post-intervention</td>
<td valign="top" align="left">191 &#x003BC;mol/L</td>
<td/>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B10">Banea et al. 2015b</xref>)</td>
<td valign="top" align="left">DRC</td>
<td valign="top" align="left">22,793 individuals, with 172 konzo cases</td>
<td valign="top" align="left" colspan="2">N/A</td>
<td valign="top" align="left">Konzo</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B67">Nhassico et al. 2015</xref>)</td>
<td valign="top" align="left">Mozambique</td>
<td valign="top" align="left">Population of 6,190 (77 Konzo cases and 50 school children and 50 women sample per village</td>
<td valign="top" align="left">Pre-intervention (Cava)</td>
<td valign="top" align="left">530 &#x003BC;mol/L</td>
<td valign="top" align="left">Konzo</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td valign="top" align="left">Post-intervention (Cava)</td>
<td valign="top" align="left">180 &#x003BC;mol/L</td>
<td/>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B51">Kambale et al. 2017</xref>)</td>
<td valign="top" align="left">DRC</td>
<td valign="top" align="left">209 children (122 konzo, 87 non-konzo)</td>
<td valign="top" align="left">Konzo children</td>
<td valign="top" align="left">522 &#x003BC;mol/L</td>
<td valign="top" align="left">Konzo</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td valign="top" align="left">Non-konzo children</td>
<td valign="top" align="left">385 &#x003BC;mol/L</td>
<td/>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B54">Kashala-Abotnes et al. 2018</xref>)</td>
<td valign="top" align="left">DRC</td>
<td valign="top" align="left">114 mother-child dyads (children aged 12&#x02013;48 months)</td>
<td valign="top" align="left">Children</td>
<td valign="top" align="left">617 &#x003BC;mol/L</td>
<td valign="top" align="left">Konzo</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td valign="top" align="left">Mothers</td>
<td valign="top" align="left">818 &#x003BC;mol/L</td>
<td/>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B4">Alitubeera et al. 2019</xref>)</td>
<td valign="top" align="left">Uganda</td>
<td valign="top" align="left">98 probable cases (11 months to 75 years)</td>
<td valign="top" align="left" colspan="2">N/A</td>
<td valign="top" align="left">Acute intoxication</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B83">Siddiqi et al. 2020</xref>)</td>
<td valign="top" align="left">Zambia</td>
<td valign="top" align="left">32 confirmed konzo cases (children aged 6-14 years and females &#x02265;15 years</td>
<td valign="top" align="left" colspan="2">281 &#x003BC;mol/L (<italic>median value</italic>)</td>
<td valign="top" align="left">Konzo</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B50">Kabamba et al. 2023</xref>)</td>
<td valign="top" align="left">DRC</td>
<td valign="top" align="left">406 adult participants (203 household couples)</td>
<td valign="top" align="left" colspan="2">950 &#x003BC;mol/L</td>
<td valign="top" align="left">Neurocognitive impairment</td>
</tr></tbody>
</table>
<table-wrap-foot>
<p>N/A, not reported or measured; <sup>&#x0002A;</sup> Urinary SCN/creatinine; <sup>&#x00023;</sup> not thiocyanate, but urine cyanide levels.</p>
</table-wrap-foot>
</table-wrap>
<p>Several studies demonstrated the impact of interventions aimed at improving cassava processing. For example, (<xref ref-type="bibr" rid="B9">Banea et al. 2013</xref>) reported a reduction from 930 &#x003BC;mol/L pre-intervention to 150 &#x003BC;mol/L post-intervention. Comparable declines were observed in (<xref ref-type="bibr" rid="B67">Nhassico et al. 2015</xref>) (from 530 &#x003BC;mol/L to 180 &#x003BC;mol/L) and (<xref ref-type="bibr" rid="B8">Banea et al. 2015a</xref>) (from 444 &#x003BC;mol/L to 191 &#x003BC;mol/L). In contrast, populations with safer cassava processing practices or lower cassava consumption exhibited significantly lower thiocyanate levels. For instance, (<xref ref-type="bibr" rid="B22">Chiwona-Karltun et al. 2000</xref>) and (<xref ref-type="bibr" rid="B74">Onabolu et al. 2001</xref>) reported levels as low as 50 &#x003BC;mol/L and 17 &#x003BC;mol/L, respectively, in non-endemic or low-consumption areas (<xref ref-type="table" rid="T6">Table 6</xref>).</p></sec>
<sec>
<title>3.4 Cassava processing methods and residual hydrogen cyanide (HCN) concentrations</title>
<p><xref ref-type="table" rid="T7">Table 7</xref> shows substantial variability in residual Hydrogen Cyanide (HCN) concentrations across different cassava processing methods and duration. Raw bitter cassava roots contained the highest HCN levels, with concentrations reaching 327 ppm (<xref ref-type="bibr" rid="B60">Ministry of Health, 1984</xref>). In contrast, properly processed cassava flour showed significantly reduced HCN levels, depending on the method and duration of processing. Sun-drying alone reduced HCN levels to between 30 and 95 ppm, while heap fermentation was more effective, lowering concentrations to as low as 17&#x02013;28 ppm (<xref ref-type="bibr" rid="B19">Cardoso et al., 2004</xref>; <xref ref-type="bibr" rid="B32">Ernesto et al., 2002</xref>). The combination of heap fermentation and sun-drying further reduced HCN to &#x0003C; 10&#x02013;20 ppm, particularly under lab-controlled fermentation conditions for 6 d (<xref ref-type="bibr" rid="B20">Chabwine et al., 2011</xref>).</p>
<table-wrap position="float" id="T7">
<label>Table 7</label>
<caption><p>Cassava processing methods and residual hydrogen cyanide (HCN) concentrations.</p></caption>
<table frame="box" rules="all">
<thead>
<tr style="background-color:#919498;color:#ffffff">
<th valign="top" align="left"><bold>References</bold></th>
<th valign="top" align="left"><bold>Cassava product</bold></th>
<th valign="top" align="left"><bold>Processing method</bold></th>
<th valign="top" align="left"><bold>Duration</bold></th>
<th valign="top" align="left"><bold>Mean HCN (ppm)</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Ministry of Health (<xref ref-type="bibr" rid="B60">1984</xref>)</td>
<td valign="top" align="left">Fresh roots (bitter)</td>
<td valign="top" align="left">Raw</td>
<td valign="top" align="left">N/A</td>
<td valign="top" align="left">327</td>
</tr>
 <tr>
<td/>
<td valign="top" align="left">Dried roots (bitter)</td>
<td valign="top" align="left">Sun-drying</td>
<td valign="top" align="left">1-2 d</td>
<td valign="top" align="left">95</td>
</tr>
 <tr>
<td/>
<td valign="top" align="left">Cassava flour</td>
<td valign="top" align="left">Sun-drying &#x0002B; pounding</td>
<td valign="top" align="left">1-2 d</td>
<td valign="top" align="left">40</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B32">Ernesto et al. 2002</xref>)</td>
<td valign="top" align="left">Cassava flour</td>
<td valign="top" align="left">Sun-drying</td>
<td valign="top" align="left">Not specified</td>
<td valign="top" align="left">46</td>
</tr>
 <tr>
<td/>
<td/>
<td valign="top" align="left">Heap fermentation</td>
<td valign="top" align="left">Not specified</td>
<td valign="top" align="left">28</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B19">Cardoso et al. 2004</xref>)</td>
<td valign="top" align="left">Cassava flour</td>
<td valign="top" align="left">Sun-drying</td>
<td valign="top" align="left">Not specified</td>
<td valign="top" align="left">30</td>
</tr>
 <tr>
<td/>
<td/>
<td valign="top" align="left">Heap fermentation</td>
<td valign="top" align="left">Not specified</td>
<td valign="top" align="left">17</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B20">Chabwine et al. 2011</xref>)</td>
<td valign="top" align="left">Cassava root</td>
<td valign="top" align="left">Heap fermentation &#x0002B; sun-drying</td>
<td valign="top" align="left">2&#x02013;3 days fermentation, 1&#x02013;2 days drying</td>
<td valign="top" align="left">20 <italic>(median value)</italic></td>
</tr>
 <tr>
<td/>
<td valign="top" align="left">Cassava root (lab-controlled)</td>
<td valign="top" align="left">Heap fermentation only</td>
<td valign="top" align="left">6 days</td>
<td valign="top" align="left">&#x0003C; 10</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B11">Banea et al. 2012</xref>)</td>
<td valign="top" align="left">Cassava flour</td>
<td valign="top" align="left">Soaking (pre-intervention)</td>
<td valign="top" align="left">1&#x02013;2 days</td>
<td valign="top" align="left">22</td>
</tr>
 <tr>
<td/>
<td/>
<td valign="top" align="left">Wetting (post-intervention)</td>
<td valign="top" align="left">2-hours sun / 5-hours shade</td>
<td valign="top" align="left">4-10</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B9">Banea et al. 2013</xref>)</td>
<td valign="top" align="left">Cassava flour</td>
<td valign="top" align="left">Soaking (pre-intervention)</td>
<td valign="top" align="left">1&#x02013;2 ddays</td>
<td valign="top" align="left">43-74</td>
</tr>
 <tr>
<td/>
<td/>
<td valign="top" align="left">Wetting (post-intervention)</td>
<td valign="top" align="left">2-hours sun / 5-h shade</td>
<td valign="top" align="left">9-18</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B8">Banea et al. 2015a</xref>)</td>
<td valign="top" align="left">Cassava flour</td>
<td valign="top" align="left">Soaking &#x0002B; drying (Pre-intervention)</td>
<td valign="top" align="left">2 days soaking / 1-4 days drying</td>
<td valign="top" align="left">19-41</td>
</tr>
 <tr>
<td/>
<td/>
<td valign="top" align="left">Wetting (post-intervention)</td>
<td valign="top" align="left">2-hours sun / 5-hours shade</td>
<td valign="top" align="left">8-12</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B67">Nhassico et al. 2015</xref>)</td>
<td valign="top" align="left">Cassava flour</td>
<td valign="top" align="left">Soaking &#x0002B; drying and heap fermentation (pre-intervention)</td>
<td valign="top" align="left">1-2 days</td>
<td valign="top" align="left">17-64</td>
</tr>
 <tr>
<td/>
<td/>
<td valign="top" align="left">Wetting (post-intervention)</td>
<td valign="top" align="left">2-hours sun / 5-hours shade</td>
<td valign="top" align="left">9-25</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B18">Bumoko et al. 2015</xref>)</td>
<td valign="top" align="left">Cassava flour</td>
<td valign="top" align="left">Shortened processing (not specified)</td>
<td valign="top" align="left">Not specified</td>
<td valign="top" align="left">30-200</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B51">Kambale et al. 2017</xref>)</td>
<td valign="top" align="left">Cassava flour</td>
<td valign="top" align="left">Shortened processing (not specified)</td>
<td valign="top" align="left">Not specified</td>
<td valign="top" align="left">30-200</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B54">Kashala-Abotnes et al. 2018</xref>)</td>
<td valign="top" align="left">Cassava flour</td>
<td valign="top" align="left">Soaking &#x0002B; sun-drying</td>
<td valign="top" align="left"> &#x02264; 3 nights</td>
<td valign="top" align="left">52</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B4">Alitubeera et al. 2019</xref>)</td>
<td valign="top" align="left">Cassava flour</td>
<td valign="top" align="left">likely soaking and drying</td>
<td valign="top" align="left">Not specified; likely shortened</td>
<td valign="top" align="left">88</td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B83">Siddiqi et al. 2020</xref>)</td>
<td valign="top" align="left">Cassava roots and leaves</td>
<td valign="top" align="left">Sun drying (main), soaking (less common)</td>
<td valign="top" align="left">Not specified; likely shortened</td>
<td valign="top" align="left">400 <italic>(median value)</italic></td>
</tr> <tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B50">Kabamba et al. 2023</xref>)</td>
<td valign="top" align="left">Cassava flour</td>
<td valign="top" align="left">likely soaking and sun-drying</td>
<td valign="top" align="left">Not specified; shortened</td>
<td valign="top" align="left">30&#x02013;200</td>
</tr></tbody>
</table>
</table-wrap>
