Novel tools and strategies for breaking schistosomiasis transmission: study protocol for an intervention study

BACKGROUND: Global elimination of schistosomiasis as a public health problem is set as target in the new World Health Organization's Neglected Tropical Diseases Roadmap for 2030. Due to a long history of interventions, the Zanzibar islands of Tanzania have reached this goal since 2017. However, challenges occur on the last mile towards interruption of transmission. Our study will investigate new tools and strategies for breaking schistosomiasis transmission. METHODS: The study is designed as an intervention study, documented through repeated cross-sectional surveys (2020-2024). The primary endpoint will be the sensitivity of a surveillance-response approach to detect and react to outbreaks of urogenital schistosomiasis over three years of implementation. The surveys and multi-disciplinary interventions will be implemented in 20 communities in the north of Pemba island. In low-prevalence areas, surveillance-response will consist of active, passive and reactive case detection, treatment of positive individuals, and focal snail control. In hotspot areas, mass drug administration, snail control and behaviour change interventions will be implemented. Parasitological cross-sectional surveys in 20 communities and their main primary schools will serve to adapt the intervention approach annually and to monitor the performance of the surveillance-response approach and impact of interventions. Schistosoma haematobium infections will be diagnosed using reagent strips and urine filtration microscopy, and by exploring novel point-of-care diagnostic tests. DISCUSSION: Our study will shed light on the field applicability and performance of novel adaptive intervention strategies, and standard and new diagnostic tools for schistosomiasis elimination. The evidence and experiences generated by micro-mapping of S. haematobium infections at community level, micro-targeting of new adaptive intervention approaches, and application of novel diagnostic tools can guide future strategic plans for schistosomiasis elimination in Zanzibar and inform other countries aiming for interruption of transmission. Trial registration ISRCTN, ISCRCTN91431493. Registered 11 February 2020, https://www.isrctn.com/ISRCTN91431493

GPS-based fine-scale mapping surveys for schistosomiasis assessment: a practical introduction and documentation of field implementation

BACKGROUND: Fine-scale mapping of schistosomiasis to guide micro-targeting of interventions will gain importance in elimination settings, where the heterogeneity of transmission is often pronounced. Novel mobile applications offer new opportunities for disease mapping. We provide a practical introduction and documentation of the strengths and shortcomings of GPS-based household identification and participant recruitment using tablet-based applications for fine-scale schistosomiasis mapping at sub-district level in a remote area in Pemba, Tanzania. METHODS: A community-based household survey for urogenital schistosomiasis assessment was conducted from November 2020 until February 2021 in 20 small administrative areas in Pemba. For the survey, 1400 housing structures were prospectively and randomly selected from shapefile data. To identify pre-selected structures and collect survey-related data, field enumerators searched for the houses' geolocation using the mobile applications Open Data Kit (ODK) and MAPS.ME. The number of inhabited and uninhabited structures, the median distance between the pre-selected and recorded locations, and the dropout rates due to non-participation or non-submission of urine samples of sufficient volume for schistosomiasis testing was assessed. RESULTS: Among the 1400 randomly selected housing structures, 1396 (99.7%) were identified by the enumerators. The median distance between the pre-selected and recorded structures was 5.4 m. A total of 1098 (78.7%) were residential houses. Among them, 99 (9.0%) were dropped due to continuous absence of residents and 40 (3.6%) households refused to participate. In 797 (83.1%) among the 959 participating households, all eligible household members or all but one provided a urine sample of sufficient volume. CONCLUSIONS: The fine-scale mapping approach using a combination of ODK and an offline navigation application installed on tablet computers allows a very precise identification of housing structures. Dropouts due to non-residential housing structures, absence, non-participation and lack of urine need to be considered in survey designs. Our findings can guide the planning and implementation of future household-based mapping or longitudinal surveys and thus support micro-targeting and follow-up of interventions for schistosomiasis control and elimination in remote areas. Trial registration ISRCTN, ISCRCTN91431493. Registered 11 February 2020, https://www.isrctn.com/ISRCTN91431493

Fine-scale-mapping of Schistosoma haematobium infections at the school and community levels and intermediate host snail abundance in the north of Pemba Island: baseline cross-sectional survey findings before the onset of a 3-year intervention study

