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<journal-id journal-id-type="publisher-id">Front. Microbiol.</journal-id>
<journal-title>Frontiers in Microbiology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Microbiol.</abbrev-journal-title>
<issn pub-type="epub">1664-302X</issn>
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<publisher-name>Frontiers Media S.A.</publisher-name>
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<article-id pub-id-type="doi">10.3389/fmicb.2025.1524287</article-id>
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<subj-group subj-group-type="heading">
<subject>Microbiology</subject>
<subj-group>
<subject>Opinion</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>The rise of non-typhoidal <italic>Salmonella</italic>: an emerging global public health concern</article-title>
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<contrib contrib-type="author" corresp="yes">
<name><surname>Kumar</surname> <given-names>Gaurav</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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<name><surname>Kumar</surname> <given-names>Sandeep</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<name><surname>Jangid</surname> <given-names>Himanshu</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<name><surname>Dutta</surname> <given-names>Joydeep</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<name><surname>Shidiki</surname> <given-names>Amrullah</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="corresp" rid="c002"><sup>&#x0002A;</sup></xref>
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<aff id="aff1"><sup>1</sup><institution>School of Bioengineering and Biosciences, Lovely Professional University, Phagwara</institution>, <addr-line>Punjab</addr-line>, <country>India</country></aff>
<aff id="aff2"><sup>2</sup><institution>Department of Microbiology, National Medical College and Teaching Hospital</institution>, <addr-line>Birgunj</addr-line>, <country>Nepal</country></aff>
<author-notes>
<fn fn-type="edited-by"><p>Edited by: Jens Andre Hammerl, Bundesinstitut f&#x000FC;r Risikobewertung, Germany</p></fn>
<fn fn-type="edited-by"><p>Reviewed by: Babak Pakbin, Texas A&#x00026;M University, United States</p></fn>
<corresp id="c001">&#x0002A;Correspondence: Amrullah Shidiki <email>amarullahsidhiqie24&#x00040;gmail.com</email></corresp>
<corresp id="c002">Gaurav Kumar <email>gauravkr01&#x00040;gmail.com</email></corresp>
</author-notes>
<pub-date pub-type="epub">
<day>04</day>
<month>02</month>
<year>2025</year>
</pub-date>
<pub-date pub-type="collection">
<year>2025</year>
</pub-date>
<volume>16</volume>
<elocation-id>1524287</elocation-id>
<history>
<date date-type="received">
<day>07</day>
<month>11</month>
<year>2024</year>
</date>
<date date-type="accepted">
<day>14</day>
<month>01</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x000A9; 2025 Kumar, Kumar, Jangid, Dutta and Shidiki.</copyright-statement>
<copyright-year>2025</copyright-year>
<copyright-holder>Kumar, Kumar, Jangid, Dutta and Shidiki</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>
<kwd-group>
<kwd>non-typhoidal <italic>Salmonella</italic></kwd>
<kwd>NTS</kwd>
<kwd>public health</kwd>
<kwd>salmonellosis</kwd>
<kwd>foodborne</kwd>
</kwd-group>
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<table-count count="1"/>
<equation-count count="0"/>
<ref-count count="41"/>
<page-count count="6"/>
<word-count count="4133"/>
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<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Infectious Agents and Disease</meta-value>
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</front>
<body>
<sec sec-type="intro" id="s1">
<title>Introduction</title>