<p>Studies involving wetting methods (i.e., 2 h sun and 5-h shade exposure) as a cassava processing intervention consistently achieved the lowest HCN levels. (eg.,) (<xref ref-type="bibr" rid="B11">Banea et al. 2012</xref>, <xref ref-type="bibr" rid="B9">2013</xref>, <xref ref-type="bibr" rid="B8">2015a</xref>) and (<xref ref-type="bibr" rid="B67">Nhassico et al. 2015</xref>) reported reductions from pre-intervention levels of 22&#x02013;74 ppm to post-intervention levels of 4&#x02013;25 ppm. In contrast, studies that documented unspecified or shortened processing methods consistently reported higher cyanide levels. (<xref ref-type="bibr" rid="B18">Bumoko et al. 2015</xref>); (<xref ref-type="bibr" rid="B51">Kambale et al. 2017</xref>); and (<xref ref-type="bibr" rid="B50">Kabamba et al. 2023</xref>) all recorded ranges between 30 and 200 ppm.</p></sec></sec>
<sec id="s4">
<title>4 Discussion</title>
<sec>
<title>4.1 Cassava&#x00027;s dual role in food security and cyanide-related health risks</title>
<p>This systematic review highlights the persistent public health risks associated with cyanide exposure from cassava consumption in SSA, despite the crop&#x00027;s critical role in regional food security. The findings reveal a complex interplay between agricultural practices, processing methods, and structural vulnerabilities within food systems that collectively shape the health outcomes of cassava consumers. In countries like the DRC and Mozambique, cassava was a critical staple, especially during periods of conflict, drought, or economic hardship. However, in these contexts, cassava plays a dual role: while it is a resilient and accessible food source, it also poses significant health risks due to its high cyanogenic glycoside content, particularly in bitter varieties. These risks were amplified when cassava was consumed without adequate processing, which remains common in many resource limited settings like SSA.</p>
<p>Despite the availability of effective processing methods such as wetting and heap fermentation, their adoption remains limited due to weaknesses and disruptions in SSA&#x00027;s food systems. For instance, wars and conflicts profoundly disrupt agricultural activities, food distribution, and household food security (<xref ref-type="bibr" rid="B95">Weldegiargis et al., 2023</xref>; <xref ref-type="bibr" rid="B64">Muriuki et al., 2023</xref>), forcing communities to rely heavily on inadequately processed cassava (<xref ref-type="bibr" rid="B28">Cliff et al., 1997</xref>). Socio-economic stress often forces households to rely on shortened or informal processing methods, which are less effective at detoxifying cassava. Moreover, the intentional cultivation of bitter varieties due to their pest resistance, storability, and yield further complicates efforts to reduce cyanide exposure (<xref ref-type="bibr" rid="B43">Imakumbili et al., 2019</xref>; <xref ref-type="bibr" rid="B21">Chiwona-Karltun et al., 1998</xref>; <xref ref-type="bibr" rid="B52">Kapinga et al., 1997</xref>). These food system challenges have intensified in recent years across SSA, exacerbated by climate change impacts such as prolonged dry spells, El Ni&#x000F1;o events, and cyclones (<xref ref-type="bibr" rid="B96">World Food Programme, 2024</xref>; <xref ref-type="bibr" rid="B93">United Nations Office for the Coordination of Humanitarian Affairs, 2022</xref>), all of which further entrench the over-reliance on cassava as a food security crop.</p></sec>
<sec>
<title>4.2 Geographical distribution of cyanide-related health risks</title>
<p>The burden of cassava-related health risks was concentrated in a few countries, most notably the DRC, Mozambique, Tanzania, and Nigeria. However, the absence of epidemiological data from other high cassava-consuming countries, such as Ghana and Malawi (<xref ref-type="bibr" rid="B2">Adebayo, 2023</xref>), may not necessarily indicate a lack of risk. In some cases, this may reflect weak surveillance systems to detect sub-lethal cyanide exposure or milder neurological symptoms that are not present as overt clinical cases. Nonetheless, it may also reflect the absence of key contributing factors such as wars and conflicts or the widespread use of safer processing practices, as observed in Malawi (<xref ref-type="bibr" rid="B22">Chiwona-Karltun et al., 2000</xref>). Furthermore, many of the studies included in this review are decades old, suggesting either a decline in research interest&#x02014;possibly due to reduced funding&#x02014;or a genuine reduction in incidence, potentially linked to increased awareness and improved cassava processing practices. This gap highlights the urgent need for renewed investment in research and the strengthening of surveillance systems to capture both acute and chronic health effects of cyanide exposure in cassava-consuming populations.</p></sec>
<sec>
<title>4.3 Health risks associated with cyanide exposure</title>
<p>The review revealed a consistent association between cassava consumption and neurological conditions such as konzo and tropical ataxic neuropathy (TAN). Konzo is characterized by a sudden onset of non-progressive spastic paraparesis, leading to severe motor impairment and often resulting in irreversible disability (<xref ref-type="bibr" rid="B53">Kashala-Abotnes et al., 2019</xref>; <xref ref-type="bibr" rid="B97">World Health Organization, 1996</xref>; <xref ref-type="bibr" rid="B88">Tyllesk&#x000E4;r et al., 1991</xref>). In contrast, TAN presents as a progressive condition involving both sensory and motor deficits, while broader neuropathies may arise from prolonged, low-level cyanide exposure (<xref ref-type="bibr" rid="B1">Adamolekun, 2011</xref>).</p>
<p>Biomarker data, particularly urinary thiocyanate levels, provided strong evidence of chronic cyanide exposure in affected populations (<xref ref-type="bibr" rid="B26">Cliff et al., 2011</xref>). In several studies (<xref ref-type="bibr" rid="B17">Bumoko et al., 2014</xref>, <xref ref-type="bibr" rid="B18">2015</xref>; <xref ref-type="bibr" rid="B86">Tshala-Katumbay et al., 2001</xref>; <xref ref-type="bibr" rid="B62">Mlingi et al., 1992</xref>), levels exceeded WHO recommended safety limit of 350 &#x003BC;mol/L (<xref ref-type="bibr" rid="B97">World Health Organization, 1996</xref>). In contrast, lower thiocyanate levels (&#x0003C; 350 &#x003BC;mol/L) were typically observed in populations with access to adequately processed cassava, reduced reliance on cassava as a staple, or the use of low-cyanide cassava varieties. These findings highlight the effectiveness of targeted mitigation strategies in reducing cyanide exposure and preventing associated health outcomes.</p></sec>
<sec>
<title>4.4 Effectiveness of cassava processing methods and recent advances</title>
<p>Processing methods play a critical role in determining the residual HCN levels in cassava products. Raw bitter cassava roots were found to contain extremely high HCN concentrations, reaching up to 327 ppm (<xref ref-type="bibr" rid="B60">Ministry of Health, 1984</xref>). In contrast, more effective processing techniques, particularly heap fermentation and the wetting method consistently reduced HCN levels to below the WHO&#x00027;s recommended safety limit of 10 ppm for cassava flour and dried cassava products (<xref ref-type="bibr" rid="B34">FAO/WHO, 2011</xref>). Post-intervention studies, particularly using the wetting method, demonstrated substantial reductions in HCN content, with some achieving levels as low as 4&#x02013;10 ppm (<xref ref-type="bibr" rid="B11">Banea et al., 2012</xref>, <xref ref-type="bibr" rid="B9">2013</xref>). However, the review also found that shortened or improperly applied methods, such as soaking for only 1&#x02013;2 days, often resulted in dangerously high HCN levels&#x02014;sometimes exceeding 400 ppm. These inadequate practices were frequently driven by time constraints, limited awareness, or lack of access to water. Such findings underscore the urgent need to promote improved cassava processing techniques, particularly the wetting method, and to strengthen community education on safe detoxification practices to reduce the risk of cyanide exposure.</p>
<p>In addition to traditional or conventional processing methods, recent innovations in cassava breeding and processing technologies offer promising solutions. Notably, bio fortified cassava varieties such as UMUCASS-38 (TMS 01/1371) and NR-8082, developed through collaborative efforts involving the [International Institute of Tropical Agriculture (IITA), <xref ref-type="bibr" rid="B48">2012</xref>] and Harvest Plus, combine high yield, drought tolerance, and enhanced pro vitamin A content with low cyanogenic potential (<xref ref-type="bibr" rid="B70">Odoemelam et al., 2020</xref>). These varieties have been shown to contain cyanide levels of approximately 17.02 &#x000B1; 0.02 ppm (UMUCASS-38) and 18.01 &#x000B1; 0.01 ppm (NR-8082) in flour form, which are well below the WHO&#x00027;s safety threshold of 50 ppm for fresh cassava roots (<xref ref-type="bibr" rid="B34">FAO/WHO, 2011</xref>). Technologies such as hydraulic pressing, mechanical peeling, and grated fermentation have also been developed to enhance detoxification and reduce processing time [International Institute of Tropical Agriculture (IITA), <xref ref-type="bibr" rid="B48">2012</xref>]. However, adoption of these innovations remains limited in many rural areas due to affordability constraints, weak extension services, and low awareness (<xref ref-type="bibr" rid="B69">Nweke et al., 2002</xref>). Cultural food preferences and the time-intensive nature of some improved methods may also hinder uptake. Expanding access to improved varieties, strengthening extension systems, and promoting behavior change communication are essential for scaling up safe cassava utilization.</p></sec>
<sec>
<title>4.5 Protein deficiency and nutritional vulnerability</title>
<p>Protein-deficient diets are a major underlying contributor to cyanide-related health risks. Many populations consuming bitter cassava lacked access to protein-rich foods that provide sulfur-containing amino acids, such as methionine and cysteine, critical for detoxifying cyanide into thiocyanate (<xref ref-type="bibr" rid="B80">Richie et al., 2023</xref>). Without sufficient intake of quality protein, the risk of conditions like konzo increased significantly (<xref ref-type="bibr" rid="B89">Tyllesk&#x000E4;r et al., 1995</xref>; <xref ref-type="bibr" rid="B25">Cliff et al., 1985</xref>; <xref ref-type="bibr" rid="B60">Ministry of Health, 1984</xref>). For instance, the [Integrated Food Security Phase Classification (IPC), <xref ref-type="bibr" rid="B44">2022a</xref>] estimated that approximately 26.4 million people in the DRC experienced high levels of acute food insecurity (IPC Phase 3 or above) between July and December 2022, driven by widespread poverty, conflict, displacement, low agricultural production, high food prices, and poor infrastructure [Integrated Food Security Phase Classification (IPC), <xref ref-type="bibr" rid="B45">2022b</xref>]. For instance, in Malawi &#x02013; a country where cassava is consumed &#x02013; protein poverty is evident, as most dietary protein comes from cereals that are low in essential amino acids like lysine and tryptophan [International Food Policy Research Institute (IFPRI), <xref ref-type="bibr" rid="B46">2020a</xref>,<xref ref-type="bibr" rid="B47">b</xref>; <xref ref-type="bibr" rid="B63">Muleya et al., 2022</xref>]. In addition, poor dietary diversity further contributes to deficiencies in micronutrients like selenium, calcium, and zinc, which are essential for neurological health and resilience to cyanide toxicity (<xref ref-type="bibr" rid="B56">Kurmi et al., 2023</xref>).</p></sec>
<sec>
<title>4.6 Cassava dependency and its implications for the broader food systems</title>
<p>This review also underscores how cassava toxicity reveals broader systemic vulnerabilities within SSA&#x00027;s food systems. In the context of worsening climate change, persistent conflict, economic fragility, and weak infrastructure, cassava remains one of the few accessible, drought-resilient crops, even when its consumption carries serious health risks. During the 2022/23 period, over 55 million people in 12 countries within the [Southern African Development Community (SADC), <xref ref-type="bibr" rid="B84">2022</xref>] were food insecure. Additionally, 35 non-international armed conflicts were active across Africa in 2024 (Geneva Academy of International Humanitarian Law, and Human Rights, <xref ref-type="bibr" rid="B39">2025</xref>). These persistent challenges reduce the viability of other staples, disrupt markets and agricultural production, and limit access to safe, nutritious diets. These pressures are unlikely to subside in the near future, reinforcing the chronic nature of cyanide toxicity. Strengthening food systems through continuous surveillance, support for diversified and climate-resilient agriculture, and the promotion of food sovereignty where communities control their food production and processing is essential for long term mitigation.</p></sec>
