Soil-transmitted helminths are intestinal parasitic worms that isproportionally affect socio-economically deprived populations in tropical and subtropical countries living under poor hygienic conditions. The intestinal helminths are transmitted by the contamination of soil with human faeces containing the worms’ eggs and by subsequent accidental ingestion of the contaminated soil with food or hands, or by penetration of the worm larvae into the skin and body of humans. The global burden attributed to soil-transmitted helminth infections is estimated to be as high as 39 million disability-adjusted life years (DALYs) lost annually. Children and pregnant women are the groups at highest risk of morbidity. The World Health Organization (WHO) widely advocates periodical deworming of school-aged children as strategy to control morbidity associated with soil-transmitted helminth infections. A global target to reach a minimum treatment coverage of 75% of school-aged children at risk by 2010 was set by the World Health Assembly in May 2001. In Zanzibar, Tanzania, soil-transmitted helminthiases were recognized as a major public health issue in the early 1990s, with 85% of the surveyed population infected with at least one of the major species, namely Ascaris lumbricoides, hookworms (Ancylostoma duodenale and Necator americanus) and Trichuris trichiura. Infections with Strongyloides stercoralis, arguably the most neglected soiltransmitted helminth, were found in 40% of schoolchildren examined in rural Zanzibar. In 1994 and 2001 national helminth control programmes were implemented by the Ministry of Health and Social Welfare (MoHSW) of Zanzibar. Since then, anthelminthic drugs have been administered annually to schoolchildren and other eligible population groups of Zanzibar and a treatment coverage of more than 80% was reached. The overreaching goal of this PhD thesis was to deepen our understanding of the epidemiology and control of soil-transmitted helminth infections in Zanzibar. There were three specific objectives. First, to compare and evaluate different diagnostic techniques for the detection of soil-transmitted helminth infections. Second, to determine the current epidemiology and risk factors of soil-transmitted helminth infections, including S. stercoralis, in environmentally and socio-economically distinct settings on Unguja. Third, to assess the long-term effect of periodic anthelminthic treatment on soiltransmitted helminth prevalences and infection intensities, including the assessment of the efficacy and safety of albendazole and mebendazole administered alone or in combination with ivermectin against T. trichiura and other soil-transmitted helminth infections. The fieldwork for this PhD thesis was split in three parts. In 2007, for an assessment of the epidemiological situation of helminth infections on Unguja, a crosssectional study was conducted in five madrassas and five primary schools in the six districts of Unguja and included 336 children. Additionally, a cross-sectional study including 401 children was carried out in Chaani and Kinyasini primary schools. The parasitological results were compared to data derived in 1994 in the same schools. Multiple stool samples were collected from each participant over consecutive days. The Kato-Katz method was employed for the diagnosis of A. lumbricoides, hookworm and T. trichiura, the Koga-agar plate method for hookworm and S. stercoralis and the Baermann method for S. stercoralis. Moreover, stool samples preserved in sodium acetate-acetic acid-formalin (SAF) were transferred to Italy and examined with the FLOTAC method. The sensitivity of the individual methods and method combinations was compared. In 2008, a cross-sectional study was conducted in a rural and a peri-urban setting on Unguja, with 658 individuals aged 5-100 years enrolled. Besides the determination of soiltransmitted helminth infections with the aforementioned methods, urine samples were analysed for Schistosoma haematobium infections, blood samples were examined for anaemia and antibodies against helminth infections, and study participants were interviewed with a questionnaire for behavioural risk factors of soil-transmitted helminth infections and associated morbidity signs. The epidemiological situation of both settings was compared and juxtaposed with helminth control activities in Zanzibar. In 2009, a randomised controlled trial was carried out, comparing monotherapies with combination therapy. During the baseline screening 1240 children from Kinyasini and Kilombero schools were enrolled. The children infected with T. trichiura (n=610) were assigned to four treatment arms. For