<p>In recent years, non-typhoidal <italic>Salmonella</italic> (NTS) infections have become a considerable threat to public health. This pathogen has increased in incidence and is a health concern mostly regarded as foodborne. It is highly important to appreciate the magnitude of the problem and act decisively and systematically to curb it. NTS infections are acquired mainly via food which is contaminated such as undercooked chicken, eggs, and even unpasteurized milk (Antony, <xref ref-type="bibr" rid="B2">2023</xref>). An estimated 94% of salmonellosis cases result from the consumption of contaminated food (Ehuwa et al., <xref ref-type="bibr" rid="B15">2021</xref>). Numerous studies have highlighted the role of non-typhoidal <italic>Salmonella</italic> (NTS) in foodborne outbreaks, identifying various serovars as significant contributors. For instance, <italic>Salmonella Heidelberg</italic> has been implicated in outbreaks (Eikmeier et al., <xref ref-type="bibr" rid="B16">2018</xref>; Motladiile, <xref ref-type="bibr" rid="B26">2019</xref>), alongside <italic>S. Typhimurium</italic> (Yang et al., <xref ref-type="bibr" rid="B41">2017</xref>; Eikmeier et al., <xref ref-type="bibr" rid="B16">2018</xref>) and <italic>S. Enteritidis</italic>, which remains a dominant serovar linked to foodborne transmission (Yang et al., <xref ref-type="bibr" rid="B41">2017</xref>; Eikmeier et al., <xref ref-type="bibr" rid="B16">2018</xref>; Sevilla-Navarro et al., <xref ref-type="bibr" rid="B33">2020</xref>). Additionally, <italic>S. Infantis</italic> (Sevilla-Navarro et al., <xref ref-type="bibr" rid="B33">2020</xref>), <italic>S. Newport</italic>, and <italic>S. Saintpaul</italic> (Eikmeier et al., <xref ref-type="bibr" rid="B16">2018</xref>) have been recognized as causes of outbreaks across various geographical regions.</p>
<p>Unlike typhoidal <italic>Salmonella</italic> which causes typhoid fever, NTS usually cause gastroenteritis with less severe cases with symptoms such as diarrhea, vomiting and pains in the abdomen, however, it is often taken lightly (Sears et al., <xref ref-type="bibr" rid="B32">2023</xref>). Most of those infected remain asymptomatic, which spreads the idea that NTS is just another case of food poisoning. On the contrary, in people whose immunity is compromised, e.g. people living with HIV or those undergoing chemotherapy, NTS can infrequently cross barriers and become deleterious. Among such individuals, moderate to severe disease may also lead to hospitalization or vegetative state and lethal outcomes in some cases. The disparity in outcomes implies that whereas recovery would be swift for a good proportion of people, some of them would have to fight for their lives.</p>
<p>This paper aims to provide a comprehensive overview of NTS as an emerging public health concern, focusing on its epidemiology, rising incidence rates, and research trends across diverse regions focusing on region-specific scientific contributions, the growing challenge of antimicrobial resistance, and the economic burden associated with NTS infections, highlighting the critical need for enhanced global research and public health strategies.</p></sec>
<sec id="s2">
<title>Epidemiology and research trends</title>
<p><italic>Salmonella</italic> species, and especially non-typhoidal ones (NTS), are of serious global health concern causing most cases of gastroenteritis that amount to &#x0007E;93.8 million incidences and almost 155,000 deaths per annum, and the most affected region is Sub-Saharan Africa where invasive NTS death rate stands at 85.9% and specifically this region further kills under five-year-old children where in such cases the active case fatality increases to 20%. In Asia, NTS are comparatively rare, but still in Pakistan, an incidence rate of 7.2 per 100,000 people years has been reported (<xref ref-type="table" rid="T1">Table 1</xref>). The presence of risk factors like inadequate food safety measures, poor sanitation, and lack of safe drinking water explain the increased burden of NTS infections in such areas, placing additional pressure on weak health systems already (Ao et al., <xref ref-type="bibr" rid="B3">2015</xref>; Das et al., <xref ref-type="bibr" rid="B14">2022</xref>; Sanni et al., <xref ref-type="bibr" rid="B31">2023</xref>). The two most common serovars, <italic>Salmonella</italic> Typhimurium and <italic>Salmonella</italic> Enteritidis account for the largest raft of cases globally (WHO, <xref ref-type="bibr" rid="B39">2018</xref>; Balasubramanian et al., <xref ref-type="bibr" rid="B6">2019</xref>; Stanaway et al., <xref ref-type="bibr" rid="B37">2019</xref>; Mohakud et al., <xref ref-type="bibr" rid="B25">2022</xref>; Crump et al., <xref ref-type="bibr" rid="B12">2023</xref>). <italic>Salmonella</italic> Typhimurium is predominant in Africa and the United States (Hagedoorn et al., <xref ref-type="bibr" rid="B19">2024</xref>), where