<sec>
<title>4.7 Strengths and limitations of the study</title>
<p>This review has several strengths that enhance the credibility and comprehensiveness of its findings. First, it employed a broad search strategy across multiple databases&#x02014;PubMed, Scopus, JSTOR, and AJOL, ensuring the inclusion of country and region-specific studies. Second, the methodological quality of all included studies was rigorously assessed using validated tools: JBI Critical Appraisal Checklist for Case Series and NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Third, the review adhered to the PRISMA guidelines, promoting transparency, reproducibility, and methodological rigor. Finally, the involvement of multiple reviewers in both the screening and risk of bias assessment processes helped enhance consistency and reduce the risk of selection bias. Despite these strengths, the review has a limitation. The exclusion of non-English language publications may have introduced language bias. However, to minimize this effect, studies with English titles and abstracts were screened for relevance, even if the full text was not available in English. While this approach helped reduce the risk of overlooking important studies, it may still have led to the omission of valuable data published in other languages.</p></sec></sec>
<sec id="s5">
<title>5 Conclusion</title>
<p>This systematic review has underscored the ongoing public health threat posed by cassava cyanide toxicity in SSA, particularly in countries like the DRC and Mozambique, where the combined effects of conflict, drought, protein-deficient diets, and unsustainable food systems continue to undermine food and nutrition security. These challenges have intensified in recent years across SSA exacerbated by climate change phenomena such as prolonged dry spells, El Ni&#x000F1;o, and cyclones, along with global economic and political instability. Together, these factors reinforce reliance on cassava as a staple crop, increasing the risk of cyanide exposure, especially in communities lacking access to improved processing methods or safer cassava varieties.</p>
<p>While notable progress has been made through the development of low-cyanide cassava varieties (e.g., bio fortified cassava varieties) and improved processing innovations (e.g., wetting method), adoption remains uneven due to limited awareness, time constraints, inadequate extension support, cultural preferences, and water scarcity. Scaling up education on effective detoxification techniques such as wetting and heap fermentation and ensuring the availability and affordability of low-HCN cassava varieties are critical steps forward. Achieving this requires not only technical solutions but also broader support for food system transformation through research investment and community-led approaches that prioritize food sovereignty.</p></sec>
</body>
<back>
<sec sec-type="data-availability" id="s6">
<title>Data availability statement</title>
<p>The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author.</p>
</sec>
<sec sec-type="author-contributions" id="s7">
<title>Author contributions</title>
<p>GO: Writing &#x02013; review &#x00026; editing, Conceptualization, Writing &#x02013; original draft, Investigation, Formal analysis, Data curation, Methodology, Visualization. WM: Investigation, Writing &#x02013; review &#x00026; editing, Conceptualization, Writing &#x02013; original draft, Visualization, Methodology, Data curation, Formal analysis. KM: Conceptualization, Writing &#x02013; review &#x00026; editing, Formal analysis, Methodology. TN-M: Conceptualization, Supervision, Methodology, Writing &#x02013; review &#x00026; editing. AK: Visualization, Supervision, Writing &#x02013; review &#x00026; editing, Methodology, Conceptualization.</p>
</sec>
<sec sec-type="funding-information" id="s8">
<title>Funding</title>
<p>The author(s) declare that no financial support was received for the research and/or publication of this article.</p>
</sec>
<ack><p>The authors would like to thank the Lilongwe University of Agriculture and Natural Resources (LUANAR), where the review has been conducted, and the librarian, Antony Nyangulu, at the university for guidance on literature search.</p>
</ack>
<sec sec-type="COI-statement" id="conf1">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec sec-type="ai-statement" id="s9">
<title>Generative AI statement</title>
<p>The author(s) declare that no Gen AI was used in the creation of this manuscript.</p>
<p>Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.</p></sec>
<sec sec-type="disclaimer" id="s10">
<title>Publisher&#x00027;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<ref-list>
<title>References</title>
<ref id="B1">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Adamolekun</surname> <given-names>B.</given-names></name></person-group> (<year>2011</year>). Neurological disorders associated with cassava diet: a review of putative etiological mecha<italic>nisms. Metab. Brain Dis</italic>. <volume>26</volume>, <fpage>79</fpage>&#x02013;<lpage>85</lpage> <pub-id pub-id-type="doi">10.1007/s11011-011-9237-y</pub-id><pub-id pub-id-type="pmid">21327546</pub-id></citation></ref>
<ref id="B2">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Adebayo</surname> <given-names>W. G.</given-names></name></person-group> (<year>2023</year>). <article-title>Cassava production in Africa: a panel analysis of the drivers and trends</article-title>. <source>Heliyon</source> <volume>9</volume>:<fpage>e19939</fpage>. <pub-id pub-id-type="doi">10.1016/j.heliyon.2023.e19939</pub-id><pub-id pub-id-type="pmid">37809559</pub-id></citation></ref>
<ref id="B3">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Akintonwa</surname> <given-names>A.</given-names></name> <name><surname>Tunwashe</surname> <given-names>O. L.</given-names></name></person-group> (<year>1992</year>). <article-title>Fatal cyanide poisoning from cassava-based <italic>Meal. Hum. Exp</italic></article-title>. <source>Toxicol.</source> <volume>11</volume>, <fpage>47</fpage>&#x02013;<lpage>49</lpage>. <pub-id pub-id-type="doi">10.1177/096032719201100107</pub-id><pub-id pub-id-type="pmid">1354460</pub-id></citation></ref>
<ref id="B4">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Alitubeera</surname> <given-names>P. H.</given-names></name> <name><surname>Eyu</surname> <given-names>P.</given-names></name> <name><surname>Kwesiga</surname> <given-names>B.</given-names></name> <name><surname>Ario</surname> <given-names>A. R.</given-names></name> <name><surname>Zhu</surname> <given-names>B.-P.</given-names></name></person-group> (<year>2019</year>). <article-title>Outbreak of cyanide poisoning caused by consumption of cassava flour - Kasese District, Uganda, September <italic>2</italic>017</article-title>. <source>MMWR</source> <volume>68</volume>, <fpage>308</fpage>&#x02013;<lpage>311</lpage>. <pub-id pub-id-type="doi">10.15585/mmwr.mm6813a3</pub-id><pub-id pub-id-type="pmid">30946738</pub-id></citation></ref>
<ref id="B5">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Aregheore</surname> <given-names>E. M.</given-names></name> <name><surname>Agunbiade</surname> <given-names>O. O.</given-names></name></person-group> (<year>1991</year>). <article-title>The toxic effects of cassava (<italic>Manihot esculenta Grantz</italic>) diets on humans: a review</article-title>. <source>Vet. Hum. Toxicol</source>. <volume>33</volume>, <fpage>274</fpage>&#x02013;<lpage>275</lpage>.<pub-id pub-id-type="pmid">1650055</pub-id></citation></ref>
<ref id="B6">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Baguma</surname> <given-names>M.</given-names></name> <name><surname>Nzabara</surname> <given-names>F.</given-names></name> <name><surname>Maheshe Balemba</surname> <given-names>G.</given-names></name> <name><surname>Malembaka</surname> <given-names>E. B.</given-names></name> <name><surname>Migabo</surname> <given-names>C.</given-names></name> <name><surname>Mudumbi</surname> <given-names>G.</given-names></name> <etal/></person-group>. (<year>2021</year>). <article-title>Konzo risk factors, determinants and etiopathogenesis: what is new? A systematic review</article-title>. <source>Neurotoxicology</source> <volume>85</volume>, <fpage>54</fpage>&#x02013;<lpage>67</lpage>. <pub-id pub-id-type="doi">10.1016/j.neuro.2021.05.001</pub-id><pub-id pub-id-type="pmid">33964344</pub-id></citation></ref>
<ref id="B7">
<citation citation-type="web"><person-group person-group-type="author"><name><surname>Bamigboye</surname> <given-names>T.</given-names></name></person-group> (<year>2023</year>). <source>Cassava: The Power Crop for Africa?s Food Future</source>. Foodlog. Available online at: <ext-link ext-link-type="uri" xlink:href="https://agrifoodnetworks.org/article/cassava-the-power-crop-for-africas-food-future">https://agrifoodnetworks.org/article/cassava-the-power-crop-for-africas-food-future</ext-link> (Accessed March 4, 2025).</citation>
</ref>
<ref id="B8">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Banea</surname> <given-names>J. P.</given-names></name> <name><surname>Bradbury</surname> <given-names>J. H.</given-names></name> <name><surname>Mandombi</surname> <given-names>C.</given-names></name> <name><surname>Nahimana</surname> <given-names>D.</given-names></name> <name><surname>Denton</surname> <given-names>I. C.</given-names></name> <name><surname>Foster</surname> <given-names>M. P.</given-names></name> <name><surname>Kuwa</surname> <given-names>N.</given-names></name></person-group> (<year>2015a</year>). <article-title>Konzo prevention in six villages in the DRC and the dependence of konzo prevalence on cyanide intake and malnutrition</article-title>. <source>Toxicol. Rep</source>. <volume>2</volume>, <fpage>609</fpage>&#x02013;<lpage>616</lpage>. <pub-id pub-id-type="doi">10.1016/j.toxrep.2015.03.014</pub-id><pub-id pub-id-type="pmid">28962396</pub-id></citation></ref>
<ref id="B9">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Banea</surname> <given-names>J. P.</given-names></name> <name><surname>Bradbury</surname> <given-names>J. H.</given-names></name> <name><surname>Mandombi</surname> <given-names>C.</given-names></name> <name><surname>Nahimana</surname> <given-names>D.</given-names></name> <name><surname>Denton</surname> <given-names>I. C.</given-names></name> <name><surname>Kuwa</surname> <given-names>N.</given-names></name> <name><surname>Tshala Katumbay</surname> <given-names>D.</given-names></name></person-group> (<year>2013</year>). <article-title>Control of konzo by detoxification of cassava flour in three villages in the Democratic Republic of Congo</article-title>. <source>Food Chem. Toxicol.</source> <volume>60</volume>, <fpage>506</fpage>&#x02013;<lpage>513</lpage>. <pub-id pub-id-type="doi">10.1016/j.fct.2013.08.012</pub-id><pub-id pub-id-type="pmid">23941775</pub-id></citation></ref>
<ref id="B10">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Banea</surname> <given-names>J. P.</given-names></name> <name><surname>Bradbury</surname> <given-names>J. H.</given-names></name> <name><surname>Nahimana</surname> <given-names>D.</given-names></name> <name><surname>Denton</surname> <given-names>I. C.</given-names></name> <name><surname>Mashukano</surname> <given-names>N.</given-names></name> <name><surname>Kuwa</surname> <given-names>N.</given-names></name></person-group> (<year>2015b</year>). <article-title>Survey of the konzo prevalence of village people and their nutrition in Kwilu District, Bandundu Province, DRC</article-title>. <source>Afr. J. Food Sci</source>. <volume>92</volume>, <fpage>43</fpage>&#x02013;<lpage>50</lpage>. <pub-id pub-id-type="doi">10.5897/AJFS2014.1206</pub-id><pub-id pub-id-type="pmid">38147025</pub-id></citation></ref>
