A polymorphism in the haptoglobin, haptoglobin related protein locus is associated with risk of human sleeping sickness within Cameroonian populations

Human African Trypanosomiasis (HAT) is a neglected disease targeted for elimination as a public health problem by 2020. Elimination requires a better understanding of the epidemiology and clinical evolution of HAT. In addition to the classical clinical evolution of HAT, asymptomatic carriers and spontaneous cure have been reported in West Africa. A genetic component to human susceptibility to HAT has been suggested to explain these newly observed responses to infection. In order to test for genetic associations with infection response, genetic polymorphism in 17 genes were tested (APOL1, IL1B, IL4, IL4R, IL6, IL8, IL12B, IL12RB1, IL10, TNFA, INFG, MIF, HLA-G, HLA-A, HP, HPR and CFH). A case-control study was performed on 180 blood samples collected from 56 cases and 124 controls from Cameroon. DNA was extracted from blood samples. After quality control, 25 samples (24 controls and 1 case) were eliminated. The genotyping undertaken on 155 individuals including 55 cases and 100 controls were investigated at 96 loci (88 SNPs and 8 indels) located on 17 genes. Associations between these loci and HAT were estimated via a case-control association test. Analyses of 64 SNPs and 4 indels out of 96 identified in the selected genes reveal that the minor allele (T) of rs8062041 in haptoglobin (HP) appeared to be protective against HAT (p = 0.0002395, OR 0.359 (CI95 [0.204-0.6319])); indicating higher frequency in cases compared to controls. This minor allele with adjusted p value of 0.0163 is associated with a lower risk (protective effect) of developing sleeping sickness. The haptoglobin related protein HPR and HP are tightly linked and both are duplicated in some people and may lead to higher activity. This increased production could be responsible of the protection associated with rs8062041 even though this SNP is within HP

Association between IL1 gene polymorphism and human African trypanosomiasis in populations of sleeping sickness foci of southern Cameroon

<div><p>Background</p><p>Human African Trypanosomiasis (HAT) is a neglected tropical disease caused by infections due to <i>Trypanosoma brucei</i> subspecies. In addition to the well-established environmental and behavioural risks of becoming infected, there is evidence for a genetic component to the response to trypanosome infection. We undertook a candidate gene case-control study to investigate genetic associations further.</p><p>Methodology</p><p>We genotyped one polymorphism in each of seven genes (<i>IL1A</i>, <i>IL1RN</i>, <i>IL4RN</i>, <i>IL6</i>, <i>HP</i>, <i>HPR</i>, and <i>HLA-G</i>) in 73 cases and 250 controls collected from 19 ethno-linguistic subgroups stratified into three major ethno-linguistic groups, 2 pooled ethno-linguistic groups and 11 ethno-linguistic subgroups from three Cameroonian HAT foci. The seven polymorphic loci tested consisted of three SNPs, three variable numbers of tandem repeat (VNTR) and one INDEL.</p><p>Results</p><p>We found that the genotype (TT) and minor allele (T) of <i>IL1A</i> gene as well as the genotype 1A3A of <i>IL1RN</i> were associated with an increased risk of getting <i>Trypanosoma brucei gambiense</i> and develop HAT when all data were analysed together and also when stratified by the three major ethno-linguistic groups, 2 pooled ethno-linguistic subgroups and 11 ethno-linguistic subgroups.</p><p>Conclusion</p><p>This study revealed that one SNP rs1800794 of <i>IL1A</i> and one VNTR rs2234663 of <i>IL1RN</i> were associated with the increased risk to be infected by <i>Trypanosoma brucei gambiense</i> and develop sleeping sickness in southern Cameroon. The minor allele T and the genotype TT of SNP rs1800794 in <i>IL1A</i> as well as the genotype 1A3A of <i>IL1RN</i> rs2234663 VNTR seem to increase the risk of getting <i>Trypanosoma brucei gambiense</i> infections and develop sleeping sickness in southern Cameroon.</p></div

