ResearchPad - helminth-infections https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Familial assimilation in transmission of raw-freshwater fish-eating practice leading to clonorchiasis]]> https://www.researchpad.co/article/elastic_article_15763 Clonorchiasis is caused by the ingestion of raw freshwater fish, which contains the infective larvae of Clonorchis sinensis. It is highly endemic in Asia, where about 15 million people are afflicted. To establish sustainable control strategy, the transmission of raw-eating practice needs to be illuminated. In this study, we conducted a survey in school students from four clonorchiasis endemic provinces in China, covering 23,222 students aged 9–18. The characteristics of raw-eating practice, impact of parents’ raw-eating practice on children, interaction of spouses’ practice was explored. It is demonstrated that raw-eating practice presents familial clustering, which is higher in those families with older children and with boys. Raw-eating practice in children is highly influenced by their parents’ raw-eating practice especially when both parents do. Additionally, there exists interaction between spouses’ raw-eating practice. The impact of husband’s raw-eating practice on his wife is higher than that of wife’s raw-eating practice on her husband. Familial assimilation dominates the transmission of raw-freshwater eating-practice, including the assimilation from parents to their children and that between spouses. This finding indicates the adoption of sustainable strategy against clonorchiasis through blocking raw-freshwater fish-eating practice.

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<![CDATA[Cost and logistics implications of a nationwide survey of schistosomiasis and other intestinal helminthiases in Sudan: Key activities and cost components]]> https://www.researchpad.co/article/elastic_article_15719 It is vital to share details of concrete experiences of conducting a nationwide disease survey. By doing so, the global health community could adapt previous experiences to expand geographic mapping programs, eventually contributing to the development of disease control and elimination strategies. A nationwide survey of schistosomiasis and intestinal helminthiases was conducted from December 2016 to March 2017 in Sudan. We aimed to describe details of the key activities and cost components required for the nationwide survey. We investigated which activities were necessary to prepare and conduct a nationwide survey of schistosomiasis and intestinal helminthiases, and the types and amounts of transportation, personnel, survey equipment, and consumables that were required. In addition, we estimated financial and economic costs from the perspectives of the donor and the Ministry of Health. Cash expenditures incurred to implement the survey were defined as financial costs. For economic costs, we considered the true value for society as a whole, and this category therefore accounted for the costs of all goods and services used for the project, including those that were not sold in the market and therefore had no market price (e.g., time spent by head teachers and teachers). We organized costs into capital and recurrent items. We ran one-way sensitivity and probabilistic analyses using Monte-Carlo methods with 10,000 draws to examine the robustness of the primary analysis results. A total of USD 1,465,902 and USD 1,516,238 was incurred for the financial and economic costs, respectively. The key cost drivers of the nationwide survey were personnel and transportation, for both financial and economic costs. Personnel and transportation accounted for around 64% and 18% of financial costs, respectively. If a government finds a way to mobilize existing government officials with no additional payments using the health system already in place, the cost of a nationwide survey could be remarkably reduced.

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<![CDATA[<i>Toxocara</i> species environmental contamination of public spaces in New York City]]> https://www.researchpad.co/article/elastic_article_14754 Toxocara canis and Toxocara cati are helminth worms that infect dogs and cats, respectively. Infected dogs and cats will defecate thousands of Toxocara eggs into the environment. Humans are incidental hosts and are exposed when consuming contaminated soils via the fecal-oral route. After leaving the gastrointestinal tract, the Toxocara larvae will enter the vasculature and can migrate to any major organ system, including lungs, ocular, and central nervous system. Symptoms can range from mild muscle aches to severe asthma, blindness, and encephalitis. Humans are not definitive hosts of the parasite and cannot transmit Toxocara eggs to the environment or other humans. There is a need for research on the sanitary impact of Toxocara for both humans and animals, especially in large urban cities such as New York City. Poverty is also associated with higher rates of toxocariasis, with more contamination in poorer neighborhoods where animal control, deworming of pets, and less sanitary conditions exist. This study aims to understand further the disparity of lower socioeconomic areas having higher rates of contaminated parks and playgrounds, comparing the five boroughs of New York City.

