Dataset Information

Contrasting epidemiology and genetic variation of Plasmodium vivax infecting Duffy-negative individuals across Africa.

ABSTRACT:

Objectives

Plasmodium vivax malaria was thought to be rare in Africans who lack the Duffy blood group antigen expression. However, recent studies indicate that P. vivax can infect Duffy-negative individuals and has spread into areas of high Duffy negativity across Africa. Our study compared epidemiological and genetic features of P. vivax between African regions.

Methods

A standardized approach was used to identify and quantify P. vivax from Botswana, Ethiopia, and Sudan, where Duffy-positive and Duffy-negative individuals coexist. The study involved sequencing the Duffy binding protein (DBP) gene and inferring genetic relationships among P. vivax populations across Africa.

Results

Among 1215 febrile patients, the proportions of Duffy negativity ranged from 20-36% in East Africa to 84% in southern Africa. Average P. vivax prevalence among Duffy-negative populations ranged from 9.2% in Sudan to 86% in Botswana. Parasite density in Duffy-negative infections was significantly lower than in Duffy-positive infections. P. vivax in Duffy-negative populations were not monophyletic, with P. vivax in Duffy-negative and Duffy-positive populations sharing similar DBP haplotypes and occurring in multiple, well-supported clades.

Conclusions

Duffy-negative Africans are not resistant to P. vivax, and the public health significance of this should not be neglected. Our study highlights the need for a standardized approach and more resources/training directed towards the diagnosis of vivax malaria in Africa.

SUBMITTER: Lo E

PROVIDER: S-EPMC9004484 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Publications

Contrasting epidemiology and genetic variation of Plasmodium vivax infecting Duffy-negative individuals across Africa.

Lo Eugenia E Russo Gianluca G Pestana Kareen K Kepple Daniel D Abagero Beka Raya BR Dongho Ghyslaine Bruna Djeunang GBD Gunalan Karthigayan K Miller Louis H LH Hamid Muzamil Mahdi Abdel MMA Yewhalaw Delenasaw D Paganotti Giacomo Maria GM

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 20210512

<h4>Objectives</h4>Plasmodium vivax malaria was thought to be rare in Africans who lack the Duffy blood group antigen expression. However, recent studies indicate that P. vivax can infect Duffy-negative individuals and has spread into areas of high Duffy negativity across Africa. Our study compared epidemiological and genetic features of P. vivax between African regions.<h4>Methods</h4>A standardized approach was used to identify and quantify P. vivax from Botswana, Ethiopia, and Sudan, where Du ...[more]

PMID: 33991680

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Project description:BackgroundMalaria in Nigeria is principally due to Plasmodium falciparum and, to a lesser extent to Plasmodium malariae and Plasmodium ovale. Plasmodium vivax is thought to be absent in Nigeria in particular and sub-Saharan Africa in general, due to the near fixation of the Duffy negative gene in this population. Nevertheless, there are frequent reports of P. vivax infection in Duffy negative individuals in the sub-region, including reports from two countries sharing border with Nigeria to the west (Republic of Benin) and east (Cameroon). Additionally, there were two cases of microscopic vivax-like malaria from Nigerian indigenous population. Hence molecular surveillance of the circulating Plasmodium species in two states (Lagos and Edo) of southwestern Nigeria was carried out.MethodsA cross-sectional survey between September 2016 and March 2017 was conducted. 436 febrile patients were included for the present work. Venous blood of these patients was subjected to RDT as well as microscopy. Further, parasite DNA was isolated from positive samples and PCR diagnostic was employed followed by direct sequencing of the 18S rRNA of Plasmodium species as well as sequencing of a portion of the promoter region of the Duffy antigen receptor for chemokines. Samples positive for P. vivax were re-amplified several times and finally using the High Fidelity Taq to rule out any bias introduced.ResultsOf the 256 (58.7%) amplifiable malaria parasite DNA, P. falciparum was, as expected, the major cause of infection, either alone 85.5% (219/256; 97 from Edo and 122 from Lagos), or mixed with P. malariae 6.3% (16/256) or with P. vivax 1.6% (4/256). Only one of the five P. vivax isolates was found to be a single infection. DNA sequencing and subsequent alignment of the 18S rRNA of P. vivax with the reference strains displayed very high similarities (100%). Remarkably, the T-33C was identified in all P. vivax samples, thus confirming that all vivax-infected patients in the current study are Duffy negative.ConclusionThe present study gave the first molecular evidence of P. vivax in Nigeria in Duffy negative individuals. Though restricted to two states; Edo in South-South and Lagos in South-west Nigeria, the real burden of this species in Nigeria and sub-Saharan Africa might have been underestimated, hence there is need to put in place a country-wide, as well as a sub-Saharan Africa-wide surveillance and appropriate control measures.

Project description: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.

Project description:BackgroundMalaria remains a significant cause of morbidity and mortality in Ethiopia with an estimated 3.8 million cases in 2021 and 61% of the population living in areas at risk of malaria transmission. Throughout the country Plasmodium vivax and Plasmodium falciparum are co-endemic, and Duffy expression is highly heterogeneous. The public health significance of Duffy negativity in relation to P. vivax malaria in Ethiopia, however, remains unclear. This study seeks to explore the prevalence and rates of P. vivax malaria infection across Duffy phenotypes in clinical and community settings.MethodsA total of 9580 and 4667 subjects from community and health facilities from a malaria endemic site and an epidemic-prone site in western Ethiopia were enrolled and examined for P. vivax infection and Duffy expression from February 2018 to April 2021. Association between Duffy expression, P. vivax and P. falciparum infections were examined for samples collected from asymptomatic community volunteers and symptomatic subjects from health centres.ResultsInfection rate of P. vivax among Duffy positives was 2-22 fold higher than Duffy negatives in asymptomatic volunteers from the community. Parasite positivity rate was 10-50 fold higher in Duffy positives than Duffy negatives among samples collected from febrile patients attending health centres and mixed P. vivax and P. falciparum infections were significantly more common than P. vivax mono infections among Duffy negative individuals. Plasmodium vivax parasitaemia measured by 18sRNA parasite gene copy number was similar between Duffy positives and Duffy negatives.ConclusionsDuffy negativity does not offer complete protection against infection by P. vivax, and cases of P. vivax in Duffy negatives are widespread in Ethiopia, being found in asymptomatic volunteers from communities and in febrile patients from health centres. These findings offer evidence for consideration when developing control and intervention strategies in areas of endemic P. vivax and Duffy heterogeneity.

Dataset Information

Contrasting epidemiology and genetic variation of Plasmodium vivax infecting Duffy-negative individuals across Africa.

Objectives

Methods

Results

Conclusions

Publications

Contrasting epidemiology and genetic variation of Plasmodium vivax infecting Duffy-negative individuals across Africa.

Similar Datasets

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