Potential cost-effectiveness of schistosomiasis treatment for reducing HIV transmission in Africa--the case of Zimbabwean women.

BACKGROUND: Epidemiological data from Zimbabwe suggests that genital infection with Schistosoma haematobium may increase the risk of HIV infection in young women. Therefore, the treatment of Schistosoma haematobium with praziquantel could be a potential strategy for reducing HIV infection. Here we assess the potential cost-effectiveness of praziquantel as a novel intervention strategy against HIV infection. METHODS: We developed a mathematical model of female genital schistosomiasis (FGS) and HIV infections in Zimbabwe that we fitted to cross-sectional data of FGS and HIV prevalence of 1999. We validated our epidemic projections using antenatal clinic data on HIV prevalence. We simulated annual praziquantel administration to school-age children. We then used these model predictions to perform a cost-effectiveness analysis of annual administration of praziquantel as a potential measure to reduce the burden of HIV in sub-Saharan Africa. FINDINGS: We showed that for a variation of efficacy between 30-70% of mass praziquantel administration for reducing the enhanced risk of HIV transmission per sexual act due to FGS, annual administration of praziquantel to school-age children in Zimbabwe could result in net savings of US$16-101 million compared with no mass treatment of schistosomiasis over a ten-year period. For a variation in efficacy between 30-70% of mass praziquantel administration for reducing the acquisition of FGS, annual administration of praziquantel to school-age children could result in net savings of US$36-92 million over a ten-year period. CONCLUSIONS: In addition to reducing schistosomiasis burden, mass praziquantel administration may be a highly cost-effective way of reducing HIV infections in sub-Saharan Africa. Program costs per case of HIV averted are similar to, and under some conditions much better than, other interventions that are currently implemented in Africa to reduce HIV transmission. As a cost-saving strategy, mass praziquantel administration should be prioritized over other less cost-effective public health interventions.

HIV and Schistosoma haematobium prevalences correlate in sub-Saharan Africa.

OBJECTIVE: Epidemiological studies have observed that genital schistosomiasis increases the risk of HIV infection in Africa. We analysed the correlation between Schistosoma haematobium prevalence and HIV prevalence across sub-Saharan African countries. DESIGN: Regression analysis of prevalence of HIV and S. haematobium across sub-Saharan African countries. METHODS: Using compiled country-level S. haematobium prevalence, HIV prevalence and other demographic and economic data from published sources, we applied univariate and multivariate regression models to assess the correlations between S. haematobium prevalence and HIV prevalence while controlling for risk factors associated with each infection. RESULTS: In 43 sub-Saharan African countries, the mean prevalence of S. haematobium was 22.4% [standard deviation (SD): 9.8%] and for HIV was 6.21% (SD: 5.71%). In multivariate analysis, adjusted for prevalence of male circumcision, years since a country's first HIV/AIDS diagnosis, geographical region and immunization coverage, each S. haematobium infection per 100 individuals was associated with a 2.9% (95% CI: 0.2-5.8%) relative increase in HIV prevalence. S. haematobium was not associated with Schistosoma mansoni, HSV-2, hepatitis C, malaria or syphilis. CONCLUSIONS: Schistosoma haematobium prevalence was associated with HIV prevalence in sub-Saharan Africa. Controlling S. haematobium may be an effective means of reducing HIV transmission in sub-Saharan Africa.

Cost-effectiveness of a community-based intervention for reducing the transmission of Schistosoma haematobium and HIV in Africa.

Epidemiological studies from sub-Saharan Africa show that genital infection with Schistosoma haematobium [corrected] may increase the risk for HIV infection in young women. Therefore, preventing schistosomiasis has the potential to reduce HIV transmission in sub-Saharan Africa. We developed a transmission model of female genital schistosomiasis and HIV infections that we fit to epidemiological data of HIV and female genital schistosomiasis prevalence and coinfection in rural Zimbabwe. We used the model to evaluate the cost-effectiveness of a multifaceted community-based intervention for preventing schistosomiasis and, consequently, HIV infections in rural Zimbabwe, from the perspective of a health payer. The community-based intervention combined provision of clean water, sanitation, and health education (WSH) with administration of praziquantel to school-aged children. Considering variation in efficacy between 10% and 70% of WSH for reducing S. haematobium [corrected] transmission, our model predicted that community-based intervention is likely to be cost-effective in Zimbabwe at an aggregated WSH cost corresponding to US $725-$1,000 per individual over a 20-y intervention period. These costs compare favorably with empirical measures of WSH provision in developing countries, indicating that integrated community-based intervention for reducing the transmission of S. haematobium [corrected] is an economically attractive strategy for reducing schistosomiasis and HIV transmission in sub-Saharan Africa that would have a powerful impact on averting infections and saving lives.

Reevaluation of epidemiological data demonstrates that it is consistent with cross-immunity among human papillomavirus types.