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<![CDATA[Harnessing helminth-driven immunoregulation in the search for novel therapeutic modalities]]> https://www.researchpad.co/article/elastic_article_14550 Parasitic helminths have coevolved with humans over millennia, intricately refining and developing an array of mechanisms to suppress or skew the host’s immune system, thereby promoting their long-term survival. Some helminths, such as hookworms, cause little to no overt pathology when present in modest numbers and may even confer benefits to their human host. To exploit this evolutionary phenomenon, clinical trials of human helminth infection have been established and assessed for safety and efficacy for a range of immune dysfunction diseases and have yielded mixed outcomes. Studies of live helminth therapy in mice and larger animals have convincingly shown that helminths and their excretory/secretory products possess anti-inflammatory drug-like properties and represent an untapped pharmacopeia. These anti-inflammatory moieties include extracellular vesicles, proteins, glycans, post-translational modifications, and various metabolites. Although the concept of helminth-inspired therapies holds promise, it also presents a challenge to the drug development community, which is generally unfamiliar with foreign biologics that do not behave like antibodies. Identification and characterization of helminth molecules and vesicles and the molecular pathways they target in the host present a unique opportunity to develop tailored drugs inspired by nature that are efficacious, safe, and have minimal immunogenicity. Even so, much work remains to mine and assess this out-of-the-box therapeutic modality. Industry-based organizations need to consider long-haul investments aimed at unraveling and exploiting unique and differentiated mechanisms of action as opposed to toe-dipping entries with an eye on rapid and profitable turnarounds.

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<![CDATA[Genetic diversity of <i>Echinococcus multilocularis</i> and <i>Echinococcus granulosus sensu lato</i> in Kyrgyzstan: The A2 haplotype of <i>E</i>. <i>multilocularis</i> is the predominant variant infecting humans]]> https://www.researchpad.co/article/elastic_article_13871 Analysis of the genetic variability in Echinococcus species from different endemic countries have contributed to the knowledge in the taxonomy and phylogeography of these parasites. The most important species of this genus, Echinococcus granulosus sensu lato and Echinococcus multilocularis, co-exist in Kyrgyzstan causing serious public health issues. E. granulosus s.l. causes cystic echinococcosis and E. multilocularis is the causative agent of alveolar echinococcosis. The most relevant finding of our study is the identification of the cob/nad2/cox1 A2 haplotype of E. multilocularis as the most commonly found in humans and dogs. However, it remains unknown if this variant of E. multilocularis, based on genetic differences in mitochondrial genes, presents differences in virulence which could have contributed to the emergence of alveolar echinococcosis in Kyrgyzstan. The results also show a number of non-previously described genetic variants of E. multilocularis and E. granulosus s.s.

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<![CDATA[Impacts of host gender on <i>Schistosoma mansoni</i> risk in rural Uganda—A mixed-methods approach]]> https://www.researchpad.co/article/elastic_article_13851 Globally, over 230 million people are infected with schistosomiasis, an infectious disease caused by parasitic helminths. Humans can get infected when they contact water which contains Schistosoma parasites. Although the disease can be treated with a drug, people get rapidly reinfected in certain high-transmission settings. Drug treatment alone may not be sufficient to eliminate this disease and additional interventions such as health promotion or improvements in water and sanitation need to be scaled up. To provide recommendations to these control programmes we carried out interdisciplinary research in Eastern Uganda to understand the influence of gender on schistosomiasis risk. We found that the water contact behaviour of boys and girls is quite similar, and we did not see differences in reinfection or genetic diversity of the parasite between boys and girls. Differences in water contact between genders is greater in adults, and further research is required for these individuals. In this setting, infection rates are high in school-aged children and there are no differences between genders. These results emphasise improved control efforts for all school-aged children in communities like these. Our interdisciplinary approach provided complementary findings. Such an integrated approach can therefore have more power to meaningfully inform policy on schistosomiasis control.

