Modifiable risk factors for diphtheria: A systematic review and meta-analysis

Objective: To identify modifiable risk factors for diphtheria and assess their strengths of association with the disease. Methods: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Electronic databases and grey literature were searched from inception until January 2023. Studies had to report on diphtheria cases and estimates of association for at least one potential risk factor or sufficient data to calculate these. The quality of non-ecological studies was assessed using the Newcastle-Ottawa Scale (NOS), while the quality of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Results: The search yielded 37,705 papers, of which 29 were ultimately included. All the non-ecological studies were of moderate to high quality. Meta-analysis of 20 studies identified three factors increasing the risk of diphtheria: incomplete vaccination (<3 doses) (pooled odds ratio (POR) = 2.2, 95% confidence interval (CI) = 1.4–3.4); contact with a person with skin lesions (POR = 4.8, 95% CI = 2.1–10.9); and low knowledge of diphtheria (POR = 2.4, 95% CI = 1.2–4.7). Contact with a case of diphtheria; sharing a bed or bedroom; sharing utensils, cups, and glasses; infrequent bathing; and low parental education were associated with diphtheria in multiple studies. Evidence for other factors was inconclusive. The quality of evidence was low or very low for all the risk factors. Conclusions: Findings from the review suggest that countries seeking to control diphtheria need to strengthen surveillance, improve vaccination coverage, and increase people's knowledge of the disease. Future research should focus on understudied or inconclusive risk factors.