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Abstract Background Sulphadoxine-pyrimethamine (SP) has been and is currently used for treatment of uncomplicated Plasmodium falciparum malaria in many African countries. Nevertheless, the response of parasites to SP treatment has shown significant variation between individuals. Methods The genes for dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) were used as markers, to investigate parasite resistance to SP in 141 children aged less than 5 years. Parasite DNA was extracted by Chelex method from blood samples collected and preserved on filter papers. Subsequently, polymerase chain reaction (PCR) and restriction fragment length polymorphism (PCR-RFLP) were applied to detect the SP resistance-associated point mutations on dhfr and dhps. Commonly reported point mutations at codons 51, 59, 108 and 164 in the dhfr and codons 437, 540 and 581 in the dhps domains were examined. Results Children infected with parasites harbouring a range of single to quintuple dhfr/dhps mutations were erratically cured with SP. However, the quintuple dhfr/dhps mutant genotypes were mostly associated with treatment failures. High proportion of SP resistance-associated point mutations was detected in this study but the adequate clinical response (89.4%) observed clinically at day 14 of follow up reflects the role of semi-immunity protection and parasite clearance in the population. Conclusion In monitoring drug resistance to SP, concurrent studies on possible confounding factors pertaining to development of resistance in falciparum malaria should be considered. The SP resistance potential detected in this study, cautions on its useful therapeutic life as an interim first-line drug against malaria in Tanzania and other malaria-endemic countries.

The 17q21.31 inversion polymorphism exists either as direct (H1) or inverted (H2) haplotypes with differential predispositions to disease and selection. We investigated its genetic diversity in 2,700 individuals, with an emphasis on African populations. We characterize eight structural haplotypes due to complex rearrangements that vary in size from 1.08-1.49 Mb and provide evidence for a 30-kb H1-H2 double recombination event. We show that recurrent partial duplications of the KANSL1 gene have occurred on both the H1 and H2 haplotypes and have risen to high frequency in European populations. We identify a likely ancestral H2 haplotype (H2?) lacking these duplications that is enriched among African hunter-gatherer groups yet essentially absent from West African populations. Whereas H1 and H2 segmental duplications arose independently and before human migration out of Africa, they have reached high frequencies recently among Europeans, either because of extraordinary genetic drift or selective sweeps. [ABSTRACT FROM AUTHOR]

A SNP in the gene encoding lactase (LCT) (C/T-13910) is associated with the ability to digest milk as adults (lactase persistence) in Europeans, but the genetic basis of lactase persistence in Africans was previously unknown. We conducted a genotype-phenotype association study in 470 Tanzanians, Kenyans and Sudanese and identified three SNPs (G/C-14010, T/G-13915 and C/G-13907) that are associated with lactase persistence and that have derived alleles that significantly enhance transcription from the LCT promoter in vitro. These SNPs originated on different haplotype backgrounds from the European C/T-13910 SNP and from each other. Genotyping across a 3-Mb region demonstrated haplotype homozygosity extending >2.0 Mb on chromosomes carrying C-14010, consistent with a selective sweep over the past ∼7,000 years. These data provide a marked example of convergent evolution due to strong selective pressure resulting from shared cultural traits—animal domestication and adult milk consumption. [ABSTRACT FROM AUTHOR]

Background: Sulphadoxine-pyrimethamine (SP) has been and is currently used for treatment of uncomplicated Plasmodium falciparum malaria in many African countries. Nevertheless, the response of parasites to SP treatment has shown significant variation between individuals. Methods: The genes for dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) were used as markers, to investigate parasite resistance to SP in 141 children aged less than 5 years. Parasite DNA was extracted by Chelex method from blood samples collected and preserved on filter papers. Subsequently, polymerase chain reaction (PCR) and restriction fragment length polymorphism (PCR-RFLP) were applied to detect the SP resistance-associated point mutations on dhfr and dhps. Commonly reported point mutations at codons 51, 59, 108 and 164 in the dhfr and codons 437, 540 and 581 in the dhps domains were examined. Results: Children infected with parasites harbouring a range of single to quintuple dhfr/dhps mutations were erratically cured with SP. However, the quintuple dhfr/dhps mutant genotypes were mostly associated with treatment failures. High proportion of SP resistance-associated point mutations was detected in this study but the adequate clinical response (89.4%) observed clinically at day 14 of follow up reflects the role of semi-immunity protection and parasite clearance in the population. Conclusion: In monitoring drug resistance to SP, concurrent studies on possible confounding factors pertaining to development of resistance in falciparum malaria should be considered. The SP resistance potential detected in this study, cautions on its useful therapeutic life as an interim firstline drug against malaria in Tanzania and other malaria-endemic countries. [ABSTRACT FROM AUTHOR]

