Familial Aggregation of Cerebral Malaria and Severe Malarial Anemia

Ranque, Stéphane; Safeukui, Innocent; Poudiougou, Belco; Traore, A.; Keita, Modibo; Traoré, Diamori; Diakité, Mahamadou; Cissé, Mahamadou B.; Keita, Marouf M.; Doumbo, Ogobara K.; Dessein, Alain

doi:10.1086/427238

Cited by 12 publications

(8 citation statements)

References 29 publications

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“…The odds of having cerebral malaria were 2.49 times higher for a child whose sibling had a history of cerebral malaria than the odds for a child whose sibling had no history of cerebral malaria (34,141). Similar results have been obtained for mild malaria and severe anemia (72,141). In addition, Mackinnon et al (97,98) found that genetic factors explained ϳ25% of the variation in the incidence of mild malaria episodes.…”

Section: Heritability Of Phenotypes Related To Malarial Infection Andsupporting

confidence: 56%

“…The results of several family studies have shown conclusively a familial aggregation of blood infection levels (1,52,142), malaria attacks (72), severe malaria (141), and antimalarial immune responses (12,155,158). Segregation analyses of parasitemia yielded significant sibling correlation coefficients, which ranged from 0.16 to 0.24 (1,52,142).…”

Section: Heritability Of Phenotypes Related To Malarial Infection Andmentioning

confidence: 99%

“…Although an initial study detected a major gene controlling parasitemia in Cameroon, segregation analyses of both parasitemia and antibody levels showed a complex genetic model in Cameroon, in Burkina Faso, and in Papua New Guinea (1,52,142,157). The odds of having cerebral malaria were 2.49 times higher for a child whose sibling had a history of cerebral malaria than the odds for a child whose sibling had no history of cerebral malaria (34,141). Similar results have been obtained for mild malaria and severe anemia (72,141).…”

Section: Heritability Of Phenotypes Related To Malarial Infection Andmentioning

confidence: 99%

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Host susceptibility to malaria in human and mice: compatible approaches to identify potential resistant genes

Hernandez-Valladares¹,

Rihet

Iraqi

2014

Physiological Genomics

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Hernandez-Valladares M, Rihet P, Iraqi FA. Host susceptibility to malaria in human and mice: compatible approaches to identify potential resistant genes. Physiol Genomics 46: 1-16, 2014. First published October 29, 2013 doi:10.1152/physiolgenomics.00044.2013.-There is growing evidence for human genetic factors controlling the outcome of malaria infection, while molecular basis of this genetic control is still poorly understood. Case-control and family-based studies have been carried out to identify genes underlying host susceptibility to malarial infection. Parasitemia and mild malaria have been genetically linked to human chromosomes 5q31-q33 and 6p21.3, and several immune genes located within those regions have been associated with malaria-related phenotypes. Association and linkage studies of resistance to malaria are not easy to carry out in human populations, because of the difficulty in surveying a significant number of families. Murine models have proven to be an excellent genetic tool for studying host response to malaria; their use allowed mapping 14 resistance loci, eight of them controlling parasitic levels and six controlling cerebral malaria. Once quantitative trait loci or genes have been identified, the human ortholog may then be identified. Comparative mapping studies showed that a couple of human and mouse might share similar genetically controlled mechanisms of resistance. In this way, char8, which controls parasitemia, was mapped on chromosome 11; char8 corresponds to human chromosome 5q31-q33 and contains immune genes, such as Il3, Il4, Il5, Il12b, Il13, Irf1, and Csf2. Nevertheless, part of the genetic factors controlling malaria traits might differ in both hosts because of specific hostpathogen interactions. Finally, novel genetic tools including animal models were recently developed and will offer new opportunities for identifying genetic factors underlying host phenotypic response to malaria, which will help in better therapeutic strategies including vaccine and drug development. malaria; genetic resistance; human; mouse model; QT mapping PLASMODIUM FALCIPARUM MALARIA remains a major cause of morbidity and mortality in many developing countries. According to the World Health Organization (WHO), the number of cases in 2012 reached 219 million [95% confidence interval (CI) 154 -289 million], among which Ͼ660,000 (95% CI 490,000 -836,000) were fatal (62, 181a). Drug-resistant parasite strains are spreading rapidly across the world, and, despite substantial efforts and encouraging results from recent trials, a fully protective malaria vaccine remains a distant prospect (154). Vaccine development faces major difficulties partly due to the genetic control of immunity to the parasite (155,156,163,176) and/or to the parasitic antigenic variation (146).The outcome of human malaria infection is thought to depend on both parasite and host genetic factors. P. falciparum genotypes have been associated with differences in disease outcome (41) and may be subject to selective pressure (34,55). The influ...

