Infectious Thoughts interview: Female Genital Schistosomiasis & linkages with HIV

In this Infectious Thoughts interview, the ISNTD speaks with Dr. Jutta Reinhard-Rupp (Head of the Merck Global Health Institute), Dr. Amadou Garba (World Health Organisation) and Dr. Vanessa Christinet (specialist in Female Genital Schistosomiasis at CIRES) and hears more about the strong rationale for HIV and schistosomiasis collaboration, the diversity of partnerships needed to accelerate and consolidate gains in NTD control and some of the research and technologies needed to fill current gaps.

Download as a PDF.

There is a clear relationship between the Female Genital Schistosomiasis (FGS) patient cohort and high risk for HIV - what is that relationship?

Jutta Reinhard-Rupp (Merck): There is some discussion around the correct term that should be used as there exists “relationship, correlation, causality, association, plausibility” which all have slightly different meanings. In my opinion, the best description at the moment is to say there is a clear plausibility that urinary schistosomiasis and HIV prevalence’s correlate in certain areas and age groups. Several papers have generated data that explain the plausibility (Feldmeier et al, 1995, Kjetland et al 2005, Jourdan et al. 2011, Kleppa et al 2014, many others) but a true causality can only be demonstrated in a longitudinal study which has not been done yet (missing funding, missing awareness etc.). The type of relationship/ plausibility is based on the following: Regarding the onset of FGS versus HIV, FGS normally starts earlier in life (i.e. genital lesions are already present providing an ideal entry point for the virus; even the respective receptor for HIV is overex-pressed in those lesions); observational studies have demonstrated that each infection with S. haematobium per 100 individuals is associated with a 2.9% relative increase in HIV infection; several mathematical modelling studies have shown such a correlation in HIV epidemics

Vanessa Christinet (CIRES): We have several elements that indicate that there may be a causal relationship between FGS and HIV. Several studies have shown an association, we have arguments for a temporal relationship and for a biological plausibility that FGS is a risk factor for HIV infection in women. Unfortunately a proper prospective study that could prove causality has not been conducted yet. This type of prospective studies needs a lot of resources and the field of schistosomiasis and FGS in particular is a neglected field of research, therefore such resources have not been invested yet. One way of studying risk factors are case control studies, which are less costly but less robust in terms of evidence.

Two case control studies have investigated if there were an association between urogenital schistosomiasis due to S. haematobium and HIV infection. They have shown a significant higher prevalence of HIV in women with uro-genital schistosomiasis compared to control women without uro-genital schistosomiasis. The results were highly significant with odd ratios up to 4. Confounding factors such as sexually transmitted infection were taken into consideration in these analyses (Downs et al., 2011; Kjetland et al., 2006). With these two studies we have some elements regarding the association between FGS due to S. haematobium and HIV.

Two studies have explored the HIV and S. haematobium epidemics in Sub-Saharan Africa. The first studied the two epidemics at the Sub-Saharan African level. It showed a correlation between the two epidemics with a higher prevalence of HIV in the highly endemic regions for S. haematobium (Ndeffo Mbah et al., 2013). The other one studied the two-epidemics at the national level in Mozambique (Brodish and Singh, 2016) and showed an increase odd of 3 after controlling for demographic and sexual risk factors.

The biological plausibility is based on the fact that FGS is responsible of lesion that alter the mucosal barrier on the cervix and which is associated with an increased risk of acquiring HIV. Moreover several studies have shown an increased concentration HIV target cells in the cervix in women with FGS compared with controls, which is another biological argument for an increased susceptibility to HIV of women with schistosomiasis. The temporal plausibility indicates that it is not HIV that is a risk factor for schistosomiasis as Schistosomiasis is mostly acquired early in childhood whereas HIV is acquired later in life for most infected women. I think we have high suspicion that schistosomiasis can be an important driver of HIV epidemic in Sub-Saharan Africa and I cannot understand how these elements can be occulted and neglected by the HIV researcher community.

Amadou Garba (World Health Organisation): In clear terms, the relationship between FGS and the risk for HIV means that women with FGS infection are at an increased risk of contracting HIV than those without. Consequently, preventing FGS in women makes them less susceptible to HIV, mostly in co endemic areas of sub Saharan Africa.

What do you hope to achieve by engaging the HIV community?

Jutta Reinhard-Rupp: FGS might be a completely underestimated factor contributing to higher HIV incidence rates in certain age groups of women. Without the HIV community knowing about this possibility (and genital lesions origin is difficult to determine), the underlying cause will continue to exist. Some HIV scientists became very interested when we talked about FGS as there are focal areas with very high HIV rates in women of 18-25y compared to the same age group in another area.

Vanessa Christinet: I think that normally HIV experts should be interested in determining vulnerability factors for Sub-Saharan women that is the population with one of the highest HIV incidence in the world (Kharsany et al., 2012). In international conferences on HIV prevention they present studies on the impact of certain aspect of vaginal flora and other factors for which we have very few objective implication on HIV infection but schistosomiasis never comes up as a possible factor although it is so frequent in Sub-Saharan Africa and although we have some patent elements of association. HIV community has much more resources that could allow conducting prospective trial investigating for example the early treatment of schistosomiasis on HIV incidence. If this strategy is one day proven to be effective, it would be a very cheap way of reducing HIV incidence and it would significantly show a reduction of the other disastrous impact of schistosomiasis on women’s health.

Amadou Garba: FGS and HIV are co-endemic in many countries in Sub Saharan Africa. Given the association between FGS and HIV and considering the goal of UNAIDS of achieving zero new HIV infection by 2030, there is a need to increase the awareness about the increased risk of women with FGS face and support FGS prevention through preventive chemotherapy for schistosomiasis. We are also advocating for FGS to be part of an integrated health delivery package for women in endemic areas. Women who suffer from FGS usually complain about pain, bleeding and often infertility. But there is low level of awareness even among medical practitioners i