Diagnosis of urinary schistosomiasis: a novel approach to compare bladder pathology measured by ultrasound and three methods for hematuria detection

We aggregated published data from field studies documenting prevalence of Schistosoma haematobium infection and bladder pathology determined by ultrasonography or hematuria detected by reagent strip, questionnaire, or visual examination. A mathematical expression was used to describe the associations between prevalence of pathology/morbidity and infection. This allows for indirect comparison of these methods, which are rarely used simultaneously. All four methods showed a similar, marked association with infection. Surprisingly, ultrasound revealed higher prevalences of pathology in schools than in communities with the same prevalence of infection, implying a need for age-related cut-off values. Reagent strip testing yielded a higher prevalence than questionnaire, which in turn was higher than by visual examination. After correction for morbidity due to other causes, a consistent ratio in prevalence of hematuria of 3:2:1 resulted for the three respective methods. The simple questionnaire approach is not markedly inferior to the other techniques, making it the best option for field use

Global elimination of leprosy by 2020: are we on track?

Background: Every year more than 200,000 new leprosy cases are registered globally. This number has been fairly stable over the past 8 years. WHO has set a target to interrupt the transmission of leprosy globally by 2020. The aim of this study is to investigate whether this target, interpreted as global elimination, is feasible given the current control strategy. We focus on the three most important endemic countries, India, Brazil and Indonesia, which together account for more than 80 % of all newly registered leprosy cases. Methods: We used the existing individual-based model SIMCOLEP to predict future trends of leprosy incidence given the current control strategy in each country. SIMCOLEP simulates the spread of M. leprae in a population that is structured in households. Current control consists of passive and active case detection, and multidrug therapy (MDT). Predictions of leprosy incidence were made for each country as well as for one high-endemic region within each country: Chhattisgarh (India), Pará State (Brazil) and Madura (Indonesia). Data for model quantification came from: National Leprosy Elimination Program (India), SINAN database (Brazil), and Netherlands Leprosy Relief (Indonesia). Results: Our projections of future leprosy incidence all show a downward trend. In 2020, the country-level leprosy incidence has decreased to 6.2, 6.1 and 3.3 per 100,000 in India, Brazil and Indonesia, respectively, meeting the elimination target of less than 10 per 100,000. However, elimination may not be achieved in time for the high-endemic regions. The leprosy incidence in 2020 is predicted to be 16.2, 21.1 and 19.3 per 100,000 in Chhattisgarh, Pará and Madura, respectively, and the target may only be achieved in another 5 to 10 years. Conclusions: Our predictions show that although country-level elimination is reached by 2020, leprosy is likely to remain a problem in the high-endemic regions (i.e. states, districts and provinces with multimillion populations), which account for most of the cases in a country

LYMFASIM, a simulation model for predicting the impact of lymphatic filariasis control: quantification for African villages.

LYMFASIM is a simulation model for lymphatic filariasis transmission and control. We quantified its parameters to simulate Wuchereria bancrofti transmission by Anopheles mosquitoes in African villages, using a wide variety of reported data. The developed model captures the general epidemiological patterns, but also the differences between communities. It was calibrated to represent the relationship between mosquito biting rate and the prevalence of microfilariae (mf) in the human population, the age-pattern in mf prevalence, and the relation between mf prevalence and geometric mean mf intensity. Explorative simulations suggest that the impact of mass treatment depends strongly on the mosquito biting rate and on the assumed coverage, compliance and efficacy. Our sensitivity analysis showed that some biological parameters strongly influence the predicted equilibrium pre-treatment mf prevalence (e.g. the lifespan of adult worms and mf). Other parameters primarily affect the post-treatment trends (e.g. severity of density dependence in the mosquito uptake of infection from the human blood, between-person variability in exposure to mosquito bites). The longitudinal data, which are being collected for evaluation of ongoing elimination programmes, can help to further validate the model. The model can help to assess when ongoing elimination activities in African populations can be stopped and to design surveillance schemes. It can be a valuable tool for decision making in the Global Programme to Eliminate Lymphatic Filariasis

The Power of Malaria Vaccine Trials Using Controlled Human Malaria Infection

Controlled human malaria infection (CHMI) in healthy human volunteers is an important and powerful tool in clinical malaria vaccine development. However, power calculations are essential to obtain meaningful estimates of protective efficacy, while minimizing the risk of adverse events. To optimize power calculations for CHMI-based malaria vaccine trials, we developed a novel non-linear statistical model for parasite kinetics as measured by qPCR, using data from mosquito-based CHMI experiments in 57 individuals. We robustly account for important sources of variation between and within individuals using a Bayesian framework. Study power is most dependent on the number of individuals in each treatment arm; inter-individual variation in vaccine efficacy and the number of blood samples taken per day matter relatively little. Due to high inter-individual variation in the number of first-generation parasites, hepatic vaccine trials required significantly more study subjects than erythrocytic vaccine trials. We provide power calculations for hypothetical malaria vaccine trials of various designs and conclude that so far, power calculations have been overly optimistic. We further illustrate how upcoming techniques like needle-injected CHMI may reduce required sample sizes

