Background
Celiac disease (CD) is historically underdiagnosed in sub-Saharan Africa (SSA), where persistent diarrhea, growth failure, and duodenal villous atrophy are routinely attributed to Environmental Enteropathy (EE), severe acute malnutrition, or parasitic infections. The lack of standardized diagnostic pathways tailored for resource-limited settings perpetuates clinical misclassification. This systematic review evaluated pooled seroprevalence, diagnostic accuracy of serological modalities, and rates of clinical misdiagnosis of CD across sub-Saharan Africa.
Methods
Following PRISMA guidelines, systematic searches were conducted across PubMed, MEDLINE, Embase, Web of Science, and African Index Medicus for studies published between 2000 and 2025. Eligible studies were studies that reported CD screening, serology, histology (Marsh classification), or clinical outcomes in SSA populations. Primary outcomes were pooled seroprevalence (anti-tissue transglutaminase IgA [anti-tTG IgA]), diagnostic accuracy of point-of-care (POC) tests versus ELISA, and initial misdiagnosis rates. Heterogeneity was evaluated using I2 statistics, and risk of bias was assessed via the Newcastle-Ottawa Scale.
Results
From 1,180 records that we identified, 24 studies encompassing 11,450 participants met inclusion criteria. Pooled anti-tTG IgA seroprevalence in high-risk groups (chronic diarrhea, stunting, Type 1 Diabetes) was 3.6% (95% CI: 2.7 - 4.8%; I2 = 62%). Over 74% of histologically confirmed CD cases (Marsh 3) were initially misdiagnosed as Environmental Enteropathy or refractory malnutrition. Rapid POC anti-tTG IgA assays demonstrated a pooled sensitivity of 94.2% (95% CI: 91.0 - 96.5% ) and specificity of 97.8% (95% CI: 96.1 - 98.9%) compared to central ELISA, while HLA-DQ2/DQ8 negativity successfully ruled out CD in 83.5% of ambiguous enteropathy cases.
Conclusion
Celiac disease is an underrecognized contributor to chronic enteropathy in sub-Saharan Africa. Utilizing European/American diagnostic paradigms leads to widespread missed diagnoses. Integrating rapid POC serology with targeted genetic exclusion offers a more accurate and cost-effective diagnostic algorithm to differentiate CD from Environmental Enteropathy in resource-constrained health systems.