Abstract

A better understanding of the occurrence and risk of Plasmodium vivax infection among Duffy-negative individuals is required to guide further research on these infections across Africa. To address this, we used a meta-analysis approach to investigate the prevalence of P. vivax infection among Duffy-negative individuals and assessed the risk of infection in these individuals when compared with Duffy-positive individuals. This study was registered with The International Prospective Register of Systematic Reviews website (ID: CRD42021240202) and followed Preferred Reporting Items for Systematic review and Meta-Analyses guidelines. Literature searches were conducted using medical subject headings to retrieve relevant studies in Medline, Web of Science, and Scopus, from February 22, 2021 to January 31, 2022. Selected studies were methodologically evaluated using the Joanna Briggs Institute (JBI) Critical Appraisal Tools to assess the quality of cross-sectional, case–control, and cohort studies. The pooled prevalence of P. vivax infection among Duffy-negative individuals and the odds ratio (OR) of infection among these individuals when compared with Duffy-positive individuals was estimated using a random-effects model. Results from individual studies were represented in forest plots. Heterogeneity among studies was assessed using Cochrane Q and I2 statistics. We also performed subgroup analysis of patient demographics and other relevant variables. Publication bias among studies was assessed using funnel plot asymmetry and the Egger’s test. Of 1593 retrieved articles, 27 met eligibility criteria and were included for analysis. Of these, 24 (88.9%) reported P. vivax infection among Duffy-negative individuals in Africa, including Cameroon, Ethiopia, Sudan, Botswana, Nigeria, Madagascar, Angola, Benin, Kenya, Mali, Mauritania, Democratic Republic of the Congo, and Senegal; while three reported occurrences in South America (Brazil) and Asia (Iran). Among studies, 11 reported that all P. vivax infection cases occurred in Duffy-negative individuals (100%). Also, a meta-analysis on 14 studies showed that the pooled prevalence of P. vivax infection among Duffy-negative individuals was 25% (95% confidence interval (CI) − 3%–53%, I2 = 99.96%). A meta-analysis of 11 studies demonstrated a decreased odds of P. vivax infection among Duffy-negative individuals (p = 0.009, pooled OR 0.46, 95% CI 0.26–0.82, I2 = 80.8%). We confirmed that P. vivax infected Duffy-negative individuals over a wide prevalence range from 0 to 100% depending on geographical area. Future investigations on P. vivax infection in these individuals must determine if Duffy-negativity remains a protective factor for P. vivax infection.

Highlights

  • MethodsCross-sectional, cohort, and case–control studies were considered if they reported P. vivax infections among Duffy-negative individuals

  • A better understanding of the occurrence and risk of Plasmodium vivax infection among Duffynegative individuals is required to guide further research on these infections across Africa

  • Fourteen ­studies[18–21,23–25,27–29,39,41–43], conducted in 16 areas and reporting P. vivax infection prevalence among Duffy-negative individuals, were included in the pooled prevalence meta-analysis. These results showed that the pooled prevalence was 25%

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Summary

Methods

Cross-sectional, cohort, and case–control studies were considered if they reported P. vivax infections among Duffy-negative individuals. The following articles were excluded: no Duffy-negative individuals among P. vivax cases, genetic analysis of the Duffy protein, no report on Duffy status, case reports and case series, experimental studies, clinical trials, and studies from which data could not be extracted. The primary study outcome was the pooled prevalence of P. vivax infection among Duffy-negative individuals. Meta-regression analysis was performed to determine the source(s) of heterogeneity of ES (pooled prevalence, OR) among studies. We performed sensitivity analysis of the pooled prevalence and the odds of infection between Duffy-negative individuals using the fixed-effects model to determine the robustness of our meta-analysis results. A significant Egger’s test (p < 0.05) indicated that funnel plot asymmetry was due to a small study effect. If the funnel plot was asymmetrical (by visualization or a significant Egger’s test), a contour-enhanced funnel plot was generated to identify if funnel plot asymmetry was due to publication bias or other causes

Results
Participants
Method for Duffy antigen genotyping
Discussion
Conclusions
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