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BackgroundIn East Africa, animal trypanosomiasis is caused by many tsetse transmitted protozoan parasites including Trypanosoma vivax, T. congolense and subspecies of T. brucei s.l. (T. b. brucei and zoonotic human infective T. b. rhodesiense) that may co-circulate in domestic and wild animals. Accurate species-specific prevalence measurements of these parasites in animal populations are complicated by mixed infections of trypanosomes within individual hosts, low parasite densities and difficulties in conducting field studies. Many Polymerase Chain Reaction (PCR) based diagnostic tools are available to characterise and quantify infection in animals. These are important for assessing the contribution of infections in animal reservoirs and the risk posed to humans from zoonotic trypanosome species. New matrices for DNA capture have simplified large scale field PCR analyses but few studies have examined the impact of these techniques on prevalence estimations.ResultsThe Whatman FTA matrix has been evaluated using a random sample of 35 village zebu cattle from a population naturally exposed to trypanosome infection. Using a generic trypanosome-specific PCR, prevalence was systematically evaluated. Multiple PCR samples taken from single FTA cards demonstrated that a single punch from an FTA card is not sufficient to confirm the infectivity status of an individual animal as parasite DNA is unevenly distributed across the card. At low parasite densities in the host, this stochastic sampling effect results in underestimation of prevalence based on single punch PCR testing. Repeated testing increased the estimated prevalence of all Trypanosoma spp. from 9.7% to 86%. Using repeat testing, a very high prevalence of pathogenic trypanosomes was detected in these local village cattle: T. brucei (34.3%), T. congolense (42.9%) and T. vivax (22.9%).ConclusionsThese results show that, despite the convenience of Whatman FTA cards and specific PCR based detection tools, the chronically low parasitaemias in indigenous African zebu cattle make it difficult to establish true prevalence. Although this study specifically applies to FTA cards, a similar effect would be experienced with other approaches using blood samples containing low parasite densities. For example, using blood film microscopy or PCR detection from liquid samples where the probability of detecting a parasite or DNA molecule, in the required number of fields of view or PCR reaction, is less than one.

A recent major cluster randomized trial of screening, active disease treatment, and mass isoniazid preventive therapy for 9 months during 2006–2011 among South African gold miners showed reduced individual-level tuberculosis incidence but no detectable population-level impact. We fitted a dynamic mathematical model to trial data and explored 1) factors contributing to the lack of population-level impact, 2) the best-achievable impact if all implementation characteristics were increased to the highest level achieved during the trial (“optimized intervention”), and 3) how tuberculosis might be better controlled with additional interventions (improving diagnostics, reducing treatment delay, providing isoniazid preventive therapy continuously to human immunodeficiency virus–positive people, or scaling up antiretroviral treatment coverage) individually and in combination. We found the following: 1) The model suggests that a small proportion of latent infections among human immunodeficiency virus–positive people were cured, which could have been a key factor explaining the lack of detectable population-level impact. 2) The optimized implementation increased impact by only 10%. 3) Implementing additional interventions individually and in combination led to up to 30% and 75% reductions, respectively, in tuberculosis incidence after 10 years. Tuberculosis control requires a combination prevention approach, including health systems strengthening to minimize treatment delay, improving diagnostics, increased antiretroviral treatment coverage, and effective preventive treatment regimens.

In commercial sex settings, patterns of HIV risk and transmission are influenced by both partner change rates and duration in a setting. The latter is not reflected in classic core group theory. Men who control the sex industry and regular clients may form an important 'sustaining population' that increases infection and undermines the impact of intervention. Intervention activities should include these groups, and examine the social organisation of sex work that underpins many of these relationships.

