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Antibody Responses to Crude Gametocyte Extract Predict Plasmodium falciparum Gametocyte Carriage in Kenya

استجابات الأجسام المضادة لخلاصة الخلايا المشيجية الخام تنبئ ببلازموديوم المنجلية نقل الخلايا المشيجية في كينيا
Authors: Brian R. Omondi; Brian R. Omondi; Michelle K. Muthui; William I. Muasya; Benedict Orindi; Ramadhan S. Mwakubambanya; Teun Bousema; +7 Authors

Antibody Responses to Crude Gametocyte Extract Predict Plasmodium falciparum Gametocyte Carriage in Kenya

Abstract

BackgroundMalaria caused by Plasmodium falciparum remains a serious global public health challenge especially in Africa. Interventions that aim to reduce malaria transmission by targeting the gametocyte reservoir are key to malaria elimination and/or eradication. However, factors that are associated with gametocyte carriage have not been fully explored. Consequently, identifying predictors of the infectious reservoir is fundamental in the elimination campaign.MethodsWe cultured P. falciparum NF54 gametocytes (to stage V) and prepared crude gametocyte extract. Samples from a total of 687 participants (aged 6 months to 67 years) representing two cross-sectional study cohorts in Kilifi, Kenya were used to assess IgG antibody responses by ELISA. We also analyzed IgG antibody responses to the blood-stage antigen AMA1 as a marker of asexual parasite exposure. Gametocytemia and asexual parasitemia data quantified by microscopy and molecular detection (QT-NASBA) were used to determine the relationship with antibody responses, season, age, and transmission setting. Multivariable logistic regression models were used to study the association between antibody responses and gametocyte carriage. The predictive power of the models was tested using the receiver operating characteristic (ROC) curve.ResultsMultivariable logistic regression analysis showed that IgG antibody response to crude gametocyte extract predicted both microscopic (OR=1.81 95% CI: 1.06–3.07, p=0.028) and molecular (OR=1.91, 95% CI: 1.11–3.29, p=0.019) P. falciparum gametocyte carriage. Antibody responses to AMA1 were also associated with both microscopic (OR=1.61 95% CI: 1.08–2.42, p=0.020) and molecular (OR=3.73 95% CI: 2.03–6.74, p<0.001) gametocytemia. ROC analysis showed that molecular (AUC=0.897, 95% CI: 0.868–0.926) and microscopic (AUC=0.812, 95% CI: 0.758–0.865) multivariable models adjusted for gametocyte extract showed very high predictive power. Molecular (AUC=0.917, 95% CI: 0.891–0.943) and microscopic (AUC=0.806, 95% CI: 0.755–0.858) multivariable models adjusted for AMA1 were equally highly predictive.ConclusionIn our study, it appears that IgG responses to crude gametocyte extract are not an independent predictor of gametocyte carriage after adjusting for AMA1 responses but may predict gametocyte carriage as a proxy marker of exposure to parasites. Serological responses to AMA1 or to gametocyte extract may facilitate identification of individuals within populations who contribute to malaria transmission and support implementation of transmission-blocking interventions.

Countries
Netherlands, United Kingdom
Keywords

Medical Microbiology - Radboud University Medical Center, Male, Adolescent, Malaria Parasite, Immunology, Plasmodium falciparum, Gametocyte, Radboud University Medical Center, Parasitemia, gametocyte extract, gametocytemia, Role of Complement System in Immune Response, Virology, Health Sciences, Pathology, Humans, Malaria, Falciparum, Child, malaria transmission, Biology, Antibody, Immunology and Microbiology, Microscopy, Carriage, FOS: Clinical medicine, Public Health, Environmental and Occupational Health, Life Sciences, antibody response, RC581-607, Kenya, Malaria, Cross-Sectional Studies, Tick-Borne Diseases and Pathogens Transmission, Child, Preschool, Immunoglobulin G, Antibody Formation, Carrier State, Medicine, Female, Parasitology, Immunologic diseases. Allergy, Radboudumc 4: lnfectious Diseases and Global Health RIHS: Radboud Institute for Health Sciences

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
3
Average
Average
Average
Green
gold