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Marked Rise in the Prevalence of Asymptomatic Plasmodium falciparum Infection in Rural Gabon.

ABSTRACT: Control strategies implemented a decade ago led to a marked reduction in the prevalence of malaria in many countries. In Dienga, southeastern Gabon, the prevalence of microscopic P. falciparum infection was 7% in 2003, close to the pre-elimination threshold of 5%. The aim of this work was to determine the prevalence of P. falciparum infection in the same community a decade later. A cohort of 370 individuals aged from 3 to 85 years living in Dienga was investigated for P. falciparum infection; during six passages (P) in 15-month period. Demographic data were collected, along with behaviors and attitudes towards malaria. Plasmodium infection was diagnosed by microscopy (ME), followed by PCR to detect submicroscopic infection. The prevalence of P. falciparum infection in P1, P2, P3, P4, P5 and P6 was respectively 43.5% (25.1% ME+, 18.4% PCR+); 40.9% (27.0% ME+, 13.9% PCR+), 52.7% (26.1% ME+, 26.6% PCR+); 34.1% (14.1% ME+, 20% PCR+), 57.7% (25.4.% ME+, 32.3% PCR+); and 46.2% (21.4% ME+, 24.8% PCR+) with an overall average of 45.9% (95%CI [37.0-54.7], 23.2% ME+ and 22.7% PCR+). P4 and P5 prevalences were statically different throughout the six passages. Microscopic prevalence was significantly higher than that observed ten years ago (23% [n = 370] vs 7% [n = 323], p < 0.001). Asymptomatic infections were the most frequent (96%). Gametocytes were detected in levels ranging from 5.9% to 13.9%. Insecticide-treated nets, indoor residual insecticides, and self-medication were used by respectively 33.2% (95%CI [29.0-37.4]), 17.7% (95%CI [15.5-19.9]) and 12.1% (95%CI [10.6-13.6]) of the study population. A near-threefold increase in P. falciparum infection has been observed in a rural area of southeastern Gabon during a 10-year period. Most infections were asymptomatic, but these subjects likely represent a parasite reservoir. These findings call for urgent reinforcement of preventive measures.

SUBMITTER: Pegha Moukandja I

PROVIDER: S-EPMC4881998 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Marked Rise in the Prevalence of Asymptomatic Plasmodium falciparum Infection in Rural Gabon.

Pegha Moukandja Irène I Biteghe Bi Essone Jean Claude JC Sagara Issaka I Kassa Kassa Roland Fabrice RF Ondzaga Julien J Lékana Douki Jean-Bernard JB Bouyou Akotet Marielle M Nkoghe Mba Dieudonne D Touré Ndouo Fousseyni S FS

PloS one 20160526 5

Control strategies implemented a decade ago led to a marked reduction in the prevalence of malaria in many countries. In Dienga, southeastern Gabon, the prevalence of microscopic P. falciparum infection was 7% in 2003, close to the pre-elimination threshold of 5%. The aim of this work was to determine the prevalence of P. falciparum infection in the same community a decade later. A cohort of 370 individuals aged from 3 to 85 years living in Dienga was investigated for P. falciparum infection; du ...[more]

PMID: 27228058

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Project description:BackgroundAsymptomatic Plasmodium falciparum parasitaemia forms a reservoir for the transmission of malaria disease in West Africa. Certain haemoglobin variants are known to protect against severe malaria infection. However, data on the potential roles of haemoglobin variants and nongenetic factors in asymptomatic malaria infection is scarce and controversial. Therefore, this study investigated the associations of iron homeostasis, inflammation, nutrition, and haemoglobin mutations with parasitaemia in an asymptomatic cohort from a P. falciparum-endemic region during the high transmission season.MethodsA sub-study population of 688 asymptomatic individuals (predominantly children and adolescents under 15 years, n = 516) from rural Burkina Faso previously recruited by the NOVAC trial (NCT03176719) between June and October 2017 was analysed. Parasitaemia was quantified with conventional haemocytometry. The haemoglobin genotype was determined by reverse hybridization assays targeting a selection of 21 HBA and 22 HBB mutations. Demographics, inflammatory markers (interleukins 6 and 10, hepcidin), nutritional status (mid upper-arm circumference and body mass index), and anaemia (total haemoglobin, ferritin, soluble transferrin receptor) were assessed as potential predictors through logistic regression.ResultsMalaria parasites were detected in 56% of subjects. Parasitaemia was associated most strongly with malnutrition. The effect size increased with malnutrition severity (OR = 6.26, CI95: 2.45-19.4, p < 0.001). Furthermore, statistically significant associations (p < 0.05) with age, cytokines, hepcidin and heterozygous haemoglobin S were observed.ConclusionsAccording to these findings, asymptomatic parasitaemia is attenuated by haemoglobin S, but not by any of the other detected genotypes. Aside from evidence for slight iron imbalance, overall undernutrition was found to predict parasitaemia; thus, further investigations are required to elucidate causality and inform strategies for interventions.

