UNICEF, the World Bank and WHO have promoted routine mass anthelminthic treatment programs as a cost-effective intervention, and school-based programs are popular.183-185 Although most studies report prevalence, reducing the intensity of the worm burden is the major aim of control programs in children, who have the highest burden. Albendazole and praziquantel have broad-spectrum anthelminthic activity against ascariasis, trichuriasis, enterobiasis, hookworm, giardiasis, strongyloidiasis and schistosomiasis at relatively low cost and with low rates of resistance to these agents. Mass treatment protocols may reduce the risk of drug resistance by targeting school-age and preschool children, by only repeating treatment at intervals greater than the nematode generation time, by combining anthelminthic drugs in control programs to reduce or delay selection for resistance, and by monitoring drug resistance to benzi-madoles using DNA probes.2 Deworming programs were held back for young children because of concerns about their safety in children under 2 years of age (as well as in pregnancy and lactation). However, a recent WHO Informal Consultation that children over 12 months of age should be included in deworming campaigns using prazi-quantel and albendazole/mebendazole on the basis of improved safety data and risk-benefit analy-
The impact of helminth infections on growth and development is a controversial but important issue. A Cochrane systematic review of 30 randomized trials involving 15 000 children on the effects of antihelminthic treatment of endemic communities on growth and cognitive performance was reported in 2000.187,188 It found only
modest weight gain of 0.1kg (0.04-0.17) after a year of follow-up and no differences in cognitive performance, so concluded that the evidence for routine anthelminthic treatment to improve growth and cognitive performance was unconvincing. Critics of the review pointed out that poorly designed trials may have failed to document an effect, that short-term treatment cannot assess the long-term benefits of regular treatment and that the review hid the greatest effect of anthelminthic treatment on growth and development in children with heavy parasitic burdens.
Since the Cochrane review, there has been a study of 614 children 12-48 months at baseline, in a community of high parasite intensity in Tanzania who were randomized to single-dose mebendazole 500 mg 3-monthly vs. placebo and followed for 12 months. It reported modest reductions in prevalence of Trichuris (75 vs. 58%), Ascaris (49 vs. 27%) and hookworm (66 vs. 60%), but the effect on worm intensity was more significant, reducing Ascaris from 126 to 12 eggs per gram of feces (epg), Trichuris from 511 to 88 epg and hookworm from 198 to 119 epg.189 A large randomized mass treatment trial of school children with albendazole and praziquantel in China, Kenya and the Philippines documented significant reductions (p < 0.0001) in mean egg counts at 45 days for hookworm (97 to 27), Ascaris (5903 to 626) and Trichuris (233 to 161), but the effects were limited by rapid reinfection (Ascaris) and single-dose albendazole ineffectiveness (Trichuris).190 The most important short-term benefits at 6 months from treatment were modest rises in hemoglobin level and reductions in hepatomegaly (Kenya only) in the children treated with praziquantel, but catch-up growth did not occur in treated children compared to controls.
Another study in the low-intensity setting of Bangladesh followed 123 children aged 2-5 years for 12 months with 2-monthly mebendazole and showed reduced prevalences of Trichuris (65 to 9%), Ascaris (78 to 8%) and hookworm (4 to 0%) while associated with an increase in giardiasis (19 to 49%), but failed to document improved growth or improvements in intermediate variables (intestinal permeability, plasma albumin, a1-antichymo-trypsin).191 The increase in giardiasis with meben-dazole was found in an earlier Bangladeshi study,192 but could be prevented by substituting albendazole, which has anti-giardial activity.
Confirmation of the limited effect of helminths on growth has come from indirect calorimetry, which showed no treatment effect on energy metabolism with low-level hookworm, Ascaris, Trichuris or Strongyloides infections.193 A Malaysian study found that intestinal helminths did not contribute to poor school attendance.194
A 9-year cohort study of 119 children in a Brazilian shantytown showed that, in this setting, the burden of diarrheal disease and helminth infections in children under 2 years were independently associated with stunting by 2-7 years of age, even controlling for confounders.195 Thus, early childhood helminth infections were associated with a 4.6-cm shortfall by age 7 years, compared to 3.6cm attributed to the mean 9.1 episodes of diarrhea before the age of 2 years. There is also indirect evidence that intestinal nematodes affect productivity in adults through both disease-related morbidity and ill-health in childhood.196 A Zairian study of 358 moderately malnourished preschool children randomized them to either vitamin A, mebendazole 500 mg 3-monthly or no treatment.197 The vitamin A-deficient children showed significant catch-up growth on vitamin A treatment, but deworming did not improve growth, because only 12 of 123 in the mebendazole group had ascariasis of low intensity, making the claim in the title of the article misleading.
A South African randomized trial of 428 schoolchildren with a high prevalence of Trichuris, hookworm and schistosomiasis found that combination treatment with 3 days of albendazole and singledose praziquantel 6-monthly and iron supplementation weekly for 10 weeks reduced worm prevalence and increased hemoglobin levels, but did not improve growth.198 A Kenyan study showed that albendazole was more effective than mebendazole in reducing worm burdens in schoolchildren.199 However, a Tanzanian study of 2294 schoolchildren from a very high prevalence setting showed that single-dose albendazole vs. mebendazole reduced the parasite burden of Ascaris by 97% vs. 97%, of Trichuris by 73% vs. 82%, and of hookworm by 98% vs. 82%, respectively.200 Moreover, the high reinfection rate in this setting meant that the impact of chemotherapy was short-lived, so 4-monthly treatment would be necessary to reduce long-term morbidity.64 In South African school children, a single dose of albendazole and prazi-quantel reduced prevalence rates of Ascaris, Trichuris and S. haematobium from 29.5 to 4.7%, 51.9 to 38.0% and 22.3 to 3.3%, respectively.
Invasive parasites which are known to cause malabsorption, weight loss or prolonged diarrhea, such as Giardia, Cryptosporidium and Strongyloides, are the most likely to affect growth, so specific studies have examined this in community settings. Giardia is the most prevalent intestinal protozoan parasite, and certainly can cause persistent diarrhea with malabsorption, weight loss and mucosal damage, but the key public health question is whether the high rates of infection without overt clinical symptoms contribute to poor growth of preschool children in the developing world. Lunn and colleagues examined this question in 60 infants in The Gambia where both giardiasis and poor growth are known to be highly prevalent.201,202 Giardia-specific plasma immuno-globulins were used for diagnosis and did not explain the observed growth faltering. Giardia infection was not associated with diarrhea in this context, but mild infections may have caused minimal abnormalities in intestinal permeability and a1-antichymotrypsin, an acute-phase reactant protein. They concluded that giardiasis was unlikely to be a major cause of the poor growth of rural Gambian infants. Rapid reinfection after treatment was also documented for giardiasis in Egypt and Peru, where 98% of children were re-infected within 6 months of tinidazole treatment and stool excretion lasted a mean of 3.2 months.203,204
Finally, studies have shown that control of intestinal parasitic infections is more than a question of mass chemotherapy, but is influenced by social and cultural factors that affect human behavior, such as treatment seeking and promiscuous defe-cation.205,206
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