Human Genetic Contribution to the Outcome of Infection with Malaria Parasites

Machado, Ana Sofia; Loucoubar, Cheikh; Grange, Laura; Bureau, Jean‐François; Sakuntabhai, Anavaj; Rácz, Paul

doi:10.5772/33652

Cited by 2 publications

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References 100 publications

(100 reference statements)

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“…15 (VSN Ltd) to account for the non-independence of individuals because of family relationships and for repeated measures from the same individual [ 36 ]. Correlated individual effects due to familial relationships were taken into account by using the pedigree-based genetic relatedness matrix that contains the genetic covariance among all pairs of individuals in the study cohort and is calculated using the pedigree information [ 37 ]. Genetic covariance and repeated measures from the same individual were modelled as random effects.…”

Section: Methodsmentioning

confidence: 99%

Risk Factors for Plasmodium falciparum Gametocyte Positivity in a Longitudinal Cohort

et al. 2015

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Malaria transmission intensity is highly heterogeneous even at a very small scale. Implementing targeted intervention in malaria transmission hotspots offers the potential to reduce the burden of disease both locally and in adjacent areas. Transmission of malaria parasites from man to mosquito requires the production of gametocyte stage parasites. Cluster analysis of a 19-year long cohort study for gametocyte carriage revealed spatially defined gametocyte hotspots that occurred during the time when chloroquine was the drug used for clinical case treatment. In addition to known risk factors for gametocyte carriage, notably young age (<15 years old) and associated with a clinical episode, blood groups B and O increased risk compared to groups A and AB. A hotspot of clinical P. falciparum clinical episodes that overlapped the gametocyte hotspots was also identified. Gametocyte positivity was found to be increased in individuals who had been treated with chloroquine, as opposed to other drug treatment regimens, for a clinical P. falciparum episode up to 30 days previously. It seems likely the hotspots were generated by a vicious circle of ineffective treatment of clinical cases and concomitant gametocyte production in a sub-population characterized by an increased prevalence of all the identified risk factors. While rapid access to treatment with an effective anti-malarial can reduce the duration of gametocyte carriage and onward parasite transmission, localised hotspots represent a challenge to malaria control and eventual eradication.

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Section: Methodsmentioning

confidence: 99%

Risk Factors for Plasmodium falciparum Gametocyte Positivity in a Longitudinal Cohort

et al. 2015

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“…To address the effect of allergic status on the risk of clinical P falciparum episodes, we performed Generalised Linear Mixed Models (GLMM) extended to pedigree data using the pedigreemm package for R to account for the non-independence of individuals because of family relationships, shared house and for repeated measures from the same individual (see online supplementary technical appendix). Correlated individual effects due to familial relationships were taken into account by using the pedigree-based genetic relatedness matrix that contains the genetic covariance among all pairs of individuals in the study cohort and is calculated using the pedigree information 34. Shared house and repeated measures from the same individual were modelled as random effects.…”

Section: Methodsmentioning

confidence: 99%

Asthma and atopic dermatitis are associated with increased risk of clinicalPlasmodium falciparummalaria

et al. 2013

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ObjectivesTo assess the impact of atopy and allergy on the risk of clinical malaria.DesignA clinical and immunological allergy cross-sectional survey in a birth cohort of 175 children from 1 month to 14 years of age followed for up to 15 years in a longitudinal open cohort study of malaria in Senegal. Malaria incidence data were available for 143 of these children (aged 4 months to 14 years of age) for up to 15 years. Mixed-model regression analysis was used to determine the impact of allergy status on malaria incidence, adjusting for age, gender, sickle-cell trait and force of infection.Main outcome measuresAsthma, allergic rhinoconjunctivitis and atopic dermatitis status, the number of clinical Plasmodium falciparum malaria episodes since birth and associated parasite density.Results12% of the children were classified as asthmatic and 10% as having atopic dermatitis. These groups had respectively a twofold (OR 2.12 95%; CI 1.46 to 3.08; p=8×10−5) and threefold (OR 3.15; 1.56 to 6.33; p=1.3×10−3) increase in the risk of clinical P falciparum malaria once older than the age of peak incidence of clinical malaria (3–4 years of age). They also presented with higher P falciparum parasite densities (asthma: mean 105.3 parasites/μL±SE 41.0 vs 51.3±9.7; p=6.2×10−3. Atopic dermatitis: 135.4±70.7 vs 52.3±11.0; p=0.014). There was no effect of allergy on the number of non-malaria clinical presentations. Individuals with allergic rhinoconjunctivitis did not have an increased risk of clinical malaria nor any difference in parasite densities.ConclusionsThese results demonstrate that asthma and atopic dermatitis delay the development of clinical immunity to P falciparum. Despite the encouraging decrease in malaria incidence rates in Africa, a significant concern is the extent to which the increase in allergy will exacerbate the burden of malaria. Given the demonstrated antiparasitic effect of antihistamines, administration to atopic children will likely reduce the burden of clinical malaria in these children, increase the efficacy of first-line treatment antimalarials and alleviate the non-infectious consequences of atopy.

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Human Genetic Contribution to the Outcome of Infection with Malaria Parasites

Cited by 2 publications

References 100 publications

Risk Factors for Plasmodium falciparum Gametocyte Positivity in a Longitudinal Cohort

Risk Factors for Plasmodium falciparum Gametocyte Positivity in a Longitudinal Cohort

Asthma and atopic dermatitis are associated with increased risk of clinicalPlasmodium falciparummalaria

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