Anna E. Phillips

Diagnosis of Schistosoma haematobium by Detection of Specific DNA Fragments from Filtered Urine Samples

Definitive diagnosis of Schistosoma haematobium infection in adult patients is a clinically important challenge. Chronically infected adults pass few eggs in the urine, which are often missed when current diagnostic methods are used. In the work presented here, we report on an alternative diagnostic method based on presence of the S. haematobium-specific Dra 1, 121 bp repeat fragment in human urine. A novel method of collecting the urine specimens in the field and filtering them through heavy Whatman No. 3 paper was introduced. After drying, the samples remained viable for several months at room temperature. To test the potential use of this method, 89 urine specimens from school children in Kollo District, Niger, were examined. In all, 52 of 89 (58.4%) were positive for hematuria, 4 of 89 (49.4%) were positive for eggs, and 51 of 89 (57.3%) showed parasite-specific DNA. These were compared with 60 filtered urine specimens obtained from random samples of adults from two study sites in Nigeria, one endemic and one non-endemic for S. haematobium. In the 30 patients from the endemic site, all 10 samples with detectable eggs and 7 of the 20 egg-negative samples were DNA positive. It was concluded that the urine filter paper method was sufficiently sensitive to detect low and cryptic infections, that DNA detection was more sensitive than egg detection, and that the filtration method facilitated specimen collection and transport from the field.

Men who have sex with men and women in Bangalore, South India, and potential impact on the HIV epidemic

Objective The aim of this study was to quantify differences in patterns of sexual behaviour among men who have sex with men and women (MSMW) compared with men who have sex with men only (MSMO), and to examine the extent to which bisexual behaviour may act as a bridge for introducing HIV infection into the general population. Methods A cross-sectional survey in Bangalore city in 2006, which sampled men seeking sex with men in public places and hammams (bath houses where transgender individuals sell sex to men). Results Among a sample of 357 men reporting same-sex behaviour; 41% also reported sex with a woman in the past year and 14% were currently married to a woman, only two of whom had informed their wives about having sex with men. Condom use was very inconsistent with all male partners, while 98% reported unprotected vaginal sex with their wives. MSMW reported lower rates of risky behaviour with other men than MSMO: fewer reported selling sex (17% vs 58%), or receptive anal sex with known (28% vs 70%) or unknown (30% vs 59%) non-commercial partners. Conclusion Bisexual behaviour was common among men seeking sex with men sampled in this survey. Although MSMW reported lower rates of risky sexual behaviour with male partners than MSMO, inconsistent condom use with both male and female partners indicates a potential means of HIV transmission into the general population. HIV prevention programmes and services should reach bisexual men who potentially expose their male and female partners to HIV.

Sexual Identity and Its Contribution to MSM Risk Behavior in Bangaluru (Bangalore), India: The Results of a Two-Stage Cluster Sampling Survey

In India, there are categories of MSM (hijras, kothis, double-deckers, panthis and bisexuals), which are generally associated with different HIV-risk behaviors. Our objective was to quantify differences across MSM identities (n = 357) and assess the extent they conform to typecasts that prevail in policy-orientated discourse. More feminine kothis (26%) and hijras (13%) mostly reported receptive sex, and masculine panthis (15%) and bisexuals (23%) insertive anal sex. However, behavior did not always conform to expectation, with 25% and 16% of the sample reporting both insertive and receptive anal intercourse with known and unknown noncommercial partners, respectively (p < 0.000). Although behavior often complied with stereotyped role and identity, male-with-male sexual practices were fluid. Reification of these categories in an intervention context may hinder our understanding of the differential HIV risk among MSM.

Gaining and sustaining schistosomiasis control: study protocol and baseline data prior to different treatment strategies in five African countries

BackgroundThe Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was established in 2008 to answer strategic questions about schistosomiasis control. For programme managers, a high-priority question is: what are the most cost-effective strategies for delivering preventive chemotherapy (PCT) with praziquantel (PZQ)? This paper describes the process SCORE used to transform this question into a harmonized research protocol, the study design for answering this question, the village eligibility assessments and data resulting from the first year of the study.MethodsBeginning in 2009, SCORE held a series of meetings to specify empirical questions and design studies related to different schedules of PCT for schistosomiasis control in communities with high (gaining control studies) and moderate (sustaining control studies) prevalence of Schistosoma infection among school-aged children. Seven studies are currently being implemented in five African countries. During the first year, villages were screened for eligibility, and data were collected on prevalence and intensity of infection prior to randomisation and the implementation of different schemes of PZQ intervention strategies.ResultsThese studies of different treatment schedules with PZQ will provide the most comprehensive data thus far on the optimal frequency and continuity of PCT for schistosomiasis infection and morbidity control.ConclusionsWe expect that the study outcomes will provide data for decision-making for country programme managers and a rich resource of information to the schistosomiasis research community.Trial registrationThe trials are registered at International Standard Randomised Controlled Trial registry (identifiers: ISRCTN99401114, ISRCTN14849830, ISRCTN16755535, ISRCTN14117624, ISRCTN95819193 and ISRCTN32045736).

