Dataset Information

Differences in PfEMP1s recognized by antibodies from patients with uncomplicated or severe malaria.

ABSTRACT: Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variants are encoded by var genes and mediate pathogenic cytoadhesion and antigenic variation in malaria. PfEMP1s can be broadly divided into three principal groups (A, B and C) and they contain conserved arrangements of functional domains called domain cassettes. Despite their tremendous diversity there is compelling evidence that a restricted subset of PfEMP1s is expressed in severe disease. In this study antibodies from patients with severe and uncomplicated malaria were compared for differences in reactivity with a range of PfEMP1s to determine whether antibodies to particular PfEMP1 domains were associated with severe or uncomplicated malaria.Parts of expressed var genes in a severe malaria patient were identified by RNAseq and several of these partial PfEMP1 domains were expressed together with others from laboratory isolates. Antibodies from Papuan patients to these parts of multiple PfEMP1 proteins were measured.Patients with uncomplicated malaria were more likely to have antibodies that recognized PfEMP1 of Group C type and recognized a broader repertoire of group A and B PfEMP1s than patients with severe malaria.These data suggest that exposure to a broad range of group A and B PfEMP1s is associated with protection from severe disease in Papua, Indonesia.

SUBMITTER: Duffy MF

PROVIDER: S-EPMC4858840 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Differences in PfEMP1s recognized by antibodies from patients with uncomplicated or severe malaria.

Duffy Michael F MF Noviyanti Rintis R Tsuboi Takafumi T Feng Zhi-Ping ZP Trianty Leily L Sebayang Boni F BF Takashima Eizo E Sumardy Fransisca F Lampah Daniel A DA Turner Louise L Lavstsen Thomas T Fowkes Freya J I FJ Siba Peter P Rogerson Stephen J SJ Theander Thor G TG Marfurt Jutta J Price Ric N RN Anstey Nicholas M NM Brown Graham V GV Papenfuss Anthony T AT

Malaria journal 20160505 1

<h4>Background</h4>Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variants are encoded by var genes and mediate pathogenic cytoadhesion and antigenic variation in malaria. PfEMP1s can be broadly divided into three principal groups (A, B and C) and they contain conserved arrangements of functional domains called domain cassettes. Despite their tremendous diversity there is compelling evidence that a restricted subset of PfEMP1s is expressed in severe disease. In this study antibodi ...[more]

PMID: 27149991

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Project description:BACKGROUND:Gaps remain in understanding the role of caregiver responses on time to seek appropriate care. The objective of this study was to describe caregiver responses to illness and the impact of these responses on time to seek appropriate care among children with malaria. METHODS:A case-control study of 325 children with severe (cases) and 325 children with uncomplicated (controls) malaria was conducted in Jinja, Uganda. Caregivers' responses to their children's illnesses and time to seek appropriate care were documented. Responses included staying at home, seeking care at drug shops, and seeking care at public health facilities classified into two types: (1) health facilities where caregiver initially sought care before enrollment, and (2) health facilities where children were provided appropriate care and enrolled in the study. Weighted Cox regression was used to determine risk factors for delays in time to seek appropriate care within 24 h of illness onset. RESULTS:Children staying home on self-medication was the most common initial response to illness among caregivers of controls (57.5%) and cases (42.4%, p?<?0.001), followed by staying at home without medication (25.2%) and seeking care at drug shops (32.0%) for caregivers of controls and cases, respectively. Seeking care at drug shops was more common among caregivers of cases than of controls (32.0% vs. 12.3%; p?<?0.001). However, compared to public health facilities, drug shops offered sub-optimal services with children less likely to have been examined (50.0% vs. 82.9%; p?<?0.001) or referred to another facility (12.5% vs. 61.4%; p?<?0.001). Upon adjustment for known risk factors for delay, initially seeking care at a drug shop (HR 0.37, p?=?0.036) was associated with delay in seeking care at a health facility where appropriate care was provided. In contrast, those initially seeking care at public health facility before enrollment were more likely to subsequently seek care at another public health facility where appropriate care was provided (HR 5.55, p?<?0.001). CONCLUSION:Caregivers should be educated on the importance of promptly seeking care at a health facility where appropriate care can be provided. The role of drug shops in providing appropriate care to children with malaria needs to be reviewed.

Project description:BackgroundControl of malaria increasingly involves administration of 8-aminoquinolines, with accompanying risk of haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Few data on the prevalence and genotypic basis of G6PD deficiency are available from Bangladesh, where malaria remains a major problem in the South (Chittagong Division). The aim of this study was to determine the prevalence of G6PD deficiency, and associated G6PD genotypes, in adults with falciparum malaria in southern Bangladesh.MethodsG6PD status was assessed via a combination of fluorescent spot testing (FST) and genotyping in 141 Bengali patients admitted with falciparum malaria to two centres in Chittagong Division from 2012 to 2014. In addition, an analysis of genomic data from 1000 Genomes Project was carried out among five healthy Indian subcontinent populations.ResultsOne male patient with uncomplicated malaria was found to have G6PD deficiency on FST and a genotype associated with deficiency (hemizygous Orissa variant). In addition, there were two female patients heterozygous for deficiency variants (Orissa and Kerala-Kalyan). These three patients had a relatively long duration of symptoms prior to admission compared to G6PD normal cases, possibly suggesting an interaction with parasite multiplication rate. In addition, one of 27 healthy local controls was deficient on FST and hemizygous for the Mahidol variant of G6PD deficiency. Examination of 1000 Genomes Project sequencing data across the Indian subcontinent showed that 19/723 chromosomes (2.63%) carried a variant associated with deficiency. In the Bengali from Bangladesh 1000 Genomes population, three of 130 chromosomes (2.31%) carried deficient alleles; this included single chromosomes carrying the Kerala-Kalyan and Orissa variants.ConclusionsIn line with other recent work, G6PD deficiency is uncommon in Bengalis in Bangladesh. Further studies of particular ethnic groups are needed to evaluate the potential risk of wide deployment of primaquine in malaria control efforts in Bangladesh.

Dataset Information

Differences in PfEMP1s recognized by antibodies from patients with uncomplicated or severe malaria.

Publications

Differences in PfEMP1s recognized by antibodies from patients with uncomplicated or severe malaria.

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