Dataset Information

Vivax malaria in Duffy-negative patients shows invariably low asexual parasitaemia: implication towards malaria control in Ethiopia.

ABSTRACT:

Background

The increase in detections of Plasmodium vivax infection in Duffy-negative individuals in Africa has challenged the dogma establishing the unique P. vivax Duffy Binding Protein-Duffy antigen receptor for chemokines (PvDBP-DARC) pathway used by P. vivax merozoites to invade reticulocytes. Information on the impact of Duffy antigen polymorphisms on the epidemiology of P. vivax malaria remains elusive. The objective of this study was to determine the distribution of asexual parasitaemia of P. vivax according to the Duffy antigen polymorphisms in Ethiopia.

Methods

DNA was extracted from dried blood spots (DBS) collected from prospectively recruited 138 P. vivax-infected patients from health centres. The identification and estimation of P. vivax asexual parasitaemia were performed by microscopic examination and quantitative real-time polymerase chain reaction (PCR). Duffy genotyping was conducted by DNA sequencing in a total of 138 P.vivax infected samples.

Results

The proportion of Duffy-negatives (FY*B^ES/FY*B^ES) in P. vivax infected patients was 2.9% (4/138). Duffy genotype FY*B/FY*B^ES (48.6%) was the most common, followed by FY*A/FY*B^ES genotype (25.4%). In one patient, the FY*02 W.01/FY*02 N.01 genotype conferring a weak expression of the Fy^b antigen was observed. All P.vivax infected Duffy-negative patients showed low asexual parasitaemia (≤ 110 parasites/µL). The median P. vivax parasitaemia in Duffy-negative patients (53 parasites/µL) was significantly lower than those found in homozygous and heterozygous individuals (P < 0.0001).

Conclusion

Plasmodium vivax in Duffy-negative patients shows invariably low asexual parasitaemia. This finding suggests that the pathway used by P. vivax to invade Duffy-negative reticulocytes is much less efficient than that used in Duffy-positives. Moreover, the low asexual parasitaemia observed in Duffy-negative individuals could constitute an 'undetected silent reservoir', thus likely delaying the elimination of vivax malaria in Ethiopia.

SUBMITTER: Abate A

PROVIDER: S-EPMC9341100 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Vivax malaria in Duffy-negative patients shows invariably low asexual parasitaemia: implication towards malaria control in Ethiopia.

Abate Andargie A Bouyssou Isabelle I Mabilotte Solenne S Doderer-Lang Cecile C Dembele Laurent L Menard Didier D Golassa Lemu L

Malaria journal 20220801 1

<h4>Background</h4>The increase in detections of Plasmodium vivax infection in Duffy-negative individuals in Africa has challenged the dogma establishing the unique P. vivax Duffy Binding Protein-Duffy antigen receptor for chemokines (PvDBP-DARC) pathway used by P. vivax merozoites to invade reticulocytes. Information on the impact of Duffy antigen polymorphisms on the epidemiology of P. vivax malaria remains elusive. The objective of this study was to determine the distribution of asexual paras ...[more]

PMID: 35915453

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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.

Project description:BACKGROUND:Malaria is one of the main public health challenges in Ethiopia that hinder the productivity and development of the country. In 2018, Ethiopia is on track to minimize the incidence of malaria by 40% as per its 2020 malaria reduction strategy. Currently, Ethiopia is working to eliminate malaria in 2030 by extending the 2020 strategy. Hence, this study aimed to analyze the trend of malaria prevalence in Wolkite health center, Gurage zone, Southern Central Ethiopia from 2015 to 2018. METHODS:A retrospective study was conducted to determine the prevalence of malaria by reviewing the malaria registration laboratory logbook at Wolkite health center from 2015 to 2018. For all patients, blood films were done for the detection of malaria cases. All the socio-demographic data, year, month and malaria data were collected using a predesigned data collection sheet from January to March, 2019. RESULTS:From a 121,230 clinically malaria suspected patients, the overall prevalence of microscopically confirmed cases were 8.56% (n?=?10,379/121,230). Plasmodium vivax was the most predominant species accounted for 69.7% (n?=?7237/10,379) followed by Plasmodium falciparum 29.3% (n?=?3044/10,379). Age group >?15 years old were more affected by malaria accounting 54% (n?=?5609/10,379) and malaria cases regarding sex were proportional (51.1% of males and 48.3% of female). Among the catchment areas, a higher number of malaria prevalence was recorded in the Wolkite town 66.2% (n?=?0.6538/10,379). Higher malaria cases were shown in the season of Spring 29.8% (n?=?3096/10,379) while lower cases 20.4% (n?=?2123/10,379) were seen in the Winter season. CONCLUSION:The prevalence of malaria in Wolkite health center showed a consistent downward trend from the year of 2015-2018. Importantly, the higher prevalence of P. vivax seems overlooked in the study area. Therefore, malaria prevention and control strategy should be reinforced to reduce the prevalence of malaria in the study area.

