Study and implementation of urogenital schistosomiasis elimination in Zanzibar (Unguja and Pemba islands) using an integrated multidisciplinary approach

ABSTRACT: BACKGROUND: Schistosomiasis is a parasitic infection that continues to be a major public health problem in many developing countries being responsible for an estimated burden of at least 1.4 million disability-adjusted life years (DALYs) in Africa alone. However, morbidity due to schistosomiasis has been greatly reduced in some parts of the world, including Zanzibar. The Zanzibar government is now committed to eliminate urogenital schistosomiasis. Over the next 3--5 years, the whole at-risk population will be administered praziquantel (40 mg/kg) biannually. Additionally, snail control and behaviour change interventions will be implemented in selected communities and the impact measured in a randomized intervention trial. METHODS: In this 5-year research study, on both Unguja and Pemba islands, urogenital schistosomiasis will be assessed in 45 communities with urine filtration and reagent strips in 4,500 schoolchildren aged 9--12 years annually, and in 4,500 first-year schoolchildren and 2,250 adults in years 1 and 5. Additionally, from first-year schoolchildren, a finger-prick blood sample will be collected and examined for Schistosoma haematobium infection biomarkers. Changes in prevalence and infection intensity will be assessed annually. Among the 45 communities, 15 were randomized for biannual snail control with niclosamide, in concordance with preventive chemotherapy campaigns. The reduction of Bulinus globosus snail populations and S. haematobium-infected snails will be investigated. In 15 other communities, interventions triggering behaviour change have been designed and will be implemented in collaboration with the community. A change in knowledge, attitudes and practices will be assessed annually through focus group discussions and in-depth interviews with schoolchildren, teachers, parents and community leaders. In all 45 communities, changes in the health system, water and sanitation infrastructure will be annually tracked by standardized questionnaire-interviews with community leaders. Additional issues potentially impacting on study outcomes and all incurring costs will be monitored and recorded. DISCUSSION: Elimination of schistosomiasis has become a priority on the agenda of the Zanzibar government and the international community. Our study will contribute to identifying what, in addition to preventive chemotherapy, needs to be done to prevent, control, and ultimately eliminate schistosomiasis, and to draw lessons for current and future schistosomiasis elimination programmes in Africa and elsewhere.Trial registrationISRCTN4883768

Systematic review of studies generating individual participant data on the efficacy of drugs for treating soil-transmitted helminthiases and the case for data-sharing

Preventive chemotherapy and transmission control (PCT) by mass drug administration is the cornerstone of the World Health Organization (WHO)’s policy to control soil-transmitted helminthiases (STHs) caused by Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm) and hookworm species (Necator americanus and Ancylostama duodenale) which affect over 1 billion people globally. Despite consensus that drug efficacies should be monitored for signs of decline that could jeopardise the effectiveness of PCT, systematic monitoring and evaluation is seldom implemented. Drug trials mostly report aggregate efficacies in groups of participants, but heterogeneities in design complicate classical meta-analyses of these data. Individual participant data (IPD) permit more detailed analysis of drug efficacies, offering increased sensitivity to identify atypical responses potentially caused by emerging drug resistance

Field Validity and Feasibility of Four Techniques for the Detection of Trichuris in Simians: A Model for Monitoring Drug Efficacy in Public Health?

Worldwide, millions of people are infected with soil-transmitted helminths, particularly in developing countries. Efforts to control these infections involve periodic mass drug treatment in endemic areas. Since these large-scale interventions are likely to intensify, monitoring of drug efficacy has become a key issue in order to detect the emergence of resistance. At present, the drop in infection intensity is under examination for monitoring the drug efficacy. However, studies comparing detection techniques based on infection intensities are scarce. Moreover, little attention has been addressed to their feasibility and their ability to estimate drug efficacies. We have compared different techniques for the detection of whipworm (Trichuris) in simian stool samples based on prevalence, infection intensities, feasibility and ability to estimate the ‘true’ drug efficacy. We have found that techniques often fail to detect low infection intensities and that not all techniques are appropriate for estimating infection intensities. The time needed to obtain a test result varied from 3.9 to 17.7 min/sample. Finally, accurate estimates of drug efficacy were only obtained in high pre-drug administration infection intensities. To conclude, along with accurate estimates of infection intensities, feasibility is a considerable criterion for the detection techniques used in drug efficacy monitoring programs

Egg excretion indicators for the measurement of soil-transmitted helminth response to treatment