<ref id="B11">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Banea</surname> <given-names>J. P.</given-names></name> <name><surname>Nahimana</surname> <given-names>G.</given-names></name> <name><surname>Mandombi</surname> <given-names>C.</given-names></name> <name><surname>Bradbury</surname> <given-names>J. H.</given-names></name> <name><surname>Denton</surname> <given-names>I. C.</given-names></name> <name><surname>Kuwa</surname> <given-names>N.</given-names></name></person-group> (<year>2012</year>). <article-title>Control of konzo in DRC using the wetting method on cassava flour</article-title>. <source>Food Chem. Toxicol</source>. <volume>50</volume>, <fpage>1334</fpage>&#x02013;<lpage>1337</lpage>. <pub-id pub-id-type="doi">10.1016/j.fct.2012.02.001</pub-id><pub-id pub-id-type="pmid">22342647</pub-id></citation></ref>
<ref id="B12">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Banea-Mayambu</surname> <given-names>J. P.</given-names></name> <name><surname>Tyllesk&#x000E4;r</surname> <given-names>T.</given-names></name> <name><surname>Gitebo</surname> <given-names>N.</given-names></name> <name><surname>Matadi</surname> <given-names>N.</given-names></name> <name><surname>Gebre-Medhin</surname> <given-names>M.</given-names></name> <name><surname>Rosling</surname> <given-names>H.</given-names></name></person-group> (<year>1997</year>). <article-title>Geographical and seasonal association between linamarin and cyanide exposure from cassava and the upper motor neurone disease konzo in former Zaire</article-title>. <source>Trop. Med. Int. Health</source> <volume>2</volume>, <fpage>1143</fpage>&#x02013;<lpage>1151</lpage>. <pub-id pub-id-type="doi">10.1046/j.1365-3156.1997.d01-215.x</pub-id><pub-id pub-id-type="pmid">9438470</pub-id></citation></ref>
<ref id="B13">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Banea-Mayambu</surname> <given-names>J. P.</given-names></name> <name><surname>Tyllesk&#x000E4;r</surname> <given-names>T.</given-names></name> <name><surname>Tyllesk&#x000E4;r</surname> <given-names>K.</given-names></name> <name><surname>Gebre-Medhin</surname> <given-names>M.</given-names></name> <name><surname>Rosling</surname> <given-names>H.</given-names></name></person-group> (<year>2000</year>). <article-title>Dietary cyanide from insufficiently processed cassava and growth retardation in children in the Democratic Republic of Congo (formerly Zaire)</article-title>. <source>Ann. Trop. Paediatr.</source> <volume>20</volume>, <fpage>34</fpage>&#x02013;<lpage>40</lpage>. <pub-id pub-id-type="doi">10.1080/02724930092048</pub-id><pub-id pub-id-type="pmid">10824211</pub-id></citation></ref>
<ref id="B14">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Bechoff</surname> <given-names>A.</given-names></name> <name><surname>Chijioke</surname> <given-names>U.</given-names></name> <name><surname>Westby</surname> <given-names>A.</given-names></name> <name><surname>Tomlins</surname> <given-names>K. I.</given-names></name></person-group> (<year>2018</year>). <article-title>&#x02018;Yellow is good for you&#x00027;: consumer perception and acceptability of fortified and biofortified cassava products</article-title>. <source>PLoS ONE</source> <volume>13</volume>:<fpage>e0203421</fpage>. <pub-id pub-id-type="doi">10.1371/journal.pone.0203421</pub-id><pub-id pub-id-type="pmid">30216344</pub-id></citation></ref>
<ref id="B15">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Bjornlund</surname> <given-names>V.</given-names></name> <name><surname>Bjornlund</surname> <given-names>H.</given-names></name> <name><surname>van Rooyen</surname> <given-names>A.</given-names></name></person-group> (<year>2022</year>). <article-title>Why food insecurity persists in sub-Saharan Africa: a review of existing evidence</article-title>. <source>Food Secur</source>. <volume>14</volume>, <fpage>845</fpage>&#x02013;<lpage>864</lpage>. <pub-id pub-id-type="doi">10.1007/s12571-022-01256-1</pub-id><pub-id pub-id-type="pmid">35136455</pub-id></citation></ref>
<ref id="B16">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Bonmarin</surname> <given-names>I.</given-names></name> <name><surname>Nunga</surname> <given-names>M.</given-names></name> <name><surname>Perea</surname> <given-names>W. A.</given-names></name></person-group> (<year>2002</year>). <article-title>Konzo outbreak, in the South-west of the Democratic Republic of Congo, 1996</article-title>. <source>J. Trop. Pediatr</source>. <volume>48</volume>, <fpage>234</fpage>&#x02013;<lpage>238</lpage>. <pub-id pub-id-type="doi">10.1093/tropej/48.4.234</pub-id><pub-id pub-id-type="pmid">12200986</pub-id></citation></ref>
<ref id="B17">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Bumoko</surname> <given-names>G. M.</given-names></name> <name><surname>Sombo</surname> <given-names>M. T.</given-names></name> <name><surname>Okitundu</surname> <given-names>L. D.</given-names></name> <name><surname>Mumba</surname> <given-names>D. N.</given-names></name> <name><surname>Kazadi</surname> <given-names>K. T.</given-names></name> <name><surname>Tamfum-Muyembe</surname> <given-names>J. J.</given-names></name> <etal/></person-group>. (<year>2014</year>). <article-title>Determinants of cognitive performance in children relying on cyanogenic cassava as staple food</article-title>. <source>Metab. Brain Dis</source>. <volume>29</volume>, <fpage>359</fpage>&#x02013;<lpage>366</lpage>. <pub-id pub-id-type="doi">10.1007/s11011-014-9492-9</pub-id><pub-id pub-id-type="pmid">24481810</pub-id></citation></ref>
<ref id="B18">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Bumoko</surname> <given-names>G. M. M.</given-names></name> <name><surname>Sadiki</surname> <given-names>N. H.</given-names></name> <name><surname>Rwatambuga</surname> <given-names>A.</given-names></name> <name><surname>Kayembe</surname> <given-names>K. P.</given-names></name> <name><surname>Okitundu</surname> <given-names>D. L.</given-names></name> <name><surname>Mumba Ngoyi</surname> <given-names>D.</given-names></name> <etal/></person-group>. (<year>2015</year>). <article-title>Lower serum levels of selenium, copper, and zinc are related to neuromotor impairments in children with konzo</article-title>. <source>J. Neurol. Sci</source>. <volume>349</volume>, <fpage>149</fpage>&#x02013;<lpage>153</lpage>. <pub-id pub-id-type="doi">10.1016/j.jns.2015.01.007</pub-id><pub-id pub-id-type="pmid">25592410</pub-id></citation></ref>
<ref id="B19">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Cardoso</surname> <given-names>A. P.</given-names></name> <name><surname>Ernesto</surname> <given-names>M.</given-names></name> <name><surname>Nicala</surname> <given-names>D.</given-names></name> <name><surname>Mirione</surname> <given-names>E.</given-names></name> <name><surname>Chavane</surname> <given-names>L.</given-names></name> <name><surname>N&#x00027;zwalo</surname> <given-names>H.</given-names></name> <etal/></person-group>. (<year>2004</year>). <article-title>Combination of cassava flour cyanide and urinary thiocyanate measurements of school children in Mozambique</article-title>. <source>Int. J. Food Sci. Nutr</source>. <volume>55</volume>, <fpage>183</fpage>&#x02013;<lpage>190</lpage>. <pub-id pub-id-type="doi">10.1080/09637480410001725265</pub-id><pub-id pub-id-type="pmid">15223594</pub-id></citation></ref>
<ref id="B20">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Chabwine</surname> <given-names>J. N.</given-names></name> <name><surname>Masheka</surname> <given-names>C.</given-names></name> <name><surname>Balol&#x00027;ebwami</surname> <given-names>Z.</given-names></name> <name><surname>Maheshe</surname> <given-names>B.</given-names></name> <name><surname>Balegamire</surname> <given-names>S.</given-names></name> <name><surname>Rutega</surname> <given-names>B.</given-names></name> <etal/></person-group>. (<year>2011</year>). <article-title>Appearance of konzo in South-Kivu, a wartorn area in the Democratic Republic of Congo</article-title>. <source>Food Chem. Toxicol</source>. <volume>49</volume>, <fpage>644</fpage>&#x02013;<lpage>649</lpage>. <pub-id pub-id-type="doi">10.1016/j.fct.2010.07.050</pub-id><pub-id pub-id-type="pmid">20691241</pub-id></citation></ref>
<ref id="B21">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Chiwona-Karltun</surname> <given-names>L.</given-names></name> <name><surname>Mkumbira</surname> <given-names>J.</given-names></name> <name><surname>Saka</surname> <given-names>J.</given-names></name> <name><surname>Bovin</surname> <given-names>M.</given-names></name> <name><surname>Mahungu</surname> <given-names>N. M.</given-names></name> <name><surname>Rosling</surname> <given-names>H.</given-names></name></person-group> (<year>1998</year>). <article-title>The importance of being bitter-a qualitative study on cassava cultivar preference in Malawi</article-title>. <source>Ecol. Food Nutr.</source> <volume>37</volume>, <fpage>219</fpage>&#x02013;<lpage>245</lpage>. <pub-id pub-id-type="doi">10.1080/03670244.1998.9991546</pub-id></citation>
</ref>
<ref id="B22">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Chiwona-Karltun</surname> <given-names>L.</given-names></name> <name><surname>Tylleskar</surname> <given-names>T.</given-names></name> <name><surname>Mkumbira</surname> <given-names>J.</given-names></name> <name><surname>Gebre-Medhin</surname> <given-names>M.</given-names></name> <name><surname>Rosling</surname> <given-names>H.</given-names></name></person-group> (<year>2000</year>). <article-title>Low dietary cyanogen exposure from frequent consumption of potentially toxic cassava in Malawi</article-title>. <source>Int. J. Food Sci. Nutr</source>. <volume>51</volume>, <fpage>33</fpage>&#x02013;<lpage>43</lpage>. <pub-id pub-id-type="doi">10.1080/096374800100886</pub-id><pub-id pub-id-type="pmid">10746103</pub-id></citation></ref>
<ref id="B23">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Ciglenecki</surname> <given-names>I.</given-names></name> <name><surname>Eyema</surname> <given-names>R.</given-names></name> <name><surname>Kabanda</surname> <given-names>C.</given-names></name> <name><surname>Taafo</surname> <given-names>F.</given-names></name> <name><surname>Mekaoui</surname> <given-names>H.</given-names></name> <name><surname>Gaffga</surname> <given-names>N.</given-names></name></person-group> (<year>2011</year>). <article-title>Konzo outbreak among refugees from Central African Republic in Eastern region, Cameroon</article-title>. <source>Food Chem. Toxicol</source>. <volume>49</volume>, <fpage>579</fpage>&#x02013;<lpage>582</lpage>. <pub-id pub-id-type="doi">10.1016/j.fct.2010.05.081</pub-id><pub-id pub-id-type="pmid">20538034</pub-id></citation></ref>
<ref id="B24">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Cliff</surname> <given-names>J.</given-names></name> <name><surname>Essers</surname> <given-names>S.</given-names></name> <name><surname>Rosling</surname> <given-names>H.</given-names></name></person-group> (<year>1986</year>). <article-title>Ankle clonus correlating with cyanide intake from cassava in rural children from Mozambique</article-title>. <source>J. Trop. Pediatr</source>. <volume>32</volume>, <fpage>186</fpage>&#x02013;<lpage>189</lpage>. <pub-id pub-id-type="doi">10.1093/tropej/32.4.186</pub-id><pub-id pub-id-type="pmid">3773036</pub-id></citation></ref>
<ref id="B25">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Cliff</surname> <given-names>J.</given-names></name> <name><surname>M&#x000E5;rtensson</surname> <given-names>J.</given-names></name> <name><surname>Lundqvist</surname> <given-names>P.</given-names></name> <name><surname>Rosling</surname> <given-names>H.</given-names></name> <name><surname>S&#x000F6;rbo</surname> <given-names>B.</given-names></name></person-group> (<year>1985</year>). <article-title>Association of high cyanide and low sulphur intake in cassava-induced spastic paraparesis</article-title>. <source>Lancet</source> <volume>326</volume>, <fpage>1211</fpage>&#x02013;<lpage>1215</lpage>. <pub-id pub-id-type="doi">10.1016/S0140-6736(85)90742-1</pub-id><pub-id pub-id-type="pmid">2866292</pub-id></citation></ref>