BACKGROUND: Schistosomiasis elimination has gained renewed priority in the WHO guidance documents published in 2020 and 2022. The SchistoBreak project, implemented in Pemba, Tanzania between 2020 and 2024, aims to assess new tools and strategies for shifting from elimination as a public health problem towards interruption of transmission. Here we report our baseline findings and discuss implications for future interventions. METHODS: In 2020, human water contact sites (HWCSs) in the study area were geolocated and snail surveys were conducted. A parasitological and questionnaire cross-sectional baseline survey was implemented in 20 communities and their 16 primary schools between November 2020 and February 2021. Urine samples were collected at the school and household levels from individuals aged >/= 4 years. Schistosoma haematobium infection was detected by urine filtration microscopy. Snail, parasitological and questionnaire-derived data were analyzed descriptively, spatially and with generalized estimated equation models. RESULTS: The intermediate host snail Bulinus globosus was detected in 19.8% (33/167) of HWCSs. The overall S. haematobium prevalence was 1.2% (26/2196) in school-aged children and 0.8% (31/3893) in community members, with 0.2% (4/2196) and 0.1% (3/3893) heavy-intensity infections, respectively. Children who studied 2 km away (odds ratio [OR]: 5.0; 95% confidence interval [CI]: 2.3-11.1). Individuals living in a house located 2 km distance (OR: 18.0; 95% CI: 2.9-111.0). Self-reported praziquantel treatment coverage was 83.2% (2015/2423) in schoolchildren in the mass drug administration (MDA) conducted in August 2020. Coverage among adult community members was 59.9% (574/958), but only 34.8% (333/958) took praziquantel correctly. CONCLUSIONS: While the S. haematobium prevalence is very low in Pemba, there are many HWCSs with B. globosus situated close to schools or houses that pose a considerable risk of recrudescence. To maintain and accelerate the progress towards interruption of transmission, targeted and cost-effective interventions that are accepted by the community are needed; for example, snail control plus focal MDA, or test-and-treat in schools and households near infested waterbodies

Selective Hyper-responsiveness of the Interferon System in Major Depressive Disorders and Depression Induced by Interferon Therapy

Though an important percentage of patients with chronic hepatitis C virus (HCV) undergoing interferon (IFN) therapy develop depressive symptoms, the role of the IFN system in the pathogenesis of depressive disorders is not well understood.50 patients with HCV infection were treated with standard combination therapy (pegylated IFN-α2a/ribavirin). IFN-induced gene expression was analyzed to identify genes which are differentially regulated in patients with or without IFN-induced depression. For validation, PBMC from 22 psychiatric patients with a severe depressive episode (SDE) and 11 controls were cultivated in vitro with pegylated IFN-α2a and gene expression was analyzed.IFN-induced depression in HCV patients was associated with selective upregulation of 15 genes, including 6 genes that were previously described to be relevant for major depressive disorders or neuronal development. In addition, increased endogenous IFN-production and selective hyper-responsiveness of these genes to IFN stimulation were observed in SDE patients.Our data suggest that selective hyper-responsiveness to exogenous (IFN therapy) or endogenous (depressive disorders) type I IFNs may lead to the development of depressive symptoms. These data could lead to the discovery of novel therapeutic approaches to treat IFN-induced and major depressive disorders

The long road to schistosomiasis elimination in Zanzibar:a systematic review covering 100 years of research, interventions and control milestones

Zanzibar is among the few places in sub-Saharan Africa where interruption of Schistosoma transmission seems an achievable goal. Our systematic review identifies and discusses milestones in schistosomiasis research, control and elimination efforts in Zanzibar over the past 100 years. The search in online databases, libraries, and the World Health Organization Archives revealed 153 records published between May 1928 and August 2022. The content of records was summarised to highlight the pivotal work leading towards urogenital schistosomiasis elimination and remaining research gaps. The greatest achievement following 100 years of schistosomiasis interventions and research is undoubtedly the improved health of Zanzibaris, exemplified by the reduction in Schistosoma haematobium prevalence from>50% historically down to<5% in 2020, and the absence of severe morbidities. Experiences from Zanzibar have contributed to global schistosomiasis guidelines, whilst also revealing challenges that impede progression towards elimination. Challenges include: transmission heterogeneity requiring micro-targeting of interventions, post-treatment recrudescence of infections in transmission hotspots, biological complexity of intermediate host snails, emergence of livestock Schistosoma species complicating surveillance whilst creating the risk for interspecies hybridisation, insufficient diagnostics performance for light intensity infections and female genital schistosomiasis, and a lack of acceptable sanitary alternatives to freshwater bodies. Our analysis of the past revealed that much can be achieved in the future with practical implementation of integrated interventions, alongside operational research. With continuing national and international commitments, interruption of S. haematobium transmission across both islands is within reach by 2030, signposting the future demise of urogenital schistosomiasis across other parts of sub-Saharan Africa

Quantitative Detection of Hepatitis B Virus DNA by Real-Time Nucleic Acid Sequence-Based Amplification with Molecular Beacon Detection

We have developed a hepatitis B virus (HBV) DNA detection and quantification system based on amplification with nucleic acid sequence-based amplification (NASBA) technology and real-time detection with molecular beacon technology. NASBA is normally applied to amplify single-stranded target RNA, producing RNA amplicons. In this work we show that with modifications like primer design, sample extraction method, and template denaturation, the NASBA technique can be made suitable for DNA target amplification resulting in RNA amplicons. A major advantage of our assay is the one-tube, isothermal nature of the method, which allows high-throughput applications for nucleic acid detection. The homogeneous real-time detection allows a closed-tube format of the assay, avoiding any postamplification handling of amplified material and therefore minimizing the risk of contamination of subsequent reactions. The assay has a detection range of 10(3) to 10(9) HBV DNA copies/ml of plasma or serum (6 logs), with good reproducibility and precision. Compared with other HBV DNA assays, our assay provides good sensitivity, a wide dynamic range, and high-throughput applicability, making it a viable alternative to those based on other amplification or detection methods