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<![CDATA[Amino acids serve as an important energy source for adult flukes of <i>Clonorchis sinensis</i>]]> https://www.researchpad.co/article/elastic_article_13829 Clonorchiasis, closely related to cholangiocarcinoma and hepatocellular carcinoma, has led to a negative socioeconomic impact in global areas especially some Asian endemic regions. Owing to the emergence of drug resistance and hypersensitivity reactions after the massive and repeated use of praziquantel as well as the lack of effective vaccines, searching for new strategies that prevent and treat clonorchiasis has become an urgent matter. Clonorchis sinensis, the causative agent of clonorchiasis, long-term inhabits the microaerobic and limited-glucose environment of the bile ducts. Adequate nutrients are essential for adult flukes to resist the adverse condition and survive in the crowed habitat. Studies on energy metabolism of adult flukes are beneficial for further exploring host-parasite interactions and developing novel anti-parasitic drugs. Our results suggest that gluconeogenesis probably plays a vital role in energy metabolism of Clonorchis sinensis and exogenous amino acids might be an essential energy source for adult flukes to successfully survive in the host. Our foundational study opens a new avenue for explaining energy metabolism of Clonorchis sinensis and provides a valuable strategy that the gluconeogenesis pathway will be a potential and novel target for the prevention and treatment of clonorchiasis.

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<![CDATA[Integrating testing for chronic strongyloidiasis within the Indigenous adult preventive health assessment system in endemic communities in the Northern Territory, Australia: An intervention study]]> https://www.researchpad.co/article/elastic_article_13848 Strongyloidiasis is a neglected tropical disease that is endemic in some Aboriginal communities in the Northern Territory. This study asks if the number and proportion of persons tested for chronic strongyloidiasis can be increased by incorporating a Strongyloides serology test into the existing routine Indigenous adult preventive health assessment system in remote endemic communities. This study demonstrated that integrating Strongyloides serology test within the Indigenous adult preventive health assessment system does increase the number and proportion of people tested in endemic communities. This intervention means that life-threatening clinical complications of strongyloidiasis can be prevented by early detection and treatment. Primary health care services have an important role in increased testing in this high-risk population. Primary health care clinicians incorporated chronic strongyloidiasis with other preventable chronic and infectious diseases. The sustainable population health systems-based approach successfully increased coverage by integrating testing for chronic strongyloidiasis into the adult preventive health assessment in health services in remote Indigenous Australian endemic communities, utilising the electronic health record system. The Strongyloides report developed to measure the change in clinical practice would be replicable in other health services with high risk populations.

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<![CDATA[A systematic review of alternative surveillance approaches for lymphatic filariasis in low prevalence settings: Implications for post-validation settings]]> https://www.researchpad.co/article/elastic_article_13802 Lymphatic filariasis (LF) is a mosquito-borne disease, which can result in complications including swelling affecting the limbs (lymphoedema) or scrotum (hydrocele). LF can be eliminated by mass drug administration (MDA) which involves whole communities taking drug treatment at regular intervals. After MDA programmes, country programmes conduct the Transmission Assessment Survey (TAS), which tests school children for LF. It is important to continue testing for LF after elimination because there can be a 10-year period between becoming infected and developing symptoms, but it is thought that the use of TAS in such settings is likely to be too expensive and also not sensitive enough to detect low-level infections. Our study assesses the results from 44 studies in areas of low LF prevalence that have investigated methods of surveillance for LF which differ from the standardised TAS approach. These include both human and mosquito studies. Results show that there is currently no standardised approach to testing, but that surveillance can be made more sensitive through the use of new diagnostic tests, such as antibody testing, and also by targeting higher risk populations. However, further research is needed to understand whether these approaches work in a range of settings and whether they are affordable on the ground.