African Americans are at higher risk for cardiometabolic disease relative to individuals with European ancestry. Yet, populations with African ancestry are greatly under-represented in human genomics studies. To alleviate this bias and better distinguish the roles of genetics and environment on cardiometabolic traits, we conducted targeted metabolomics to measure levels of >700 lipids in 718 Africans and integrated with genomic data from >7M single nucleotide polymorphisms genotyped in the same individuals. These individuals are from 14 ethnic groups from diverse regions of Africa (Botswana, Cameroon, Ethiopia, Tanzania) and with diverse subsistence patterns (agriculturalists, pastoralists, hunter-gatherers). In contrast to US populations, most individuals were sampled from rural areas with relatively homogenous diets and, thus, we could better quantify lipids typically found at low levels in US individuals. Furthermore, several groups have similar genetic ancestry but distinct diets, and vice versa, enabling us to distinguish the role of genetic ancestry and environment on lipid variation. We identified 305 independent genetic variants associated with 103 lipid species, >50 of which have not previously been reported in similar studies of European/US populations (e.g. at ROCK2, ARHGEF28, DHODH, ALDH1A2). We observe correlations between subsistence and lipid profiles but show that genetic ancestry also plays an important role in variation within and between populations. For example, Eastern African pastoralists with a diet rich in milk and blood have relatively high levels of di-and tri-glycerides, but within each lipid class, levels are influenced by genotype. The Fulani pastoralists from Cameroon, with a high incidence of hypertension and diabetes but low BMI, also have relatively high levels of triglycerides, suggesting diet is predominantly influencing lipid levels and that genetic factors unrelated to lipid metabolism are influencing risk for disease in that population. Disclosure: R. Ma: None. H. Li: Consultant; Self; Eli Lilly and Company. C. Burant: None. S. A. Tishkoff: None. M. Hansen: None. A. Ranciaro: None. S. R. Thompson: None. W. Beggs: None. S. W. Mpoloka: None. G. G. Mokone: None. T. B. Nyambo: None. G. Michailidis: None. Funding: American Diabetes Association (1-19-VSN-02 to S.A.T.); National Institutes of Health (GM134957-01) [ABSTRACT FROM AUTHOR]

POPULATION: Identifiler—Employees and students of Muhimibili University College of Health Sciences in Dar es Salaam representing 19 widely distributed administrative districts and 42 tribes within the country. [ABSTRACT FROM AUTHOR]

Background: The distribution of human parvovirus B19 (HPV B19) infection is ubiquitous and occurs worldwide. The virus has high tropism to red blood cells progenitor's cells leading to temporary infection of bone marrow and transient arrest of erythropoiesis. People with frequent episodes of hemolytic anemia including sickle cell disease (SCD) and thalassemia are at increased risk of infection. This study aimed at assessing prevalence and factors associated with HPV B19 infections among hospitalized SCD patients., Methodology: This was a cross-sectional hospital-based study among SCD patients hospitalized at Muhimbili National Hospital. HPV B19 was detected using RT-PCR. Hematological and Chemistry tests were done using Sysmex XT2000i and Chemistry analyzer respectively., Results: A total of 329 SCD patients, median age 15 years (interquartile range 7-22 years) were tested for HPV B19. The prevalence of HPV B19 was 29%. In multivariate logistic regression model, HPV B19 infection was associated with pain (OR=4.28, 95%CI: 1.20-15.19; p=0.025), low neutrophil counts (OR=0.57, 95%CI: 0.35-0.92, p=0.022) and MCH (OR=0.92, 95%CI: 0.85-0.99; p=0.033). Individuals infected with HPV B19 had slightly higher prevalence of severe anaemia (30.4% vs. 20.3%, p=0.054) and HIV infection (6.0% vs. 2.1%, p=0.083) in the univariate analysis. Considering the effect of HPV B19 virus on spleen, aplastic anemia and platelet counts in SCD patients, our study did not find any association with these parameters (p=0.244; p= 0.205 and p=0.567 respectively)., Conclusion: The prevalence of HPV B19 among hospitalized SCD patients at MNH was high. SCD patients with HPV B19 were more likely to present with pain, low neutrophils levels, and MCH. HIV infection might be associated with a high risk of HPV infection in SCD patients; however, this requires further investigation., Competing Interests: Competing interests: The authors have declared that no competing interests exist.

Objective: The aim of this survey was to compare the seroprevalences ofHelicobacter Pylori (H. pylori) and chronic atrophic gastritis (CAG) in Tanzania and the Dominican Republic, both of which are tropical countries, and thereafter compare the prevalences in Tanzania and the Dominican Republic with prevalences from our previous studies done in Japan (1991) and China (1996/97)., Methods: Community-based study in which 573 inhabitants of Tanzania and 1,215 inhabitants of the Dominican Republic answered detailed questionnaires on upper digestive tract diseases, and then underwent screening for gastric cancer by serum pepsinogen and testing for antibody toH. pylori., Results: After adjusting to the 'Age-Standardized Rate' (ASR) using the world population in 1995, the seroprevalences ofH. pylori infection in male and female subjects for Tanzania (m=85.3% & f=88.2%) were very high compared to those for the Dominican Republic (m=63.5% & f=62.4%) and Japan (m=62.0% & f=46.8%), and similar to those of China (m=78.0% & f=77.3%). Also, the agestandardized prevalences of CAG in males and females for Tanzania (m-0.237& f=0.458). were higher than those of the Dominican Republic (m=0.168 & f=0.211) and China (m=0.111 & f=0.107) and compared well with those of Japan (m=0.266 & f=0.352)., Conclusions: Although Tanzania and the Dominican Republic are both developing countries, Tanzania had a very high age-standardized prevalence ofH. pylori and CAG compared to that of the Dominican Republic, which showed a trend similar to that of Japan.