it is frequently associated with beef and poultry. In contrast, <italic>Salmonella</italic> Enteritidis is more prevalent in Europe and Asia (Hagedoorn et al., <xref ref-type="bibr" rid="B19">2024</xref>), commonly linked to imported chicken (Bloomfield et al., <xref ref-type="bibr" rid="B8">2023</xref>; Mkangara, <xref ref-type="bibr" rid="B24">2023</xref>). Beyond these, several other non-typhoidal <italic>Salmonella</italic> (NTS) serovars significantly contribute to foodborne illnesses worldwide. <italic>Salmonella</italic> Infantis is increasingly linked to human infections and is commonly found in chicken, pork, and retail foods in the UK (Bloomfield et al., <xref ref-type="bibr" rid="B8">2023</xref>). <italic>Salmonella</italic> Newport, associated with beef, is a notable serovar in the U.S. with invasive disease potential. <italic>Salmonella</italic> Dublin, primarily tied to cattle, is prevalent in Europe and Africa but also infects humans. <italic>Salmonella</italic> Heidelberg is mainly found in the Americas, frequently linked to poultry. Meanwhile, Salmonella Weltevreden is prominent in seafood from Asia and North America (Hagedoorn et al., <xref ref-type="bibr" rid="B19">2024</xref>).</p>
<table-wrap position="float" id="T1">
<label>Table 1</label>
<caption><p>Epidemiology trends of non-typhoidal <italic>Salmonella</italic> (NTS) across regions.</p></caption>
<table frame="box" rules="all">
<thead>
<tr style="background-color:#919498;color:#ffffff">
<th valign="top" align="left"><bold>Region</bold></th>
<th valign="top" align="left"><bold>Incidence</bold></th>
<th valign="top" align="left"><bold>Common serotypes</bold></th>
<th valign="top" align="left"><bold>Antibiotic resistance (%)</bold></th>
<th valign="top" align="left"><bold>Mortality rate (%)</bold></th>
<th valign="top" align="left"><bold>Hospitalization rate (%)</bold></th>
<th valign="top" align="left"><bold>References</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Sub-Saharan Africa</td>
<td valign="top" align="left">535,000 cases (2017)</td>
<td valign="top" align="left"><italic>S. Typhimurium</italic> (ST313), <italic>S. Enteritidis</italic></td>
<td valign="top" align="left">30%&#x02212;50% multidrug resistance, including cephalosporins</td>
<td valign="top" align="left">15%&#x02212;25%</td>
<td valign="top" align="left">High due to invasive disease</td>
<td valign="top" align="left">Crump et al., <xref ref-type="bibr" rid="B12">2023</xref>; Stanaway et al., <xref ref-type="bibr" rid="B37">2019</xref></td>
</tr> <tr>
<td valign="top" align="left">Southeast Asia</td>
<td valign="top" align="left">Varies, &#x0007E;7 per 100,000 PYO (Pakistan)</td>
<td valign="top" align="left"><italic>S. Typhimurium, S. Enteritidis</italic></td>
<td valign="top" align="left">Moderate resistance (especially fluoroquinolones)</td>
<td valign="top" align="left">&#x0003C; 1%</td>
<td valign="top" align="left">Moderate</td>
<td valign="top" align="left">Stanaway et al., <xref ref-type="bibr" rid="B37">2019</xref></td>
</tr> <tr>
<td valign="top" align="left">Philippines</td>
<td valign="top" align="left">Moderate prevalence</td>
<td valign="top" align="left"><italic>S. Enteritidis</italic> (60.9%), <italic>S. Typhimurium</italic> (13%)</td>
<td valign="top" align="left">Ampicillin (23.2%), Ciprofloxacin (8.7%)</td>
<td valign="top" align="left"><bold>Estimated 5%&#x02212;10%</bold> based on regional data</td>
<td valign="top" align="left"><bold>It is likely high</bold>, particularly in young children</td>
<td valign="top" align="left">Sia et al., <xref ref-type="bibr" rid="B34">2023</xref></td>
</tr> <tr>
<td valign="top" align="left">United States</td>
<td valign="top" align="left">Estimated 16 per 100,000</td>
<td valign="top" align="left"><italic>S. Enteritidis, S. Typhimurium</italic></td>
<td valign="top" align="left">Increasing resistance to fluoroquinolones</td>
<td valign="top" align="left">&#x0003C; 0.1%</td>
<td valign="top" align="left">Low</td>
<td valign="top" align="left">WHO, <xref ref-type="bibr" rid="B39">2018</xref></td>
</tr> <tr>
<td valign="top" align="left">Europe</td>
<td valign="top" align="left">Estimated 14 per 100,000</td>
<td valign="top" align="left"><italic>S. Enteritidis, S. Infantis</italic></td>
<td valign="top" align="left">Increasing multidrug resistance</td>