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<![CDATA[Gender norms and mass deworming program access in Comé, Benin: A qualitative assessment of gender-associated opportunities and challenges to achieving high mass drug administration coverage]]> https://www.researchpad.co/article/N0cbc3c85-9c5e-43fe-983c-4afc7d1b8db3

The World Health Organization’s Neglected Tropical Disease Roadmap has accelerated progress towards eliminating select neglected tropical diseases (NTDs). This momentum has catalyzed research to determine the feasibility of interrupting transmission of soil-transmitted helminths (STH) using community-wide mass drug administration (MDA). This study aims to identify potential gender-specific facilitators and barriers to accessing and participating in community-wide STH MDA, with the goal of ensuring programs are equitable and maximize the probability of interrupting STH transmission. This research was conducted prior to the launch of community-wide MDA for STH in Comé, Benin. A total of 10 focus group discussions (FGDs) were conducted separately among 40 men, 38 women, and 15 community drug distributors (CDDs). Salient themes included: both men and women believe that community-wide MDA would reduce the financial burden associated with self-treatment, particularly for low income adults. Community members believe MDA should be packaged alongside water, sanitation, and other health services. Women feel past community-wide programs have been disorganized and are concerned these distributions will be similar. Women also expressed interest in increased engagement in the implementation of future community-based public health programs. Men often did not perceive themselves to be at great risk for STH infection and did not express a high demand for treatment. Finally, the barriers discussed by CDDs generally did not align with gender-specific concerns, but rather represented concerns shared by both genders. A door-to-door distribution strategy for STH MDA is preferred by women in this study, as this platform empowers women to participate as health decision makers for their family. In addition, involving women in planning and implementation of community-wide programs may help to increase treatment coverage and compliance.

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<![CDATA[Ivermectin as an adjuvant to anti-epileptic treatment in persons with onchocerciasis-associated epilepsy: A randomized proof-of-concept clinical trial]]> https://www.researchpad.co/article/N2a703e18-6320-408f-bd4d-1f677396d877

Introduction

Recent findings from onchocerciasis-endemic foci uphold that increasing ivermectin coverage reduces the epilepsy incidence, and anecdotal evidence suggests seizure frequency reduction in persons with onchocerciasis-associated epilepsy, when treated with ivermectin. We conducted a randomized clinical trial to assess whether ivermectin treatment decreases seizure frequency.

Methods

A proof-of-concept randomized clinical trial was conducted in the Logo health zone in the Ituri province, Democratic Republic of Congo, to compare seizure frequencies in onchocerciasis-infected persons with epilepsy (PWE) randomized to one of two treatment arms: the anti-epileptic drug phenobarbital supplemented with ivermectin, versus phenobarbital alone. The primary endpoint was defined as the probability of being seizure-free at month 4. A secondary endpoint was defined as >50% reduction in seizure frequency at month 4, compared to baseline. Both endpoints were analyzed using multiple logistic regression. In longitudinal analysis, the probability of seizure freedom during the follow-up period was assessed for both treatment arms by fitting a logistic regression model using generalized estimating equations (GEE).

Results

Ninety PWE enrolled between October and November 2017 were eligible for analysis. A multiple logistic regression analysis showed a borderline association between ivermectin treatment and being seizure-free at month 4 (OR: 1.652, 95% CI 0.975–2.799; p = 0.062). There was no significant difference in the probability of experiencing >50% reduction of the seizure frequency at month 4 between the two treatment arms. Also, treatment with ivermectin did not significantly increase the odds of being seizure-free during the individual follow-up visits.

Conclusion

Whether ivermectin has an added value in reducing the frequency of seizures in PWE treated with AED remains to be determined. A larger study in persons with OAE on a stable AED regimen and in persons with recent epilepsy onset should be considered to further investigate the potential beneficial effect of ivermectin treatment in persons with OAE.

Trial registration

Registration: www.clinicaltrials.gov; NCT03052998.