Safety and efficacy of praziquantel syrup (Epiquantel®) against Schistosoma haematobium and Schistosoma mansoni in preschool-aged children in Niger

Given the characteristic age-prevalence curve of Schistosoma infection, preventive chemotherapy with praziquantel is primarily targeted at school-aged children, whilst, in highly endemic areas, other high-risk groups might be included for regular treatment. Nevertheless, schistosomiasis can affect children well before they reach school-age, but this population group is usually excluded from preventive chemotherapy. We assessed the safety and efficacy of praziquantel syrup (Epiquantel®) in preschool-aged children in three villages of Niger. Children aged ≤72 months provided multiple urine and stool samples that were microscopically examined using standard protocols. Schistosoma-positive children were treated with praziquantel syrup at a dose of 40 mg/kg after a meal of millet porridge. Children remained under medical supervision for 4h and adverse events were recorded. Additionally, a questionnaire was administrated to the mothers/guardians 24h post-treatment for further probing of adverse events. Treatment efficacy was evaluated 3 and 6 weeks post-treatment using multiple stool and urine samples. A third of the 243 treated children reported adverse events within 4h, whilst a further 6.2% reported adverse events upon probing 24h post-treatment. Abdominal pain, bloody diarrhoea and sleepiness were the most common adverse events, but these were transient and self-limiting. Praziquantel syrup showed moderate-to-high efficacy against Schistosoma haematobium with egg reduction rates of 69.4% and 71.2% 3 and 6 weeks post-treatment and cure rates of 85.7% (95% confidence interval (CI) 79.7-90.5%) and 94.9% (95% CI 90.5-97.6%), respectively. Considerably lower cure and egg reduction rates were observed against Schistosoma mansoni (e.g. cure rate at 6-week post-treatment follow-up was only 50.6% (95% CI 39.9-61.2%). Concluding, praziquantel syrup is well tolerated in preschool-aged children with moderate-to-high efficacy against S. haematobium, but considerably lower efficacy against S. mansoni in Niger. A larger study is warranted to investigate the observed differences in species-specific susceptibilities and to assess operational issues and community-effectiveness.

Informal confidential voting interviewing in a sexual risk assessment of men who have sex with men (MSM) and transgenders (hijra) in Bangalore, India.

Objective The accuracy of self-reporting sensitive sexual risk behaviours is highly susceptible to misreporting. Informal confidential voting interviews (ICVIs) may minimise social desirability bias by increasing the privacy of the interview setting. The objective was to investigate determinants of risky behaviour among men who have sex with men (MSM) and ‘hijra’ (transgenders) reported through two interviewing tools: ICVIs and face-to-face interviews (FTFIs). Methods Cluster random sampling was used to recruit MSM in 85 cruising sites in Bangalore, including eight hammams (bath houses) and 77 public locations where MSM and hijra cruise for sex. Individuals were randomly allocated to one of the data collection methods(5 : 2 FTFI : ICVI). Data were analysed using standard regression and a profile regression approach that associates clusters of behaviours with our outcome (FTFI vs ICVI). Results A total of 372 MSM and hijra were interviewed for the FTFIs and 153 respondents completed ICVIs. Participants were more likely to report injecting drug use (4% vs 1%; p=0.008) and paying to have sex with a female sex worker (FSW) in the last year (28% vs 8%; p=0.001) in the ICVIs. There were no differences to questions on sociodemographics, sexual debut with another male, non-condom use (12% vs 14%), ever selling sex to men (58% vs 56%), current female partner (26% vs 20%) and non-condom use with a main female partner (17% vs 19%). Conclusions The significant differences between interview modes for certain outcomes, such as intravenous drug use and sex with a FSW, demonstrate how certain behaviour is stigmatised among the MSM community. Nevertheless, the lack of effect of the interviewing tool in other outcomes may indicate either less reporting bias in reporting this behaviour or environmental factors such as the interviewers not adequately screening themselves from the respondent or a potential disadvantage of using other MSM as interviewers.

A comparison of two mathematical models of the impact of mass drug administration on the transmission and control of schistosomiasis

Highlights • This paper compares two mathematical models describing the transmission dynamics of schistosome infection and the impact of mass drug administration.• The models differ structurally in a number of ways, including the dynamics of the intermediate snail host and the treatment of adult worms within the human host.• The models are validated against data taken from a mass-drug administration trial in Mozambique.• The differences between the model predictions and the data are discussed in the context of the structural differences between the models.

