Dataset Information

Modelling the epidemiology of residual Plasmodium vivax malaria in a heterogeneous host population: A case study in the Amazon Basin.

ABSTRACT: The overall malaria burden in the Americas has decreased dramatically over the past two decades, but residual transmission pockets persist across the Amazon Basin, where Plasmodium vivax is the predominant infecting species. Current elimination efforts require a better quantitative understanding of malaria transmission dynamics for planning, monitoring, and evaluating interventions at the community level. This can be achieved with mathematical models that properly account for risk heterogeneity in communities approaching elimination, where few individuals disproportionately contribute to overall malaria prevalence, morbidity, and onwards transmission. Here we analyse demographic information combined with routinely collected malaria morbidity data from the town of Mâncio Lima, the main urban transmission hotspot of Brazil. We estimate the proportion of high-risk subjects in the host population by fitting compartmental susceptible-infected-susceptible (SIS) transmission models simultaneously to age-stratified vivax malaria incidence densities and the frequency distribution of P. vivax malaria attacks experienced by each individual over 12 months. Simulations with the best-fitting SIS model indicate that 20% of the hosts contribute 86% of the overall vivax malaria burden. Despite the low overall force of infection typically found in the Amazon, about one order of magnitude lower than that in rural Africa, high-risk individuals gradually develop clinical immunity following repeated infections and eventually constitute a substantial infectious reservoir comprised of asymptomatic parasite carriers that is overlooked by routine surveillance but likely fuels onwards malaria transmission. High-risk individuals therefore represent a priority target for more intensive and effective interventions that may not be readily delivered to the entire community.

SUBMITTER: Corder RM

PROVIDER: S-EPMC7108741 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Modelling the epidemiology of residual Plasmodium vivax malaria in a heterogeneous host population: A case study in the Amazon Basin.

Corder Rodrigo M RM Ferreira Marcelo U MU Gomes M Gabriela M MGM

PLoS computational biology 20200313 3

The overall malaria burden in the Americas has decreased dramatically over the past two decades, but residual transmission pockets persist across the Amazon Basin, where Plasmodium vivax is the predominant infecting species. Current elimination efforts require a better quantitative understanding of malaria transmission dynamics for planning, monitoring, and evaluating interventions at the community level. This can be achieved with mathematical models that properly account for risk heterogeneity ...[more]

PMID: 32168349

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Project description:BACKGROUND:There is a growing body of evidence linking micronutrient deficiencies and malaria incidence arising mostly from P. falciparum endemic areas. We assessed the impact of micronutrient deficiencies on malaria incidence and vice versa in the Brazilian state of Amazonas. METHODOLOGY/PRINCIPAL FINDINGS:We evaluated children <10 years old living in rural communities in the state of Amazonas, Brazil, from May 2010 to May 2011. All children were assessed for sociodemographic, anthropometric and laboratory parameters, including vitamin A, beta-carotene, zinc and iron serum levels at the beginning of the study (May 2010) and one year later (May 2011). Children were followed in between using passive surveillance for detection of symptomatic malaria. Those living in the study area at the completion of the observation period were reassessed for micronutrient levels. Univariate Cox-proportional Hazards models were used to assess whether micronutrient deficiencies had an impact on time to first P. vivax malaria episode. We included 95 children median age 4.8 years (interquartile range [IQR]: 2.3-6.6), mostly males (60.0%) and with high maternal illiteracy (72.6%). Vitamin A deficiencies were found in 36% of children, beta-carotene deficiency in 63%, zinc deficiency in 61% and iron deficiency in 51%. Most children (80%) had at least one intestinal parasite. During follow-up, 16 cases of vivax malaria were diagnosed amongst 13 individuals. Micronutrient deficiencies were not associated with increased malaria incidence: vitamin A deficiency [Hazard ratio (HR): 1.51; P-value: 0.45]; beta-carotene [HR: 0.47; P-value: 0.19]; zinc [HR: 1.41; P-value: 0.57] and iron [HR: 2.31; P-value: 0.16]). Upon reevaluation, children with al least one episode of malaria did not present significant changes in micronutrient levels. CONCLUSION:Micronutrient serum levels were not associated with a higher malaria incidence nor the malaria episode influenced micronutrient levels. Future studies targeting larger populations to assess micronutrients levels in P. vivax endemic areas are warranted in order to validate these results.