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<![CDATA[Crystal structures of Triosephosphate Isomerases from Taenia solium and Schistosoma mansoni provide insights for vaccine rationale and drug design against helminth parasites]]> https://www.researchpad.co/article/N340e3046-cb91-4c84-8d1b-fb2a65cf4cdb

Triosephosphate isomerases (TPIs) from Taenia solium (TsTPI) and Schistosoma mansoni (SmTPI) are potential vaccine and drug targets against cysticercosis and schistosomiasis, respectively. This is due to the dependence of parasitic helminths on glycolysis and because those proteins elicit an immune response, presumably due to their surface localization. Here we report the crystal structures of TsTPI and SmTPI in complex with 2-phosphoglyceric acid (2-PGA). Both TPIs fold into a dimeric (β-α)8 barrel in which the dimer interface consists of α-helices 2, 3, and 4, and swapping of loop 3. TPIs from parasitic helminths harbor a region of three amino acids knows as the SXD/E insert (S155 to E157 and S157 to D159 in TsTPI and SmTPI, respectively). This insert is located between α5 and β6 and is proposed to be the main TPI epitope. This region is part of a solvent-exposed 310–helix that folds into a hook-like structure. The crystal structures of TsTPI and SmTPI predicted conformational epitopes that could be used for vaccine design. Surprisingly, the epitopes corresponding to the SXD/E inserts are not the ones with the greatest immunological potential. SmTPI, but not TsTPI, habors a sole solvent exposed cysteine (SmTPI-S230) and alterations in this residue decrease catalysis. The latter suggests that thiol-conjugating agents could be used to target SmTPI. In sum, the crystal structures of SmTPI and TsTPI are a blueprint for targeted schistosomiasis and cysticercosis drug and vaccine development.

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<![CDATA[Implementation of a practical and effective pilot intervention against transmission of Taenia solium by pigs in the Banke district of Nepal]]> https://www.researchpad.co/article/5c7d95d7d5eed0c484734daa

Taenia solium is a zoonotic cestode parasite which causes human neurocysticercosis. Pigs transmit the parasite by acting as the intermediate host. An intervention was implemented to control transmission of T. solium by pigs in Dalit communities of Banke District, Nepal. Every 3 months, pigs were vaccinated with the TSOL18 recombinant vaccine (Cysvax, IIL, India)) and, at the same time, given an oral treatment with 30mg/kg oxfendazole (Paranthic 10% MCI, Morocco). The prevalence of porcine cysticercosis was determined in both an intervention area as well as a similar no intervention control area, among randomly selected, slaughter-age pigs. Post mortem assessments were undertaken both at the start and at the end of the intervention. Participants conducting the post mortem assessments were blinded as to the source of the animals being assessed. At the start of the intervention the prevalence of porcine cysticercosis was 23.6% and 34.5% in the control and intervention areas, respectively. Following the intervention, the prevalence of cysticercosis in pigs from the control area was 16.7% (no significant change), whereas no infection was detected after complete slicing of all muscle tissue and brain in animals from the intervention area (P = 0.004). These findings are discussed in relation to the feasibility and sustainability of T. solium control. The 3-monthly vaccination and drug treatment intervention in pigs used here is suggested as an effective and practical method for reducing T. solium transmission by pigs. The results suggest that applying the intervention over a period of years may ultimately reduce the number of tapeworm carriers and thereby the incidence of NCC.

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<![CDATA[Resolving "worm wars": An extended comparison review of findings from key economics and epidemiological studies]]> https://www.researchpad.co/article/5c8acc2bd5eed0c48498f08c ]]> <![CDATA[Comparing the performance of urine and copro-antigen detection in evaluating Opisthorchis viverrini infection in communities with different transmission levels in Northeast Thailand]]> https://www.researchpad.co/article/5c6730b3d5eed0c484f37f31