<ref id="B26">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Cliff</surname> <given-names>J.</given-names></name> <name><surname>Muquingue</surname> <given-names>H.</given-names></name> <name><surname>Nhassico</surname> <given-names>D.</given-names></name> <name><surname>Nzwalo</surname> <given-names>H.</given-names></name> <name><surname>Bradbury</surname> <given-names>J. H.</given-names></name></person-group> (<year>2011</year>). <article-title>Konzo and continuing cyanide intoxication from cassava in Mozambique</article-title>. <source>Food Chem. Toxicol.</source> <volume>49</volume>, <fpage>631</fpage>&#x02013;<lpage>635</lpage>. <pub-id pub-id-type="doi">10.1016/j.fct.2010.06.056</pub-id><pub-id pub-id-type="pmid">20654676</pub-id></citation></ref>
<ref id="B27">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Cliff</surname> <given-names>J.</given-names></name> <name><surname>Nicala</surname> <given-names>D.</given-names></name></person-group> (<year>1997</year>). <article-title>Long term follow-up of konzo patients</article-title>. <source>Trans. R. Soc. Trop. Med. Hyg</source>. <volume>91</volume>, <fpage>447</fpage>&#x02013;<lpage>449</lpage>. <pub-id pub-id-type="doi">10.1016/S0035-9203(97)90279-0</pub-id><pub-id pub-id-type="pmid">9373651</pub-id></citation></ref>
<ref id="B28">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Cliff</surname> <given-names>J.</given-names></name> <name><surname>Nicala</surname> <given-names>D.</given-names></name> <name><surname>Saute</surname> <given-names>F.</given-names></name> <name><surname>Givragy</surname> <given-names>R.</given-names></name> <name><surname>Azambuja</surname> <given-names>G.</given-names></name> <name><surname>Taela</surname> <given-names>A.</given-names></name> <etal/></person-group>. (<year>1997</year>). <article-title>Konzo associated with war in Mozambique</article-title>. <source>Trop. Med. Int. Health</source> <volume>2</volume>, <fpage>1068</fpage>&#x02013;<lpage>1074</lpage>. <pub-id pub-id-type="doi">10.1046/j.1365-3156.1997.d01-178.x</pub-id><pub-id pub-id-type="pmid">9391509</pub-id></citation></ref>
<ref id="B29">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Cliff</surname> <given-names>J.</given-names></name> <name><surname>Nicala</surname> <given-names>D.</given-names></name> <name><surname>Saute</surname> <given-names>F.</given-names></name> <name><surname>Givragy</surname> <given-names>R.</given-names></name> <name><surname>Azambuja</surname> <given-names>G.</given-names></name> <name><surname>Taela</surname> <given-names>A.</given-names></name> <etal/></person-group>. (<year>1999</year>). <article-title>Ankle clonus and thiocyanate, linamarin, and inorganic sulphate excretion in school children in communities with konzo, Mozambique</article-title>. <source>J. Trop. Pediatr</source>. <volume>45</volume>, <fpage>139</fpage>&#x02013;<lpage>142</lpage>. <pub-id pub-id-type="doi">10.1093/tropej/45.3.139</pub-id><pub-id pub-id-type="pmid">10401190</pub-id></citation></ref>
<ref id="B30">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Cooke</surname> <given-names>A.</given-names></name> <name><surname>Smith</surname> <given-names>D.</given-names></name> <name><surname>Booth</surname> <given-names>A.</given-names></name></person-group> (<year>2012</year>). <article-title>Beyond PICO: The SPIDER tool for qualitative evidence <italic>s</italic>ynthesis</article-title>. <source>Qual. Health Res.</source> <volume>22</volume>, <fpage>1435</fpage>&#x02013;<lpage>1443</lpage>. <pub-id pub-id-type="doi">10.1177/1049732312452938</pub-id><pub-id pub-id-type="pmid">22829486</pub-id></citation></ref>
<ref id="B31">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Diasolua Ngudi</surname> <given-names>D.</given-names></name> <name><surname>Banea-Mayambu</surname> <given-names>J.-P.</given-names></name> <name><surname>Lambein</surname> <given-names>F.</given-names></name> <name><surname>Kolsteren</surname> <given-names>P.</given-names></name></person-group> (<year>2011</year>). <article-title>Konzo and dietary pattern in cassava-consuming populations of Popokabaka, Democratic Republic of Congo</article-title>. <source>Food Chem. Toxicol</source>. <volume>49</volume>, <fpage>613</fpage>&#x02013;<lpage>619</lpage>. <pub-id pub-id-type="doi">10.1016/j.fct.2010.06.053</pub-id><pub-id pub-id-type="pmid">20655972</pub-id></citation></ref>
<ref id="B32">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Ernesto</surname> <given-names>M.</given-names></name> <name><surname>Cardoso</surname> <given-names>A. P.</given-names></name> <name><surname>Nicala</surname> <given-names>D.</given-names></name> <name><surname>Mirione</surname> <given-names>E.</given-names></name> <name><surname>Massaza</surname> <given-names>F.</given-names></name> <name><surname>Cliff</surname> <given-names>J.</given-names></name> <etal/></person-group>. (<year>2002</year>). <article-title>Persistent konzo and cyanogen toxicity from cassava in northern Mozambique</article-title>. <source>Acta Trop.</source> <volume>82</volume>, <fpage>357</fpage>&#x02013;<lpage>362</lpage>. <pub-id pub-id-type="doi">10.1016/S0001-706X(02)00042-6</pub-id><pub-id pub-id-type="pmid">12039675</pub-id></citation></ref>
<ref id="B33">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Essers</surname> <given-names>A. J. A.</given-names></name> <name><surname>Alsen</surname> <given-names>P.</given-names></name> <name><surname>Rosling</surname> <given-names>H.</given-names></name></person-group> (<year>1992</year>). <article-title>Insufficient processing of cassava induced acute intoxications and the paralytic disease konzo in a rural area of Mozambique</article-title>. <source>Ecol. Food Nutr</source>. <volume>28</volume>, <fpage>61</fpage>&#x02013;<lpage>67</lpage>. <pub-id pub-id-type="doi">10.1080/03670244.1992.9991222</pub-id></citation>
</ref>
<ref id="B34">
<citation citation-type="web"><person-group person-group-type="author"><collab>FAO/WHO</collab></person-group> (<year>2011</year>). <source>Evaluation of Certain Food Additives and Contaminants: Seventy-Fourth Report of the Joint FAO/WHO Expert Committee on Food Additives (JECFA</source>). WHO Technical Report Series No. 966. Geneva: World Health Organization. Available online at: <ext-link ext-link-type="uri" xlink:href="https://apps.who.int/food-additives-contaminants-jecfa-database/Home/Chemical/1086">https://apps.who.int/food-additives-contaminants-jecfa-database/Home/Chemical/1086</ext-link> (Accessed July 2, 2025).</citation>
</ref>
<ref id="B35">
<citation citation-type="web"><person-group person-group-type="author"><collab>FAOSTAT</collab></person-group> (<year>2025</year>). <source>Cassava production trends (2000&#x02013;2023</source>). Food and Agriculture Organization of the United Nations. Available online at: <ext-link ext-link-type="uri" xlink:href="https://www.fao.org/faostat">https://www.fao.org/faostat</ext-link> (Accessed May 16, 2025).</citation>
</ref>
<ref id="B36">
<citation citation-type="web"><person-group person-group-type="author"><collab>Food and Agriculture Organization of the United Nations (FAO)</collab></person-group> (<year>2022</year>). <source>Exploring Cassava Futures: Building Cassava Climate Resilient Pathways In Lao PDR</source>. FAO. Available online at: <ext-link ext-link-type="uri" xlink:href="https://openknowledge.fao.org/server/api/core/bitstreams/98589197-5042-4321-b699-430c504f3091/content">https://openknowledge.fao.org/server/api/core/bitstreams/98589197-5042-4321-b699-430c504f3091/content</ext-link> (Accessed November 7, 2024).</citation>
</ref>
<ref id="B37">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Forkum</surname> <given-names>A. T.</given-names></name> <name><surname>Wung</surname> <given-names>A. E.</given-names></name> <name><surname>Kelese</surname> <given-names>M. T.</given-names></name> <name><surname>Ndum</surname> <given-names>C. M.</given-names></name> <name><surname>Lontum</surname> <given-names>A.</given-names></name> <name><surname>Kamga</surname> <given-names>E. B.</given-names></name> <etal/></person-group>. (<year>2025</year>). <article-title>Safety of cassava and cassava-based products: a systematic review</article-title>. <source>Front. Sust. Food Syst</source>. <volume>9</volume>:<fpage>1497609</fpage>. <pub-id pub-id-type="doi">10.3389/fsufs.2025.1497609</pub-id></citation>
</ref>
<ref id="B38">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Fukushima</surname> <given-names>A. R.</given-names></name> <name><surname>Nicoletti</surname> <given-names>M. A.</given-names></name> <name><surname>Rodrigues</surname> <given-names>A. J.</given-names></name> <name><surname>Pressutti</surname> <given-names>C.</given-names></name> <name><surname>Almeida</surname> <given-names>J.</given-names></name> <name><surname>Brand&#x000E3;o</surname> <given-names>T.</given-names></name> <etal/></person-group>. (<year>2016</year>). <article-title>Cassava flour: quantification of cyanide content</article-title>. <source>Food Nutr. Sci.</source> <volume>7</volume>, <fpage>592</fpage>&#x02013;<lpage>599</lpage>. <pub-id pub-id-type="doi">10.4236/fns.2016.77060</pub-id><pub-id pub-id-type="pmid">32653027</pub-id></citation></ref>
<ref id="B39">
<citation citation-type="web"><person-group person-group-type="author"><collab>Geneva Academy of International Humanitarian Law and Human Rights.</collab></person-group> (<year>2025</year>). <source>Today&#x00027;s Armed Conflicts &#x02013; Rule of Law in Armed Conflict (RULAC</source>) <italic>Portal</italic>. Geneva: Geneva Academy. Available online at: <ext-link ext-link-type="uri" xlink:href="https://www.geneva-academy.ch/galleries/today-s-armed-conflicts">https://www.geneva-academy.ch/galleries/today-s-armed-conflicts</ext-link> [Accessed Jul. 9, 2025].</citation>
</ref>
<ref id="B40">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Hood</surname> <given-names>A. S. C.</given-names></name> <name><surname>Shackelford</surname> <given-names>G. E.</given-names></name> <name><surname>Christie</surname> <given-names>A. P.</given-names></name> <name><surname>Usieta</surname> <given-names>H. O.</given-names></name> <name><surname>Martin</surname> <given-names>P. A.</given-names></name> <name><surname>Sutherland</surname> <given-names>W. J.</given-names></name> <etal/></person-group>. (<year>2023</year>). <article-title>A systematic map of cassava farming practices and their agricultural and environmental impacts using new ontologies: agri-ontologies 1.0</article-title>. <source>Ecol. Solut. Evid.</source> <volume>4</volume>:<fpage>e12249</fpage>. <pub-id pub-id-type="doi">10.1002/2688-8319.12249</pub-id></citation>
</ref>
<ref id="B41">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Howlett</surname> <given-names>W. P.</given-names></name> <name><surname>Brubaker</surname> <given-names>G.</given-names></name> <name><surname>Mlingi</surname> <given-names>N.</given-names></name> <name><surname>Rosling</surname> <given-names>H.</given-names></name></person-group> (<year>1992</year>). <article-title>A geographical cluster of konzo in Tanzania</article-title>. <source>J. Trop. Geogr. Neurol</source>. <volume>2</volume>, <fpage>102</fpage>&#x02013;<lpage>108</lpage>.</citation>
</ref>
<ref id="B42">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Howlett</surname> <given-names>W. P.</given-names></name> <name><surname>Brubaker</surname> <given-names>G. R.</given-names></name> <name><surname>Mlingi</surname> <given-names>N.</given-names></name> <name><surname>Rosling</surname> <given-names>H.</given-names></name></person-group> (<year>1990</year>). <article-title>Konzo, an epidemic upper motor neuron disease studied in Tanzania</article-title>. <source>Brain</source> <volume>113</volume>, <fpage>223</fpage>&#x02013;<lpage>235</lpage>. <pub-id pub-id-type="doi">10.1093/brain/113.1.223</pub-id><pub-id pub-id-type="pmid">2302534</pub-id></citation></ref>
<ref id="B43">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Imakumbili</surname> <given-names>M. L. E.</given-names></name> <name><surname>Semu</surname> <given-names>E.</given-names></name> <name><surname>Semoka</surname> <given-names>J. M. R.</given-names></name> <name><surname>Abass</surname> <given-names>A.</given-names></name> <name><surname>Mkamilo</surname> <given-names>G.</given-names></name></person-group> (<year>2019</year>). &#x02018;Farmers&#x00027; perceptions on the causes of cassava root bitterness: a case of konzo-affected Mtwara region, Tanzania&#x00027;, <italic>PLoS ONE</italic> 14:e0215527. <pub-id pub-id-type="doi">10.1371/journal.pone.0215527</pub-id><pub-id pub-id-type="pmid">30998724</pub-id></citation></ref>
