The search strategy, designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, aimed to capture studies pertinent to the efficacy of FMD vaccines in Africa (15). The population targeted included livestock such as cattle, sheep, goats, and pigs within African countries. The intervention of interest was defined as the administration of FMD vaccine to livestock species in Africa. It included all types FMD vaccination programs practiced in Africa, covering a range of vaccine types, regimens, and delivery methods. Comparative analysis was carried out between vaccinated and unvaccinated populations and among various vaccination strategies, whenever data allowed. The risk ratio (R.R.) of FMD incidence was used as a primary outcome measure. Both experimental and observational study designs—randomized controlled trials, case–control and cohort studies were included in the study.

To identify studies relevant to FMD in domestic livestock species within African regions, focusing on antibody titer post-vaccination and utilizing standard immunological assays, a comprehensive literature search was conducted across PubMed, Web of Science, and Scopus databases. The search covered all articles published until 19/05/2023. The search strings for each database were: PubMed: (“foot and mouth disease”[Title/Abstract] OR FMD*[Title/Abstract]) AND (cattle[Title/Abstract] OR bovine[Title/Abstract] OR “Bos taurus”[Title/Abstract] OR goat[Title/Abstract] OR caprine[Title/Abstract] OR “Capra aegagrus hircus”[Title/Abstract] OR sheep[Title/Abstract] OR ovine[Title/Abstract] OR “Ovis aries”[Title/Abstract] OR pig[Title/Abstract] OR porcine[Title/Abstract] OR swine[Title/Abstract] OR “Sus scrofa domesticus”[Title/Abstract]). In Web of Science: TS = (“foot and mouth disease” OR FMD*) AND (TS = (cattle) OR TS = (bovine) OR TS = (“Bos taurus”) OR TS = (goat) OR TS = (caprine) OR TS = (“Capra aegagrus hircus”) OR TS = (sheep) OR TS = (ovine) OR TS = (“Ovis aries”) OR TS = (pig) OR TS = (porcine) OR TS = (swine) OR TS = (“Sus scrofa domesticus”)). In Scopus: TITLE-ABS-KEY(“foot and mouth disease” OR FMD*) AND (TITLE-ABS-KEY(cattle) OR TITLE-ABS-KEY(bovine) OR TITLE-ABS-KEY(“Bos taurus”) OR TITLE-ABS-KEY(goat) OR TITLE-ABS-KEY(caprine) OR TITLE-ABS-KEY(“Capra aegagrus hircus”) OR TITLE-ABS-KEY(sheep) OR TITLE-ABS-KEY(ovine) OR TITLE-ABS-KEY(“Ovis aries”) OR TITLE-ABS-KEY(pig) OR TITLE-ABS-KEY(porcine) OR TITLE-ABS-KEY(swine) OR TITLE-ABS-KEY(“Sus scrofa domesticus”)).

The Covidence platform¹ was used to facilitate the screening and extraction process of the collected studies. Primarily, the title and abstract and then the full text of each article were screened for relevance based on the inclusion and exclusion criteria (Table 1). Each of the collected articles was screened by three co-authors (AKW, GMW, and TTA), and conflicts in screening were resolved either by a third senior author or through consensus among the three authors.

The studies were eligible for inclusion in our systematic review if they fulfilled the criteria listed in Table 1. This systematic and meta-analysis study excluded studies that did not take place in Africa, studies that did not use an FMDV vaccine as an intervention, studies that used animal populations of unspecified or mixed species, review articles, meta-analyses, news reports, and any research lacking data that can be extracted. The details of the exclusion criteria are listed in Table 1. The included studies were further categorized for qualitative and quantitative analyses based on the study design. For quantitative analysis, studies that provided detailed data on the number of animals vaccinated, the number of animals unvaccinated, and the immune response observed in each group were selected. Studies included in the final screening that lacked specific data on the number of animals vaccinated, the number of animals unvaccinated, and the observed immune responses in each group were allocated only to the qualitative analysis.

Data were extracted using Covidence, including author information, publication year, animal species, country, farming system, study design, sample type, species, vaccine type, and FMD detection method. The total number of animals or herds tested, FMD-positive cases, and age distribution were also collected. For articles included in qualitative analysis, the Joanna Briggs Institute Qualitative Assessment and Review Instrument (JBI-QARI)² with slight modification was used to assess article quality.