<td valign="top" align="left">Very low</td>
<td valign="top" align="left">Low</td>
<td valign="top" align="left">Hagedoorn et al., <xref ref-type="bibr" rid="B19">2024</xref></td>
</tr></tbody>
</table>
</table-wrap>
<p>During the literature review, using the Scopus database, a bibliometric analysis of NTS research publications from 1982 to 2024 shows that most studies have been conducted in the USA, Brazil, European countries, African nations, India, China, Pakistan, and Bangladesh (<xref ref-type="fig" rid="F1">Figure 1</xref>). Although this analysis highlights the geographic regions where NTS research is concentrated, it does not perfectly align with the actual epidemiological data. However, it suggests that these are the areas where NTS cases are being most actively reported and studied.</p>
<fig id="F1" position="float">
<label>Figure 1</label>
<caption><p>Region-specific Scientific publication frequency of scientific papers reported the NTS epidemiological. Data was collected from the Scopus Database (Between 1982-Oct 2024).</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fmicb-16-1524287-g0001.tif"/>
</fig>
<p>The disproportionate focus on certain regions, coupled with the lack of comprehensive data from resource-limited countries, underlines the need for more focused research in these underserved areas to better understand the disease&#x00027;s true impact. More targeted epidemiological studies are essential to guide public health strategies and interventions in the regions most affected by NTS.</p></sec>
<sec id="s3">
<title>Rising incidences of NTS and research trends</title>
<p>The incidence of NTS infections has been steadily increasing, particularly affecting vulnerable groups such as young children, the elderly, and immunocompromised individuals. In these populations, NTS can escalate into severe and invasive infections, including bacteremia and meningitis, requiring prompt medical intervention (Arii et al., <xref ref-type="bibr" rid="B5">2002</xref>; Magwedere et al., <xref ref-type="bibr" rid="B23">2015</xref>; Ballal et al., <xref ref-type="bibr" rid="B7">2016</xref>; Chen et al., <xref ref-type="bibr" rid="B11">2023</xref>). However, in low-resource settings, where access to timely healthcare is often limited, the risk of life-threatening outcomes is heightened.</p>
<p>As indicated by the bibliometric analysis of research publications from 1982 to 2024, there has been a noticeable rise in the number of studies focused on NTS outbreaks worldwide (<xref ref-type="fig" rid="F2">Figure 2</xref>). While this increase in research publications does not directly reflect the epidemiology of NTS, it signals a growing recognition of the issue and the efforts being made to address it globally.</p>
<fig id="F2" position="float">
<label>Figure 2</label>
<caption><p>Annual publication data of scientific papers reported in the NTS epidemiological studies. Data was collected from the Scopus Database (Between 1982-Oct 2024).</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fmicb-16-1524287-g0002.tif"/>
</fig>
<p>The rising number of NTS cases can be attributed to several factors, including inadequate food safety measures, poor hygiene, and limited public health awareness. In areas with weaker health infrastructures, the challenge of controlling NTS is more pronounced, underscoring the urgent need for comprehensive strategies to tackle this escalating public health threat.</p></sec>
<sec id="s4">
<title>Drug resistance in NTS</title>
<p>One of the most pressing challenges with NTS is the growing occurrence of antibiotic-resistant strains. Over the years, this pathogen has become resistant to several key antibiotic classes, such as fluoroquinolones and third-generation cephalosporins, which are often used to treat severe infections. Globally, non-typhoidal <italic>Salmonella</italic> (NTS) shows high levels of antibiotic resistance. Among them, some regions like Guangzhou, China, documented ampicillin resistance up to 92.16%, while among Southeast Asia, which includes the Philippines, resistance to ciprofloxacin is at 8.7% (Gong et al., <xref ref-type="bibr" rid="B18">2022</xref>; Sia et al., <xref ref-type="bibr" rid="B34">2023</xref>). Researches indicate a sharp rise in resistance to ciprofloxacin and ceftriaxone in recent years, with some regions