Albendazole and Mebendazole Administered Alone or in Combination with Ivermectin against Trichuris trichiura: A Randomized Controlled Trial

Background. Single-dose albendazole and mebendazole show limited efficacy in the treatment of trichuriasis. The combination of albendazole with ivermectin improves efficacy, but a mebendazole-ivermectin combination has not been previously investigated. Methods. We performed a randomized controlled trial in 2 schools in Zanzibar, Tanzania, to assess the efficacy and safety of albendazole (400 mg) plus placebo, albendazole plus ivermectin (200 µg/kg), mebendazole (500 mg) plus placebo, and mebendazole plus ivermectin in children with a parasitologically confirmed Trichuris trichiura infection. Cure rate (CR) and egg reduction rate were assessed by intent-to-treat analysis. Adverse events were monitored within 48 h after treatment. Results. Complete data records were available for 548 children. The highest CR against T. trichiura was achieved with a mebendazole-ivermectin combination (55%). Low CRs were observed with albendazole-ivermectin (38%), mebendazole (19%), and albendazole (10%). Compared with placebo, the use of ivermectin statistically significantly increased the CRs from 14% to 47% (odds ratio, 0.19; 95% confidence interval [CI], 0.12-0.28). The highest egg reduction rate (97%; 95% CI, 95%-98%) was observed using the mebendazole-ivermectin combination, followed by albendazole-ivermectin (91%; 95% CI, 87%-94%), mebendazole (67%; 95% CI, 52%-77%), and albendazole (40%; 95% CI, 22%-56%). The adverse events, reported by 136 children, were generally mild, with no significant difference between the treatment arms. Conclusions. Addition of ivermectin improves the therapeutic outcomes of both albendazole and mebendazole against T. trichiura and may be considered for use in soil-transmitted helminth control programs and individual patient management. Trial registration. isrctn.org Identifier: ISRCTN0833660

Albendazole and Mebendazole Administered Alone or in Combination with Ivermectin against Trichuris trichiura: A Randomized Controlled Trial

Background. Single-dose albendazole and mebendazole show limited efficacy in the treatment of trichuriasis. The combination of albendazole with ivermectin improves efficacy, but a mebendazole-ivermectin combination has not been previously investigated. Methods. We performed a randomized controlled trial in 2 schools in Zanzibar, Tanzania, to assess the efficacy and safety of albendazole (400 mg) plus placebo, albendazole plus ivermectin (200 µg/kg), mebendazole (500 mg) plus placebo, and mebendazole plus ivermectin in children with a parasitologically confirmed Trichuris trichiura infection. Cure rate (CR) and egg reduction rate were assessed by intent-to-treat analysis. Adverse events were monitored within 48 h after treatment. Results. Complete data records were available for 548 children. The highest CR against T. trichiura was achieved with a mebendazole-ivermectin combination (55%). Low CRs were observed with albendazole-ivermectin (38%), mebendazole (19%), and albendazole (10%). Compared with placebo, the use of ivermectin statistically significantly increased the CRs from 14% to 47% (odds ratio, 0.19; 95% confidence interval [CI], 0.12-0.28). The highest egg reduction rate (97%; 95% CI, 95%-98%) was observed using the mebendazole-ivermectin combination, followed by albendazole-ivermectin (91%; 95% CI, 87%-94%), mebendazole (67%; 95% CI, 52%-77%), and albendazole (40%; 95% CI, 22%-56%). The adverse events, reported by 136 children, were generally mild, with no significant difference between the treatment arms. Conclusions. Addition of ivermectin improves the therapeutic outcomes of both albendazole and mebendazole against T. trichiura and may be considered for use in soil-transmitted helminth control programs and individual patient management. Trial registration. isrctn.org Identifier: ISRCTN0833660

Measuring Morbidity Associated with Urinary Schistosomiasis: Assessing Levels of Excreted Urine Albumin and Urinary Tract Pathologies

Urinary schistosomiasis is a debilitating disease caused by a parasitic worm that dwells in the blood vessels, particularly those surrounding the human bladder wall. Although not directly associated with high patient mortality, this disease is linked to both short-term morbidity, e.g. visible blood in urine (acute), as well as long-term sequelae, e.g. urinary tract pathologies (chronic). Numerous control programmes based upon chemotherapy have been implemented in sub-Saharan Africa in an attempt to reduce the burden of disease inflicted, particularly in children. Although there are rapid tests to assess the prevalence of acute manifestations of disease (i.e. blood in urine), namely urine-reagent strips, monitoring of chronic manifestations (i.e. urinary tract pathologies) is still rather laborious, time-consuming and requires specialised equipment, e.g. portable ultrasonography, as well as highly trained staff. This study has attempted to evaluate associations between albuminuria (albumin in urine, a new application for the HemoCue photometer) and urinary tract pathologies, and consequently assess this new biochemical marker as a potential rapid proxy of chronic disease sequelae typical in children in areas where urinary schistosomiasis is of public health importance

Comparative cost assessment of the Kato-Katz and FLOTAC techniques for soil-transmitted helminth diagnosis in epidemiological surveys