Who mixes with whom among men who have sex with men? Implications for modelling the HIV epidemic in southern India

In India, the identity of men who have sex with men (MSM) is closely related to the role taken in anal sex (insertive, receptive or both), but little is known about sexual mixing between identity groups. Both role segregation (taking only the insertive or receptive role) and the extent of assortative (within-group) mixing are known to affect HIV epidemic size in other settings and populations. This study explores how different possible mixing scenarios, consistent with behavioural data collected in Bangalore, south India, affect both the HIV epidemic, and the impact of a targeted intervention. Deterministic models describing HIV transmission between three MSM identity groups (mostly insertive Panthis/Bisexuals, mostly receptive Kothis/Hijras and versatile Double Deckers), were parameterised with behavioural data from Bangalore. We extended previous models of MSM role segregation to allow each of the identity groups to have both insertive and receptive acts, in differing ratios, in line with field data. The models were used to explore four different mixing scenarios ranging from assortative (maximising within-group mixing) to disassortative (minimising within-group mixing). A simple model was used to obtain insights into the relationship between the degree of within-group mixing, R0 and equilibrium HIV prevalence under different mixing scenarios. A more complex, extended version of the model was used to compare the predicted HIV prevalence trends and impact of an HIV intervention when fitted to data from Bangalore. With the simple model, mixing scenarios with increased amounts of assortative (within-group) mixing tended to give rise to a higher R0 and increased the likelihood that an epidemic would occur. When the complex model was fit to HIV prevalence data, large differences in the level of assortative mixing were seen between the fits identified using different mixing scenarios, but little difference was projected in future HIV prevalence trends. An oral pre-exposure prophylaxis (PrEP) intervention was modelled, targeted at the different identity groups. For intervention strategies targeting the receptive or receptive and versatile MSM together, the overall impact was very similar for different mixing patterns. However, for PrEP scenarios targeting insertive or versatile MSM alone, the overall impact varied considerably for different mixing scenarios; more impact was achieved with greater levels of disassortative mixing.

Optimising cluster survey design for planning schistosomiasis preventive chemotherapy

Background The cornerstone of current schistosomiasis control programmes is delivery of praziquantel to at-risk populations. Such preventive chemotherapy requires accurate information on the geographic distribution of infection, yet the performance of alternative survey designs for estimating prevalence and converting this into treatment decisions has not been thoroughly evaluated. Methodology/Principal findings We used baseline schistosomiasis mapping surveys from three countries (Malawi, Côte d’Ivoire and Liberia) to generate spatially realistic gold standard datasets, against which we tested alternative two-stage cluster survey designs. We assessed how sampling different numbers of schools per district (2–20) and children per school (10–50) influences the accuracy of prevalence estimates and treatment class assignment, and we compared survey cost-efficiency using data from Malawi. Due to the focal nature of schistosomiasis, up to 53% simulated surveys involving 2–5 schools per district failed to detect schistosomiasis in low endemicity areas (1–10% prevalence). Increasing the number of schools surveyed per district improved treatment class assignment far more than increasing the number of children sampled per school. For Malawi, surveys of 15 schools per district and 20–30 children per school reliably detected endemic schistosomiasis and maximised cost-efficiency. In sensitivity analyses where treatment costs and the country considered were varied, optimal survey size was remarkably consistent, with cost-efficiency maximised at 15–20 schools per district. Conclusions/Significance Among two-stage cluster surveys for schistosomiasis, our simulations indicated that surveying 15–20 schools per district and 20–30 children per school optimised cost-efficiency and minimised the risk of under-treatment, with surveys involving more schools of greater cost-efficiency as treatment costs rose.

Interpreting ambiguous ‘trace’ results in Schistosoma mansoni CCA Tests: Estimating sensitivity and specificity of ambiguous results with no gold standard

Background The development of new diagnostics is an important tool in the fight against disease. Latent Class Analysis (LCA) is used to estimate the sensitivity and specificity of tests in the absence of a gold standard. The main field diagnostic for Schistosoma mansoni infection, Kato-Katz (KK), is not very sensitive at low infection intensities. A point-of-care circulating cathodic antigen (CCA) test has been shown to be more sensitive than KK. However, CCA can return an ambiguous ‘trace’ result between ‘positive’ and ‘negative’, and much debate has focused on interpretation of traces results. Methodology/Principle findings We show how LCA can be extended to include ambiguous trace results and analyse S. mansoni studies from both Côte d’Ivoire (CdI) and Uganda. We compare the diagnostic performance of KK and CCA and the observed results by each test to the estimated infection prevalence in the population. Prevalence by KK was higher in CdI (13.4%) than in Uganda (6.1%), but prevalence by CCA was similar between countries, both when trace was assumed to be negative (CCAtn: 11.7% in CdI and 9.7% in Uganda) and positive (CCAtp: 20.1% in CdI and 22.5% in Uganda). The estimated sensitivity of CCA was more consistent between countries than the estimated sensitivity of KK, and estimated infection prevalence did not significantly differ between CdI (20.5%) and Uganda (19.1%). The prevalence by CCA with trace as positive did not differ significantly from estimates of infection prevalence in either country, whereas both KK and CCA with trace as negative significantly underestimated infection prevalence in both countries. Conclusions Incorporation of ambiguous results into an LCA enables the effect of different treatment thresholds to be directly assessed and is applicable in many fields. Our results showed that CCA with trace as positive most accurately estimated infection prevalence.