In the systematic review and meta-analysis of FMD vaccine trials in Africa, the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool was employed to evaluate the risk of bias in non-randomized studies (16). This tool examined seven domains: risk of bias due to confounding, selection of participants, classification of interventions, deviations from intended interventions, missing data, measurement of outcomes, and selection of the reported results. Two independent reviewers assessed these domains, categorizing them as having low, moderate, serious, or critical risk of bias or no information. A third independent reviewer resolved discrepancies. A study was considered to have an overall low risk of bias if all domains were judged as low risk and as having a critical risk of bias if any domain was judged as high risk. The Cochrane Risk of Bias 2.0 tool was intended for randomized trials (17).

The meta-analysis was conducted using the random effects model (18), which is implemented in the metabin function in R (19). The primary measure of interest was RR, which compares the risk of an event which is the occurrence of FMD among the study subjects, (vaccinated and unvaccinated groups). The pooled risk ratio was represented with a 95% confidence interval. The ability of the vaccine to provide protection against FMD in vaccinated populations compared to unvaccinated ones, referred to here as FMD vaccine efficacy (20), was measured using vaccine efficacy, VE, which is calculated as 1-RR (21). RR was calculated as:

Where:

NVivo 20.0 software (22) was used for systematic identification, coding, and thematic categorization of risk factors and variables. Each of the included studies for qualitative analysis was analyzed based on thematic areas such as vaccine type, adjuvant type, risk factor type, vaccination strategy and country.

Initially, a total of 13,418 articles were collected. After removing duplicates, we screened 7,259 articles at the title and abstract screening stage. At the full-text level, 329 studies were assessed for eligibility. During the full-text-based screening, 21 studies were included for data extraction. After data extraction and quality assessment, three studies were excluded due to data quality or methodology, leaving only 17 studies for final data analysis. Although all included studies were assessed for bias, none met the criteria for exclusion based on the results of this bias assessment. Among these, 17 were included in the qualitative analysis, while 14 articles initially met the eligibility criteria for the quantitative analysis; nine of these articles were excluded due to having either a zero RR or a zero in the denominator during the RR calculation. As a result, only five studies were ultimately included in the meta-analysis (Figure 1).

Information about each study, including the year of publication, country of study, study design, duration of study, species of animals, breeds of animals, and age group, is displayed in Supplementary Table 1. Details regarding the FMDV vaccine type, the number of vaccinated and unvaccinated individuals, the percentage of effective interventions that resulted in seroprotection, the vaccine serotype, the serotypes circulating in the field, and the specific immune assay used were also recorded (Supplementary Table 2).

The dataset comprising 17 articles offered an analysis of FMD vaccine efficacy in Africa, covering a period from 1996 to 2023. The majority of these studies occurred in South Africa and Egypt, and they used a variety of research methodologies, such as randomized controlled trials, cohort studies, and case–control studies, and lasted from 21 days to 40 weeks. Most of these studies were on bovine species, particularly local breeds. However, some studies also included ovine and porcine species. Most of the bovine species included in the study came from dairy farms, where they were raised from birth, while the others were likely introduced from elsewhere.

The studies predominantly used inactivated vaccines, incorporating specific serotypes like O, A, and SAT2 and explored a broad spectrum of vaccination aspects, such as efficacy, potency, immune response, and the influence of adjuvants. The size of study populations varied, ranging from small groups of around 4 animals to larger cohorts involving up to 191 animals. Moreover, the protection rates post-vaccination showed variation, with some studies reporting complete protection (100%) in certain cases.

These studies also provided insights into the prevalence of FMD in unvaccinated animals, demonstrating the incidence of positive test results. Methodologically, a range of techniques, including serum neutralization test (SNT), ELISA, and RT-qPCR, were employed to detect and analyze the virus and assess the immune response. Overall, the objectives of these studies were multifaceted, primarily focused on understanding the efficacy of routine vaccinations, the immune response in vaccinated animals, and assessing the performance of different vaccine formulations in diverse field conditions.

