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Brief Report: Differential Associations of Interleukin 6 and Intestinal Fatty Acid-Binding Protein With Progressive Untreated HIV-1 Infection in Rakai, Uganda.

ABSTRACT: The significance of HIV-associated immune activation and microbial translocation in Sub-Saharan African population remains poorly defined. We assessed biomarkers of inflammation, microbial translocation, and cellular activation and found most factors elevated in Ugandan HIV-1 seroconverters compared with community-matched controls. In contrast to previous findings in Western cohorts, C-reactive protein, neopterin, and intestinal fatty acid binding protein were not elevated. Higher T-cell activation and IL-6 were associated with faster disease progression. Surprisingly, intestinal fatty acid binding protein, indicative of enterocyte turnover, was higher in slow than in fast progressors. These data suggest differential relationships among biomarkers of intestinal barrier integrity and innate immune activation between developed countries and Sub-Saharan Africa.

SUBMITTER: Olwenyi OA

PROVIDER: S-EPMC6310136 | biostudies-other | 2016 May

REPOSITORIES: biostudies-other

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Brief Report: Differential Associations of Interleukin 6 and Intestinal Fatty Acid-Binding Protein With Progressive Untreated HIV-1 Infection in Rakai, Uganda.

Olwenyi Omalla A OA Naluyima Prossy P Cham Fatim F Quinn Thomas C TC Serwadda David D Sewankambo Nelson K NK Gray Ronald H RH Sandberg Johan K JK Michael Nelson L NL Wabwire-Mangen Fred F Robb Merlin L ML Eller Michael A MA

Journal of acquired immune deficiency syndromes (1999) 20160501 1

The significance of HIV-associated immune activation and microbial translocation in Sub-Saharan African population remains poorly defined. We assessed biomarkers of inflammation, microbial translocation, and cellular activation and found most factors elevated in Ugandan HIV-1 seroconverters compared with community-matched controls. In contrast to previous findings in Western cohorts, C-reactive protein, neopterin, and intestinal fatty acid binding protein were not elevated. Higher T-cell activat ...[more]

PMID: 26630672

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Project description:HIV and malaria exert co-pathogenic effects. Malaria surveillance data are necessary for public health strategies to reduce the burden of disease in high HIV prevalence settings.This was a longitudinal cohort study to assess the burden of malaria in rural Rakai, Uganda. Households were visited monthly for 1 year to identify confirmed clinical malaria (CCM), or parasitaemia with temperature >37.5 °C, and asymptomatic parasitaemia (AP). Interviews of the adult or child's caregiver and clinical and laboratory assessments were conducted. Rapid diagnostic testing for malaria and anaemia was performed if participants were febrile and anti-malarial treatment given per Uganda Ministry of Health 2010 guidelines. Blood was drawn at every household visit to assess for parasitaemia, and blood smears were assessed at the Rakai Health Science Programme laboratory.A total of 1640 participants were enrolled, including 975 children aged 6 months up to 10 years, 393 adult caregivers, and 272 adolescent/adult household members from 393 randomly selected households in two representative communities. 1459 (89 %) participants completed all study visits. CCM was identified in 304 (19 %) participants, with the highest incidence rate for CCM of 0.38 per person-year (ppy) identified in children <5 years, and rates decreased with age; the rates were 0.27, 0.16, and 0.09 ppy for ages 5-<10 years, 10-<18 years, and adults 18+ years, respectively. AP was identified in 943 (57 %) participants; the incidence rate was 1.99 ppy for <5 years, 2.72 ppy for 5-<10 years, 2.55 ppy for 10-<18 years, and 0.86 ppy among adults, with 92 % of cases being attributed to Plasmodium falciparum by smear. 994 (61 %) individuals had at least one positive smear; 342 (21 %) had one positive result, 203 (12 %) had two, 115 (7 %) had three, and 334 (21 %) had >3 positive smears during follow-up. Seasonal rates generally followed the rains and peaked during July, then decreased through November before increasing again.Plasmodium falciparum infection remains high in rural Uganda. Increased malaria control interventions should be prioritized. Trial registration Clinicaltrials.gov identifier NCT01265407.

Project description:UNLABELLED:Bacterial vaginosis (BV) is a common vaginal bacterial imbalance associated with risk for HIV and poor gynecologic and obstetric outcomes. Male circumcision reduces BV-associated bacteria on the penis and decreases BV in female partners, but the link between penile microbiota and female partner BV is not well understood. We tested the hypothesis that having a female partner with BV increases BV-associated bacteria in uncircumcised men. We characterized penile microbiota composition and density (i.e., the quantity of bacteria per swab) by broad-coverage 16S rRNA gene-based sequencing and quantitative PCR (qPCR) in 165 uncircumcised men from Rakai, Uganda. Associations between penile community state types (CSTs) and female partner's Nugent score were assessed. We found seven distinct penile CSTs of increasing density (CST1 to 7). CST1 to 3 and CST4 to 7 were the two major CST groups. CST4 to 7 had higher prevalence and abundance of BV-associated bacteria, such as Mobiluncus and Dialister, than CST1 to 3. Men with CST4 to 7 were significantly more likely to have a female partner with a high Nugent score (P = 0.03). Men with two or more extramarital partners were significantly more likely to have CST4 to 7 than men with only marital partners (CST4 to 7 prevalence ratio, 1.84; 95% confidence interval [CI], 1.16 to 2.92). Female partner Nugent BV is significantly associated with penile microbiota. Our data support the exchange of BV-associated bacteria through intercourse, which may explain BV recurrence and persistence. IMPORTANCE:Bacterial vaginosis (BV) is sexually associated but not considered a sexually transmitted disease. Our findings suggest that the uncircumcised penis is an important niche for BV-associated genital anaerobes. In addition, we found a link between extramarital sexual relationships and BV-associated bacteria in men, which parallels earlier findings of the association between sexual activity and BV in women. This suggests the sexual transmissibility of BV-associated bacteria. Reducing bacterial exchange by barrier methods and managing carriage of BV-associated bacteria in men may decrease BV persistence and recurrence in women.

Dataset Information

Brief Report: Differential Associations of Interleukin 6 and Intestinal Fatty Acid-Binding Protein With Progressive Untreated HIV-1 Infection in Rakai, Uganda.

Publications

Brief Report: Differential Associations of Interleukin 6 and Intestinal Fatty Acid-Binding Protein With Progressive Untreated HIV-1 Infection in Rakai, Uganda.

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