Candidate genes-based investigation of susceptibility to Human African Trypanosomiasis in Cote d'Ivoire

Human African Trypanosomiasis (HAT) or sleeping sickness is a Neglected Tropical Disease. Long regarded as an invariably fatal disease, there is increasing evidence that infection by T. b. gambiense can result in a wide range of clinical outcomes, including latent infections, which are long lasting infections with no parasites detectable by microscopy. The determinants of this clinical diversity are not well understood but could be due in part to parasite or host genetic diversity in multiple genes, or their interactions. A candidate gene association study was conducted in Côte d’Ivoire using a case-control design which included a total of 233 subjects (100 active HAT cases, 100 controls and 33 latent infections). All three possible pairwise comparisons between the three phenotypes were tested using 96 SNPs in16 candidate genes (IL1, IL4, IL4R, IL6, IL8, IL10, IL12, IL12R, TNFA, INFG, MIF, APOL1, HPR, CFH, HLA-A and HLA-G). Data from 77 SNPs passed quality control. There were suggestive associations at three loci in IL6 and TNFA in the comparison between active cases and controls, one SNP in each of APOL1, MIF and IL6 in the comparison between latent infections and active cases and seven SNP in IL4, HLA-G and TNFA between latent infections and controls. No associations remained significant after Bonferroni correction, but the Benjamini Hochberg false discovery rate test indicated that there were strong probabilities that at least some of the associations were genuine. The excess of associations with latent infections despite the small number of samples available suggests that these subjects form a distinct genetic cluster different from active HAT cases and controls, although no clustering by phenotype was observed by principle component analysis. This underlines the complexity of the interactions existing between host genetic polymorphisms and parasite diversity

Candidate gene polymorphisms study between human African trypanosomiasis clinical phenotypes in Guinea

Human African trypanosomiasis (HAT), a lethal disease induced by Trypanosoma brucei gambiense, has a range of clinical outcomes in its human host in West Africa: an acute form progressing rapidly to second stage, spontaneous self-cure and individuals able to regulate parasitaemia at very low levels, have all been reported from endemic foci. In order to test if this clinical diversity is influenced by host genetic determinants, the association between candidate gene polymorphisms and HAT outcome was investigated in populations from HAT active foci in Guinea.Samples were collected from 425 individuals; comprising of 232 HAT cases, 79 subjects with long lasting positive and specific serology but negative parasitology and 114 endemic controls. Genotypes of 28 SNPs in eight genes passed quality control and were used for an association analysis. IL6 rs1818879 allele A (p = 0.0001, OR = 0.39, CI95 = [0.24-0.63], BONF = 0.0034) was associated with a lower risk of progressing from latent infection to active disease. MIF rs36086171 allele G seemed to be associated with an increased risk (p = 0.0239, OR = 1.65, CI95 = [1.07-2.53], BONF = 0.6697) but did not remain significant after Bonferroni correction. Similarly MIF rs12483859 C allele seems be associated with latent infections (p = 0.0077, OR = 1.86, CI95 = [1.18-2.95], BONF = 0.2157). We confirmed earlier observations that APOL1 G2 allele (DEL) (p = 0.0011, OR = 2.70, CI95 = [1.49-4.91], BONF = 0.0301) is associated with a higher risk and APOL1 G1 polymorphism (p = 0.0005, OR = 0.45, CI95 = [0.29-0.70], BONF = 0.0129) with a lower risk of developing HAT. No associations were found with other candidate genes.Our data show that host genes are involved in modulating Trypanosoma brucei gambiense infection outcome in infected individuals from Guinea with IL6 rs1818879 being associated with a lower risk of progressing to active HAT. These results enhance our understanding of host-parasite interactions and, ultimately, may lead to the development of new control tools

Macrophage migrating inhibitory factor expression is associated with Trypanosoma brucei gambiense infection and is controlled by trans-acting expression quantitative trait loci in the Guinean population