BackgroundThere is urgent need for effective HIV prevention methods that women can initiate. The CAPRISA 004 trial showed that a tenofovir-based vaginal microbicide had significant impact on HIV incidence among women. This study uses the trial findings to estimate the population-level impact of the gel on HIV and HSV-2 transmission, and price thresholds at which widespread product introduction would be as cost-effective as male circumcision in urban South Africa.MethodsThe estimated ‘per sex-act’ HIV and HSV-2 efficacies were imputed from CAPRISA 004. A dynamic HIV/STI transmission model, parameterised and fitted to Gauteng (HIV prevalence of 16.9% in 2008), South Africa, was used to estimate the impact of gel use over 15 years. Uptake was assumed to increase linearly to 30% over 10 years, with gel use in 72% of sex-acts. Full economic programme and averted HIV treatment costs were modelled. Cost per DALY averted is estimated and a microbicide price that equalises its cost-effectiveness to that of male circumcision is estimated.ResultsUsing plausible assumptions about product introduction, we predict that tenofovir gel use could lead to a 12.5% and 4.9% reduction in HIV and HSV-2 incidence respectively, by year 15. Microbicide introduction is predicted to be highly cost-effective (under $300 per DALY averted), though the dose price would need to be just $0.12 to be equally cost-effective as male circumcision. A single dose or highly effective (83% HIV efficacy per sex-act) regimen would allow for more realistic threshold prices ($0.25 and $0.33 per dose, respectively).ConclusionsThese findings show that an effective coitally-dependent microbicide could reduce HIV incidence by 12.5% in this setting, if current condom use is maintained. For microbicides to be in the range of the most cost-effective HIV prevention interventions, product costs will need to decrease substantially.

Background: Multiple sclerosis (MS) is a common complex disorder, with new treatment options emerging each year. Social media is being increasingly used to investigate opinions about drugs, diseases and procedures. In this descriptive exploratory study, we sought to investigate opinions about currently available MS treatments. Methods: The Twitter resource Topsy was searched for tweets mentioning the following MS treatments: Aubagio, Avonex, Betaferon or Betaseron, Copaxone, Extavia, Gilenya, Lemtrada, Novantrone, Rebif, Tysabri and Tecfidera between 1 Jan 2006 to 31 Jul 2014. Tweets were normalised and sentiment analysis performed. Results: In total, there were 60037 unique tweets mentioning an MS treatment. About half of the tweets contained non-neutral sentiment. Mean sentiment scores were different for treatments ranging from -0.191to 0.282 when investigating all tweets. These differences in sentiment scores between treatments were statistically significant (P<0.001). Sentiment scores tended to be higher for oral MS treatments than injectable treatments. Conclusions: Many tweets about MS treatments have a non-neutral sentiment. The analysis of social media appears to be a potential avenue for exploring patient opinion about MS treatments.

In this article we evaluate the use of approximate visibility for efficient global illumination. Traditionally, accurate visibility is used in light transport. However, the indirect illumination we perceive on a daily basis is rarely of high-frequency nature, as the most significant aspect of light transport in real-world scenes is diffuse, and thus displays a smooth gradation. This raises the question of whether accurate visibility is perceptually necessary in this case. To answer this question, we conduct a psychophysical study on the perceptual influence of approximate visibility on indirect illumination. This study reveals that accurate visibility is not required and that certain approximations may be introduced.

BackgroundActive case detection through mass community screening is a major control strategy against human African trypanosomiasis (HAT, sleeping sickness) caused by T. brucei gambiense. However, its impact can be limited by incomplete attendance at screening sessions (screening coverage) and diagnostic inaccuracy.MethodsWe developed a model-based approach to estimate the true prevalence and the fraction of cases detected during mass screening, based on observed prevalence, and adjusting for incomplete screening coverage and inaccuracy of diagnostic algorithms for screening, confirmation and HAT stage classification. We applied the model to data from three Médecins Sans Frontières projects in Uganda (Adjumani, Arua-Yumbe) and Southern Sudan (Kiri).ResultsWe analysed 604 screening sessions, targeting about 710 000 people. Cases were about twice as likely to attend screening as non-cases, with no apparent difference by stage. Past incidence, population size and repeat screening rounds were strongly associated with observed prevalence. The estimated true prevalence was 0.46% to 0.90% in Kiri depending on the analysis approach, compared to an observed prevalence of 0.45%; 0.59% to 0.87% in Adjumani, compared to 0.92%; and 0.18% to 0.24% in Arua-Yumbe, compared to 0.21%. The true ratio of stage 1 to stage 2 cases was around two-three times higher than that observed, due to stage misclassification. The estimated detected fraction was between 42.2% and 84.0% in Kiri, 52.5% to 79.9% in Adjumani and 59.3% to 88.0% in Arua-Yumbe.ConclusionsIn these well-resourced projects, a moderate to high fraction of cases appeared to be detected through mass screening. True prevalence differed little from observed prevalence for monitoring purposes. We discuss some limitations to our model that illustrate several difficulties of estimating the unseen burden of neglected tropical diseases.