<ref id="B44">
<citation citation-type="web"><person-group person-group-type="author"><collab>Integrated Food Security Phase Classification (IPC)</collab></person-group> (<year>2022a</year>). <source>Democratic Republic of the Congo: Over 26 Million People Experiencing High Levels of Acute Food Insecurity</source>, 70. Available online at: <ext-link ext-link-type="uri" xlink:href="https://www.ipcinfo.org/ipcinfo-website/alerts-archive/issue-70/en/">https://www.ipcinfo.org/ipcinfo-website/alerts-archive/issue-70/en/</ext-link> (Accessed July 8, 2025).</citation>
</ref>
<ref id="B45">
<citation citation-type="web"><person-group person-group-type="author"><collab>Integrated Food Security Phase Classification (IPC)</collab></person-group> (<year>2022b</year>). <source>Democratic Republic of the Congo: Acute Food Insecurity Situation July - December 2022 and Projection for January - June 2023</source>. Rome: IPC Global Partners. Available online at: <ext-link ext-link-type="uri" xlink:href="https://www.ipcinfo.org/ipc-country-analysis/details-map/en/c/1155972/?iso3=COD">https://www.ipcinfo.org/ipc-country-analysis/details-map/en/c/1155972/?iso3=COD</ext-link> (Accessed July 8, 2025).</citation>
</ref>
<ref id="B46">
<citation citation-type="web"><person-group person-group-type="author"><collab>International Food Policy Research Institute (IFPRI)</collab></person-group> (<year>2020a</year>). <source>Nutrient Consumption and Dietary Patterns in Malawi</source>. Available online at: <ext-link ext-link-type="uri" xlink:href="https://ebrary.ifpri.org/digital/api/collection/p15738coll2/id/133599/download">https://ebrary.ifpri.org/digital/api/collection/p15738coll2/id/133599/download</ext-link> (Accessed July 5, 2025).</citation>
</ref>
<ref id="B47">
<citation citation-type="web"><person-group person-group-type="author"><collab>International Food Policy Research Institute (IFPRI)</collab></person-group> (<year>2020b</year>). <source>Malawi Strategy Support Program: Supporting Evidence-Based Policy Planning for Food Security and Nutrition</source>. <publisher-loc>Washington, DC</publisher-loc>: <publisher-name>IFPRI</publisher-name>. Available online at: <ext-link ext-link-type="uri" xlink:href="https://www.ifpri.org/program/malawi-strategy-support-program">https://www.ifpri.org/program/malawi-strategy-support-program</ext-link> (Accessed July 4, 2025).</citation>
</ref>
<ref id="B48">
<citation citation-type="book"><person-group person-group-type="author"><collab>International Institute of Tropical Agriculture (IITA)</collab></person-group> (<year>2012</year>). <source>Cassava Processing and Utilization. IITA Research Guide Series</source>. <publisher-loc>Ibadan</publisher-loc>: <publisher-name>IITA</publisher-name>.</citation>
</ref>
<ref id="B49">
<citation citation-type="web"><person-group person-group-type="author"><collab>Joanna Briggs Institute (JBI)</collab></person-group> (<year>2017</year>). <source>JBI Critical Appraisal Checklist for Case Series</source>. The University of Adelaide. Available online at: <ext-link ext-link-type="uri" xlink:href="https://jbi.global/critical-appraisal-tools">https://jbi.global/critical-appraisal-tools</ext-link></citation>
</ref>
<ref id="B50">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kabamba</surname> <given-names>V. H.</given-names></name> <name><surname>Luwa</surname> <given-names>D. O.</given-names></name> <name><surname>Banea</surname> <given-names>J. P. M.</given-names></name> <name><surname>Giordani</surname> <given-names>B.</given-names></name> <name><surname>Boivin</surname> <given-names>M. J.</given-names></name> <name><surname>Mumba-Ngoyi</surname> <given-names>D.</given-names></name> <etal/></person-group>. (<year>2023</year>). <article-title>Screening for neurocognitive deficits in adult populations reliant on toxic cassava as the main source of food</article-title>. <source>Ann. Afr. M&#x000E9;d.</source> <volume>16</volume>, <fpage>e5028</fpage>&#x02013;<lpage>e5038</lpage>. <pub-id pub-id-type="doi">10.4314/aamed.v16i2.2</pub-id></citation>
</ref>
<ref id="B51">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kambale</surname> <given-names>K. J.</given-names></name> <name><surname>Ali</surname> <given-names>E. R.</given-names></name> <name><surname>Sadiki</surname> <given-names>N. H.</given-names></name> <name><surname>Kayembe</surname> <given-names>K. P.</given-names></name> <name><surname>Mvumbi</surname> <given-names>L. G.</given-names></name> <name><surname>Yandju</surname> <given-names>D. L.</given-names></name> <etal/></person-group>. (<year>2017</year>). <article-title>Lower sulfurtransferase detoxification rates of cyanide in konzo-a tropical spastic paralysis linked to cassava cyanogenic poisoning</article-title>. <source>Neurotoxicology</source> <volume>59</volume>, <fpage>256</fpage>&#x02013;<lpage>262</lpage>. <pub-id pub-id-type="doi">10.1016/j.neuro.2016.05.016</pub-id><pub-id pub-id-type="pmid">27246648</pub-id></citation></ref>
<ref id="B52">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kapinga</surname> <given-names>R.</given-names></name> <name><surname>Mlingi</surname> <given-names>N.</given-names></name> <name><surname>Rosling</surname> <given-names>H.</given-names></name></person-group> (<year>1997</year>). <article-title>Reasons for use of bitter cassava in Southern Tanzania</article-title>. <source>Afr. J. Trop. Root Crops</source> <volume>2</volume>, <fpage>81</fpage>&#x02013;<lpage>84</lpage>.</citation>
</ref>
<ref id="B53">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kashala-Abotnes</surname> <given-names>E.</given-names></name> <name><surname>Okitundu</surname> <given-names>D.</given-names></name> <name><surname>Mumba</surname> <given-names>D.</given-names></name> <name><surname>Boivin</surname> <given-names>M. J.</given-names></name> <name><surname>Tyllesk&#x000E4;r</surname> <given-names>T.</given-names></name> <name><surname>Tshala-Katumbay</surname> <given-names>D.</given-names></name></person-group> (<year>2019</year>). <article-title>Konzo: a distinct neurological disease associated with food (cassava) cyanogenic poisoning</article-title>. <source>Brain Res. Bull</source>. <volume>145</volume>, <fpage>87</fpage>&#x02013;<lpage>91</lpage>. <pub-id pub-id-type="doi">10.1016/j.brainresbull.2018.07.001</pub-id><pub-id pub-id-type="pmid">29981837</pub-id></citation></ref>
<ref id="B54">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kashala-Abotnes</surname> <given-names>E.</given-names></name> <name><surname>Sombo</surname> <given-names>M. T.</given-names></name> <name><surname>Okitundu</surname> <given-names>D. L.</given-names></name> <name><surname>Kunyu</surname> <given-names>M.</given-names></name> <name><surname>Makila-Mabe</surname> <given-names>G. B.</given-names></name> <name><surname>Tyllesk&#x000E4;r</surname> <given-names>T.</given-names></name> <etal/></person-group>. (<year>2018</year>). <article-title>Dietary cyanogen exposure and early child neurodevelopment: an observational study from the Democratic Republic of Congo</article-title>. <source>PLoS ONE</source> <volume>13</volume>:<fpage>e0193261</fpage>. <pub-id pub-id-type="doi">10.1371/journal.pone.0193261</pub-id><pub-id pub-id-type="pmid">29664942</pub-id></citation></ref>
<ref id="B55">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kuliahsari</surname> <given-names>D. E.</given-names></name> <name><surname>Sari</surname> <given-names>I. N. I.</given-names></name> <name><surname>Estiasih</surname> <given-names>T.</given-names></name></person-group> (<year>2021</year>). <article-title>Cyanide detoxification methods in food: a review</article-title>. <source>IOP Conf. Ser. Earth Environ. Sci.</source> <volume>733</volume>:<fpage>012099</fpage>. <pub-id pub-id-type="doi">10.1088/1755-1315/733/1/012099</pub-id></citation>
</ref>
<ref id="B56">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kurmi</surname> <given-names>A.</given-names></name> <name><surname>Jayswal</surname> <given-names>D. K.</given-names></name> <name><surname>Saikia</surname> <given-names>D.</given-names></name> <name><surname>Lal</surname> <given-names>N.</given-names></name></person-group> (<year>2023</year>). <article-title>&#x0201C;Current perspective on malnutrition and human health,&#x0201D;</article-title> in <source>Nano-Biofortification for Human and Environmental Health</source>, eds. V. D. Rajput and S. K. Verma (New York, NY: Springer), <fpage>155</fpage>&#x02013;<lpage>177</lpage>. <pub-id pub-id-type="doi">10.1007/978-3-031-35147-1_9</pub-id></citation>
</ref>
<ref id="B57">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Lykkesfeldt</surname> <given-names>J.</given-names></name> <name><surname>Lindberg M&#x000F8;ller</surname> <given-names>B.</given-names></name></person-group> (<year>1994</year>). Cyanogenic glycosides in cassava, <italic>Manihot esculenta Crantz. Acta Chem. Scand</italic>. <volume>48</volume>, <fpage>178</fpage>&#x02013;<lpage>180</lpage>. <pub-id pub-id-type="doi">10.3891/acta.chem.scand.48-0178</pub-id></citation>
</ref>
<ref id="B58">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Makene</surname> <given-names>W. J.</given-names></name> <name><surname>Wilson</surname> <given-names>J.</given-names></name></person-group> (<year>1972</year>). <article-title>Biochemical studies in Tanzanian patients with ataxic tropical neuropathy</article-title>. <source>J. Neurol. Neurosurg. Psychiatry</source> <volume>35</volume>, <fpage>31</fpage>&#x02013;<lpage>33</lpage>. <pub-id pub-id-type="doi">10.1136/jnnp.35.1.31</pub-id><pub-id pub-id-type="pmid">5026008</pub-id></citation></ref>
<ref id="B59">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>McMahon</surname> <given-names>J. M.</given-names></name> <name><surname>White</surname> <given-names>W. L. B.</given-names></name> <name><surname>Sayre</surname> <given-names>R. T.</given-names></name></person-group> (<year>1995</year>). <article-title>Review article: cyanogenesis in cassava (<italic>Manihot esculenta Crantz</italic>). <italic>J. Exp</italic></article-title>. <source>Bot.</source> <volume>46</volume>, <fpage>731</fpage>&#x02013;<lpage>741</lpage>. <pub-id pub-id-type="doi">10.1093/jxb/46.7.731</pub-id><pub-id pub-id-type="pmid">12432039</pub-id></citation></ref>
<ref id="B60">
<citation citation-type="journal"><person-group person-group-type="author"><collab>Ministry of Health</collab></person-group> (<year>1984</year>). <article-title>Mantakassa: an epidemic of spastic paraparesis associated with chronic cyanide intoxication in a cassava staple area of Mozambique. II. Nutritional factors and hydrocyanic acid content of cassava products</article-title>. <source>Bull. World Health Organ.</source> <volume>62</volume>, <fpage>485</fpage>&#x02013;<lpage>492</lpage>.</citation>
</ref>
<ref id="B61">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Mlingi</surname> <given-names>N.</given-names></name> <name><surname>Kimatta</surname> <given-names>S.</given-names></name> <name><surname>Rosling</surname> <given-names>H.</given-names></name></person-group> (<year>1991</year>). <article-title>Konzo, a paralytic disease observed in southern Tanzania</article-title>. <source>Trop. Doct.</source> <volume>21</volume>, <fpage>24</fpage>&#x02013;<lpage>25</lpage>. <pub-id pub-id-type="doi">10.1177/004947559102100110</pub-id><pub-id pub-id-type="pmid">1998217</pub-id></citation></ref>
<ref id="B62">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Mlingi</surname> <given-names>N.</given-names></name> <name><surname>Poulter</surname> <given-names>N. H.</given-names></name> <name><surname>Rosling</surname> <given-names>H.</given-names></name></person-group> (<year>1992</year>). <article-title>An outbreak of acute intoxications from consumption of insufficiently processed cassava in Tanzania</article-title>. <source>Nutr. Res</source>. <volume>12</volume>, <fpage>677</fpage>&#x02013;<lpage>687</lpage>. <pub-id pub-id-type="doi">10.1016/S0271-5317(05)80565-2</pub-id></citation>
</ref>