reporting resistance rates of up to 30% for ciprofloxacin and 25% for ceftriaxone (Hengkrawit and Tangjade, <xref ref-type="bibr" rid="B21">2022</xref>; Yang et al., <xref ref-type="bibr" rid="B40">2023</xref>). In countries such as Vietnam and Taiwan, multidrug resistance (MDR) among NTS strains has reached concerning levels, with studies showing that up to 53.8% of isolates were MDR between 2014 and 2019 (Hengkrawit and Tangjade, <xref ref-type="bibr" rid="B21">2022</xref>). The situation is even more alarming in Bangladesh, where 94% of <italic>Salmonella</italic> strains from broiler chickens have been reported as multidrug-resistant (Yang et al., <xref ref-type="bibr" rid="B40">2023</xref>). Multidrug resistance (MDR) has been an increasing problem with as high as 47% in China and 50% in sub-Saharan Africa (Crump et al., <xref ref-type="bibr" rid="B12">2023</xref>; Gong et al., <xref ref-type="bibr" rid="B18">2022</xref>). Moreover, third-generation cephalosporins, which include ceftriaxone, have also developed resistance at 2.2% level in the Philippines (Sia et al., <xref ref-type="bibr" rid="B34">2023</xref>) and as high as 25% in other regions (Nelson et al., <xref ref-type="bibr" rid="B28">2020</xref>; Chang et al., <xref ref-type="bibr" rid="B10">2021</xref>). Sulfonamide resistance is similarly concerning, with reports showing around 43% resistance among isolates (Hengkrawit and Tangjade, <xref ref-type="bibr" rid="B21">2022</xref>). A study highlighted that nearly all NTS isolates from poultry were resistant to tetracycline, emphasizing the impact of agricultural practices on resistance development (Nelson et al., <xref ref-type="bibr" rid="B28">2020</xref>). Although carbapenem resistance is less common, it has been detected in some NTS strains. A study found that about 10.7% of isolates were resistant to carbapenems (Poomchuchit et al., <xref ref-type="bibr" rid="B30">2021</xref>). Clearly, the resistance has reached alarming levels in view of the prevalence of antibiotics both in human healthcare and animal husbandry practices (Crump et al., <xref ref-type="bibr" rid="B13">2015</xref>; Adesiji et al., <xref ref-type="bibr" rid="B1">2018</xref>), resulting in the emergence of &#x0201C;superbugs&#x0201D; that are hard to treat (Wang and Sun, <xref ref-type="bibr" rid="B38">2015</xref>; Siddiky et al., <xref ref-type="bibr" rid="B35">2022</xref>). In countries where there is little regulation preventing people from buying antibiotics without prescriptions, the problem is even worse. There is a growing incidence of NTS strains with multi-drug resistance (Ogasawara et al., <xref ref-type="bibr" rid="B29">2008</xref>; Hendriksen et al., <xref ref-type="bibr" rid="B20">2019</xref>), thereby reducing the effectiveness of usual therapies and add strain to the control of Health Systems. Such resistance makes the treatment of infections limited and increases the period of illness especially for the invasive NTS. In low-resource areas where there is limited access to cheap, effective antimicrobial agents, this problem also significantly increases the death rates.</p></sec>
<sec id="s5">
<title>The economic burden of NTS</title>
<p>NTS exerts significant economic burden in terms of healthcare expenditures, productivity losses, and the associated demand on public health systems especially in countries where the spread of infection is rampant. The combination between the cost of treatment for infections and the associated economic losses due to absenteeism is too much for any economy to bear (Mulla and Cole, <xref ref-type="bibr" rid="B27">2004</xref>; Sanni et al., <xref ref-type="bibr" rid="B31">2023</xref>). High-income countries also experience a similar trend, where the direct medical costs (DMCs) constitute the highest expenditure drivers for all NTS as well as invasive NTS (iNTS) cases. The average treatment price for NTS patients is USD 545.9 in Taiwan and USD 21,179.8 in T&#x000FC;rkiye, while management and handling of iNTS differs from case to case, varying from USD 1,973.1 in Taiwan to USD 32,507.5 in the USA (Kim et al., <xref ref-type="bibr" rid="B22">2024</xref>). However, it is perplexing that very few studies have been conducted on the economics in the developing and resource-limited areas (Aqeel et al., <xref ref-type="bibr" rid="B4">2024</xref>), where the already strained health systems may even suffer more, thus hindering economic growth and expansion more significantly.</p></sec>