To combat and eventually eliminate the transmission of the liver fluke Opisthorchis viverrini, an accurate and practical diagnostic test is required. A recently established urine antigen detection test using monoclonal antibody-based enzyme-linked-immunosorbent assay (mAb-ELISA) has shown promise due to its high diagnostic accuracy and the use of urine in place of fecal samples. To further test the utility of this urine assay, we performed a cross sectional study of 1,043 people in 3 opisthorchiasis endemic communities in northeast Thailand by applying urine antigen detection together with copro-antigen detection methods. The quantitative formalin-ethyl acetate concentration technique (FECT) was concurrently performed as a reference method. The prevalence of O. viverrini determined by urine antigen detection correlated well with that by copro-antigen detection and both methods showed 10–15% higher prevalence than FECT. Within the fecal negative cases by FECT, 29% and 43% were positive by urine and copro-antigen detection, respectively. The prevalence and intensity profiles determined by antigen detection and FECT showed similar patterns of increasing trends of infection with age. The concentration of antigen measured in urine showed a positive relationship with the concentration of copro-antigen, both of which were positively correlated with fecal egg counts. The data observed in this study indicate that urine antigen detection had high diagnostic accuracy and was in concordance with copro-antigen detection. Due to the ease and noninvasiveness of sample collection, the urine assay has high potential for clinical diagnosis as well as population screening in the program for the control and elimination of opisthorchiasis.

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<![CDATA[The long run impact of early childhood deworming on numeracy and literacy: Evidence from Uganda]]> https://www.researchpad.co/article/5c5ca2c8d5eed0c48441eadd

Background

Up to 1.45 billion people currently suffer from soil transmitted helminth infection, with the largest burden occurring in Africa and Asia. Safe and cost effective deworming treatment exists, but there is a debate about mass distribution of this treatment in high prevalence settings. While the World Health Organization recommends mass administration of anthelmintic drugs for preschool and school-aged children in high (>20%) prevalence settings, and several long run follow up studies of an influential trial have suggested large benefits that persist over time, recent systematic reviews have called this recommendation into question.

Methods and findings

This paper analyzes the long-term impact of a cluster-randomized trial in eastern Uganda that provided mass deworming treatment to preschool aged children from 2000 to 2003 on the numeracy and literacy skills of children and young adults living in those villages in 2010-2015. This study uses numeracy and literacy data collected seven to twelve years after the end of the deworming trial in a randomly selected subset of communities from the original trial, by an education-focused survey that had no relationship to the deworming study. Building on an earlier working paper which used data from 2010 and 2011 survey rounds, this paper uses an additional four years of numeracy and literacy data (2012, 2013, 2014, and 2015). Aggregating data from all survey rounds, the difference between numeracy scores in treatment versus control communities is 0.07 standard deviations (SD) (95% CI -0.10, 0.24, p = 0.40), the difference in literacy scores is 0.05 SD (95% CI -0.16, 0.27, p = 0.62), and the difference in total scores is 0.07 SD (95% CI -0.11, 0.25, p = 0.44). There are significant differences in program impact by gender, with numeracy and literacy differentially positively affected for girls, and by age, with treatment effects larger for the primary school aged subsample. There are also significant treatment interactions for those living in households with more treatment-eligible children. There is no evidence of differential treatment effects on age at program eligibility or number of years of program eligibility.

Conclusions

Mass deworming of preschool aged children in high prevalence communities in Uganda resulted in no statistically significant gains in numeracy or literacy 7-12 years after program completion. Point estimates were positive but imprecise; the study lacked sufficient power to rule out substantial positive effects or more modest negative effects. However, there is suggestive evidence that deworming was relatively more beneficial for girls, primary school aged children, and children living in households with other treated children.

Research approval

As this analysis was conducted on secondary data which is publicly available, no research approval was sought or received. All individual records were anonymized by the data provider prior to public release.

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<![CDATA[Knowledge, attitudes and practices with regard to schistosomiasis prevention and control: Two cross-sectional household surveys before and after a Community Dialogue intervention in Nampula province, Mozambique]]> https://www.researchpad.co/article/5c65dce7d5eed0c484dec4db

Background

The Community Dialogue Approach is a promising social and behaviour change intervention, which has shown potential for improving health seeking behaviour. To test if this approach can strengthen prevention and control of schistosomiasis at community level, Malaria Consortium implemented a Community Dialogue intervention in four districts of Nampula province, Mozambique, between August 2014 and September 2015.

