Presence of additional Plasmodium vivax malaria in Duffy negative individuals from Southwestern Nigeria

Abstract

Background: Malaria in sub-Saharan Africa (sSA) is thought to be mostly caused by Plasmodium falciparum. Recently, growing reports of cases due to Plasmodium ovale, Plasmodium malariae, and Plasmodium vivax have been increasingly observed to play a role in malaria epidemiology in sSA. This in fact is due to the usage of very sensitive diagnostic tools (e.g. PCR), which have highlighted the underestimation of non-falciparum malaria in this sub-region. Plasmodium vivax was historically thought to be absent in sSA due to the high prevalence of the Duffy negativity in individuals residing in this sub-continent. Recent studies reporting detection of vivax malaria in Duffy-negative individuals from Mali, Mauritania, Cameroon challenge this notion. Methods: Following previous report of P. vivax in Duffy-negative individuals in Nigeria, samples were further collected and assessed RDT and/or microscopy. Thereafter, malaria positive samples were subjected to conventional PCR method and DNA sequencing to confirm both single/mixed infections as well as the Duffy status of the individuals. Results: Amplification of Plasmodium gDNA was successful in 59.9% (145/242) of the evaluated isolates and as expected P. falciparum was the most predominant (91.7%) species identified. Interestingly, four P. vivax isolates were identified either as single (3) or mixed (one P. falciparum/P. vivax) infection. Sequencing results confirmed all vivax isolates as truly vivax malaria and the patient were of Duffy-negative genotype. Conclusion: Identification of additional vivax isolates among Duffy-negative individuals from Nigeria, substantiate the expanding body of evidence on the ability of P. vivax to infect RBCs that do not express the DARC gene. Hence, such genetic-epidemiological study should be conducted at the country level in order to evaluate the true burden of P. vivax in Nigeria.

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

“…However, recent studies reported several cases of P. vivax infection in Duffy-negative people in different parts of Africa (Zimmerman, 2017, Gunalan et al, 2018, including countries where Duffy-negatives are predominant (Brazeau et al, 2018, Mendes et al, 2011, Motshoge et al, 2016, Niangaly et al, 2017, Russo et al, 2017) (Table 1). In addition, 29 African countries including six previously undocumented endemic countries (Benin, J o u r n a l P r e -p r o o f Comoros, Mozambique, Senegal, Zambia and Zimbabwe) have reported P. vivax clinical cases, infected vectors or asymptomatic parasitemia (Niang et al, 2018, Oboh et al, 2020, Poirier et al, 2016. These reports indicate that the endemic range of P. vivax has extended beyond East Africa and penetrated into areas of very high Duffy-negativity (Gunalan et al, 2018.…”

Alternative Invasion Mechanisms and Host Immune Response to Plasmodium vivax Malaria: Trends and Future Directions

“…The documentation of P. vivax infections in different parts of Africa where Duffy-negative individuals are predominant [161][162][163][164][165][166][167][168] suggested that there are alternative pathways for erythrocyte invasion. It is apparent that Duffy-negative individuals are no longer resistant to P. vivax malaria.…”

Contrasting Epidemiology and Genetic Variation of <em>Plasmodium vivax</em> Infecting Duffy Negatives across Africa

“…However, recent studies reported several cases of P. vivax infection in Duffy-negative people in different parts of Africa [5,6], including countries where Duffy-negatives are predominant [7][8][9][10][11] (Table 1). In addition, 29 African countries including six previously undocumented endemic countries (Benin, Comoros, Mozambique, Senegal, Zambia and Zimbabwe) have reported P. vivax clinical cases, infected vectors or asymptomatic parasitemia [12][13][14]. These reports indicate that the endemic range of P. vivax has extended beyond East Africa and penetrated into areas of very high Duffy-negativity [6,15].…”

“…The epidemiological and genetic features of P. vivax from different parts of Africa will fill critical gap in understanding how widespread this phenomenon is impacting malaria control and the important effect of P. vivax as a cause of anemia. 1 2 Pf-Pv co-infections; 2 Duffy-Ag available only among Plasmodium spp pos; 3 33 Pf-Pv co-infections; 4 2 Pf-Pv co-infections; 5 1 Pf-Pv co-infection; 6 31 children Duffy neg affected by malaria enrolled in a precedent study (anemia study); 7 only Pv pos analysed (153 Pv mono-infections and 30 Pf-Pv co-infections); 8 34 Plasmodium mixed-infections (species not specified); 9 42 co-infections (25 Pf-Pv, 5 Pf-Pm, 9 Pv-Pm, 1 Pv-Po, 1 Pf-Pv-Pm, 1 Pf-Pv-Pm-Po); 10 37 co-infections (25 Pf-Pv, 9 Pv-Pm, 1 Pv-Po, 1 Pf-Pv-Pm, 1 Pf-Pv-Pm-Po); 11 9 Pf-Pv and 1 Pf-Pv-Pm co-infections; 12 2 Pf-Pv co-infections; 13 3 Pf-Pv and 1 Pf-Pv-Pm coinfections; 14 Duffy-Ag assessed among 228 participants (including all those infected); 15 2 Pf-Pv co-infections; 16 4 Pf-Pv co-infections; 17 4 Pf-Pv co-infections; 18 48 school children followed during 2 years (4 samples for each children, 192 total samples analyzed) 19 only Plasmodium spp pos sample analysed; 20 4 Pf-Pv coinfections; 21 (Figure 1). Finger-prick blood samples were obtained from patients who visited the health facilities.…”