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The complex relationship of exposure to new Plasmodium infections and incidence of clinical malaria in Papua New Guinea.

ABSTRACT: The molecular force of blood-stage infection (molFOB) is a quantitative surrogate metric for malaria transmission at population level and for exposure at individual level. Relationships between molFOB, parasite prevalence and clinical incidence were assessed in a treatment-to-reinfection cohort, where P.vivax (Pv) hypnozoites were eliminated in half the children by primaquine (PQ). Discounting relapses, children acquired equal numbers of new P. falciparum (Pf) and Pv blood-stage infections/year (Pf-molFOB = 0-18, Pv-molFOB = 0-23) resulting in comparable spatial and temporal patterns in incidence and prevalence of infections. Including relapses, Pv-molFOB increased >3 fold (relative to PQ-treated children) showing greater heterogeneity at individual (Pv-molFOB = 0-36) and village levels. Pf- and Pv-molFOB were strongly associated with clinical episode risk. Yearly Pf clinical incidence rate (IR = 0.28) was higher than for Pv (IR = 0.12) despite lower Pf-molFOB. These relationships between molFOB, clinical incidence and parasite prevalence reveal a comparable decline in Pf and Pv transmission that is normally hidden by the high burden of Pv relapses. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov NCT02143934.

SUBMITTER: Hofmann NE

PROVIDER: S-EPMC5606846 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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The complex relationship of exposure to new Plasmodium infections and incidence of clinical malaria in Papua New Guinea.

Hofmann Natalie E NE Karl Stephan S Wampfler Rahel R Kiniboro Benson B Teliki Albina A Iga Jonah J Waltmann Andreea A Betuela Inoni I Felger Ingrid I Robinson Leanne J LJ Mueller Ivo I

eLife 20170901

The molecular force of blood-stage infection (molFOB) is a quantitative surrogate metric for malaria transmission at population level and for exposure at individual level. Relationships between molFOB, parasite prevalence and clinical incidence were assessed in a treatment-to-reinfection cohort, where P.vivax (Pv) hypnozoites were eliminated in half the children by primaquine (PQ). Discounting relapses, children acquired equal numbers of new P. falciparum</ ...[more]

PMID: 28862132

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Project description:Plasmodium vivax has the ability to relapse from dormant parasites in the liver weeks or months after inoculation, causing further blood-stage infection and potential onward transmission. Estimates of the force of blood-stage infections arising from primary infections and relapses are important for designing intervention strategies. However, in endemic settings their relative contributions are unclear. Infections are frequently asymptomatic, many individuals harbor multiple infections, and while high-resolution genotyping of blood samples enables individual infections to be distinguished, primary infections and relapses cannot be identified. We develop a model and fit it to longitudinal genotyping data from children in Papua New Guinea to estimate the incidence and seasonality of P vivax primary infection and relapse. The children, aged one to three years at enrolment, were followed up over 16 months with routine surveys every two months. Blood samples were taken at the routine visits and at other times if the child was ill. Samples positive by microscopy or a molecular method for species detection were genotyped using high-resolution capillary electrophoresis for P vivax MS16 and msp1F3, and P falciparum msp2. The data were summarized as longitudinal patterns of success or failure to detect a genotype at each routine time-point (eg 001000001). We assume that the seasonality of P vivax primary infection is similar to that of P falciparum since they are transmitted by the same vectors and, because P falciparum does not have the ability to relapse, the seasonality can be estimated. Relapses occurring during the study period can be a consequence of infections occurring prior to the study: we assume that the seasonal pattern of primary infections repeats over time. We incorporate information from parasitological and entomology studies to gain leverage for estimating the parameters, and take imperfect detection into account. We estimate the force of P vivax primary infections to be 11.5 (10.5, 12.3) for a three-year old child per year and the mean number of relapses per infection to be 4.3 (4.0, 4.6) over 16 months. The peak incidence of relapses occurred in the two month interval following the peak interval for primary infections: the contribution to the force of blood-stage infection from relapses is between 71% and 90% depending on the season. Our estimates contribute to knowledge of the P vivax epidemiology and have implications for the timing of intervention strategies targeting different stages of the life cycle.

Project description:BACKGROUND:In the past decade, national malaria control efforts in Papua New Guinea (PNG) have received renewed support, facilitating nationwide distribution of free long-lasting insecticidal nets (LLINs), as well as improvements in access to parasite-confirmed diagnosis and effective artemisinin-combination therapy in 2011-2012. METHODS:To study the effects of these intensified control efforts on the epidemiology and transmission of Plasmodium falciparum and Plasmodium vivax infections and investigate risk factors at the individual and household level, two cross-sectional surveys were conducted in the East Sepik Province of PNG; one in 2005, before the scale-up of national campaigns and one in late 2012-early 2013, after 2 rounds of LLIN distribution (2008 and 2011-2012). Differences between studies were investigated using Chi square (?2), Fischer's exact tests and Student's t-test. Multivariable logistic regression models were built to investigate factors associated with infection at the individual and household level. RESULTS:The prevalence of P. falciparum and P. vivax in surveyed communities decreased from 55% (2005) to 9% (2013) and 36% to 6%, respectively. The mean multiplicity of infection (MOI) decreased from 1.8 to 1.6 for P. falciparum (p?=?0.08) and from 2.2 to 1.4 for P. vivax (p?<?0.001). Alongside these reductions, a shift towards a more uniform distribution of infections and illness across age groups was observed but there was greater heterogeneity across the study area and within the study villages. Microscopy positive infections and clinical cases in the household were associated with high rate infection households (>?50% of household members with Plasmodium infection). CONCLUSION:After the scale-up of malaria control interventions in PNG between 2008 and 2012, there was a substantial reduction in P. falciparum and P. vivax infection rates in the studies villages in East Sepik Province. Understanding the extent of local heterogeneity in malaria transmission and the driving factors is critical to identify and implement targeted control strategies to ensure the ongoing success of malaria control in PNG and inform the development of tools required to achieve elimination. In household-based interventions, diagnostics with a sensitivity similar to (expert) microscopy could be used to identify and target high rate households.

Dataset Information

The complex relationship of exposure to new Plasmodium infections and incidence of clinical malaria in Papua New Guinea.

Publications

The complex relationship of exposure to new <i>Plasmodium</i> infections and incidence of clinical malaria in Papua New Guinea.

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