First bovine vaccine to prevent human schistosomiasis - a cluster randomised Phase 3 clinical trial

Objective: Schistosomiasis is a neglected tropical parasitic disease caused by blood flukes of the genus Schistosoma. Schistosoma japonicum is zoonotic in China, the Philippines, and Indonesia, with bovines acting as major reservoirs of human infection. The primary objective of the trial was to examine the impact of a combination of human mass chemotherapy, snail control through mollusciciding, and SjCTPI bovine vaccination on the rate of human infection. Methods: A 5-year phase IIIa cluster randomized control trial was conducted among 18 schistosomiasis-endemic villages comprising 18,221 residents in Northern Samar, The Philippines. Results: Overall, bovine vaccination resulted in a statistically significant decrease in human infection (relative risk [RR] = 0.75; 95% confidence interval [CI] = 0.69 to 0.82) across all trial follow-ups. The best outcome of the trial was when bovine vaccination was combined with snail mollusciciding. This combination resulted in a 31% reduction (RR = 0.69; 95% CI = 0.61 to 0.78) in human infection. Conclusion: This is the first trial to demonstrate the effectiveness of a bovine vaccine for schistosomiasis in reducing human schistosome infection. The trial is registered with Australian New Zealand Clinical Trials Registry (ACTRN12619001048178)

Biennial versus annual treatment for schistosomiasis and its impact on liver morbidity

Objective: This study assessed the impact of annual versus biennial praziquantel treatment regimens on the prevalence, intensity of infection, and liver fibrosis dynamics of Asiatic schistosomiasis (caused by Schistosoma japonicum) among individuals residing in 18 endemic barangays in Northern Samar, Philippines. Methods: Five hundred and sixty-five subjects who reported symptoms of gastrointestinal illness and/or were believed to have clinical morbidity based on physical examination were selected for cohort follow-up. Results: The mean prevalence of schistosomiasis was 34% and the mean intensity of infection was 123.1 eggs per gram. Moderate to severe hepatic fibrosis (grade II/III) was demonstrated in approximately 25% of the study population. As expected, a greater reduction in both the prevalence and intensity of infection was documented with two treatment rounds versus one. Overall, hepatic fibrosis (grades I–III) regressed in only 24.3% of those who received a single treatment and in only 19.3% of those who received two doses. The prevalence of grade II–III fibrosis at baseline (25.2%) remained unchanged 2 years after treatment. Conclusions: These findings suggest that in order to reverse moderate to severe liver fibrosis due to schistosomiasis and improve clinical outcomes, a higher clinical dosage of praziquantel (i.e., 60–80 mg/kg) may be required over an extended duration

Mass drug administration and the sustainable control of schistosomiasis: an evaluation of treatment compliance in the rural Philippines

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.Background Preventive chemotherapy is the current global control strategy for schistosomiasis. The WHO target coverage rate is at least 75% for school-aged children. In the Philippines, the reported national coverage rate (43.5%) is far below the WHO target. This study examined the factors associated with non-compliance to mass drug administration. Methods A cross-sectional survey was conducted in 2015 among 2189 adults in the province of Northern Samar, the Philippines using a structured face-to-face survey questionnaire. Results The overall rate of non-compliance to mass drug administration (MDA) in the last treatment round was 27%. Females (aOR = 1.67, P = 0.033) were more likely to be non-compliant. Respondents who believed that schistosomiasis was acquired by open defecation and poor sanitation (aOR = 1.41, P = 0.015), and by drinking unclean water (aOR = 2.09, P = 0.001) were more likely to refuse treatment. Uncertainties on whether schistosomiasis can be treated (aOR = 2.39, P = 0.033), their fear of adverse reactions to praziquantel (aOR = 1.94, P = 0.021), misconceptions about alternative forms of treatment (aOR = 1.45, P = 0.037), and that praziquantel is used for purposes other than deworming (aOR = 2.15, P = 0.021) were all associated with a higher odd of non-compliance. In contrary, being a farmer (aOR = 0.62, P =0.038), participation in past MDA (aOR = 0.30, P < 0.001), informed about impending MDA (aOR = 0.08, P < 0.001), and having heard of schistosomiasis (aOR = 0.22, P = 0.045) were all significantly associated with reduced non-compliance. Conclusions To improve drug compliance for schistosomiasis there is an urgent need for intensive health education campaigns before conducting MDA that would not only provide disease specific information, but also deal with prevailing misconceptions about transmission, prevention, treatment, and drug side-effects.This work was supported by Australian National Health and Medical Research Council

Mass drug administration and the sustainable control of schistosomiasis: Community health workers are vital for global elimination efforts

Objectives: Schistosomiasis control is centred on preventive chemotherapy through mass drug administration (MDA). However, endemic countries continue to struggle to attain target coverage rates and patient compliance. In the Philippines, barangay health workers (BHWs) play a vital role in the coordination of MDA, acting as advocates, implementers, and educators. The aim of this study was to determine whether BHW knowledge and attitudes towards schistosomiasis and MDA is sufficient and correlated with resident knowledge and drug compliance. Methods: A cross-sectional survey was conducted in 2015 among 2186 residents and 224 BHWs in the province of Northern Samar, the Philippines using a structured survey questionnaire. Results: BHWs showed good familiarity on how schistosomiasis is acquired and diagnosed. Nevertheless, both BHWs and residents had poor awareness of the signs and symptoms of schistosomiasis, disease prevention, and treatment options. There was no correlation between the knowledge scores of the BHWs and the residents (r = 0.080, p = 0.722). Kruskal–Wallis analysis revealed significant differences in BHW knowledge scores between the low (3.29, 95% confidence interval 3.16–3.36), moderate (3.61, 95% confidence interval 3.49–3.69), and high (4.05, 95% confidence interval 3.77–4.13) compliance village groups (p = 0.002), with the high compliance areas having the highest mean knowledge scores. Conclusions: This study highlights the importance of community health workers in obtaining the World Health Organization drug coverage rate of 75% and improving compliance with MDA in the community. Investing in the education of community health workers with appropriate disease-specific training is crucial if disease elimination is ultimately to be achieved

Diagnosing schistosomiasis-induced liver morbidity: implications for global control

Background Subclinical morbidity due to schistosomiasis was evaluated in 565 patients, and the enhanced liver fibrosis (ELF) test was assessed for the first time as a potential screening tool for disease. Methods The prevalence and intensity of infection were determined by Kato–Katz thick smear stool examination at baseline and 2 years after curative treatment. The degree of hepatic fibrosis was assessed by ultrasound. Non-invasive serum biomarkers of hepatic fibrosis were also evaluated. Results The baseline human prevalence and infection intensity were found to be moderately high at 34% and 123 eggs per gram, respectively. However, hepatic parenchymal fibrosis occurred in 50% of subjects, with grade II fibrosis in 19% and grade III in 6%. The ELF score and higher serum levels of tissue inhibitor of metalloproteinase 1 (TIMP-1) and hyaluronic acid (HA) correlated with the grade of liver fibrosis. Conclusions The findings of this study demonstrated that praziquantel treatment had a short-term impact on both the prevalence and intensity of infection, but less of an impact on established morbidity. Higher TIMP-1 and HA serum levels, and an ELF cut-off score of 8 were found to be correlated with the grade of liver fibrosis; these values may, therefore, assist physicians in identifying individuals at greater risk of disease