Project description:BackgroundDuffy Binding Protein (PvDBP) binding to the Duffy antigen receptor for chemokine (DARC) is essential for Plasmodium vivax invasion of human reticulocytes. PvDBP copy number variation (CNV) might increase parasite invasion and thus parasitemia. We examined the spatial distribution of PvDBP CNVs and DARC genotypes and their association with parasitemia in P. vivax endemic settings in Ethiopia.Methodology/principal findingsP. vivax isolates (n = 435) collected from five P. vivax endemic settings in Ethiopia were genotyped by amplifying the GATA1 transcription factor-binding site of the Duffy blood group and the CNV of PvDBP was quantified. Parasitemia was determined using 18S-based qPCR. The majority of participants were Duffy positive (96.8%, 421/435). Of the few Duffy negative individuals, most (n = 8) were detected from one site (Gondar). Multiple copies of PvDBP were detected in 83% (363/435) isolates with significant differences between sites (range 60%-94%). Both heterozygous (p = 0.005) and homozygous (p = 0.006) patients were more likely to have been infected by parasites with multiple PvDBP copies than Duffy negatives. Parasitemia was higher among the Duffy positives (median 17,218 parasites/µL; interquartile range [IQR] 2,895-104,489) than Duffy negatives (170; 78-24,132, p = 0.004) as well as in infections with 2 to 3 PvDBP copies (20,468; 3,649-110,632, p = 0.001) and more than 3 PvDBP copies (17,139; 2,831-95,946, p = 0.004) than single copy (5,673; 249-76,605).Conclusions/significanceA high proportion of P. vivax infection was observed in Duffy positives in this study, yet few Duffy negatives were found infected with P. vivax. The significant prevalence of multi-copy PvDBP observed among Ethiopian P. vivax isolates explains the high prevalence and parasitemia observed in clinical cases. This suggests that vivax malaria is a public health concern in the country where the Duffy positive population predominates. Investigating the relative contribution to the maintenance of the infectious reservoir of infections with different genotyping backgrounds (both host and parasite) might be required.

Project description:BackgroundOver a third of the world's population is at risk of Plasmodium vivax-induced malaria. The unique aspect of the parasite's biology and interactions with the human host make it harder to control and eliminate the disease. Glucose-6-phosphate dehydrogenase (G6PD) deficiency and Duffy-negative blood groups are two red blood cell (RBC) variations that can confer protection against malaria.MethodsMolecular genotyping of G6PD and Duffy variants was performed in 225 unrelated patients (97 with uncomplicated and 128 with severe vivax malaria) recruited at a Reference Centre for Infectious Diseases in Manaus. G6PD and Duffy variants characterizations were performed using Real Time PCR (qPCR) and PCR-RFLP, respectively.ResultsThe Duffy blood group system showed a phenotypic distribution Fy(a + b-) of 70 (31.1%), Fy(a + b +) 96 (42.7%), Fy(a-b +) 56 (24.9%) and Fy(a-b-) 1 (0.44%.) The genotype FY*A/FY*B was predominant in both uncomplicated (45.3%) and severe malaria (39.2%). Only one Duffy phenotype Fy(a-b) was found and this involved uncomplicated vivax malaria. The G6PD c.202G > A variant was found in 11 (4.88%) females and 18 (8.0%) males, while c.376A > G was found in 20 females (8.88%) and 23 (10.22%) male patients. When combined GATA mutated and c.202G > A and c.376A > G mutated, was observed at a lower frequency in uncomplicated (3.7%) in comparison to severe malaria (37.9%). The phenotype Fy(a-b +) (p = 0.022) with FY*B/FY*B (p = 0.015) genotype correlated with higher parasitaemia.ConclusionsA high prevalence of G6PD c202G > A and c.376A > G and Duffy variants is observed in Manaus, an endemic area for vivax malaria. In addition, this study reports for the first time the Duffy null phenotype Fy(a-b-) in the population of the Amazonas state. Moreover, it is understood that the relationship between G6PD and Duffy variants can modify clinical symptoms in malaria caused by P. vivax and this deserves to be further investigated and explored among this population.

Dataset Information

Vivax malaria in Duffy-negative patients shows invariably low asexual parasitaemia: implication towards malaria control in Ethiopia.

Background

Methods

Results

Conclusion

Publications

Vivax malaria in Duffy-negative patients shows invariably low asexual parasitaemia: implication towards malaria control in Ethiopia.

Similar Datasets

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