BACKGROUND: Periodic administration of anthelmintic drugs is a cost-effective intervention for morbidity control of soil-transmitted helminth (STH) infections. However, with programs expanding, drug pressure potentially selecting for drug-resistant parasites increases. While monitoring anthelmintic drug efficacy is crucial to inform country control program strategies, different factors must be taken into consideration that influence drug efficacy and make it difficult to standardize treatment outcome measures. We aimed to identify suitable approaches to assess and compare the efficacy of different anthelmintic treatments. METHODOLOGY: We built an individual participant-level database from 11 randomized controlled trials and two observational studies in which subjects received single-agent or combination therapy, or placebo. Eggs per gram of stool were calculated from egg counts at baseline and post-treatment. Egg reduction rates (ERR; based on mean group egg counts) and individual-patient ERR (iERR) were utilized to express drug efficacy and analyzed after log-transformation with a linear mixed effect model. The analyses were separated by follow-up duration (14-21 and 22-45 days) after drug administration. PRINCIPAL FINDINGS: The 13 studies enrolled 5,759 STH stool-positive individuals; 5,688 received active medication or placebo contributing a total of 11,103 STH infections (65% had two or three concurrent infections), of whom 3,904 (8,503 infections) and 1,784 (2,550 infections) had efficacy assessed at 14-21 days and 22-45 days post-treatment, respectively. Neither the number of helminth co-infections nor duration of follow-up affected ERR for any helminth species. The number of participants treated with single-dose albendazole was 689 (18%), with single-dose mebendazole 658 (17%), and with albendazole-based co-administrations 775 (23%). The overall mean ERR assessed by day 14-21 for albendazole and mebendazole was 94.5% and 87.4%, respectively on Ascaris lumbricoides, 86.8% and 40.8% on hookworm, and 44.9% and 23.8% on Trichuris trichiura. The World Health Organization (WHO) recommended criteria for efficacy were met in 50%, 62%, and 33% studies of albendazole for A. lumbricoides, T. trichiura, and hookworm, respectively and 25% of mebendazole studies. iERR analyses showed similar results, with cure achieved in 92% of A. lumbricoides-infected subjects treated with albendazole and 93% with mebendazole; corresponding figures for hookworm were 70% and 17%, and for T. trichiura 22% and 20%. CONCLUSIONS/SIGNIFICANCE: Combining the traditional efficacy assessment using group averages with individual responses provides a more complete picture of how anthelmintic treatments perform. Most treatments analyzed fail to meet the WHO minimal criteria for efficacy based on group means. Drug combinations (i.e., albendazole-ivermectin and albendazole-oxantel pamoate) are promising treatments for STH infections

Atrial conduction delay as a possible arrhythmogenic mechanism in paroxysmal idiopathic atrial fibrillation

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The focal attention window size explains letter substitution errors in reading

Acquired Neglect Dyslexia is often associated with right-hemisphere brain damage and is mainly characterized by omissions and substitutions in reading single words. Martelli et al. proposed in 2011 that these two types of error are due to different mechanisms. Omissions should depend on neglect plus an oculomotor deficit, whilst substitutions on the difficulty with which the letters are perceptually segregated from each other (i.e., crowding phenomenon). In this study, we hypothesized that a deficit of focal attention could determine a pathological crowding effect, leading to imprecise letter identification and consequently substitution errors. In Experiment 1, three brain-damaged patients, suffering from peripheral dyslexia, mainly characterized by substitutions, underwent an assessment of error distribution in reading pseudowords and a T detection task as a function of cue size and timing, in order to measure focal attention. Each patient, when compared to a control group, showed a deficit in adjusting the attentional focus. In Experiment 2, a group of 17 right-brain-damaged patients were asked to perform the focal attention task and to read single words and pseudowords as a function of inter-letter spacing. The results allowed us to confirm a more general association between substitution-type reading errors and the performance in the focal attention task

The anthelmintic efficacy of plant-derived cysteine proteinases against the rodent gastrointestinal nematode, Heligmosomoides polygyrus, in vivo