Project description:BackgroundMalaria burden remains high in the sub-Saharan region where helminths are prevalent and where children are often infected with both types of parasites. Although the effect of helminths on malaria infection is evident, the impact of these co-infections is not clearly elucidated yet and the scarce findings are conflicting. In this study, we investigated the effect of schistosomiasis, considering soil-transmitted helminths (STH), on prevalence and incidence of Plasmodium falciparum infection.MethodologyThis longitudinal survey was conducted in school-age children living in two rural communities in the vicinity of Lambaréné, Gabon. Thick blood smear light microscopy, urine filtration and the Kato-Katz technique were performed to detect malaria parasites, S. haematobium eggs and, STH eggs, respectively. P. falciparum carriage was assessed at inclusion, and incidence of malaria and time to the first malaria event were recorded in correlation with Schistosoma carriage status. Stratified multivariate analysis using generalized linear model was used to assess the risk of plasmodium infection considering interaction with STH, and survival analysis to assess time to malaria.Main findingsThe overall prevalence on subject enrolment was 30%, 23% and 9% for S. haematobium, P. falciparum infections and co-infection with both parasites, respectively. Our results showed that schistosomiasis in children tends to increase the risk of plasmodium infection but a combined effect with Trichuris trichiura or hookworm infection clearly increase the risk (aOR = 3.9 [95%CI: 1.7-9.2]). The incidence of malaria over time was 0.51[95%CI: 0.45-0.57] per person-year and was higher in the Schistosoma-infected group compared to the non-infected group (0.61 vs 0.43, p = 0.02), with a significant delay of time-to first-malaria event only in children aged from 6 to 10-years-old infected with Schistosoma haematobium.ConclusionsOur results suggest that STH enhance the risk for P. falciparum infection in schistosomiasis-positive children, and when infected, that schistosomiasis enhances susceptibility to developing malaria in young children but not in older children.

Project description:BACKGROUND:Mannose binding lectin (MBL) has an important role in the activation of the complement system and opsonization of pathogenic microorganisms. Frequent polymorphisms found in the MBL2 gene affect the concentration and functionality of the protein and are associated with enhanced susceptibility to severe malaria in African children. Most MBL2 typing strategies were designed to the analysis of selected variants, the significance of whole haplotypes is poorly known. In this work, a new typing strategy was developed and validated in an association analysis of MBL2 with adult asymptomatic infection. METHODS:MBL2 allele-specific fragments of 144 healthy Gabonese adults were amplified by using haplotype-specific sequencing (HSS), a new strategy that combines sequence-specific PCR and sequence-based typing. The Gabonese were investigated for the presence of Plasmodium falciparum parasitaemia by the amplification of parasite genes, immunochromatographic antigen detection and microscopic analysis. HSS results were also compared with a previously used real-time PCR (RT-PCR) method in 72 Euro-Brazilians. RESULTS:Fourteen polymorphisms were identified beside the commonly investigated promoter (H, L; X, Y; P, Q) and exon 1 (A, O; O = B, C or D) variants. The MBL2*LYPA/LYPA genotype was associated with the absence of asymptomatic infection (P = 0.017), whereas the MBL2*LYQC haplotype and YA/YO + YO/YO genotypes were associated with positive parasite counts in asymptomatic adults (P = 0.033 and 0.018, respectively). The associations were specific to LYPA (identical to the reference sequence Y16577) and LYQC (Y16578) and would not have been revealed by standard genotyping, as there was no association with LYPA and LYQC haplotypes carrying new polymorphisms defined by sequence-based typing. In contrast, HSS and RT-PCR produced very similar results in the less diverse European-derived population. CONCLUSION:In this work, a new typing strategy for a highly polymorphic gene was developed and validated focusing on the asymptomatic status of P. falciparum-infected adults. In populations with high nucleotide diversity, it allowed for the identification of associations with fine-scaled haplotypes that would not have been found using common typing techniques. In this preliminary study, MBL2 haplotypes or SNPs linked to them were found associated with susceptibility to infection and parasitaemia control of asymptomatic adults.

