Acute Schistosoma mansoni Infection Increases Susceptibility to Systemic SHIV Clade C Infection in Rhesus Macaques after Mucosal Virus Exposure

Abstract

BackgroundIndividuals living in sub-Saharan Africa represent 10% of the world's population but almost 2/3 of all HIV-1/AIDS cases. The disproportionate HIV-1 infection rates in this region may be linked to helminthic parasite infections that affect many individuals in the developing world. However, the hypothesis that parasite infection increases an individual's susceptibility to HIV-1 has never been prospectively tested in a relevant in vivo model.Methodology/Principal FindingsWe measured whether pre-existing infection of rhesus monkeys with a parasitic worm would facilitate systemic infection after mucosal AIDS virus exposure. Two groups of animals, one consisting of normal monkeys and the other harboring Schistosoma mansoni, were challenged intrarectally with decreasing doses of R5-tropic clade C simian-human immunodeficiency virus (SHIV-C). Systemic infection occurred in parasitized monkeys at viral doses that remained sub-infectious in normal hosts. In fact, the 50% animal infectious (AID50) SHIV-C dose was 17-fold lower in parasitized animals compared to controls (P<0.001). Coinfected animals also had significantly higher peak viral RNA loads than controls (P<0.001), as well as increased viral replication in CD4+ central memory cells (P = 0.03).Conclusions/SignificanceOur data provide the first direct evidence that acute schistosomiasis significantly increases the risk of de novo AIDS virus acquisition, and the magnitude of the effect suggests that control of helminth infections may be a useful public health intervention to help decrease the spread of HIV-1.

Association of Schistosomiasis and HIV Infection in Tanzania

“…Studies in macaques showed that the rectal inoculum of SHIV required for SHIV acquisition was 17 times lower in macaques with than without S. mansoni infection. 4 In contrast, prior S. mansoni infection did not significantly change the required infectious dose when SHIV was inoculated intravenously. 4,27 Researchers postulated that S. mansoni infection increased the number of activated CD4+ T cells in the gut-associated lymphoid tissue (GALT) and thereby increased the optimal targets for SHIV infection.…”

“…4 In contrast, prior S. mansoni infection did not significantly change the required infectious dose when SHIV was inoculated intravenously. 4,27 Researchers postulated that S. mansoni infection increased the number of activated CD4+ T cells in the gut-associated lymphoid tissue (GALT) and thereby increased the optimal targets for SHIV infection. Mouse models of schistosomiasis show that S. mansoni eggs induce a Th17 CD4+ T-cell response in the gut mucosa.…”

“…Rhesus macaques with active S. mansoni infection were 17 times more susceptible to simian HIV (SHIV) acquisition after rectal inoculation than macaques without S. mansoni. 4 Although a variety of interactions between S. mansoni and HIV infection in humans have been described, [5][6][7][8][9][10] a direct association between active S. mansoni and HIV has not been documented in humans. If S. mansoni is a risk factor for HIV acquisition, this finding could have major implications for HIV prevention work in much of the world.…”

HIV Target Cells in Schistosoma haematobium-Infected Female Genital Mucosa

“…1 The waterborne parasite is co-endemic with human immunodeficiency virus (HIV) infection and several studies have suggested an association between the two diseases. [2][3][4][5][6] The lower female reproductive tract is the main site of HIV-1 transmission, and is also the predilection site for female genital Schistosoma haematobium ova deposition. [7][8][9] Similar to sexually transmitted infections (STIs), it has been suggested that genital lesions caused by S. haematobium ova may provide points of entry for HIV.…”

Schistosomiasis PCR in Vaginal Lavage as an Indicator of Genital Schistosoma haematobium Infection in Rural Zimbabwean Women

“…3,6 It has been suggested that schistosomiasis could be responsible for increased susceptibility to HIV, and a study in Zimbabwe reported a 3-fold higher odds ratio for HIV seropositivity in women with genital schistosomiasis, compared to those without. [7][8][9] This raises the possibility that treatment and prevention of genital schistosomiasis may have an impact on HIV transmission in areas where both infections are prevalent. Improvements in the detection of genital schistosomiasis would be an important component of such a strategy.…”