Prevalence of clinically relevant UGT1A alleles and haplotypes in African populations

Variation of a short (TA)(n) repeat sequence (rs8175347) covering the TATA box of UGT1A1 (UDP-glucuronosyltransferase1A1) is associated with hyperbilirubinaemia (Gilbert's syndrome) and adverse drug reactions, and is used for dosage advice for irinotecan. Several reports indicate that the low-activity (risk) alleles ((TA)(7) and (TA)(8) )) are very frequent in Africans but the patterns of association with other variants in the UGT1A gene complex that may modulate these responses are not well known. rs8175347 and two other clinically relevant UGT1A variants (rs11692021 and rs10929302) were assayed in 2616 people from Europe and Africa. Low-activity (TA)(n) alleles frequencies were highest in equatorial Africa, (TA)(7,) being the most common in Cameroon, Ghana, southern Sudan, and in Ethiopian Anuak. Haplotypic diversity was also greatest in equatorial Africa, but in Ethiopia was very variable across ethnic groups. Resequencing of the promoter of a sample subset revealed no novel variations, but rs34547608 and rs887829 were typed and shown to be tightly associated with (TA)(n) . Our results illustrate the need for investigation of the effect of UGT1A variants other than (TA)(n) on the risk of irinotecan toxicity, as well as hyperbilirubinaemia due to hemolytic anaemia or human immunodeficiency virus protease inhibitors, so that appropriate pharmacogenetic advice can be given.     

Determinants of vct uptake among pregnant women attending two ANC clinics in Addis Ababa City: unmatched case control study

BACKGROUND: With HAART PMTCT interventions can reduce the risk of MTCT below 2%. However, low uptake of VCT is challenging effectiveness of PMTCT programs in sub-Saharan Africa. The aim of this study is to identify factors that determine VCT uptake among pregnant women attending ANC services. METHODS: A case-control study was conducted from August 30, 2005 - November 30, 2005 among pregnant women attending ANC PMTCT services at Teklehaimanot Health Center and Gandhi memorial Hospital in Addis Ababa City. Cases were pregnant mothers who accepted VCT (n=202) and controls were pregnant mothers who refused VCT (n=200). Data was collected by counselor nurses working at the respective services RESULTS: Factors that determine VCT acceptance were women's perceived ability to cope with a positive result (OR = 5.5, 95% CI 3.5-8.5, MHOR = 6.3, 95% CI 3.9-10.2); perceived favorable reaction of husband's after sharing positive test result (OR = 2.7 95% CI 1.4-5.1, MHOR = 2.9, 95% CI 1.4-5.7); perceived positive community response (OR = 2.2 95% CI 1.1-4.2, MHOR = 2.6 95% CI 1.3-5.2); perceived ability to get continuous medical care if found out to be positive (OR = 2.0, 95% CI 1.2-3.5, MHOR = 2.4, 95% CI 1.3-4.5). CONCLUSION: Women's perceived ability to cope with a positive result, accesses to medical care, fear of husband's negative reaction and the stigma and discrimination following a positive test result were key determinants of uptake of VCT. Therefore, increasing uptake of VCT/PMTCT services needs policy makers and service providers' effort to promote couple counseling, intensifying the fight against stigma and discrimination and ensuring continuous HIV/AIDS related medical care.     

Bloody Traditional Procedures Performed During Infancy in the Oropharyngeal Area Among HIV+ Children: Implication from the Perspective of Mother-to-Child Transmission of HIV

Although bloody traditional procedures are very common in Ethiopia, this is the first report on infants. None of the literature attributed such practices as risk factor for mother-to-child transmission (MTCT) of HIV. Analysis was done to 1,163 children and found that 552 (47.5%) bloody traditional procedures were performed in the oral cavity to 399 (34.3%): uvulectomy 41.8%, milk tooth extraction 33.7% and tonsillectomy 24.5%. Multinomial logistic regression showed strong association of uvulectomy with Tigray ethnicity. Milk teeth extractions were highest among girls, rural residence, Tigray and Amhara ethnicity. When procedures performed, children were under 1 month (88.9% of tonsillectomies), under 6 months (83.5% of uvulectomies) and 4–6 months (54.3% of milk tooth extractions) of age. More than 97% for whom procedures performed were breast fed, and about 88% were from the northern part of the country. Taking into account the deep invasiveness of the procedures, they are assumed as one of the strong risk factors for MTCT of HIV during lactation.     