Genetic structure of

Despite the economic impact of trypanosome infections, few investigations have been undertaken on the population genetics and transmission dynamics of animal trypanosomes. In this study, microsatellite markers were used to investigate the population genetics of Trypanosoma congolense “forest type”, with the ultimate goal of understanding its transmission dynamics between tsetse flies and domestic animals. Blood samples were collected from pigs, sheep, goats and dogs in five villages in Fontem, South-West region of Cameroon. In these villages, tsetse were captured, dissected and their mid-guts collected. DNA was extracted from blood and tsetse mid-guts and specific primers were used to identify T. congolense “forest type”. All positive samples were genetically characterized with seven microsatellite markers. Genetic analyses were performed on samples showing single infections of T. congolense “forest type”. Of the 299 blood samples, 137 (46%) were infected by T. congolense “forest type”. About 3% (54/1596) of tsetse fly mid-guts were infected by T. congolense “forest type”. Of 182 samples with T. congolense “forest type”, 52 were excluded from the genetic analysis. The genetic analysis on the 130 remaining samples revealed polymorphism within and between subpopulations of the target trypanosome. The dendrogram of genetic similarities was subdivided into two clusters and three sub-clusters, indicating one major and several minor genotypes of T. congolense “forest type” in tsetse and domestic animals. The low FSTvalues suggest low genetic differentiation and no sub-structuration within subpopulations. The same T. congolense genotypes appear to circulate in tsetse and domestic animals

Genetic structure of Trypanosoma congolense “forest type” circulating in domestic animals and tsetse flies in the South-West region of Cameroon

Despite the economic impact of trypanosome infections, few investigations have been undertaken on the population genetics and transmission dynamics of animal trypanosomes. In this study, microsatellite markers were used to investigate the population genetics of Trypanosoma congolense “forest type”, with the ultimate goal of understanding its transmission dynamics between tsetse flies and domestic animals. Blood samples were collected from pigs, sheep, goats and dogs in five villages in Fontem, South-West region of Cameroon. In these villages, tsetse were captured, dissected and their mid-guts collected. DNA was extracted from blood and tsetse mid-guts and specific primers were used to identify T. congolense “forest type”. All positive samples were genetically characterized with seven microsatellite markers. Genetic analyses were performed on samples showing single infections of T. congolense “forest type”. Of the 299 blood samples, 137 (46%) were infected by T. congolense “forest type”. About 3% (54/1596) of tsetse fly mid-guts were infected by T. congolense “forest type”. Of 182 samples with T. congolense “forest type”, 52 were excluded from the genetic analysis. The genetic analysis on the 130 remaining samples revealed polymorphism within and between subpopulations of the target trypanosome. The dendrogram of genetic similarities was subdivided into two clusters and three sub-clusters, indicating one major and several minor genotypes of T. congolense “forest type” in tsetse and domestic animals. The low FSTvalues suggest low genetic differentiation and no sub-structuration within subpopulations. The same T. congolense genotypes appear to circulate in tsetse and domestic animals

Molecular characterization of lower vaginal swabs for Human papilloma virus in association with Chlamydia trachomatis infection in Cameroonian Women

Human papilloma virus (HPV) infection is an etiological factor for cervical cancer development and Chlamydia trachomatis (Ct) is considered as a cofactor. Understanding the dynamics of HPV and Ct infection could help to explain the incidence of early onset of cervical cancer (CC) observed in Cameroon.Lower vaginal swabs and sera from sexually active women were analyzed for HPV and Ct infection in association with risk factors. Questionnaires were used to document patients’ lifestyle and risk factors.A total of 206 women participated in the study average 28.1 ± 8 years (16–50 years). HPV prevalence was 23.3% with subtypes 16 and 18 at respectively 2.9% and 1%. Ct infection totalised 40.8%, of which 23.8% were HPV- Ct co-infections. HPV infection was inversely associated with age (p = 0.028). We found a positive association between Ct infection and the number of sex partners (p = 0.012) and a negative association with parity (p = 0.032). There was no significant association between HPV and Ct infections.High rates of HPV and Ct infections could be an indicator of cervical cancer risk in the near future. There is therefore an urgent need for sensitization as well as implementation of appropriate preventive measures. Keywords: HPV, Chlamydia trachomatis, Risk factor, Co-infection, Cervical cancer, Cameroo

Loci with significant associations with HAT.

<p>Loci with significant associations with HAT.</p

HAT foci where samples were collected.

<p>HAT foci where samples were collected.</p

Locations of SNPs genotyped on HP/HPR region.

<p>Locations of SNPs genotyped on HP/HPR region.</p