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Section: Heritability Of Phenotypes Related To Malarial Infection Andsupporting

confidence: 56%

Section: Heritability Of Phenotypes Related To Malarial Infection Andmentioning

confidence: 99%

Section: Heritability Of Phenotypes Related To Malarial Infection Andmentioning

confidence: 99%

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Host susceptibility to malaria in human and mice: compatible approaches to identify potential resistant genes

Hernandez-Valladares¹,

Rihet

Iraqi

2014

Physiological Genomics

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“…This study included 341 children with SM (either CM or SA) and 42 children with uncomplicated malaria (UM) ( Table 1) hospitalized in the pediatric department of Gabriel Toure Hospital in Bamako, Mali [17][18][19].…”

Section: Methodsmentioning

confidence: 99%

Genetic Evidence for the Aggravation ofPlasmodium falciparumMalaria by Interleukin 4

Cabantous

Poudiougou²,

Oumar

et al. 2009

J INFECT DIS

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“…Furthermore, because related individuals often share a common environment (such as a house), and environmental factors play a major role in the risk of infectious diseases, environmental and genetic effects are inseparable in most field study designs (for example, those that have pairs of full-sibs, each pair living in a different house [1,3–5]). In order to separate these effects, it is necessary to study sets of individuals of varying genetic relatedness who live together in the same house: information on genetically related individuals who live in different households also helps.…”

Section: Introductionmentioning

confidence: 99%

Heritability of Malaria in Africa

et al. 2005

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BackgroundWhile many individual genes have been identified that confer protection against malaria, the overall impact of host genetics on malarial risk remains unknown.Methods and FindingsWe have used pedigree-based genetic variance component analysis to determine the relative contributions of genetic and other factors to the variability in incidence of malaria and other infectious diseases in two cohorts of children living on the coast of Kenya. In the first, we monitored the incidence of mild clinical malaria and other febrile diseases through active surveillance of 640 children 10 y old or younger, living in 77 different households for an average of 2.7 y. In the second, we recorded hospital admissions with malaria and other infectious diseases in a birth cohort of 2,914 children for an average of 4.1 y. Mean annual incidence rates for mild and hospital-admitted malaria were 1.6 and 0.054 episodes per person per year, respectively. Twenty-four percent and 25% of the total variation in these outcomes was explained by additively acting host genes, and household explained a further 29% and 14%, respectively. The haemoglobin S gene explained only 2% of the total variation. For nonmalarial infections, additive genetics explained 39% and 13% of the variability in fevers and hospital-admitted infections, while household explained a further 9% and 30%, respectively.ConclusionGenetic and unidentified household factors each accounted for around one quarter of the total variability in malaria incidence in our study population. The genetic effect was well beyond that explained by the anticipated effects of the haemoglobinopathies alone, suggesting the existence of many protective genes, each individually resulting in small population effects. While studying these genes may well provide insights into pathogenesis and resistance in human malaria, identifying and tackling the household effects must be the more efficient route to reducing the burden of disease in malaria-endemic areas.

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Familial Aggregation of Cerebral Malaria and Severe Malarial Anemia

Abstract: Our data suggest strong familial aggregation of CM and SMA.

Cited by 12 publications

References 29 publications

Host susceptibility to malaria in human and mice: compatible approaches to identify potential resistant genes

Host susceptibility to malaria in human and mice: compatible approaches to identify potential resistant genes

Genetic Evidence for the Aggravation ofPlasmodium falciparumMalaria by Interleukin 4

Heritability of Malaria in Africa

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