Infection by Trypanosoma brucei gambiense is characterized by a wide array of clinical outcomes, ranging from asymptomatic to acute disease and even spontaneous cure. In this study, we investigated the association between macrophage migrating inhibitory factor (MIF), an important pro-inflammatory cytokine that plays a central role in both innate and acquired immunity, and disease outcome during T. b. gambiense infection. A comparative expression analysis of patients, individuals with latent infection and controls found that MIF had significantly higher expression in patients (n=141; 1.25 +/- 0.07; p<.0001) and latent infections (n=25; 1.23 +/- 0.13; p=.0005) relative to controls (n=46; 0.94 +/- 0.11). Furthermore, expression decreased significantly after treatment (patients before treatment n=33; 1.40 +/- 0.18 versus patients after treatment n=33; 0.99 +/- 0.10, p=.0001). We conducted a genome wide eQTL analysis on 29 controls, 128 cases and 15 latently infected individuals for whom expression and genotype data were both available. Four loci, including one containing the chemokine CXCL13, were found to associate with MIF expression. Genes at these loci are candidate regulators of increased expression of MIF after infection. Our study is the first data demonstrating that MIF expression is elevated in T. b. gambiense-infected human hosts but does not appear to contribute to pathology

Baseline survey of animal trypanosomosis in the region of the Boucle du Mouhoun, Burkina Faso

In view of gathering baseline information about the prevalence of animal trypanosomosis, the Pan African Tsetse and Trypanosomiasis Eradication Campaign (PATTEC) funded a cross sectional survey in the Region of the Boucle du Mouhoun which constitutes the Northern limit of the tsetse distribution in Burkina. This cross sectional study was carried out in 53 villages located in the 6 provinces of the region. A total of 2002 cattle, 1466 small ruminants and 481 donkeys were sampled. This survey showed that about 25% of the cattle had been treated with trypanocidal drugs within 3 months before the survey compared to 3% and 0.42% for the small ruminants and donkeys respectively. Parasitological prevalence in cattle was low: 0.77% (95% C.I. 0.30-1.95%). No goats and three donkeys were found infected with trypanosomes. Infections were mainly due to Trypanosoma vivax (75.0%) with cases of T. congolense (25.0%). In cattle, the serological prevalence of trypanosomosis, for the entire Region of the Boucle du Mouhoun, was 34.2% (95%C.I. 26.1-43.4%). For sheep, goats and donkeys, the prevalence were of 20.9% (95%C.I. 12.2-33.5%), 8.5% (95%C.I. 5.7-12.5%) and 5.8% (95%C.I. 3.9-8.6%) respectively.The age and distance to the river were the two main risk factors associated with seropositivity.PATTEC coordinating teamhttp://www.elsevier.com/locate/rvschb2013ab201

Improved PCR-RFLP for the Detection of Diminazene Resistance in Trypanosoma congolense under Field Conditions Using Filter Papers for Sample Storage

Animal African trypanosomiasis (AAT) is caused by different species of the pro- tozoan parasite Trypanosoma and affects a wide range of domestic animals. Trypano- soma congolense is widespread in the whole of sub-Saharan Africa and is the species causing considerable losses in livestock pro- duction, often affecting the health status of humans through endangering the food supply of rural communities. It is estimated that 50 million cattle are at risk of the disease and that the direct and indirect annual losses related to AAT reach US$4.5 billion [1]

No evidence for association with APOL1 kidney disease risk alleles and Human African Trypanosomiasis in two Ugandan populations:

Human African trypanosomiasis (HAT) manifests as an acute form caused by Trypanosoma brucei rhodesiense (Tbr) and a chronic form caused by Trypanosoma brucei gambiense (Tbg). Previous studies have suggested a host genetic role in infection outcomes, particularly for APOL1. We have undertaken a candidate gene association studies (CGAS) in a Ugandan Tbr and a Tbg HAT endemic area, to determine whether polymorphisms in IL10, IL8, IL4, HLAG, TNFA, TNX4LB, IL6, IFNG, MIF, APOL1, HLAA, IL1B, IL4R, IL12B, IL12R, HP, HPR, and CFH have a role in HAT

Les glossines (Diptera : Glossinidae)

International audienc

The impact of participation in Diversity Field Fora on farmer management of millet and sorghum varieties in Mali

Malian farmers have been cultivating millet and sorghum for millennia, but they are slow to adopt and develop modern varieties because it is difficult to observe the difference in yields in their fields, given the challenging local growing conditions. Farmer participatory approaches are therefore recommended. This paper applies an instrumental variables method to survey data from Mali to evaluate the impacts of Diversity Field Fora, a type of farmer field school which aims to boost millet and sorghum yields by showing farmers how to manage diverse varieties. Impact indicators are expected and recalled millet and sorghum yields, the total number of unique attributes of millet and sorghum varieties stocked as seed, and the relative deprivation of the household farm with respect to these indicators. The findings suggest the project has had results at one of two sites where it has been implemented with the same local leadership and more intensively over a longer time frame