Gastrointestinal (GI) nematodes are important disease-causing organisms, controlled primarily through treatment with synthetic drugs, but the efficacy of these drugs has declined due to widespread resistance, and hence new drugs, with different modes of action, are required. Some medicinal plants, used traditionally for the treatment of worm infections, contain cysteine proteinases known to damage worms irreversibly in vitro. Here we (i) confirm that papaya latex has marked efficacy in vivo against the rodent gastrointestinal nematode, Heligmosomoides polygyrus, (ii) demonstrate the dosedependent nature of the activity (>90% reduction in egg output and 80% reduction in worm burden at the highest active enzyme concentration of 133 nmol), (iii) establish unequivocally that it is the cysteine proteinases that are the active principles in vivo (complete inhibition of enzyme activity when pre-incubated with the cysteine proteinase-specific inhibitor, E-64) and (iv) show that activity is confined to worms that are in the intestinal lumen. The mechanism of action was distinct from all current synthetic anthelmintics, and was the same as that in vitro, with the enzymes attacking and digesting the protective cuticle. Treatment had no detectable side-effects on immune cell numbers in the mucosa (there was no difference in the numbers of mast cells and goblet cells between the treated groups) and mucosal architecture (length of intestinal villi). Only the infected and untreated mice had much shorter villi than the other 3 groups, which was a consequence of infection and not treatment. Plant-derived cysteine proteinases are therefore prime candidates for development as novel drugs for the treatment of GI nematode infections

A Comparison of the Sensitivity and Fecal Egg Counts of the McMaster Egg Counting and Kato-Katz Thick Smear Methods for Soil-Transmitted Helminths

Currently, in public health, the reduction in the number of eggs excreted in stools after drug administration is used to monitor the efficacy of drugs against parasitic worms. Yet, studies comparing diagnostic methods for the enumeration of eggs in stool are few. We compared the Kato-Katz thick smear (Kato-Katz) and McMaster egg counting (McMaster) methods, which are commonly used diagnostic methods in public and animal health, respectively, for the diagnosis and enumeration of eggs of roundworms, whipworms and hookworms in 1,536 stool samples from children in five trials across Africa, Asia and South America. The Kato-Katz method was the most sensitive for the detection of roundworms, but there was no significant difference in sensitivity between the methods for hookworms and whipworms. The sensitivity of the methods differed across the trials and magnitude of egg counts. The Kato-Katz method resulted in significantly higher egg counts, but these were subject to lack of accuracy caused by intrinsic properties of this method. McMaster provided more reliable estimates of drug efficacies. We conclude that the McMaster is an alternative method for monitoring large-scale treatment programs. It allows accurate monitoring of drug efficacy and can be easily performed under field conditions

Effect of Heterogeneous Mixing and Vaccination on the Dynamics of Anthelmintic Resistance: A Nested Model

Anthelmintic resistance is a major threat to current measures for helminth control in humans and animals. The introduction of anthelmintic vaccines, as a complement to or replacement for drug treatments, has been advocated as a preventive measure. Here, a computer-based simulation, tracking the dynamics of hosts, parasites and parasite-genes, shows that, depending on the degree of host-population mixing, the frequency of totally recessive autosomes associated with anthelmintic resistance can follow either a fast dynamical regime with a low equilibrium point or a slow dynamical regime with a high equilibrium point. For fully dominant autosomes, only one regime is predicted. The effectiveness of anthelminthic vaccines against resistance is shown to be strongly influenced by the underlying dynamics of resistant autosomes. Vaccines targeting adult parasites, by decreasing helminth fecundity or lifespan, are predicted to be more effective than vaccines targeting parasite larvae, by decreasing host susceptibility to infection, in reducing the spread of resistance. These results may inform new strategies to prevent, monitor and control the spread of anthelmintic resistance, including the development of viable anthelmintic vaccines

Mapping Asbestos-Cement Roofing with Hyperspectral Remote Sensing over a Large Mountain Region of the Italian Western Alps

The World Health Organization estimates that 100 thousand people in the world die every year from asbestos-related cancers and more than 300 thousand European citizens are expected to die from asbestos-related mesothelioma by 2030. Both the European and the Italian legislations have banned the manufacture, importation, processing and distribution in commerce of asbestos-containing products and have recommended action plans for the safe removal of asbestos from public and private buildings. This paper describes the quantitative mapping of asbestos-cement covers over a large mountainous region of Italian Western Alps using the Multispectral Infrared and Visible Imaging Spectrometer sensor. A very large data set made up of 61 airborne transect strips covering 3263 km2 were processed to support the identification of buildings with asbestos-cement roofing, promoted by the Valle d’Aosta Autonomous Region with the support of the Regional Environmental Protection Agency. Results showed an overall mapping accuracy of 80%, in terms of asbestos-cement surface detected. The influence of topography on the classification’s accuracy suggested that even in high relief landscapes, the spatial resolution of data is the major source of errors and the smaller asbestos-cement covers were not detected or misclassified