Methodology/Principal findings

Cross-sectional household surveys were conducted before (N = 791) and after (N = 792) implementation of the intervention to assess its impact on knowledge, attitudes and practices at population level. At both baseline and endline, awareness of schistosomiasis was high at over 90%. After the intervention, respondents were almost twice as likely to correctly name a risk behaviour associated with schistosomiasis (baseline: 18.02%; endline: 30.11%; adjusted odds ratio: 1.91; 95% confidence interval: 1.14–2.58). Increases were also seen in the proportion of people who knew that schistosomiasis can be spread by infected persons and who could name at least one correct transmission route (baseline: 25.74%; endline: 32.20%; adjusted odds ratio: 1.36; 95% confidence interval: 1.01–1.84), those who knew that there is a drug that treats the disease (baseline: 29.20%, endline: 47.55%; adjusted odds ratio: 2.19; 95% confidence interval: 1.67–2.87) and those who stated that they actively protect themselves from the disease and cited an effective behaviour (baseline: 40.09%, endline: 59.30%; adjusted odds ratio: 2.14; 95% confidence interval: 1.40–3.28). The intervention did not appear to lead to a reduction in misconceptions. In particular, the belief that the disease is sexually transmitted continued to be widespread.

Conclusions/Significance

Given its overall positive impact on knowledge and behaviour at population level, Community Dialogue can play an important role in schistosomiasis prevention and control. The intervention could be further strengthened by better enabling communities to take suitable action and linking more closely with community governance structures and health system programmes.

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<![CDATA[A novel cell-free method to culture Schistosoma mansoni from cercariae to juvenile worm stages for in vitro drug testing]]> https://www.researchpad.co/article/5c58d63ed5eed0c484031973

Background

The arsenal in anthelminthic treatment against schistosomiasis is limited and relies almost exclusively on a single drug, praziquantel (PZQ). Thus, resistance to PZQ could constitute a major threat. Even though PZQ is potent in killing adult worms, its activity against earlier stages is limited. Current in vitro drug screening strategies depend on newly transformed schistosomula (NTS) for initial hit identification, thereby limiting sensitivity to new compounds predominantly active in later developmental stages. Therefore, the aim of this study was to establish a highly standardized, straightforward and reliable culture method to generate and maintain advanced larval stages in vitro. We present here how this method can be a valuable tool to test drug efficacy at each intermediate larval stage, reducing the reliance on animal use (3Rs).

Methodology/Principal findings

Cercariae were mechanically transformed into skin-stage (SkS) schistosomula and successfully cultured for up to four weeks with no loss in viability in a commercially available medium. Under these serum- and cell-free conditions, development halted at the lung-stage (LuS). However, the addition of human serum (HSe) propelled further development into liver stage (LiS) worms within eight weeks. Skin and lung stages, as well as LiS, were submitted to 96-well drug screening assays using known anti-schistosomal compounds such as PZQ, oxamniquine (OXM), mefloquine (MFQ) and artemether (ART). Our findings showed stage-dependent differences in larval susceptibility to these compounds.

Conclusion

With this robust and highly standardized in vitro assay, important developmental stages of S. mansoni up to LiS worms can be generated and maintained over prolonged periods of time. The phenotype of LiS worms, when exposed to reference drugs, was comparable to most previously published works for ex vivo harvested adult worms. Therefore, this in vitro assay can help reduce reliance on animal experiments in search for new anti-schistosomal drugs.