BACKGROUND: The Kato-Katz technique is widely used for the diagnosis of soil-transmitted helminthiasis in epidemiological surveys and is believed to be an inexpensive method. The FLOTAC technique shows a higher sensitivity for the diagnosis of light-intensity soil-transmitted helminth infections but is reported to be more complex and expensive. We assessed the costs related to the collection, processing and microscopic examination of stool samples using the Kato-Katz and FLOTAC techniques in an epidemiological survey carried out in Zanzibar, Tanzania. METHODS: We measured the time for the collection of a single stool specimen in the field, transfer to a laboratory, preparation and microscopic examination using standard protocols for the Kato-Katz and FLOTAC techniques. Salaries of health workers, life expectancy and asset costs of materials, and infrastructure costs were determined. The average cost for a single or duplicate Kato-Katz thick smears and the FLOTAC dual or double technique were calculated. RESULTS: The average time needed to collect a stool specimen and perform a single or duplicate Kato-Katz thick smears or the FLOTAC dual or double technique was 20 min and 34 sec (20:34 min), 27:21 min, 28:14 min and 36:44 min, respectively. The total costs for a single and duplicate Kato-Katz thick smears were US$1.73 and US$ 2.06, respectively, and for the FLOTAC double and dual technique US$2.35 and US$ 2.83, respectively. Salaries impacted most on the total costs of either method. CONCLUSIONS: The time and cost for soil-transmitted helminth diagnosis using either the Kato-Katz or FLOTAC method in epidemiological surveys are considerable. Our results can help to guide healthcare decision makers and scientists in budget planning and funding for epidemiological surveys, anthelminthic drug efficacy trials and monitoring of control intervention

A single FLOTAC is more sensitive than triplicate Kato-Katz for the diagnosis of low-intensity soil-transmitted helminth infections

Accurate diagnostic tools are pivotal for patient management and surveillance of helminth control programmes, particularly in the current era of preventive chemotherapy. Three consecutive stool samples were obtained from 279 schoolchildren from Zanzibar, an island where anthelminthic drugs have been administered on a large scale for more than a decade. All stool samples were examined with the Kato-Katz method. Additionally, one sample per child was preserved in sodium acetate-acetic acid-formalin solution, and examined with the FLOTAC technique. Considering the pooled results of both methods as diagnostic ‘gold' standard, the observed prevalences of Trichuris trichiura, hookworm and Ascaris lumbricoides were 63.4, 35.8 and 22.9%, respectively. The sensitivity of examining a single stool sample by FLOTAC for diagnosing T. trichiura, hookworm and A. lumbricoides was 88.7, 83.0 and 82.8%, respectively. Lower sensitivities were observed for Kato-Katz even after examining three stool samples: 71.8, 46.0 and 70.3%, respectively. Kato-Katz revealed considerably higher infection intensities than FLOTAC. The κ agreement between a single FLOTAC and triplicate Kato-Katz was 0.63 for diagnosing A. lumbricoides and 0.50 for T. trichiura, but only 0.30 for hookworm. The high sensitivity of FLOTAC holds promise for patient management, monitoring soil-transmitted helminth transmission and endpoint(s) of control at the population leve

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

Patterns and Risk Factors of Helminthiasis and Anemia in a Rural and a Peri-urban Community in Zanzibar, in the Context of Helminth Control Programs

In many parts of the developing world, parasitic worms and anemia are of considerable public health and economic importance. We studied the patterns and risk factors of parasitic worm infections in a rural and a peri-urban community on Zanzibar Island, Tanzania, in the context of national deworming programs. We invited 658 individuals aged between 5 and 100 years and examined their stool and urine for the presence of parasitic worm eggs. Additionally, we obtained a finger-prick blood sample to estimate the level of anemia and to assess for specific immune reactions against parasitic worm infections. We found that, despite large-scale deworming efforts in Zanzibar over the past 15 years, three-quarter of the rural participants and half of the peri-urban residents were infected with parasitic worms. Every second participant was anemic. Risk factors for a parasitic worm infection were age, sex, consumption of raw vegetables or salad, recent travel history, and socio-economic status. For a sustainable control of parasitic worm infections and prevention of anemia, access to safe and efficacious drugs, complemented with health education and improvements in water supply and adequate sanitation are necessary

Micro-epidemiology of urinary schistosomiasis in Zanzibar: Local risk factors associated with distribution of infections among schoolchildren and relevance for control.

Although it is well recognised that both behavioural and environmental factors play a role in determining small-scale heterogeneities in schistosomiasis transmission, empirical evidence of their relative importance is often limited. A study was conducted around Chaani, a village in northern Unguja (Zanzibar) where urinary schistosomiasis is endemic, in order to shed light upon the micro-epidemiology of Schistosoma haematobium and patterns of infection within schoolchildren and the intermediate host snail Bulinus globosus, that may help in adjusting recently implemented control programmes. Malacological surveys were conducted to identify transmission foci and questionnaires were devised to assess recalled water-contact patterns of 150 schoolchildren who had been screened for S. haematobium infection, finding an overall prevalence of 50.6%. Boys were more frequently and more heavily infected than girls and, accordingly, mean exposure scores were significantly higher for boys than girls. Univariate statistics revealed significant associations between infection and specific water-contact activities, including washing/bathing (odds ratio [OR]=3.01, 95% confidence interval [CI]=1.36-6.67) and playing (OR=4.03, 95% CI=1.51-10.70) in streams/ponds. In multivariate analysis, however, the strongest predictor of infection was proximity of the child's home to a site harbouring S. haematobium-infected B. globosus (P<0.001), suggesting that geography may be a better proxy for exposure than self-reported water contact. Surveillance programmes may therefore wish to prioritise evaluation of environmental risk to pinpoint transmission at the micro-geographical level, although water-contact questionnaires are also recommended as a complementary tool to rapidly identify the behaviour patterns of children at most risk of infection in the rural communities of Zanzibar. Such knowledge is a prerequisite for focusing and improving schistosomiasis control at the local level