<sec id="s6">
<title>Recommendations for control</title>
<p>The increase in NTS calls for an all-inclusive and all-embracing approach. First, there is need to say that global food safety standards must be improved. This means there should be better management of systems of food production, better hygiene practices and attitudes enforced and practices of handling food in a safe manner taught to the public (CDC Yellow Book, <xref ref-type="bibr" rid="B9">2024</xref>). Maintenance of the older systems is not an option given the over-reliance on the existing systems. Instead, the governments must focus on cutting-edge detection technologies which are capable of controlling the spread of further infection in record time after outbreak. Another area that calls for attention is the management of antibiotic resistance. This entails putting measures in place to curb the use of antibiotics in food animals, encouraging the research and development of better antibiotics, and most importantly, use of antibiotics by physicians on the patient only when necessary (Fagbamila et al., <xref ref-type="bibr" rid="B17">2023</xref>). In this regard, it is also important to conduct public information campaigns about the dangers of antibiotics to the public. It is also important to note that (Smith et al., <xref ref-type="bibr" rid="B36">2016</xref>) improving the availability of clean water and sanitation in developing countries is important since these are public health interventions that can significantly help contain NTS as well as other enteric infections.</p>
<p>In addition, it is necessary to enhance global efforts for monitoring NTS outbreaks and the resistance to antibiotics. It calls for nations to work together effectively in order to determine all those populations at risk and measure the impact of the risk by activating specific measures. Organizations such as World Health Organization and Food and Agriculture Organization must lobby for better food safety and responsible use of antibiotics all over the world.</p></sec>
<sec sec-type="conclusions" id="s7">
<title>Conclusion</title>
<p>The conclusion here is that there is an increasing occurrence of NTS which poses a global health threat that needs urgent and targeted measures. The completion of strengthening food safety and quality as well as addressing antibiotics resistance and ensuring proper sanitation and provision for clean water are important measures in mitigating this pathogen. The cost implications are high but such threats can be managed through strategic works and sustained commitment over a period of time in place of resources. In order to prevent millions of people&#x00027;s health from being compromised, such threats have to be dealt with as quickly as possible. In sickness, health groups should work toward NTS no longer being a public health threat that is under wraps.</p></sec>
</body>
<back>
<sec sec-type="author-contributions" id="s8">
<title>Author contributions</title>
<p>GK: Conceptualization, Methodology, Supervision, Visualization, Writing &#x02013; original draft, Writing &#x02013; review &#x00026; editing. SK: Formal analysis, Writing &#x02013; original draft. HJ: Investigation, Methodology, Writing &#x02013; original draft. JD: Visualization, Writing &#x02013; original draft, Writing &#x02013; review &#x00026; editing. AS: Conceptualization, Supervision, Writing &#x02013; review &#x00026; editing.</p>
</sec>
<sec sec-type="funding-information" id="s9">
<title>Funding</title>
<p>The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.</p>
</sec>
<ack><p>We would like to express our genuine appreciation to Lovely Professional University, and National Medical College and Teaching Hospital for creating an academic atmosphere and offering resources that greatly supported the successful culmination of this in-depth review paper.</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="s10">
<title>Generative AI statement</title>
<p>The author(s) declare that no Gen AI was used in the creation of this manuscript.</p></sec>
<sec sec-type="disclaimer" id="s11">
<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>
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