Life-Threatening Malaria in African Children

Ranque, Stéphane; Poudiougou, Belco; Traoré, Abdoulaye; Keita, Modibo; Oumar, Aboubacar Alassane; Safeukui, Innocent; Marquet, Sandrine; Cabantous, Stéphanie; Diakité, Mahamadou; Mintha, Daouda; Cissé, Mahamadou B.; Keita, Marouf M.; Dessein, Alain; Doumbo, Ogobara K.

doi:10.1097/inf.0b013e31815988ed

Cited by 26 publications

(21 citation statements)

References 19 publications

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“…Malian children with CM were recruited as described previously (14)(15)(16)(17). The children with CM were hospitalized between 1999 and 2003 in the pediatric department of the Gabriel Toure Hospital in Bamako (Mali).…”

Section: Methodsmentioning

confidence: 99%

The IL17F and IL17RA Genetic Variants Increase Risk of Cerebral Malaria in Two African Populations

et al. 2016

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jCerebral malaria (CM) is a neurological complication of infection with Plasmodium falciparum that is partly caused by cytokine-mediated inflammation. It is not known whether interleukin-17 (IL-17) cytokines, which regulate inflammation, control the development of CM. To evaluate the involvement of IL-17 cytokines in CM, we analyzed 46 common polymorphisms in IL17A, IL17F, and IL17RA (which encodes the common receptor chain of the members of the IL-17 family) in two independent African populations. A case-control study involving 115 Nigerian children with CM and 160 controls from the community (CC) showed that IL17F reference single nucleotide polymorphism (SNP) 6913472 (rs6913472) (P ‫؍‬ 0.004; odds ratio [OR] ‫؍‬ 3.12), IL17F rs4715291 (P ‫؍‬ 0.004; OR ‫؍‬ 2.82), IL17RA rs12159217 (P ‫؍‬ 0.01; OR ‫؍‬ 2.27), and IL17RA rs41396547 (P ‫؍‬ 0.026; OR ‫؍‬ 3.15) were independently associated with CM. A replication study was performed in 240 nuclear Malian family trios (two parents with one CM child). We replicated the association for 3 SNPs, IL17F rs6913472 (P ‫؍‬ 0.03; OR ‫؍‬ 1.39), IL17RA rs12159217 (P ‫؍‬ 0.01; OR ‫؍‬ 1.52), and IL17RA rs41396547 (P ‫؍‬ 0.04; OR ‫؍‬ 3.50). We also found that one additional SNP, IL17RA rs41433045, in linkage disequilibrium (LD) with rs41396547, was associated with CM in both Nigeria and Mali (P ‫؍‬ 0.002; OR ‫؍‬ 4.12 in the combined sample). We excluded the possibility that SNPs outside IL17F and IL17RA, in strong LD with the associated SNPs, could account for the observed associations. Furthermore, the results of a functional study indicated that the aggravating GA genotype of IL17F rs6913472 was associated with lower IL-17F concentrations. Our findings show for the first time that IL17F and IL17RA polymorphisms modulate susceptibility to CM and provide evidence that IL-17F protects against CM. C erebral malaria (CM) is one of the most severe complications of infection with Plasmodium falciparum and occurs predominantly in young children under 5 years of age and in "nonimmune" adults. The clinical characteristics of CM are an unarousable coma lasting for at least 1 h, with or without generalized convulsions, and asexual P. falciparum parasitemia with normal cerebrospinal fluid and no other cause of encephalopathy. This reversible encephalopathy is characterized by the sequestration of infected red blood cells (IRBC) in the capillaries of the brain together with the accumulation of leukocytes, platelets, and uninfected red blood cells (URBC) causing mechanical obstruction of microvessels and excessive activation of immune cells. Other pathological consequences are brain edema, alterations of the integrity of the blood-brain barrier (BBB), microhemorrhages, and tissue necrosis (1). However, despite the large number of studies that have investigated CM, the orchestration of the pathogenic mechanisms leading to CM is not well understood.Proinflammatory cytokines are thought to contribute to brain pathology in CM. Interleukin-17A (IL-17A) and IL-17F, the best-studied members of the IL-...

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Section: Methodsmentioning

confidence: 99%

The IL17F and IL17RA Genetic Variants Increase Risk of Cerebral Malaria in Two African Populations

et al. 2016

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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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“…(WHO 2004) A reduction in the frequency of severe anaemia beyond 24 months of life with a two fold increase in prevalence of cerebral malaria across same age band had earlier been reported in Ghana and Mali. (Oduro et al, 2007, Ranque et al, 2008 The fact that most cases of severe anaemia are seen in children less than 2years of age is attributable to the smaller red cell mass and the relatively lower immunity to the malaria parasite compared to the older children. (Newton & Krishna, 1998) This study demonstrated a progressive and consistent reduction in proportion of severe malaria anaemia with increasing age supporting the assertion that repeated exposure to malaria with advancing age increased acquired immunity to the parasite with a reduction in severity of malaria presentation.…”

Section: Discussionmentioning

confidence: 99%