Treatment and prevention of trichuriasis : efficacy of albendazole in disadvantaged children at Rawsonville Primary School, Western Cape Province, South Africa

[摘要] ENGLISH ABSTRACT:Children in socioeconomically disadvantaged communities in the Western Cape and elsewhere in SouthAfrica are frequently infected by Trichuris trichiura. Although albendazole and mebendazole are listedas essential drugs for treatment of humans, it is well known that trichuriasis is relatively refractory toanthelmintic treatment. There are some reports that mebendazole is more effective against Trichuris andit is available as generics that are relatively cheap. On the other hand, albendazole is better forhookworm and may have some effect against Giardia duodenalis, which is common in the samecommunities. Moreover, albendazole is used in a deworming programme in KwaZulu-Natal, at a doseo f400 mg stat, given once or twice a year depending on the health region in that province.In terms of diagnosis, infection by intestinal helminthiasis can be determined and monitored by simple,non-invasive, sustainable and cost effective methods. The epidemiological significance of highprevalence extends far beyond the worms per se because they are an index of environmental conditionsthat pose a risk of several other diseases. These include infection by organisms that can cause epidemicsof enteric disease. These facts pertain within a deteriorating milieu in terms of human ecology, becausethe informal sector of the population is burgeoning under dynamic forces that include urbanisation,migration, poverty and disease.The study reported in this thesis had three main objectives within the context and concepts of therealities described in the previous two paragraphs. The first was to review and consider all informationon trichuriasis that could be detected in the literature, and to relate the result to South African needs.The second was to test efficacy of albendazole against trichuriasis in children from a community whereit is the predominant worm infection, by means of a well designed and controlled study. Finally, it was necessary to consider other results associated with treatment. These included possible drug resistanceand effects on growth, eosinophilia, iron status and toxicity.The literature survey established that South Africa lags behind many other developing countries indefining and addressing the problem of helminthiasis as a whole. The conventional epidemiology oftrichuriasis as described in the literature is based mainly on studies in the West Indies. Surveyscompleted recently in the Western Cape Province of South Africa confirm some of the epidemiologicalconcepts, with two notable exceptions. First, the age-related prevalence peaked in children who were14 years old in a suburb of Cape Town. This is older that in West Indian children. The seconddifference is probably more important and was detected in children at schools serving the informal sectoro f Khayelitsha. This is densely populated and the sanitation is often not effective and is sometimestotally lacking. The distribution of egg counts in 316 Khayelitsha children was not overdispersed to lowcounts, which is perceived as invariably the situation in the West Indies. In the Khayelitsha survey,approximately 25% of children had more than 10 000 eggs per g of faeces.The randomised controlled treatment trial tested a series of four albendazole treatments, at doses of400,800 and 1200 mg (given as 400 mg/day), repeated at intervals of approximately four months in matchedgroups of children. Results indicate that mass deworming programmes in South Africa should not usealbendazole at a dose o f400 mg stat for control of infection by Trichuris trichiura. The package insertof the product tested (Zentel®, SmithKline Beecham) recommends that in heavy mixed infestationinvolving Trichuris, a single daily dose may be inadequate and the dose may be given for threeconsecutive days. This statement is not accurate because even when infection by Trichuris was notintense, as defined internationally in terms of egg counts per g of faeces, and it was the only helminthpresent, the cure rate achieved by repeated doses of 400 mg of albendazole was not satisfactory.Moreover, 48% (15/31) of treated children remained continuously infected, although egg counts were clearly reduced. This result demonstrates that continuous use of a dose of 400 mg which is themaximum stat dose permitted in South Africa, is likely to facilitate development of true geneticresistance to albendazole by T. trichiura. Doses of 800 and 1200 mg were more efficacious andcontinuous infection reduced to 21% (9/43) and 2.5% (1/39), respectively. A dose of 800 mg forroutine use in mass deworming programmes, as 400 mg/day, can be recommended on the basis ofsufficiently efficacious treatment, simplification of compliance, and reduction of cost. The frequencyof treatment within such programmes should probably be three times per year when prevalence of severeinfection exceeds 10% (severe infection is defined internationally as an egg count of more that 10 000per g of faeces). When severe infection is less frequent, treatment could be less often, but moredefinitive research of this aspect is necessary under local conditions. There was some evidence thatincidence increased seasonally during summer and autumn in the community concerned.A range of other results was recorded. The possibility of genetic resistance to albendazole by Trichuristrichiura was not excluded. There was significant reduction of eosinophiha during treatment withalbendazole. This may have immunological implications for incidence, prevention and progression ofother diseases. Treatment appeared to be beneficial in terms of growth and iron status, but there wasnot sufficient statistical power to confirm this. No evidence of toxicity at the highest dose (1200 mggiven as 400 mg/day for three days) was detected.

[发布机构] Stellenbosch University