Efficacy of albendazole and mebendazole alone or in combination with ivermectin against Trichuris trichiura and other soil-transmitted helminths in schoolchildren in Zanzibar, Tanzania

Background
Soil-transmitted helminths negatively impact on health and wellbeing, and chronic infections delay physical and cognitive development of children, reduce school attendance and work capacity at later age. Large parts of the population in Zanzibar, Tanzania, are affected by soil-transmitted helminths. In order to reduce morbidity attributable to soil-transmitted helminth infections, a control programme that periodically administers anthelminthic drugs to school-aged children was launched in mid 1990. In the meantime children are fairly regularly treated with albendazole (single oral dose of 400 mg) or mebendazole (single oral dose of 500 mg). As a result, infection prevalence and intensities have declined. However, current treatment policies have only a minimal effect on Trichuris trichiura, which might explain why still about half of the children who we surveyed in collaboration with the helminth control laboratory Unguja (HCLU) of the Ministry of Health and Social Welfare Zanzibar (MoHSW) in two Zanzibari schools in 2007 were infected with this helminth species.

Objectives
The field project funded by the KFPE “Jeunes Chercheurs” programme was carried out in partnership with the HCLU and with two European research groups. The goal and objectives of the project were to strengthen helminth control programmes in Zanzibar through the following joint research and control activities: (i) assessing the efficacy and safety of albendazole and mebendazole alone and in combination with ivermectin with an emphasis on T. trichiura; (ii) determining the efficacy of single-dose treatment with albendazole or mebendazole against other soil-transmitted helminths (A. lumbricoides and hookworm); and (iii) evaluating the diagnostic performance of the FLOTAC technique before and after anthelminthic treatment and its applicability for large-scale epidemiological field surveys in a setting characterized by low helminth infection intensities.

Methods: In total 1068 children from Kinyasini and Kilombero schools were screened for soil-transmitted helminth infections. One stool sample per child was examined twice with the Kato-Katz method at HCLU. Children positive for T. trichiura and meeting other inclusion criteria (n = 537) were entered into a randomized controlled trial and assigned either albendazole, mebendazole or their combination with ivermectin. These children were asked for 2 more stool samples for follow up 3-5 weeks after drug administration. All stool samples were examined with duplicate Kato-Katz thick smears and randomly selected samples (n = 250) were additionally examined with a single FLOTAC before and after treatment. Adverse events were assessed with a pre-tested questionnaire 48 hours after treatment. We followed an intention-to-treat analysis, using cure rate (CR) and egg reduction rate (ERR) determined by the Kato-Katz method as primary outcomes. At the end of the study all children visiting the 2 schools were treated with albendazole (400 mg) free of charge.

Results
Baseline prevalences of T. trichiura, hookworm and A. lumbricoides were 62.8%, 16.2% and 8.0%, respectively. Overall, 548 children had complete data records and were included in final analyses. The CR against T. trichiura was 55.1% using mebendazole plus ivermectin, 37.9% using albendazole plus ivermectin, 18.8% using mebendazole alone, and 9.8% using albendazole alone. The respective ERRs were 96.7%, 91.1%, 66.7% and 40.3%. In children with multiple helminth infections CRs for A. lumbricoides were 100% using albendazole alone or mebendazole plus ivermectin, 92.9% (ERR: 99.9%) for albendazole plus ivermectin and 77.8% (ERR: 99.8%) for mebendazole alone (n=64). CRs for hookworm were 66.7% (ERR: 95.5%) using albendazole plus ivermectin, 59.0% (ERR: 94.3%) for albendazole alone, 35.3% (ERR: 78.4%) for mebendazole alone and 25.7% (ERR: 49.4%) for mebendazole plus ivermectin (n=138). Adverse events were mainly mild and transient in all four treatment groups. The prevalences of A. lumbricoides and T. trichiura determined with FLOTAC were slightly higher than results obtained with duplicate Kato-Katz thick smears from the same stool sample, the prevalences of hookworm were considerable lower.

 

Conclusion and recommendations
Our study shows that in settings where multiple helminth infections are common, combination therapy should be considered to enhance drug efficacy and reduce transmission of, and morbidity due to, soil-transmitted helminths. This strategy will impact not only A. lumbricoides and hookworm, but also on the prevalence and intensity of T. trichiura infections and might delay the development and spread of benzimidazole resistance. To gain and sustain control of soil-transmitted helminthiasis in endemic settings and thus to achieve a long-term benefit for the local population, control programmes should consider more comprehensive intervention packages, including combination therapy and health education, and governments should further improve access to clean water and sanitation.

The FLOTAC method needs additional validation and must reliably prove a higher sensitivity before it can be recommended as valuable tool for helminth diagnosis in endemic settings and reference laboratories.

                                 
1. Collection of stool samples for soil-transmitted helminth diagnosis in Zanzibar (picture taken by Stefanie Knopp, 2009)

 

                                   
2. Training of the FLOTAC method in the Helminth Control Laboratory in Zanzibar (picture taken by Stefanie Knopp, 2009)

                                    
3. Treatment against worms in Zanzibar (picture taken by Stefanie Knopp, 2009)

 

Address details

Stefanie Knopp
Department of Public Health and Epidemiology
Swiss Tropical Institute
Socinstrasse 57
P.O. Box
CH- 4002 Basel
Switzerland
E-Mail: s.knopp@unibas.ch

Khalfan A. Mohammed
Helminth Unit
Ministry of Health and Social Welfare
P.O Box 236
Zanzibar
United Republic of Tanzania
E-Mail: kamsharjy@live.co.uk