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Novel serologic biomarkers provide accurate estimates of recent Plasmodium falciparum exposure for individuals and communities.

ABSTRACT: Tools to reliably measure Plasmodium falciparum (Pf) exposure in individuals and communities are needed to guide and evaluate malaria control interventions. Serologic assays can potentially produce precise exposure estimates at low cost; however, current approaches based on responses to a few characterized antigens are not designed to estimate exposure in individuals. Pf-specific antibody responses differ by antigen, suggesting that selection of antigens with defined kinetic profiles will improve estimates of Pf exposure. To identify novel serologic biomarkers of malaria exposure, we evaluated responses to 856 Pf antigens by protein microarray in 186 Ugandan children, for whom detailed Pf exposure data were available. Using data-adaptive statistical methods, we identified combinations of antibody responses that maximized information on an individual's recent exposure. Responses to three novel Pf antigens accurately classified whether an individual had been infected within the last 30, 90, or 365 d (cross-validated area under the curve = 0.86-0.93), whereas responses to six antigens accurately estimated an individual's malaria incidence in the prior year. Cross-validated incidence predictions for individuals in different communities provided accurate stratification of exposure between populations and suggest that precise estimates of community exposure can be obtained from sampling a small subset of that community. In addition, serologic incidence predictions from cross-sectional samples characterized heterogeneity within a community similarly to 1 y of continuous passive surveillance. Development of simple ELISA-based assays derived from the successful selection strategy outlined here offers the potential to generate rich epidemiologic surveillance data that will be widely accessible to malaria control programs.

SUBMITTER: Helb DA

PROVIDER: S-EPMC4538641 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Novel serologic biomarkers provide accurate estimates of recent Plasmodium falciparum exposure for individuals and communities.

Helb Danica A DA Tetteh Kevin K A KK Felgner Philip L PL Skinner Jeff J Hubbard Alan A Arinaitwe Emmanuel E Mayanja-Kizza Harriet H Ssewanyana Isaac I Kamya Moses R MR Beeson James G JG Tappero Jordan J Smith David L DL Crompton Peter D PD Rosenthal Philip J PJ Dorsey Grant G Drakeley Christopher J CJ Greenhouse Bryan B

Proceedings of the National Academy of Sciences of the United States of America 20150727 32

Tools to reliably measure Plasmodium falciparum (Pf) exposure in individuals and communities are needed to guide and evaluate malaria control interventions. Serologic assays can potentially produce precise exposure estimates at low cost; however, current approaches based on responses to a few characterized antigens are not designed to estimate exposure in individuals. Pf-specific antibody responses differ by antigen, suggesting that selection of antigens with defined kinetic profiles will improv ...[more]

PMID: 26216993

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Project description:BackgroundMalaria remains a serious health threat in the Amazonas Region of Peru and approximately 95% of the cases, mainly Plasmodium vivax, are found in native communities of The Rio Santiago District, Condorcanqui Province. In 2019, more than one thousand malaria cases were reported, with an unusual number of Plasmodium falciparum autochthonous cases. The present study aims to report this P. falciparum outbreak while describing the epidemiology of malaria and the risk factors associated in the native communities of Amazonas, Peru.MethodsThe DIRESA-Amazonas in collaboration with the Condorcanqui Health Network and the Institute of Tropical Diseases of the UNTRM carried out a malaria Active Case Detection (ACD III) between January 31st and February 10th of 2020. A total of 2718 (47.4%) individuals from 21 native communities grouped in eight sanitary districts, were screened for malaria infections. Each participant was screened for malaria using microscopy. Follow-up surveys were conducted for all malaria positive individuals to collect socio-demographic data. Spatial clustering of infection risk was calculated using a generalized linear model (GLM). Analysis of risk considered factors such as gender, age, type of infection, symptomatology, and parasitaemia.ResultsThe study suggests that the P. falciparum index case was imported from Loreto and later spread to other communities of Rio Santiago during 2019. The ACD III reported 220 (8.1%) malaria cases, 46 P. falciparum, 168 P. vivax and 6 mixed infections. SaTScan analysis detected a cluster of high infection risk in Middle Rio Santiago and a particular high P. falciparum infection risk cluster in Upper Rio Santiago. Interestingly, the evaluation of different risk factors showed significant associations between low parasitaemia and P. falciparum asymptomatic cases.ConclusionThis is the first report of a P. falciparum outbreak in native communities of Condorcanqui, Amazonas. Timely identification and treatment of symptomatic and asymptomatic cases are critical to achieve malaria control and possible elimination in this area. However, the current malaria situation in Condorcanqui is uncertain, given that malaria ACD activities have been postponed due to COVID-19.

Project description:BackgroundMultiplex bead assays (MBA) that measure IgG antibodies to the carboxy-terminal 19-kDa sub-unit of the merozoite surface protein 1 (MSP119) are currently used to determine malaria seroprevalence in human populations living in areas with both stable and unstable transmission. However, the species specificities of the IgG antibody responses to the malaria MSP119 antigens have not been extensively characterized using MBA.MethodsRecombinant Plasmodium falciparum (3D7), Plasmodium malariae (China I), Plasmodium ovale (Nigeria I), and Plasmodium vivax (Belem) MSP119 proteins were covalently coupled to beads for MBA. Threshold cut-off values for the assays were estimated using sera from US citizens with no history of foreign travel and by receiver operator characteristic curve analysis using diagnostic samples. Banked sera from experimentally infected chimpanzees, sera from humans from low transmission regions of Haiti and Cambodia (N = 12), and elutions from blood spots from humans selected from a high transmission region of Mozambique (N = 20) were used to develop an antigen competition MBA for antibody cross-reactivity studies. A sub-set of samples was further characterized using antibody capture/elution MBA, IgG subclass determination, and antibody avidity measurement.ResultsTotal IgG antibody responses in experimentally infected chimpanzees were species specific and could be completely suppressed by homologous competitor protein at a concentration of 10 μg/ml. Eleven of 12 samples from the low transmission regions and 12 of 20 samples from the high transmission area had antibody responses that were completely species specific. For 7 additional samples, the P. falciparum MSP119 responses were species specific, but various levels of incomplete heterologous competition were observed for the non-P. falciparum assays. A pan-malaria MSP119 cross-reactive antibody response was observed in elutions of blood spots from two 20-30 years old Mozambique donors. The antibody response from one of these two donors had low avidity and skewed almost entirely to the IgG3 subclass.ConclusionsEven when P. falciparum, P. malariae, P. ovale, and P. vivax are co-endemic in a high transmission setting, most antibody responses to MSP119 antigens are species-specific and are likely indicative of previous infection history. True pan-malaria cross-reactive responses were found to occur rarely.

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Novel serologic biomarkers provide accurate estimates of recent Plasmodium falciparum exposure for individuals and communities.

Publications

Novel serologic biomarkers provide accurate estimates of recent Plasmodium falciparum exposure for individuals and communities.

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