It was found that in Africa, the most widely used form of FMD vaccine was an inactivated viral vaccine combined with an adjuvant, except in one study (23), a reverse genetically synthesized vaccine. In all these studies, the vaccines were designed to provide immunity against the following specific FMD virus serotypes: O, A, SAT 1, SAT 2, and SAT 3. Cameroon is home to four different FMD virus serotypes (FMDV; O, A, SAT1, SAT2) thus, a trivalent inactivated vaccination carried out to combat the three most common serotypes—O, A, and SAT2 (24). Similarly, Egypt and Kenya have also been experiencing these serotypes (25). According six studies, one from Cameron (24) and five from Egypt (26–30), the O, A, and SAT2 FMDV serotypes were found prevalent in the field which had correspondence to the vaccine strain. In these studies, the trivalent inactivated vaccine consisting of O, A, and SAT2 was used during efficacy testing. On the other hand, vaccine efficacy trial against A and O FMDV serotype was employed in three studies (31, 32) in Egypt and (33) in South Africa despites the field strains are (O, A, and SAT2) and SAT1, SAT2 and SAT3 FMDV serotypes, respectively, in these regions. In some studies in Egypt (26, 34, 35) vaccine efficacy evaluation was conducted against O serotype. In South Africa, only SAT serotypes were widespread, and vaccine tests showed trivalent inactivated vaccine against SAT1, SAT2, and SAT3 of distinct strains (M. CLOETE, 2008) (36), Furthermore, the efficacy test for one vaccine also targeted a monovalent vaccine specifically designed to combat the SAT2 serotype (23). However, vaccination strategies and programs vary by country; these key highlights are presented below.

Using oil-based adjuvants or adjuvants with oil in FMD vaccines may be more effective than the conventional aluminum hydroxide gel and saponin adjuvants, as they result in higher immune responses in cattle (43). One of the six cattle vaccinated with the ISA 50 vaccine was protected from live virus challenge despite the presence of neutralizing antibodies to the SAT 2B antigen at the time of challenge. SA 206B-adjuvanted FMD vaccine without saponin protected pigs against live heterologous virus challenge 36 days post-vaccination (44). In Egypt, the evaluation of three different types of vaccines in sheep revealed that the double oil emulsion–FMD vaccine using Spane 80 as emulsifier showed much higher antibody titers and longer duration of immunity than the other two vaccine preparations (34). In South Africa, the mean titers of three oil-based preparations were higher than those induced by the Alhydrogel and Saposin-based vaccines (36). A single administration of the heptavalent ISA 206 VG oil-adjuvanted vaccine prepared from A-Africa-IV, A-Iran05, O-Manisa, O-PanAsia2, SAT-2 LIB-12 and O-EA3, SAT-2 Gharbia, strains resulted in a high mean neutralizing antibody titer 28 days post-vaccination (30).

African FMDV vaccination programs have faced various challenges and exhibited mixed results across different regions. In Kenya, there have been instances of FMD outbreaks in both vaccinated and unvaccinated cattle (41). In Egypt, local commercial vaccines showed protective effects, but there were observations of disease occurrence in both vaccinated and non-vaccinated animals (29, 39). Since export has never been an objective of regional livestock raising in Cameroon, the country has never had a structured FMD control program (24). In South Africa, FMD vaccination has been a critical component of disease control, especially given the country’s diverse wildlife reservoirs that can harbor the virus. South Africa uses a zoning strategy, with specific areas designated as FMD-free zones where vaccination is not routinely practiced. In contrast, vaccination is more common in other areas, particularly those bordering wildlife reserves or neighboring countries with endemic FMD. The effectiveness of vaccination programs in South Africa and other African nations often hinges on several factors: the selection of appropriate vaccine strains to match circulating serotypes, efficient vaccine distribution and administration, and regular surveillance and monitoring. However, challenges such as logistical hurdles, limited resources, and the presence of multiple FMDV serotypes complicate these efforts.

In this meta-analysis, the findings from five studies were pooled to assess the efficacy of FMDV vaccination. The studies included in our analysis were (23, 25, 37, 41, 44). The pooled results from the random-effects model suggested RR of 0.31 and a VE of 0.69 (69%). The analysis showed that the FMD vaccination reduced the risk of FMDV infection by approximately 69% in the vaccinated group compared to the unvaccinated group.

A higher level of heterogeneity was observed among the studies analyzed in the present findings (Figure 2). Test for heterogeneity yielded a Q-value of 46.97 (with 4 degrees of freedom), which was statistically significant (p < 0.05), confirming the presence of significant variability among the included studies.