BACKGROUND: The degree of cross-immunity between human papillomavirus (HPV) types is fundamental both to the epidemiological dynamics of HPV and to the impact of HPV vaccination. Epidemiological data on HPV infections has been repeatedly interpreted as inconsistent with cross-immunity. METHODS: We reevaluate the epidemiological data using a model to determine the odds ratios of multiple to single infections expected in the presence or absence of cross-immunity. We simulate a virtual longitudinal survey to determine the effect cross-immunity has on the prevalence of multiple infections. We calibrate our model to epidemiological data and estimate the extent of type replacement following vaccination against specific HPV types. RESULTS: We find that cross-immunity can produce odds ratios of infection comparable with epidemiological observations. We show that the sample sizes underlying existing surveys have been insufficient to identify even intense cross-immunity. We also find that the removal of HPV type 16, type 18, and types 6 and 11 would increase the prevalence of nontargeted types by 50%, 29%, and 183%, respectively. CONCLUSIONS: Cross-immunity between HPV types is consistent with epidemiological data, contrary to previous interpretations. Cross-immunity may cause significant type replacement following vaccination, and therefore should be considered in future vaccine studies and epidemiological models.

Vaccination and the evolutionary ecology of human papillomavirus.

New and upcoming vaccines provide protection against types 16 and 18 of human papillomavirus (HPV), which are responsible for an estimated 70% of all cervical cancers. One vaccine also protects against HPV types 6 and 11, which cause more than 90% of genital warts. We use a mathematical model of HPV transmission and immunity to explore the effect of vaccination on the evolution of HPV types. If vaccination provides cross-immunity at least equal to that of natural infection, it may contract the niche space available to other HPV types a million-fold. If natural infection provides greater cross-immunity than vaccination, vaccination may expand available niche space up to 470-fold. The balance of epidemiologic data suggests vaccination will reduce the available niche space.

Prevention of nosocomial transmission of extensively drug-resistant tuberculosis in rural South African district hospitals: an epidemiological modelling study.

BACKGROUND: Extensively drug-resistant (XDR) tuberculosis has spread among hospitalised patients in South Africa, but the epidemic-level effect of hospital-based infection control strategies remains unknown. We modelled the plausible effect of rapidly available infection control strategies on the overall course of the XDR tuberculosis epidemic in a rural area of South Africa. METHODS: We investigated the effect of administrative, environmental, and personal infection control measures on the epidemic trajectory of XDR tuberculosis in the rural community of Tugela Ferry. Assessments were done with a mathematical model incorporating over 2 years of longitudinal inpatient and community-based data. The model simulated inpatient airborne tuberculosis transmission, community tuberculosis transmission, and the effect of HIV and antiretroviral therapy. FINDINGS: If no new interventions are introduced, about 1300 cases of XDR tuberculosis are predicted to occur in the area of Tugela Ferry by the end of 2012, more than half of which are likely to be nosocomially transmitted. Mask use alone would avert fewer than 10% of cases in the overall epidemic, but could prevent a large proportion of cases of XDR tuberculosis in hospital staff. The combination of mask use with reduced hospitalisation time and a shift to outpatient therapy could prevent nearly a third of XDR tuberculosis cases. Supplementing this approach with improved ventilation, rapid drug resistance testing, HIV treatment, and tuberculosis isolation facilities could avert 48% of XDR tuberculosis cases (range 34-50%) by the end of 2012. However, involuntary detention could result in an unexpected rise in incidence due to restricted isolation capacity. INTERPRETATION: A synergistic combination of available nosocomial infection control strategies could prevent nearly half of XDR tuberculosis cases, even in a resource-limited setting. XDR tuberculosis transmission will probably continue in the community, indicating the need to develop and implement parallel community-based programmes.

Evaluating candidate agents of selective pressure for cystic fibrosis.

Cystic fibrosis is the most common lethal single-gene mutation in people of European descent, with a carrier frequency upwards of 2%. Based upon molecular research, resistances in the heterozygote to cholera and typhoid fever have been proposed to explain the persistence of the mutation. Using a population genetic model parameterized with historical demographic and epidemiological data, we show that neither cholera nor typhoid fever provided enough historical selective pressure to produce the modern incidence of cystic fibrosis. However, we demonstrate that the European tuberculosis pandemic beginning in the seventeenth century would have provided sufficient historical, geographically appropriate selective pressure under conservative assumptions. Tuberculosis has been underappreciated as a possible selective agent in producing cystic fibrosis but has clinical, molecular and now historical, geographical and epidemiological support. Implications for the future trajectory of cystic fibrosis are discussed. Our result supports the importance of novel investigations into the role of arylsulphatase B deficiency in cystic fibrosis and tuberculosis.

Modeling targeted ivermectin treatment for controlling river blindness.

There is considerable host heterogeneity in exposure to onchocerciasis. We incorporate this heterogeneity into a model of onchocerciasis transmission that we use to evaluate intervention strategies targeting specific portions of the human population for treatment with ivermectin. Our model predicts that targeted allocation of ivermectin in a highly heterogeneous population will reduce the public health burden of onchocerciasis using 20-25% of the doses of untargeted allocation. Targeted allocation therefore poses significantly lower risk of adverse effects, while potentially delaying the emergence and spread of ivermectin resistance, relative to untargeted allocation.