Feasibility of controlling hookworm infection through preventive chemotherapy: a simulation study using the individual-based WORMSIM modelling framework

Background: Globally, hookworms infect 440 million people in developing countries. Especially children and women of childbearing age are at risk of developing anaemia as a result of infection. To control hookworm infection and disease (i.e. reduce the prevalence of medium and heavy infection to <1 %), the World Health Organization has set the target to provide annual or semi-annual preventive chemotherapy (PC) with albendazole (ALB) or mebendazole (MEB) to at least 75 % of all children and women of childbearing age in endemic areas by 2020. Here, we predict the feasibility of achieving <1 % prevalence of medium and heavy infection, based on simulations with an individual-based model. Methods: We developed WORMSIM, a new generalized individual-based modelling framework for transmission and control of helminths, and quantified it for hookworm transmission based on published data. We simulated the impact of standard and more intense PC strategies on trends in hookworm infection, and explored the potential additional impact of interventions that improve access to water, sanitation, and hygiene (WASH). The individual-based framework allowed us to take account of inter-individual heterogeneities in exposure and contribution to transmission of infection, as well as in participation in successive PC rounds. Results: We predict that in low and medium endemic areas, current PC strategies (including targeting of WCBA) will achieve control of hookworm infection (i.e. the parasitological target) within 2 years. In highly endemic areas, control can be achieved with semi-annual PC with ALB at 90 % coverage, combined with interventions that reduce host contributions to the environmental reservoir of infection by 50 %. More intense PC strategies (high frequency and coverage) can help speed up control of hookworm infection, and may be necessary in some extremely highly endemic settings, but are not a panacea against systematic non-participation to PC. Conclusions: Control of hookworm infection by 2020 is feasible with current PC strategies (including targeting of WCBA). In highly endemic areas, PC should be combined with health education and/or WASH interventions

Prey choice and search speed:Why simple optimality fails to explain the prey choice of Oystercatchers <i>Haematopus ostralegus</i> feeding on <i>Nereis diversicolor</i> and <i>Macoma balthica</i>

Oystercatchers breeding on the saltmarsh of Schiermonnikoog rely on two staple foods during the breeding season: the bivalve Macoma balthica and the worm Nereis diversicolor. Both prey are highly profitable, yet individual birds tend to specialize on either of the two prey species for prolonged periods of time, contradicting the simple or 'classic' optimal prey choice model. Although male Oystercatchers often specialize on Macoma, while females often specialize on Nereis, none of the intensively studied individuals was so inefficient at handling either prey that this could have been the reason for excluding one of the prey from the diet. Furthermore, the two prey did not have different distributions in space, nor could short-term fluctuations in prey availability explain the specialization of individuals. It appears that Oystercatchers hunting for Macoma search at a slower speed and make more pecks per distance searched than do birds hunting for Nereis. This accords with the suggestion that, from the point of view of the Oystercatcher, buried Macoma are more cryptic than Nereis which emerge from their burrows to feed on the surrounding substrate. The incompatibility of searching for the two prey at the same time explains why the simple optimal prey choice model does not apply in this and probably many other cases. As argued by Gendron &amp; Staddon (1983), the problem of search speed and the problem of prey choice cannot be treated independently.</p

Leprosy New Case Detection Trends and the Future Effect of Preventive Interventions in Pará State, Brazil: A Modelling Study

Background: Leprosy remains a public health problem in Brazil. Although the overall number of new cases is declining, there are still areas with a high disease burden, such as Pará State in the north of the country. We aim to predict future trends in new case detection rate (NCDR) and explore the potential impact of contact tracing and chemoprophylaxis on NCDR in Pará State. Methods: We used SIMCOLEP, an existing individual-based model for the transmission and control of M. leprae, in a population structured by households. The model was quantified to simulate the population and observed NCDR of leprosy in Pará State for the period 1990 to 2014. The baseline scenario was the current control program, consisting of multidrug therapy, passive case detection, and active case detection from 2003 onwards. Future projections of the NCDR were made until 2050 given the continuation of the current control program (i.e. baseline). We further investigated the potential impact of two scenarios for future control of leprosy: 1) discontinuation of contact tracing; and 2) continuation of current control in combination with chemoprophylaxis. Both scenarios started in 2015 and were projected until 2050. Results: The modelled NCDR in Pará State after 2014 shows a continuous downward trend, reaching the official elimination target of 10 cases per 100,000 population by 2030. The cessation of systematic contact tracing would not result in a higher NCDR in the long run. Systematic contact tracing in combination with chemoprophylaxis for contacts would reduce the NCDR by 40% and bring attainment of the elimination target two years forward to 2028. Conclusion: The NCDR of leprosy continues to decrease in Pará State. Elimination of leprosy as a public health problem could possibly be achieved around 2030, if the current control p