Sensitivity and specificity of a urine circulating anodic antigen test for the diagnosis of Schistosoma haematobium in low endemic settings

Elimination of schistosomiasis as a public health problem and interruption of transmission in selected areas are key goals of the World Health Organization for 2025. Conventional parasitological methods are insensitive for the detection of light-intensity infections. Techniques with high sensitivity and specificity are required for an accurate diagnosis in low-transmission settings and verification of elimination. We determined the accuracy of a urine-based up-converting phosphor-lateral flow circulating anodic antigen (UCP-LF CAA) assay for Schistosoma haematobium diagnosis in low-prevalence settings in Zanzibar, Tanzania.; A total of 1,740 urine samples were collected in 2013 from children on Pemba Island, from schools where the S. haematobium prevalence was >2%, 2-5%, and 5-10%, based on a single urine filtration. On the day of collection, all samples were tested for microhematuria with reagent strips and for the presence of S. haematobium eggs with microscopy. Eight months later, 1.5 ml of urine from each of 1,200 samples stored at -20°C were analyzed by UCP-LF CAA assay, while urine filtration slides were subjected to quality control (QCUF). In the absence of a true 'gold' standard, the diagnostic performance was calculated using latent class analyses (LCA).; The 'empirical' S. haematobium prevalence revealed by UCP-LF CAA, QCUF, and reagent strips was 14%, 5%, and 4%, respectively. LCA revealed a sensitivity of the UCP-LF CAA, QCUF, and reagent strips of 97% (95% confidence interval (CI): 91-100%), 86% (95% CI: 72-99%), and 67% (95% CI: 52-81%), respectively. Test specificities were consistently above 90%. The UCP-LF CAA assay shows high sensitivity for the diagnosis of S. haematobium in low-endemicity settings. Empirically, it detects a considerably higher number of infections than microscopy. Hence, the UCP-LF CAA employed in combination with QCUF, is a promising tool for monitoring and surveillance of urogenital schistosomiasis in low-transmission settings targeted for elimination

Interaction of PARP2 with DNA structures mimicking DNA repair intermediates

Poly(ADP-ribosyl)ation is a posttranslational protein modification significant for the genomic stability and cell survival in response to DNA damage. Poly(ADP-ribosyl)ation is catalyzed by poly(ADP-ribose)polymerases (PARPs). Whereas the role of PARP1 in response to DNA damage has been widely illustrated, the contribution of another DNA-dependent PARP, PARP2, has not been studied so far. Aim. To find out specific DNA targets of PARP2. Methods. The EMSA and the PARP activity tests were used. Results. We evaluated Kd values of PARP2-DNA complexes for several DNA structures mimicking intermediates of different DNA metabolizing processes and tested these DNA as «activators» of PARP1 and PARP2 in poly(ADP-ribose) synthesis. Conclusions. Like PARP1, PARP2 does not show correlation between the activation efficiency and Kd values for DNA. PARP2 was activated most effectively in the presence of over5DNA

Praziquantel coverage in schools and communities targeted for the elimination of urogenital schistosomiasis in Zanzibar: a cross-sectional survey

© 2015 Knopp et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The attached file is the published version of the article

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

Development of novel multiplex microsatellite polymerase chain reactions to enable high-throughput population genetic studies of Schistosoma haematobium

© 2015 Webster et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The attached file is the published version of the article

Elimination of Schistosomiasis Transmission in Zanzibar: Baseline Findings before the Onset of a Randomized Intervention Trial.