<ref id="B63">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Muleya</surname> <given-names>M.</given-names></name> <name><surname>Tang</surname> <given-names>K.</given-names></name> <name><surname>Broadley</surname> <given-names>M. R.</given-names></name> <name><surname>Salter</surname> <given-names>A. M.</given-names></name> <name><surname>Joy</surname> <given-names>E. J. M.</given-names></name></person-group> (<year>2022</year>). <article-title>&#x02018;Limited supply of protein and lysine is prevalent among the poorest households in Malawi and exacerbated by low protein quality&#x00027;</article-title>. <source>Nutrients</source> <volume>14</volume>:<fpage>2430</fpage>. <pub-id pub-id-type="doi">10.3390/nu14122430</pub-id><pub-id pub-id-type="pmid">35745160</pub-id></citation></ref>
<ref id="B64">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Muriuki</surname> <given-names>J.</given-names></name> <name><surname>Hudson</surname> <given-names>D.</given-names></name> <name><surname>Fuad</surname> <given-names>S.</given-names></name></person-group> (<year>2023</year>). <article-title>The impact of conflict on food security: evidence from household data in Ethiopia and Malawi</article-title>. <source>Agric. Food Secur</source>. <volume>12</volume>, <fpage>1</fpage>&#x02013;<lpage>20</lpage>. <pub-id pub-id-type="doi">10.1186/s40066-023-00447-z</pub-id><pub-id pub-id-type="pmid">34639298</pub-id></citation></ref>
<ref id="B65">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Mwanza</surname> <given-names>J. C. K.</given-names></name> <name><surname>Tshala-Katumbay</surname> <given-names>D.</given-names></name> <name><surname>Kayembe</surname> <given-names>D. L.</given-names></name> <name><surname>Eeg-Olofsson</surname> <given-names>K. E.</given-names></name> <name><surname>Tyllesk&#x000E4;r</surname> <given-names>T.</given-names></name></person-group> (<year>2003</year>). <article-title>Neuro-ophthalmologic findings in konzo, an upper motor neuron disorder in Africa</article-title>. <source>Eur. J. Ophthalmol</source>. <volume>13</volume>, <fpage>383</fpage>&#x02013;<lpage>389</lpage>. <pub-id pub-id-type="doi">10.1177/112067210301300409</pub-id><pub-id pub-id-type="pmid">12872796</pub-id></citation></ref>
<ref id="B66">
<citation citation-type="web"><person-group person-group-type="author"><collab>National Heart Lung, and Blood Institute (NHLBI).</collab></person-group> (<year>2013</year>). <source>Study Quality Assessment Tools</source>. U.S. Department of Health and Human Services. Available online at: <ext-link ext-link-type="uri" xlink:href="https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools">https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools</ext-link> (Accessed June 27, 2025).</citation>
</ref>
<ref id="B67">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Nhassico</surname> <given-names>D.</given-names></name> <name><surname>Bradbury</surname> <given-names>J. H.</given-names></name> <name><surname>Cliff</surname> <given-names>J.</given-names></name> <name><surname>Majonda</surname> <given-names>R.</given-names></name> <name><surname>Cuambe</surname> <given-names>C.</given-names></name> <name><surname>Denton</surname> <given-names>I. C.</given-names></name> <etal/></person-group>. (<year>2015</year>). <article-title>Use of the wetting method on cassava flour in three konzo villages in Mozambique reduces cyanide intake and may prevent konzo in future droughts</article-title>. <source>Food Sci. Nutr</source>. <volume>3</volume>, <fpage>513</fpage>&#x02013;<lpage>520</lpage>. <pub-id pub-id-type="doi">10.1002/fsn3.317</pub-id><pub-id pub-id-type="pmid">27386105</pub-id></citation></ref>
<ref id="B68">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Nhassico</surname> <given-names>D.</given-names></name> <name><surname>Muquingue</surname> <given-names>H.</given-names></name> <name><surname>Cliff</surname> <given-names>J.</given-names></name> <name><surname>Cumbana</surname> <given-names>A.</given-names></name> <name><surname>Bradbury</surname> <given-names>J. H.</given-names></name></person-group> (<year>2008</year>). <article-title>Rising African cassava production, diseases due to high cyanide intake and control measures</article-title>. <source>J. Sci. Food Agric</source>. <volume>88</volume>, <fpage>2043</fpage>&#x02013;<lpage>2049</lpage>. <pub-id pub-id-type="doi">10.1002/jsfa.3337</pub-id></citation>
</ref>
<ref id="B69">
<citation citation-type="book"><person-group person-group-type="author"><name><surname>Nweke</surname> <given-names>F. I.</given-names></name> <name><surname>Spencer</surname> <given-names>D. S. C.</given-names></name> <name><surname>Lynam</surname> <given-names>J. K.</given-names></name></person-group> (<year>2002</year>). <source>The Cassava transformation: Africa&#x00027;s Best-Kept Secret.</source> <publisher-loc>East Lansing, MI</publisher-loc>: <publisher-name>Michigan State University Press</publisher-name>.</citation>
</ref>
<ref id="B70">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Odoemelam</surname> <given-names>C. S.</given-names></name> <name><surname>Percival</surname> <given-names>B.</given-names></name> <name><surname>Ahmad</surname> <given-names>Z.</given-names></name> <name><surname>Chang</surname> <given-names>M. W.</given-names></name> <name><surname>Scholey</surname> <given-names>D.</given-names></name> <name><surname>Burton</surname> <given-names>E.</given-names></name> <etal/></person-group>. (<year>2020</year>). <article-title>Characterization of yellow root cassava and food products: investigation of cyanide and &#x003B2;-carotene concentrations</article-title>. <source>BMC Res. Notes</source> <volume>13</volume>:<fpage>333</fpage>. <pub-id pub-id-type="doi">10.1186/s13104-020-05175-2</pub-id><pub-id pub-id-type="pmid">32653027</pub-id></citation></ref>
<ref id="B71">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Okafor</surname> <given-names>P. N.</given-names></name></person-group> (<year>2004</year>). <article-title>Assessment of cyanide overload in cassava consuming populations of Nigeria and the cyanide content of some cassava based foods</article-title>. <source>Afr. J. Biotechnol</source>. <volume>3</volume>, <fpage>358</fpage>&#x02013;<lpage>361</lpage>. <pub-id pub-id-type="doi">10.5897/AJB2004.000-2068</pub-id><pub-id pub-id-type="pmid">38147025</pub-id></citation></ref>
<ref id="B72">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Oluwole</surname> <given-names>O. S. A.</given-names></name> <name><surname>Oludiran</surname> <given-names>A.</given-names></name></person-group> (<year>2013</year>). <article-title>Geospatial association of endemicity of ataxic polyneuropathy and highly cyanogenic cassava cultivars</article-title>. <source>Int. J. Health Geogr</source>. <volume>12</volume>:<fpage>41</fpage>. <pub-id pub-id-type="doi">10.1186/1476-072X-12-41</pub-id><pub-id pub-id-type="pmid">24034556</pub-id></citation></ref>
<ref id="B73">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Oluwole</surname> <given-names>O. S. A.</given-names></name> <name><surname>Onabolu</surname> <given-names>A. O.</given-names></name> <name><surname>Mtunda</surname> <given-names>K.</given-names></name> <name><surname>Mlingi</surname> <given-names>N.</given-names></name></person-group> (<year>2007</year>). &#x02018;Characterization of cassava (<italic>Manihot esculenta Crantz</italic>) varieties in Nigeria and Tanzania, and farmers&#x00027; perception of toxicity of cassava,&#x00027; <italic>J. Food Compos. Anal</italic>. <volume>20</volume>, <fpage>559</fpage>&#x02013;<lpage>567</lpage>. <pub-id pub-id-type="doi">10.1016/j.jfca.2007.04.004</pub-id></citation>
</ref>
<ref id="B74">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Onabolu</surname> <given-names>A. O.</given-names></name> <name><surname>Oluwole</surname> <given-names>O. S. A.</given-names></name> <name><surname>Bokanga</surname> <given-names>M.</given-names></name> <name><surname>Rosling</surname> <given-names>H.</given-names></name></person-group> (<year>2001</year>). <article-title>Ecological variation of intake of cassava food and dietary cyanide load in Nigerian communities</article-title>. <source>Public Health Nutr</source>. <volume>4</volume>, <fpage>871</fpage>&#x02013;<lpage>876</lpage>. <pub-id pub-id-type="doi">10.1079/PHN2001127</pub-id><pub-id pub-id-type="pmid">11527510</pub-id></citation></ref>
<ref id="B75">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Osuntokun</surname> <given-names>B. O.</given-names></name> <name><surname>Durowoju</surname> <given-names>J. E.</given-names></name> <name><surname>McFarlane</surname> <given-names>H.</given-names></name> <name><surname>Wilson</surname> <given-names>J.</given-names></name></person-group> (<year>1968</year>). <article-title>Plasma amino-acids in the Nigerian nutritional ataxic neuropathy</article-title>. <source>Br. Med. J</source>. <volume>3</volume>, <fpage>647</fpage>&#x02013;<lpage>649</lpage>. <pub-id pub-id-type="doi">10.1136/bmj.3.5619.647</pub-id><pub-id pub-id-type="pmid">5673213</pub-id></citation></ref>
<ref id="B76">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Osuntokun</surname> <given-names>B. O.</given-names></name> <name><surname>Monekosso</surname> <given-names>G. L.</given-names></name> <name><surname>Wilson</surname> <given-names>J.</given-names></name></person-group> (<year>1969</year>). <article-title>Relationship of a degenerative tropical neuropathy to diet: report of a field <italic>s</italic>urvey</article-title>. <source>Br. Med. J</source>. <volume>1</volume>, <fpage>547</fpage>&#x02013;<lpage>550</lpage>. <pub-id pub-id-type="doi">10.1136/bmj.1.5643.547</pub-id><pub-id pub-id-type="pmid">5764702</pub-id></citation></ref>
<ref id="B77">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Otekunrin</surname> <given-names>O. A.</given-names></name></person-group> (<year>2024</year>). &#x02018;Cassava (<italic>Manihot esculenta Crantz</italic>): a global scientific footprint&#x02014;production, trade, and bibliometric insights&#x00027;, <italic>Discover Agric</italic>. <volume>2</volume>:<fpage>94</fpage>. <pub-id pub-id-type="doi">10.1007/s44279-024-00121-3</pub-id></citation>
</ref>
<ref id="B78">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Page</surname> <given-names>M. J.</given-names></name> <name><surname>McKenzie</surname> <given-names>J. E.</given-names></name> <name><surname>Bossuyt</surname> <given-names>P. M.</given-names></name> <name><surname>Boutron</surname> <given-names>I.</given-names></name> <name><surname>Hoffmann</surname> <given-names>T. C.</given-names></name> <name><surname>Mulrow</surname> <given-names>C. D.</given-names></name> <etal/></person-group>. (<year>2021</year>). <article-title>The PRISMA 2020 statement: an updated guideline for reporting systematic reviews</article-title>. <source>BMJ</source> <volume>372</volume>:<fpage>n71</fpage>. <pub-id pub-id-type="doi">10.1136/bmj.n71</pub-id><pub-id pub-id-type="pmid">33782057</pub-id></citation></ref>
<ref id="B79">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Panghal</surname> <given-names>A.</given-names></name> <name><surname>Munezero</surname> <given-names>C.</given-names></name> <name><surname>Sharma</surname> <given-names>P.</given-names></name> <name><surname>Chhikara</surname> <given-names>N.</given-names></name></person-group> (<year>2021</year>). <article-title>Cassava toxicity, detoxification and its food applications: a review</article-title>. <source>Toxin Rev</source>. <volume>40</volume>, <fpage>1</fpage>&#x02013;<lpage>16</lpage>. <pub-id pub-id-type="doi">10.1080/15569543.2018.1560334</pub-id></citation>
</ref>
<ref id="B80">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Richie</surname> <given-names>J. P.</given-names></name> <name><surname>Sinha</surname> <given-names>R.</given-names></name> <name><surname>Dong</surname> <given-names>Z.</given-names></name> <name><surname>Nichenametla</surname> <given-names>S. N.</given-names></name> <name><surname>Ables</surname> <given-names>G. P.</given-names></name> <name><surname>Ciccarella</surname> <given-names>A.</given-names></name> <etal/></person-group>. (<year>2023</year>). <article-title>Dietary methionine and total sulfur amino acid restriction in healthy adults</article-title>. <source>J. Nutr. Health Aging</source> <volume>27</volume>, <fpage>111</fpage>&#x02013;<lpage>123</lpage>. <pub-id pub-id-type="doi">10.1007/s12603-023-1883-3</pub-id><pub-id pub-id-type="pmid">36806866</pub-id></citation></ref>