Project description:BACKGROUND:Because clustering of Plasmodium falciparum infection had been noted previously, the clustering of infection was examined at four field sites in West Africa: Dangassa and Dioro in Mali, Gambissara in The Gambia and Madina Fall in Senegal. METHODS:Clustering of infection was defined by the percent of persons with positive slides for asexual P. falciparum sleeping in a house which had been geopositioned. Data from each site were then tested for spatial, temporal and spatio-temporal clustering in relation to the prevalence of infection from smear surveys. RESULTS:These studies suggest that clustering of P. falciparum infection also affects the effectiveness of control interventions. For example, the clustering of infection in Madina Fall disappeared in 2014-2016 after vector control eliminated the only breeding site in 2013. In contrast, the temporal clustering of infection in Dioro (rainy season of 2014, dry season of 2015) was consistent with the loss of funding for Dioro in the second quarter of 2014 and disappeared when funds again became available in late 2015. The clustering of infection in rural (western) areas of Gambissara was consistent with known rural-urban differences in the prevalence of infection and with the thatched roofs, open eaves and mud walls of houses in rural Gambissara. In contrast, the most intense transmission was in Dangassa, where the only encouraging observation was a lower prevalence of infection in the dry season. Taken together, these results suggest: (a) the transmission of infection was stopped in Madina Fall by eliminating the only known breeding site, (b) the prevalence of infection was reduced in Dioro after financial support became available again for malaria control in the second half of 2015, (c) improvements in housing should improve malaria control by reducing the number of vectors in rural communities such as western Gambissara, and (d) beginning malaria control during the dry season may reduce transmission in hyperendemic areas such as Dangassa. CONCLUSIONS:From a conceptual perspective, testing for spatial, temporal and spatio-temporal clustering based on epidemiologic data permits the generation of hypotheses for the clustering observed and the testing of candidate interventions to confirm or refute those hypotheses.

Project description:BackgroundAsymptomatic Plasmodium infections are characterized by the absence of clinical disease and the ability to restrict parasite replication. Increasing levels of regulatory T cells (Tregs) in Plasmodium falciparum infections have been associated with the risk of developing clinical disease, suggesting that individuals with asymptomatic infections may have reduced Treg frequency. However, the relationship between Tregs, cellular activation and parasite control in asymptomatic malaria remains unclear.MethodsIn a cross-sectional study, the levels of Tregs and other T cell activation phenotypes were compared using flow cytometry in symptomatic, asymptomatic and uninfected children before and after stimulation with infected red blood cell lysates (iRBCs). In addition, the association between these T cell phenotypes and parasitaemia were investigated.ResultsIn children with asymptomatic infections, levels of Tregs and activated T cells were comparable to those in healthy controls but significantly lower than those in symptomatic children. After iRBC stimulation, levels of Tregs remained lower for asymptomatic versus symptomatic children. In contrast, levels of activated T cells were higher for asymptomatic children. Strikingly, the pre-stimulation levels of two T cell activation phenotypes (CD8+CD69+ and CD8+CD25+CD69+) and the post-stimulation levels of two regulatory phenotypes (CD4+CD25+Foxp3+ and CD8+CD25+Foxp3+) were significantly positively correlated with and explained 68% of the individual variation in parasitaemia. A machine-learning model based on levels of these four phenotypes accurately distinguished between asymptomatic and symptomatic children (sensitivity = 86%, specificity = 94%), suggesting that these phenotypes govern the observed variation in disease status.ConclusionCompared to symptomatic P. falciparum infections, in children asymptomatic infections are characterized by lower levels of Tregs and activated T cells, which are associated with lower parasitaemia. The results indicate that T cell regulatory and activation phenotypes govern both parasitaemia and disease status in paediatric malaria in the studied sub-Saharan African population.

Dataset Information

Marked Rise in the Prevalence of Asymptomatic Plasmodium falciparum Infection in Rural Gabon.

Publications

Marked Rise in the Prevalence of Asymptomatic Plasmodium falciparum Infection in Rural Gabon.

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