Gaining and sustaining control of schistosomiasis and, whenever feasible, achieving local elimination are the year 2020 targets set by the World Health Organization. In Zanzibar, various institutions and stakeholders have joined forces to eliminate urogenital schistosomiasis within 5 years. We report baseline findings before the onset of a randomized intervention trial designed to assess the differential impact of community-based praziquantel administration, snail control, and behavior change interventions. In early 2012, a baseline parasitological survey was conducted in ∼20,000 people from 90 communities in Unguja and Pemba. Risk factors for schistosomiasis were assessed by administering a questionnaire to adults. In selected communities, local knowledge about schistosomiasis transmission and prevention was determined in focus group discussions and in-depths interviews. Intermediate host snails were collected and examined for shedding of cercariae. The baseline Schistosoma haematobium prevalence in school children and adults was 4.3% (range: 0-19.7%) and 2.7% (range: 0-26.5%) in Unguja, and 8.9% (range: 0-31.8%) and 5.5% (range: 0-23.4%) in Pemba, respectively. Heavy infections were detected in 15.1% and 35.6% of the positive school children in Unguja and Pemba, respectively. Males were at higher risk than females (odds ratio (OR): 1.45; 95% confidence interval (CI): 1.03-2.03). Decreasing adult age (OR: 1.04; CI: 1.02-1.06), being born in Pemba (OR: 1.48; CI: 1.02-2.13) or Tanzania (OR: 2.36; CI: 1.16-4.78), and use of freshwater (OR: 2.15; CI: 1.53-3.03) showed higher odds of infection. Community knowledge about schistosomiasis was low. Only few infected Bulinus snails were found. The relatively low S. haematobium prevalence in Zanzibar is a promising starting point for elimination. However, there is a need to improve community knowledge about disease transmission and prevention. Control measures tailored to the local context, placing particular attention to hot-spot areas, high-risk groups, and individuals, will be necessary if elimination is to be achieved

Baseline Trachoma Surveys in Kaskazini A and Micheweni Districts of Zanzibar: Results of Two Population-Based Prevalence Surveys Conducted with the Global Trachoma Mapping Project.

PURPOSE: Based on health care records and trachoma rapid assessments, trachoma was suspected to be endemic in Kaskazini A and Micheweni districts of Zanzibar. This study aimed to investigate the prevalence of trachomatous inflammation-follicular (TF), and trachomatous trichiasis (TT) in each of those districts. METHODS: The survey was undertaken in Kaskazini A and Micheweni districts on Unguja and Pemba Islands, respectively. A multi-stage cluster random sampling design was applied, whereby 25 census enumeration areas (clusters) and 30 households per cluster were included. Consenting eligible participants (children aged 1-9 years and people aged 15 years and older) were examined for trachoma using the World Health Organization simplified grading system. RESULTS: A total of 1673 households were surveyed and 6407 participants (98.0% of those enumerated) were examined for trachoma. Examinees included a total of 2825 children aged 1-9 years and 3582 people aged 15 years and older. TF prevalence in 1-9-year-olds was 2.7% (95% confidence interval, CI, 2.7-4.1%) in Kazkazini A and 11.4% (95% CI 6.6-16.5%) in Micheweni. Among people aged 15 years and older, TT prevalence was 0.01% (95% CI 0.00-0.04%) in Kazkazini A and 0.21% (95% CI 0.08-0.39%) in Micheweni. CONCLUSION: Trachoma is a public health problem in Micheweni district, where implementation of all four components of the SAFE strategy (surgery, antibiotics, facial cleanliness, and environmental improvement), including mass drug administration with azithromycin, is required. These findings will facilitate planning for trachoma elimination

Efficacy, safety and acceptability of a new chewable formulationversusthe solid tablet of mebendazole against hookworm infections in children: an open-label, randomized controlled trial