<ref id="B81">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Rivadeneyra-Dom&#x000ED;nguez</surname> <given-names>E.</given-names></name> <name><surname>Rodr&#x000ED;guez-Landa</surname> <given-names>J. F.</given-names></name></person-group> (<year>2020</year>). <article-title>Preclinical and clinical research on the toxic and neurological effects of cassava (<italic>Manihot esculenta Crantz</italic>) consumption</article-title>. <source>Metabol. Brain Dis.</source> <volume>35</volume>, <fpage>65</fpage>&#x02013;<lpage>74</lpage>. <pub-id pub-id-type="doi">10.1007/s11011-019-00522-0</pub-id><pub-id pub-id-type="pmid">31802307</pub-id></citation></ref>
<ref id="B82">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Salvador</surname> <given-names>E. M.</given-names></name> <name><surname>Steenkamp</surname> <given-names>V.</given-names></name> <name><surname>McCrindle</surname> <given-names>C. M. E.</given-names></name></person-group> (<year>2014</year>). <article-title>Production, consumption and nutritional value of cassava (<italic>Manihot esculenta Crantz</italic>) in Mozambique: an overview</article-title>. <source>J. Agric. Biotechnol. Sust. Dev</source>. <volume>6</volume>, <fpage>29</fpage>&#x02013;<lpage>38</lpage>. <pub-id pub-id-type="doi">10.5897/JABSD2014.0224</pub-id><pub-id pub-id-type="pmid">38147025</pub-id></citation></ref>
<ref id="B83">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Siddiqi</surname> <given-names>O. K.</given-names></name> <name><surname>Kapina</surname> <given-names>M.</given-names></name> <name><surname>Kumar</surname> <given-names>R.</given-names></name> <name><surname>Ngomah Moraes</surname> <given-names>A.</given-names></name> <name><surname>Kabwe</surname> <given-names>P.</given-names></name> <name><surname>Mazaba</surname> <given-names>M. L.</given-names></name> <etal/></person-group>. (<year>2020</year>). Konzo outbreak in the Western Province of Zambia. Neurology, <volume>94</volume>, <fpage>e1495</fpage>&#x02013;<lpage>e1501</lpage>. <pub-id pub-id-type="doi">10.1212/WNL.0000000000009017</pub-id><pub-id pub-id-type="pmid">32127386</pub-id></citation></ref>
<ref id="B84">
<citation citation-type="web"><person-group person-group-type="author"><collab>Southern African Development Community (SADC)</collab></person-group> (<year>2022</year>). <source>Synthesis Report on The State of Food and Nutrition Security and Vulnerability in Southern Africa 2022</source>. Gaborone: SADC regional vulnerability assessment and analysis programme. Available online at: <ext-link ext-link-type="uri" xlink:href="https://www.sadc.int/sites/default/files/2022-08/SADC_RVAA_Synthesis_Report_2022-ENG.pdf">https://www.sadc.int/sites/default/files/2022-08/SADC_RVAA_Synthesis_Report_2022-ENG.pdf</ext-link> (Accessed July 7, 2025).</citation>
</ref>
<ref id="B85">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Talsma</surname> <given-names>E. F.</given-names></name> <name><surname>Brouwer</surname> <given-names>I. D.</given-names></name> <name><surname>Verhoef</surname> <given-names>H.</given-names></name> <name><surname>Mbera</surname> <given-names>G. N.</given-names></name> <name><surname>Mwangi</surname> <given-names>A. M.</given-names></name> <name><surname>Demir</surname> <given-names>A. Y.</given-names></name> <etal/></person-group>. (<year>2016</year>). <article-title>Biofortified yellow cassava and vitamin A status of Kenyan children: a randomized controlled trial</article-title>. <source>Am. J. Clin. Nutr</source>. <volume>103</volume>, <fpage>258</fpage>&#x02013;<lpage>267</lpage>. <pub-id pub-id-type="doi">10.3945/ajcn.114.100164</pub-id><pub-id pub-id-type="pmid">26675768</pub-id></citation></ref>
<ref id="B86">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Tshala-Katumbay</surname> <given-names>D.</given-names></name> <name><surname>Banea-Mayambu</surname> <given-names>J. P.</given-names></name> <name><surname>Kazadi-Kayembe</surname> <given-names>T.</given-names></name> <name><surname>Nunga-Matadi</surname> <given-names>R.</given-names></name> <name><surname>Bikangi-Nkiabungu</surname> <given-names>F.</given-names></name> <name><surname>Edebol Eeg-Olofsson</surname> <given-names>K.</given-names></name> <etal/></person-group>. (<year>2001</year>). <article-title>Neuroepidemiology of konzo, a spastic para-tetraparesis of acute onset in a new area of the Democratic Republic of Congo</article-title>. <source>Afr. J. Neurol. Sci.</source> <volume>20</volume>, <fpage>13</fpage>&#x02013;<lpage>20</lpage>. <pub-id pub-id-type="doi">10.4314/ajns.v20i1.7520</pub-id></citation>
</ref>
<ref id="B87">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Tyllesk&#x000E4;r</surname> <given-names>T.</given-names></name> <name><surname>Banea</surname> <given-names>M.</given-names></name> <name><surname>Bikangi</surname> <given-names>N.</given-names></name> <name><surname>Cooke</surname> <given-names>R. D.</given-names></name> <name><surname>Poulter</surname> <given-names>N. H.</given-names></name> <name><surname>Rosling</surname> <given-names>H.</given-names></name></person-group> (<year>1992</year>). <article-title>Cassava cyanogens and konzo, an upper motoneuron disease found in Africa</article-title>. <source>Lancet</source> <volume>339</volume>, <fpage>208</fpage>&#x02013;<lpage>211</lpage>. <pub-id pub-id-type="doi">10.1016/0140-6736(92)90006-O</pub-id><pub-id pub-id-type="pmid">1346173</pub-id></citation></ref>
<ref id="B88">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Tyllesk&#x000E4;r</surname> <given-names>T.</given-names></name> <name><surname>Banea</surname> <given-names>M.</given-names></name> <name><surname>Bikangi</surname> <given-names>N.</given-names></name> <name><surname>Fresco</surname> <given-names>L.</given-names></name> <name><surname>Persson</surname> <given-names>L. A.</given-names></name> <name><surname>Rosling</surname> <given-names>H.</given-names></name></person-group> (<year>1991</year>). <article-title>Epidemiological evidence from Zaire for a dietary etiology of konzo, an upper motor neuron disease</article-title>. <source>Bull. World Health Organ</source>. 69, 581-589.<pub-id pub-id-type="pmid">1959159</pub-id></citation></ref>
<ref id="B89">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Tyllesk&#x000E4;r</surname> <given-names>T.</given-names></name> <name><surname>Banea</surname> <given-names>M.</given-names></name> <name><surname>Bikangi</surname> <given-names>N.</given-names></name> <name><surname>Nahimana</surname> <given-names>G.</given-names></name> <name><surname>Persson</surname> <given-names>L. &#x000C5;.</given-names></name> <name><surname>Rosling</surname> <given-names>H.</given-names></name></person-group> (<year>1995</year>). <article-title>Dietary determinants of a non-progressive spastic paraparesis (konzo): a case-referent study in a high incidence area of Zaire</article-title>. <source>Int. J. Epidemiol.</source> <volume>24</volume>, <fpage>949</fpage>&#x02013;<lpage>956</lpage>. <pub-id pub-id-type="doi">10.1093/ije/24.5.949</pub-id><pub-id pub-id-type="pmid">8557452</pub-id></citation></ref>
<ref id="B90">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Tyllesk&#x000E4;r</surname> <given-names>T.</given-names></name> <name><surname>Howlett</surname> <given-names>W. P.</given-names></name> <name><surname>Rwiza</surname> <given-names>H. T.</given-names></name> <name><surname>Aquilonius</surname> <given-names>S. M.</given-names></name> <name><surname>St&#x000E2;lberg</surname> <given-names>E.</given-names></name> <name><surname>Linden</surname> <given-names>B.</given-names></name> <etal/></person-group>. (<year>1993</year>). <article-title>Konzo: a distinct disease entity with selective upper motor neuron damage</article-title>. <source>J. Neurol. Neurosurg. Psychiatry</source> <volume>56</volume>, <fpage>638</fpage>&#x02013;<lpage>643</lpage>. <pub-id pub-id-type="doi">10.1136/jnnp.56.6.638</pub-id><pub-id pub-id-type="pmid">8509777</pub-id></citation></ref>
<ref id="B91">
<citation citation-type="web"><person-group person-group-type="author"><name><surname>Ulimwengu</surname> <given-names>J.</given-names></name></person-group> (<year>2024</year>). <source>Africa Pathway to Food Systems Transformation: Challenges and Opportunities.</source> IFPRI Insights Available online at: <ext-link ext-link-type="uri" xlink:href="https://www.ifpri.org/newsletter/ifpri-insights-january-2024/">https://www.ifpri.org/newsletter/ifpri-insights-january-2024/</ext-link> (Accessed January 16, 2025).<pub-id pub-id-type="pmid">39441882</pub-id></citation></ref>
<ref id="B92">
<citation citation-type="web"><person-group person-group-type="author"><collab>UNICEF</collab></person-group> (<year>2023</year>). <source>Vitamin A Deficiency</source>. <person-group person-group-type="author"><collab>UNICEF</collab></person-group>DATA. Available online at: <ext-link ext-link-type="uri" xlink:href="https://data.unicef.org/topic/nutrition/vitamin-a-deficiency/">https://data.unicef.org/topic/nutrition/vitamin-a-deficiency/</ext-link> (Accessed May 22, 2025).</citation>
</ref>
<ref id="B93">
<citation citation-type="web"><person-group person-group-type="author"><collab>United Nations Office for the Coordination of Humanitarian Affairs</collab></person-group> (<year>2022</year>). <source>OCHA Annual Report 2022</source>. United Nations Office for the Coordination of Humanitarian Affairs. Available online at: <ext-link ext-link-type="uri" xlink:href="https://www.unocha.org/publications/report/world/ocha-annual-report-2022">https://www.unocha.org/publications/report/world/ocha-annual-report-2022</ext-link> (Accessed April 13, 2025).</citation>
</ref>
<ref id="B94">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>van Heijst</surname> <given-names>A. N.</given-names></name> <name><surname>Maes</surname> <given-names>R. A.</given-names></name> <name><surname>Mtanda</surname> <given-names>A. T.</given-names></name> <name><surname>Chuwa</surname> <given-names>L. M.</given-names></name> <name><surname>Rwiza</surname> <given-names>H. T.</given-names></name> <name><surname>Moshi</surname> <given-names>N. H.</given-names></name></person-group> (<year>1994</year>). <article-title>Chronic cyanide poisoning in relation to blindness and tropical neuropathy</article-title>. <source>J. Toxicol. Clin. Toxicol</source>. <volume>32</volume>, <fpage>549</fpage>&#x02013;<lpage>556</lpage>. <pub-id pub-id-type="doi">10.3109/15563659409011059</pub-id><pub-id pub-id-type="pmid">7932914</pub-id></citation></ref>
<ref id="B95">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Weldegiargis</surname> <given-names>A. W.</given-names></name> <name><surname>Abebe</surname> <given-names>H. T.</given-names></name> <name><surname>Abraha</surname> <given-names>H. E.</given-names></name> <name><surname>Abrha</surname> <given-names>M. M.</given-names></name> <name><surname>Tesfay</surname> <given-names>T. B.</given-names></name> <name><surname>Belay</surname> <given-names>R. E.</given-names></name> <etal/></person-group>. (<year>2023</year>). <article-title>Armed conflict and household food insecurity: evidence from war-torn Tigray, Ethiopia</article-title>. <source>Confl. Health</source> <volume>17</volume>, <fpage>1</fpage>&#x02013;<lpage>9</lpage>. <pub-id pub-id-type="doi">10.1186/s13031-023-00520-1</pub-id><pub-id pub-id-type="pmid">37147686</pub-id></citation></ref>
<ref id="B96">
<citation citation-type="web"><person-group person-group-type="author"><collab>World Food Programme</collab></person-group> (<year>2024</year>). <source>WFP&#x00027;s Updated Climate Change Policy - 2024</source>. World Food Programme. Available online at: <ext-link ext-link-type="uri" xlink:href="https://www.wfp.org/publications/wfps-updated-climate-change-policy-2024">https://www.wfp.org/publications/wfps-updated-climate-change-policy-2024</ext-link> (Accessed April 13, 2025).</citation>
</ref>
<ref id="B97">
<citation citation-type="journal"><person-group person-group-type="author"><collab>World Health Organization</collab></person-group> (<year>1996</year>). <source>Konzo: A Distinct Type of Upper Motor Neuron Disease.</source> WHO document WHO/EHG/96.1<pub-id pub-id-type="pmid">8509777</pub-id></citation></ref>
</ref-list>
</back>
</article>