diagnosis, four Kato-Katz thick smears before and 3-5 weeks after treatment were employed and results were compared with outcomes derived by the FLOTAC method. After several years of helminth control in Zanzibar, the prevalence of soiltransmitted helminth infections on Unguja is still high, ranging between 22% in the urban and 70% in the North A district. Infection intensities are mostly light, and hence the diagnosis based on egg-positivity in stool sample has become a challenge. The sensitivity of the coprological methods can be increased with (i) a rigorous adherence to the bench aids provided by WHO (Kato-Katz method); (ii) the examination of multiple stool samples per individual; (iii) multiple examinations from the same stool sample; and (iv) the combination of diagnostic methods. FLOTAC shows a high sensitivity for the diagnosis of A. lumbricoides (~80%) and T. trichiura (~90%). However, the method needs further evaluation and standardization to produce reliable results for hookworm diagnosis. Its potential for application in resource-poor settings and its suitability for drug efficacy assessment needs additional investigation. On Unguja, soil-transmitted helminthiases are most prevalent in the North A district. Infections with multiple species helminth infections are common, particularly in children from rural areas. Anaemia is prevalent, but was not associated with any soil-transmitted helminth infection in our study. Risk factors for soil-transmitted helminth infections are setting- and species-specific and include, besides demographic factors, the consumption of raw vegetables or salad, no hand-washing after defecation and a recent travel history. T. trichiura is the predominant soil-transmitted helminth species on Unguja, with highest prevalences found in Kilombero school (71%). In contrast to hookworm (-77%) and A. lumbricoides (-71%), the prevalence of T. trichiura was not markedly reduced in the past years (-46%). This phenomenon can be explained by the low efficacies of the drugs albendazole (cure rate (CR): 10%; egg reduction rate (ERR): 40%) and mebendazole (CR: 19%; ERR: 67%) commonly applied in Zanzibar’s school-based helminth control programmes. The addition of ivermectin increased the efficacy of particularly mebendazole (CR: 55%; ERR: 97%), but also of albendazole (CR: 38%; ERR: 91%) against T. trichiura. Both drugs and drug combinations were highly efficacious against A. lumbricoides (ERR: >99%). The treatment outcome of albendazole (CR: 59%; ERR: 94%) was better than that of mebendazole (CR: 35%; ERR:78%) against hookworm infections, but ivermectin did not improve treatment outcomes. Adverse events were mostly mild and disappeared within 48 hours after treatment, and did not differ between the treatment regimens. The CRs assessed with FLOTAC were lower than with the Kato-Katz method for all three soil-transmitted helminth species. The Zanzibar helminth control programmes have successfully reduced soiltransmitted helminth prevalences and infection intensities, and hence morbidity. Poverty alleviation accompanied by an increased access of households to improved sanitation has likely reduced the infection rate. Soil-transmitted helminth control on Unguja can now focus on prevalence and transmission control, but will need to revise measures for a sustainable progress. Alternation of albendazole and mebendazole should be considered to more effectively target both hookworm and T. trichiura. For improved treatment outcomes against T. trichiura, and to also target S. stercoralis and ectoparasites, albendazole and mebendazole should be combined with ivermectin whenever people are eligible for this kind of therapy. Since new infections cannot be prevented by anthelminthic drugs alone, and because T. trichiura, the helminth species that is responsible for the majority of infections on Unguja, is cured ineffectively with the currently available drugs, an increase in hygiene and sanitation is indispensable for sustainable control of soil-transmitted helminths in Zanzibar and elsewhere. A far-reaching dissemination of appealing and plausible health education and communication to school-aged children and communities will be necessary to create the environment for community-led improvements in sanitation (latrine construction, sewage disposal and access to clean water), and to assure their adequate use. Only public consent and the wish for better sanitation at local scale, hand-in-hand with governmental and nongovernmental supported poverty alleviation measures can finally result in soil-transmitted helminth elimination in Zanzibar and elsewhere
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