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<![CDATA[A Biomphalaria glabrata peptide that stimulates significant behaviour modifications in aquatic free-living Schistosoma mansoni miracidia]]> https://www.researchpad.co/article/5c50c464d5eed0c4845e86d4

The human disease schistosomiasis (or bilharzia) is caused by the helminth blood fluke parasite Schistosoma mansoni, which requires an intermediate host, the freshwater gastropod snail Biomphalaria glabrata (the most common intermediate host). The free-swimming parasite miracidia utilise an excellent chemosensory sense to detect and locate an appropriate host. This study investigated the biomolecules released by the snail that stimulate changes in the behaviour of the aquatic S. mansoni miracidia. To achieve this, we have performed an integrated analysis of the snail-conditioned water, through chromatography and bioassay-guided behaviour observations, followed by mass spectrometry. A single fraction containing multiple putative peptides could stimulate extreme swimming behaviour modifications (e.g. velocity, angular variation) similar to those observed in response to crude snail mucus. One peptide (P12;—R-DITSGLDPEVADD-KR—) could replicate the stimulation of miracidia behaviour changes. P12 is derived from a larger precursor protein with a signal peptide and multiple dibasic cleavage sites, which is synthesised in various tissues of the snail, including the central nervous system and foot. P12 consists of an alpha helix secondary structure as indicated by circular dichroism spectroscopy. This information will be helpful for the development of approaches to manipulate this parasites life cycle, and opens up new avenues for exploring other parasitic diseases which have an aquatic phase using methods detailed in this investigation.

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<![CDATA[Integrated seroprevalence-based assessment of Wuchereria bancrofti and Onchocerca volvulus in two lymphatic filariasis evaluation units of Mali with the SD Bioline Onchocerciasis/LF IgG4 Rapid Test]]> https://www.researchpad.co/article/5c5b52c4d5eed0c4842bcfb9

Background

Mali has become increasingly interested in the evaluation of transmission of both Wuchereria bancrofti and Onchocerca volvulus as prevalences of both infections move toward their respective elimination targets. The SD Bioline Onchocerciasis/LF IgG4 Rapid Test was used in 2 evaluation units (EU) to assess its performance as an integrated surveillance tool for elimination of lymphatic filariasis (LF) and onchocerciasis.

Methodology/Principal findings

A cross sectional survey with SD Bioline Onchocerciasis/LF IgG4 Rapid Test was piggy-backed onto a transmission assessment survey (TAS) (using the immunochromatographic card test (ICT) Binax Filariasis Now test for filarial adult circulating antigen (CFA) detection) for LF in Mali among 6–7 year old children in 2016 as part of the TAS in two EUs namely Kadiolo-Kolondieba in the region of Sikasso and Bafoulabe -Kita-Oussoubidiagna-Yelimane in the region of Kayes.

In the EU of Kadiolo- Kolondieba, of the 1,625 children tested, the overall prevalence of W. bancrofti CFA was 0.62% (10/1,625) [CI = 0.31–1.09]; while that of IgG4 to Wb123 was 0.19% (3/1,600) [CI = 0.04–0.50]. The number of positives tested with the two tests were statistically comparable (p = 0.09). In the EU of Bafoulabe-Kita-Oussoubidiagna-Yelimane, an overall prevalence of W. bancrofti CFA was 0% (0/1,700) and that of Wb123 IgG4 antibody was 0.06% (1/1,700), with no statistically significant difference between the two rates (p = 0.99).

In the EU of Kadiolo- Kolondieba, the prevalence of Ov16-specific IgG4 was 0.19% (3/1,600) [CI = 0.04–0.50]. All 3 positives were in the previously O. volvulus-hyperendemic district of Kolondieba. In the EU of Bafoulabe-Kita-Oussoubidiagna-Yelimane, an overall prevalence of Ov16-specific IgG4 was 0.18% (3/1,700) [CI = 0.04–0.47]. These 3 Ov16 IgG4 positives were from previously O.volvulus-mesoendemic district of Kita.

Conclusions/Significance

The SD Bioline Onchocerciasis/LF IgG4 Rapid test appears to be a good tool for integrated exposure measures of LF and onchocerciasis in co-endemic areas.

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