Altered Cervical Mucosal Gene Expression and Lower Interleukin 15 Levels in Women With Schistosoma haematobium Infection but Not in Women With Schistosoma mansoni Infection.

BACKGROUND: Schistosomiasis increases the risk of human immunodeficiency virus (HIV) acquisition in women by mechanisms that are incompletely defined. Our objective was to determine how the cervical environment is impacted by Schistosoma haematobium or Schistosoma mansoni infection by quantifying gene expression in the cervical mucosa and cytokine levels in cervicovaginal lavage fluid. METHODS: We recruited women with and those without S. haematobium infection and women with and those without S. mansoni infection from separate villages in rural Tanzania with high prevalences of S. haematobium and S. mansoni, respectively. Infection status was determined by urine and stool microscopy and testing for serum circulating anodic antigen. RNA was extracted from cervical cytobrush samples for transcriptome analysis. Cytokine levels were measured by magnetic bead immunoassay. RESULTS: In the village where S. haematobium was prevalent, 110 genes were differentially expressed in the cervical mucosa of 18 women with versus 39 without S. haematobium infection. Among the 27 cytokines analyzed in cervicovaginal lavage fluid from women in this village, the level of interleukin 15 was lower in the S. haematobium-infected group (62.8 vs 102.9 pg/mL; adjusted P = .0013). Differences were not observed in the S. mansoni-prevalent villages between 11 women with and 29 without S. mansoni infection. CONCLUSIONS: We demonstrate altered cervical mucosal gene expression and lower interleukin 15 levels in women with S. haematobium infection as compared to those with S. mansoni infection, which may influence HIV acquisition and cancer risks. Studies to determine the effects of antischistosome treatment on these mucosal alterations are needed.

Schistosoma mansoni Infection Is Associated With Increased Monocytes and Fewer Natural Killer T Cells in the Female Genital Tract.

Schistosoma mansoni infection may impair genital mucosal antiviral immunity, but immune cell populations have not been well characterized. We characterized mononuclear cells from cervical brushings of women with and without S mansoni infection. We observed lower frequencies of natural killer T cells and higher frequencies of CD14+ monocytes in infected women.

HIV-1 Viral Loads Are Not Elevated in Individuals Co-infected With Schistosoma spp. After Adjustment for Duration of HIV-1 Infection.

Studies of the role of Schistosoma co-infections on plasma HIV-1 RNA (HIV-1 viral load) have yielded incongruent results. The role of duration of HIV-1 infection on the link between Schistosoma and HIV-1 viral load has not been previously investigated. We aimed to assess the impact of HIV-1/Schistosoma co-infections on viral load in Antiretroviral Treatment (ART)-naïve HIV-1 infected people taking into account the duration of HIV-1 infection. We describe 79 HIV-infected outpatients greater than 18 years of age who had never used ART in Mwanza, Tanzania. Schistosomiasis testing was done by urine and stool microscopy and by serum Schistosoma circulating anodic antigen (CAA) testing. Schistosoma positivity was defined as having either test positive. We conducted univariable and multivariable linear regressions to assess the relationship between Schistosoma infection and the log10 of viral load. Duration of HIV infection was calculated using the first measured CD4+ T-cell (CD4) count as a function of normal CD4 count decay per calendar year in drug naïve individuals. An active Schistosoma infection was demonstrated in 46.8% of the patients. The median log10 viral load was 4.5[3.4-4.9] log10 copies/mL in Schistosoma uninfected patients and 4.3[3.7-4.6] log10 copies/mL in Schistosoma infected patients. Schistosoma co-infection was negatively associated with the log10 of viral load after adjustment for Schistosoma intensity as measured by CAA, CD4 counts at time of testing, and duration of HIV-1 infection (ß = -0.7[-1.3;-0.1], p = 0.022). Schistosoma co-infection was not associated with viral load in univariable analysis. There was also no interaction between Schistosoma positivity and duration of HIV-1 infection. Our study is the first, to our knowledge, to report adjustment for duration of HIV-1 infection when analyzing the relationship between HIV-1 viral load and Schistosoma spp. We found that time infected with HIV-1 has a major effect on the relationship between HIV-1 viral load and Schistosoma infection and may be a critical explanatory factor in the disparate findings of studies on HIV-1 viral load and schistosomiasis. The log10 viral load difference found indicates that Schistosoma co-infection does not make HIV progression worse, and could possibly lead to slower HIV disease progression.

Schistosomiasis and Human Immunodeficiency Virus in Men in Tanzania.

AbstractSchistosomiasis is a parasitic worm infection that affects over 260 million individuals worldwide. Women with schistosome infections have been demonstrated to have a 4-fold increase in the odds of human immunodeficiency virus (HIV) infection compared with women without schistosome infections. A relationship between schistosome and HIV infections has not been clearly defined in men. Among 674 men aged 18-50 years living in rural Tanzania, we identified 429 (63.6%) who had a schistosome infection as defined by serum positivity for schistosome circulating anodic antigen, visualization of parasite eggs in urine or stool, or both. HIV infection was identified in 38 (5.6%). The odds of HIV infection was 1.3 [95% confidence interval = 0.6-2.5] (P = 0.53) among men with any schistosome infection (Schistosoma haematobium or Schistosoma mansoni), and it was 1.4 [0.6-3.3] (P = 0.43) among men with S. haematobium infection. Men with S. haematobium infection were significantly more likely to report the symptom of hemospermia than men without S. haematobium infection. We conclude that schistosome infections appear to have little to no association with HIV infection in men.

Indoor Air Pollution and Delayed Measles Vaccination Increase the Risk of Severe Pneumonia in Children: Results from a Case-Control Study in Mwanza, Tanzania.

BACKGROUND: Mortality due to severe pneumonia during childhood in resource-constrained settings is high, but data to provide basis for interventions to improve survival are limited. The objective of this study was to determine the risk factors for severe pneumonia in children aged under five years old in Mwanza, Tanzania. METHODS: We conducted a case-control study of children aged 2 to 59 months at Sekou-Toure regional hospital in Mwanza City, north-western, Tanzania from May 2013 to March 2014. Cases were children with severe pneumonia and controls were children with other illnesses. Data on demography, social-economical status, nutritional status, environmental factors, vaccination status, vitamin A supplementation and deworming, and nasopharyngeal carriage were collected and analysed using logistic regression. RESULTS: 117 patients were included in the study. Of these, 45 were cases and 72 controls. Cases were younger than controls, but there were no differences in social-economic or nutritional status between the two groups. In multiple regression, we found that an increased risk of severe pneumonia was associated with cooking indoors (OR 5.5, 95% CI: 1.4, 22.1), and delayed measles vaccination (OR 3.9, 95% CI: 1.1, 14.8). The lack of vitamin A supplementation in the preceding six month and Enterobacter spp nasopharyngeal carriage were not associated with higher risk of severe pneumonia. Age ≥24 months (OR 0.2, 95% CI: 0.04, 0.8) and not receiving antibiotics before referral (OR 0.3, 95% CI 0.1, 0.9) were associated with lower risk for severe pneumonia. CONCLUSIONS: Indoor air pollution and delayed measles vaccination increase the risk for severe pneumonia among children aged below five years. Interventions to reduce indoor air pollution and to promote timely administration of measles vaccination are urgently needed to reduce the burden of severe pneumonia in children in Tanzania.