Background; : Soil-transmitted helminths (STHs) infect almost 1·5 billion people worldwide. The control of STH infections is based on preventive chemotherapy using either albendazole or mebendazole. Before being widely used, a sufficient body of evidence on efficacy, safety and acceptability is warranted for the new chewable child-friendly formulation of mebendazole that was recently developed.; Methods; : We conducted a randomised controlled superiority trial in four primary schools and kindergartens on Pemba Island, Tanzania. We considered eligible children aged 3 to 12 years with a hookworm infection intensity of at least 50 eggs per gram (EPG) of stool and no chronic diseases. Participants were allocated to treatment arms (ratio 1:1) using a computer generated random sequence. Our primary outcome was geometric mean based egg reduction rate (ERR) against hookworm assessed 14-21 days post-treatment. This trial complete and is registered with ClinicalTrials.gov, number NCT03995680 (June 24, 2019).; Findings; : 397 children were eligible and randomised into the solid (198) or chewable (199) tablet arms, of whom 393 were analysed. We found no significant difference between both formulations in terms of ERR (solid 70·8% versus chewable 68·5%, difference in ERRgeometric mean 2·3%-points, 95% CI -7·8 to 12·6, p = 0.65) and CR (11·2 versus 12·7%, 95% CI -4·9 to 7·9, p = 0.65) against hookworm infections. Adverse events were mild in both treatment arms.; Interpretations; : Though we could not demonstrate superiority in terms of efficacy of the new formulation, the difference between arms was small and therefore, the chewable formulation could be safely used as an alternative to swallowable tablets, in particular in young children who may have swallowing difficulties. This might help increase compliance and, consequently, enhance the effect of preventive chemotherapy

Multiple and Multidimensional life transitions in the context of life-limiting health conditions:Longitudinal study focussing on perspectives of Young Adults, Families and Professionals

Background: There is a dearth of literature that investigates life transitions of young adults (YAs) with life-limiting conditions, families and professionals. The scant literature that is available has methodological limitations, including not listening to the voice of YAs, collecting data retrospectively, at one time point, from one group’s perspective and single case studies. The aim of this study was to address the gaps found in our literature review and provide a clearer understanding of the multiple and multi-dimensional life transitions experienced by YAs and significant others, over a period of time. Methods: This qualitative study used a longitudinal design and data were collected using semi-structured interviews over a 6-month period at 3 time points. Participants included 12 YAs with life-limiting conditions and their nominated significant others (10 family members and 11 professionals). Data were analysed using a thematic analysis approach. Results: Life transitions of YA and significant others are complex; they experience multiple and multi-dimensional transitions across several domains. The findings challenge the notion that all life transitions are triggered by health transitions of YAs, and has highlighted environmental factors (attitudinal and systemic) that can be changed to facilitate smoother transitions in various aspects of their lives. Conclusions: This study makes a unique and significant contribution to literature. It provides evidence and rich narratives for policy makers and service providers to change policies and practices that are in line with the needs of YAs with life-limiting conditions as they transition to adulthood. Families and professionals have specific training needs that have not yet been met fully

Earliest Triassic microbialites in the South China Block and other areas; controls on their growth and distribution

Earliest Triassic microbialites (ETMs) and inorganic carbonate crystal fans formed after the end-Permian mass extinction (ca. 251.4 Ma) within the basal Triassic Hindeodus parvus conodont zone. ETMs are distinguished from rarer, and more regional, subsequent Triassic microbialites. Large differences in ETMs between northern and southern areas of the South China block suggest geographic provinces, and ETMs are most abundant throughout the equatorial Tethys Ocean with further geographic variation. ETMs occur in shallow-marine shelves in a superanoxic stratified ocean and form the only widespread Phanerozoic microbialites with structures similar to those of the Cambro-Ordovician, and briefly after the latest Ordovician, Late Silurian and Late Devonian extinctions. ETMs disappeared long before the mid-Triassic biotic recovery, but it is not clear why, if they are interpreted as disaster taxa. In general, ETM occurrence suggests that microbially mediated calcification occurred where upwelled carbonate-rich anoxic waters mixed with warm aerated surface waters, forming regional dysoxia, so that extreme carbonate supersaturation and dysoxic conditions were both required for their growth. Long-term oceanic and atmospheric changes may have contributed to a trigger for ETM formation. In equatorial western Pangea, the earliest microbialites are late Early Triassic, but it is possible that ETMs could exist in western Pangea, if well-preserved earliest Triassic facies are discovered in future work