Project description:BackgroundThe landscape of malaria transmission in the Peruvian Amazon is temporally and spatially heterogeneous, presenting different micro-geographies with particular epidemiologies. Most cases are asymptomatic and escape routine malaria surveillance based on light microscopy (LM). Following the implementation of control programs in this region, new approaches to stratify transmission and direct efforts at an individual and community level are needed. Antibody responses to serological exposure markers (SEM) to Plasmodium vivax have proven diagnostic performance to identify people exposed in the previous 9 months.MethodologyWe measured antibody responses against 8 SEM to identify recently exposed people and determine the transmission dynamics of P. vivax in peri-urban (Iquitos) and riverine (Mazán) communities of Loreto, communities that have seen significant recent reductions in malaria transmission. Socio-demographic, geo-reference, LM and qPCR diagnosis data were collected from two cross-sectional surveys. Spatial and multilevel analyses were implemented to describe the distribution of seropositive cases and the risk factors associated with exposure to P. vivax.Principal findingsLow local transmission was detected by qPCR in both Iquitos (5.3%) and Mazán (2.7%); however, seroprevalence indicated a higher level of (past) exposure to P. vivax in Mazán (56.5%) than Iquitos (38.2%). Age and being male were factors associated with high odds of being seropositive in both sites. Higher antibody levels were found in individuals >15 years old. The persistence of long-lived antibodies in these individuals could overestimate the detection of recent exposure. Antibody levels in younger populations (<15 years old) could be a better indicator of recent exposure to P. vivax.ConclusionsThe large number of current and past infections detected by SEMs allows for detailed local epidemiological analyses, in contrast to data from qPCR prevalence surveys which did not produce statistically significant associations. Serological surveillance will be increasingly important in the Peruvian Amazon as malaria transmission is reduced by continued control and elimination efforts.

Project description:BackgroundNew frontier settlements across the Amazon Basin pose a major challenge for malaria elimination in Brazil. Here we describe the epidemiology of malaria during the early phases of occupation of farming settlements in Remansinho area, Brazilian Amazonia. We examine the relative contribution of low-density and asymptomatic parasitemias to the overall Plasmodium vivax burden over a period of declining transmission and discuss potential hurdles for malaria elimination in Remansinho and similar settings.MethodsEight community-wide cross-sectional surveys, involving 584 subjects, were carried out in Remansinho over 3 years and complemented by active and passive surveillance of febrile illnesses between the surveys. We used quantitative PCR to detect low-density asexual parasitemias and gametocytemias missed by conventional microscopy. Mixed-effects multiple logistic regression models were used to characterize independent risk factors for P. vivax infection and disease.Principal findings/conclusionsP. vivax prevalence decreased from 23.8% (March-April 2010) to 3.0% (April-May 2013), with no P. falciparum infections diagnosed after March-April 2011. Although migrants from malaria-free areas were at increased risk of malaria, their odds of having P. vivax infection and disease decreased by 2-3% with each year of residence in Amazonia. Several findings indicate that low-density and asymptomatic P. vivax parasitemias may complicate residual malaria elimination in Remansinho: (a) the proportion of subpatent infections (i.e. missed by microscopy) increased from 43.8% to 73.1% as P. vivax transmission declined; (b) most (56.6%) P. vivax infections were asymptomatic and 32.8% of them were both subpatent and asymptomatic; (c) asymptomatic parasite carriers accounted for 54.4% of the total P. vivax biomass in the host population; (d) over 90% subpatent and asymptomatic P. vivax had PCR-detectable gametocytemias; and (e) few (17.0%) asymptomatic and subpatent P. vivax infections that were left untreated progressed to clinical disease over 6 weeks of follow-up and became detectable by routine malaria surveillance.

Project description:BackgroundFollowing the scale-up of intervention efforts, malaria burden has decreased dramatically in Solomon Islands (SI). Submicroscopic and asymptomatic Plasmodium vivax infections are now the major challenge for malaria elimination in this country. Since children have higher risk of contracting malaria, this study investigated the dynamics of Plasmodium spp. infections among children including the associated risk factors of residual P. vivax burden.MethodsAn observational cohort study was conducted among 860 children aged 0.5-12 years in Ngella (Central Islands Province, SI). Children were monitored by active and passive surveillances for Plasmodium spp. infections and illness. Parasites were detected by quantitative real-time PCR (qPCR) and genotyped. Comprehensive statistical analyses of P. vivax infection prevalence, molecular force of blood stage infection (molFOB) and infection density were conducted.ResultsPlasmodium vivax infections were common (overall prevalence: 11.9%), whereas Plasmodium falciparum infections were rare (0.3%) but persistent. Although children acquire an average of 1.1 genetically distinct P. vivax blood-stage infections per year, there was significant geographic heterogeneity in the risks of P. vivax infections across Ngella (prevalence: 1.2-47.4%, p < 0.01; molFOB: 0.05-4.6/year, p < 0.01). Malaria incidence was low (IR: 0.05 episodes/year-at-risk). Age and measures of high exposure were the key risk factors for P. vivax infections and disease. Malaria incidence and infection density decreased with age, indicating significant acquisition of immunity. G6PD deficient children (10.8%) that did not receive primaquine treatment had a significantly higher prevalence (aOR: 1.77, p = 0.01) and increased risk of acquiring new bloodstage infections (molFOB aIRR: 1.51, p = 0.03), underscoring the importance of anti-relapse treatment.ConclusionResidual malaria transmission in Ngella exhibits strong heterogeneity and is characterized by a high proportion of submicroscopic and asymptomatic P. vivax infections, alongside sporadic P. falciparum infections. Implementing an appropriate primaquine treatment policy to prevent P. vivax relapses and specific targeting of control interventions to high risk areas will be required to accelerate ongoing control and elimination activities.

Dataset Information

Modelling the epidemiology of residual Plasmodium vivax malaria in a heterogeneous host population: A case study in the Amazon Basin.

Publications

Modelling the epidemiology of residual Plasmodium vivax malaria in a heterogeneous host population: A case study in the Amazon Basin.

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