Sickle cell trait is not associated with endemic Burkitt lymphoma: an ethnicity and malaria endemicity-matched case-control study suggests factors controlling EBV may serve as a predictive biomarker for this pediatric cancer.

Endemic Burkitt lymphoma (eBL) is associated with Epstein-Barr virus (EBV) and Plasmodium falciparum coinfections. Malaria appears to dysregulate immunity that would otherwise control EBV, thereby contributing to eBL etiology. Juxtaposed to human genetic variants associated with protection from malaria, it has been hypothesized that such variants could decrease eBL susceptibility, historically referred to as "the protective hypothesis." Past studies attempting to link sickle cell trait (HbAS), which is known to be protective against malaria, with protection from eBL were contradictory and underpowered. Therefore, using a case-control study design, we examined HbAS frequency in 306 Kenyan children diagnosed with eBL compared to 537 geographically defined and ethnically matched controls. We found 23.8% HbAS for eBL patients, which was not significantly different compared to 27.0% HbAS for controls [odds ratio (OR) = 0.85; 95% confidence interval (CI) 0.61-1.17; p-value = 0.33]. Even though cellular EBV titers, indicative of the number of latently infected B cells, were significantly higher (p-value < 0.0003) in children residing in malaria holoendemic compared to hypoendemic areas, levels were not associated with HbAS genotype. Combined, this suggests that although HbAS protects against severe malaria and hyperparasitemia, it is not associated with viral control or eBL protection. However, based on receiver operating characteristic curves factors that enable the establishment of EBV persistence, in contrast to those involved in EBV lytic reactivation, may have utility as an eBL precursor biomarker. This has implications for future human genetic association studies to consider variants influencing control over EBV in addition to malaria as risk factors for eBL.

Medicinal plants used for management of malaria among the Luhya community of Kakamega East sub-County, Kenya.

BACKGROUND: Malaria remains a major health problem worldwide especially in sub-Saharan Africa. In Kenya, 80% of the population is at risk of contracting the disease. Pregnant mothers and children under five years are the most affected by this disease. Antimalarial drug resistance poses a major threat in the fight against malaria necessitating continuous search for new antimalarial drugs. Due to inadequate and inaccessible health facilities, majority of people living in rural communities heavily depend on traditional medicine which involves the use of medicinal plants for the management of malaria. Most of these indigenous knowledge is undocumented and risks being lost yet such information could be useful in the search of new antimalarial agents. AIM OF STUDY: An ethnobotanical survey was carried out among the Luhya community of Kakamega East sub-County, a malaria epidemic region, with the aim of documenting the plants used in the management of malaria. MATERIALS AND METHODS: Semi-structured questionnaires were used to collect information from 21 informants who included traditional medicine practitioners and other caregivers who had experience in use of plants in management of malaria. These were drawn from 4 villages located in Kakamega East sub-county, within Kakamega County based on their differences in topography. Information recorded included plant names, parts used, mode of preparation and administration and the sources of plant materials. A literature search was conducted using PubMed and google scholar to identify the reported traditional uses of these plants and studied antiplasmodial activities. RESULTS: In this study, 57% of the informants were aged above 50 years and a total of 61% had either no formal education or had only attained primary school education. A total of 42 plant species belonging to 24 families were identified. Most plants used in the management of malaria in this community belonged to Lamiaceae (18%), Leguminosae (9%) and Compositae (9%) plant families. Plants mostly used included Melia azedarach L, Aloe spp, Ajuga integrifolia Buch. Ham, Vernonia amygdalina Del., Rotheca myricoides (Hochst.) Steane and Mabb, Fuerstia africana T.C.E.Fr., Zanthoxylum gilletii (De Wild.) P.G.Waterman and Leucas calostachys Oliv. Rumex steudelii Hochst.ex A. Rich and Phyllanthus sepialis Müll. Arg are reported for the first time in the management of malaria. Although Clerodendrum johnstonii Oliv. (Jeruto et al., 2011) and Physalis peruviana L.(Ramadan et al., 2015) are reported in other studies for management of malaria, no studies have been carried out to demonstrate their antiplasmodial activity. The plant parts mostly used were the leaves (36%) and stem barks (26%). Majority of these plants were prepared as decoctions by boiling and allowed to cool before administration (66%) while infusions accounted for 28% of the preparations. The literature mined supports the use of these plants for the management of malaria since most of them have demonstrated in-vitro and in-vivo antiplasmodial activities. CONCLUSION: Most of the reported plant species in this study have been investigated for antiplasmodial activity and are in agreement with the ethnomedical use. Two (2) plants are reported for the first time in the management of malaria. There is need for documentation and preservation of the rich ethnomedical knowledge within this community given that most of the practitioners are advanced in age and less educated. There is also the danger of over-exploitation of plant species as most of them are obtained from the wild, mainly Kakamega forest. Therefore, there is need for determining the economically and medicinally important plants in this community and planning for their preservation.

Evidence for genetic linkage between a polymorphism in the GNAS gene and malaria in South Indian population.

The complex imprinted GNAS locus which encodes G-alpha subunit (Gαs) is involved in a number of G-protein coupled signaling pathways in eukaryotic cells. Erythrocyte invasion by Plasmodium falciparum parasites is significantly regulated by protein of GNAS gene. This study was designed to evaluate the association between single nucleotide polymorphisms (SNPs) present in GNAS locus and susceptibility to malaria. In this case control study, individuals affected by P. falciparum malaria (n=230), Plasmodium vivax malaria (n=230) and normal controls (n=230) were tested for the association of eighteen (18) known SNPs to evaluate their role in the onset of the disease. There was no significant difference in genotype frequencies of all the SNPs tested between P. falciparum and P. vivax affected individuals. However, when Bonferroni correction for multiple comparisons were performed as a control, our results demonstrated alleles and genotypes of rs7121: C>T (NC_000020.10:g.57478807C>T), a silent polymorphism situated in the exon 5, were significantly (p<0.05) associated with susceptibility to malaria in the South Indians participants. Our results demonstrate that population specific polymorphisms that exist in GNAS gene may alter the risk of occurrence of malaria.