C-reactive protein (CRP) promoter polymorphisms influence circulating CRP levels in a genome-wide association study of African Americans

C-reactive protein (CRP) is an acute phase reactant protein produced primarily by the liver. Circulating CRP levels are influenced by genetic and non-genetic factors, including infection and obesity. Genome-wide association studies (GWAS) provide an unbiased approach towards identifying loci influencing CRP levels. None of the six GWAS for CRP levels has been conducted in an African ancestry population. The present study aims to: (i) identify genetic variants that influence serum CRP in African Americans (AA) using a genome-wide association approach and replicate these findings in West Africans (WA), (ii) assess transferability of major signals for CRP reported in European ancestry populations (EA) to AA and (iii) use the weak linkage disequilibrium (LD) structure characteristic of African ancestry populations to fine-map the previously reported CRP locus. The discovery cohort comprised 837 unrelated AA, with the replication of significant single-nucleotide polymorphisms (SNPs) assessed in 486 WA. The association analysis was conducted with 2 366 856 genotyped and imputed SNPs under an additive genetic model with adjustment for appropriate covariates. Genome-wide and replication significances were set at P < 5 × 10(-8) and P < 0.05, respectively. Ten SNPs in?(CRP pseudogene-1) CRPP1 and CRP genes were associated with serum CRP (P = 2.4 × 10(-09) to 4.3 × 10(-11)). All but one of the top-scoring SNPs associated with CRP in AA were successfully replicated in WA. CRP signals previously identified in EA samples were transferable to AAs, and we were able to fine-map this signal, reducing the region of interest from the 25 kb of LD around the locus in the HapMap CEU sample to only 8 kb in our AA sample.     

Effects of a food supplement rich in arginine in patients with smear positive pulmonary tuberculosis--a randomised trial

In tuberculosis (TB), the production of nitric oxide (NO) is confirmed but its importance in host defense is debated. Our aim was to investigate whether a food supplement rich in arginine could enhance clinical improvement in TB patients by increased NO production. Smear positive TB patients from Gondar, Ethiopia (n = 180) were randomized to a food supplementation rich in arginine (peanuts, equivalent to 1 g of arginine/day) or with a low arginine content (wheat crackers, locally called daboqolo) during four weeks. The primary outcome was cure rate according to the WHO classification and secondary outcomes were sputum smear conversion, weight gain, sedimentation rate, reduction of cough and chest X-ray improvement as well as levels of NO in urine (uNO) or exhaled air (eNO) at two months. There was no effect of the intervention on the primary outcome (OR 1.44, 95% CI: 0.69–3.0, p = 0.39) or secondary outcomes. In the subgroup analysis according to HIV status, peanut supplemented HIV+/TB patients showed increased cure rate (83.8% (31/37) vs 53.1% (17/32), p < 0.01). A low baseline eNO (<10 ppb) in HIV+/TB patients was associated with a decreased cure rate. We conclude that nutritional supplementation with a food supplement rich in arginine did not have any overall clinical effect. In the subgroup of HIV positive TB patients, it significantly increased the cure rate and as an additional finding in this subgroup, low initial levels of NO in exhaled air were associated with a poor clinical outcome but this needs to be confirmed in further studies.ClinicalTrials.gov identifier: NCT00857402 (www.clinicaltrials.gov)     

Chlamydial infection during trachoma monitoring: are the most difficult‐to‐reach children more likely to be infected?

Objectives During mass antibiotic distributions for trachoma, certain individuals are difficult to locate and go untreated. These untreated individuals may serve as a source of community reinfection. The importance of this difficult‐to‐locate, untreated population is unclear. We sought to determine whether individuals who are difficult to locate were more likely to be infected with ocular chlamydia than those who were easier to locate. Methods We monitored 12 Ethiopian communities 1 year after a third annual mass azithromycin treatment for trachoma. Conjunctival swabbing for chlamydial RNA was performed in a random sample of children from each community. If insufficient numbers of children were enrolled on the first monitoring day, we returned on subsequent days. Results Of the 12 communities, 10 required more than one monitoring day. On average, 16.1% (95% CI 7.9–30.0) of children were enrolled after the initial day. Evidence of chlamydia was found in 7.1% (95% CI 2.7–17.4) of 0‐ to 9‐year‐old children. No ocular swabs collected after the initial day were positive for chlamydial RNA. Children examined after the initial monitoring day were significantly less likely to have ocular chlamydial infection than children seen on the initial day; Mantel–Haenszel common OR = 0 (95% CI 0–0.77). Conclusions In a setting of repeated annual mass azithromycin treatments, after approximately 80% of individuals have been located in a community, extra efforts to find absent individuals may not yield significantly more cases of ocular chlamydia.