Over the past two decades there have been significant achievements in the control of a handful of important human tropical infections [1]. These achievements include the substantive reductions in the prevalence and incidence of the so-called neglected diseases such as lymphatic filariasis, onchocerciasis, guinea worm, leprosy, and trachoma (Box 1) [2].







Each of these neglected diseases is a poverty-promoting and often stigmatizing condition occurring primarily in rural areas of low-income countries (Box 2) [3]. They are ancient afflictions, described in the Bible and other ancient texts, which have burdened humanity for millennia [3]. But now, as a result of aggressive regional vertical interventions, there is a possibility that some neglected tropical infections could be eventually controlled to the point of elimination in some areas of endemicity [2–8]. In the case of guinea worm infection, disease eradication might also soon be possible [9].


Box 2. Common Features of the Neglected Tropical Diseases




Ancient afflictions that have burdened humanity for centuries


Poverty-promoting conditions


Associated with stigma


Rural areas of low-income countries and fragile states


No commercial markets for products that target these diseases


Interventions, when applied, have a history of success

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"Rapid-impact interventions": how a policy of integrated control for Africa's neglected tropical diseases could benefit the poor.

Preliminary studies indicated that single-dose (500 mg) mebendazole gave disappointing results in the treatment of hookworm infections (Necator americanus) in Mali. A placebo-controlled, randomized trial conducted with the participation of 103 infected subjects (background hookworm prevalence > 50%) confirmed that mebendazole (Vermox) did not reduce parasite burdens significantly, as assessed through fecal egg counts. In contrast, a group of subjects treated with pyrantel (Combantrin) experienced a significant reduction in fecal worm egg counts (overall, both sexes combined showed a 75% reduction). Male subjects carried significantly more intense infections compared with females, but there was no gender difference in response to treatment. A standard egg hatch assay showed that N. americanus from our subjects in Mali was more resistant to benzimidazoles compared with a laboratory-maintained strain that had not been exposed to anthelmintics in more than 100 generations (50% effective dose = 0.12 and 0.07 microg/ml of thiabendazole, respectively), suggesting that, among other possibilities, the development of resistance to the benzimidazoles by N. americanus may have contributed to the drug failure. Whatever the underlying explanation, our results indicate that single-dose treatment with mebendazole is an ineffective treatment for hookworm infections and despite its relatively cheap cost and wide availability, mebendazole should not be considered a drug of choice in the mass treatment of hookworm infections in this region of Mali.

Failure of mebendazole in treatment of human hookworm infections in the southern region of Mali

Failure of pyrantel in treatment of human hookworm infections (Ancylostoma duodenale) in the Kimberley region of North West Australia

Helminth parasites were studied in the wood mouse, Apodemus sylvaticus, in southern England in September of each of four successive years (1994-1997). Nine species of helminths were recorded: five nematodes (Heligmosomoides polygyrus, Syphacia stroma, Pelodera strongyloides, Trichuris muris, Capillaria murissylvatici), two cestodes (Microsomacanthus crenata, Taenia taeniaeformis) and two trematodes (Corrigia vitta, Brachylaemus recurvum). In total, 134 mice were examined and 91.8% carried at least one species of helminth. The majority of mice carried two to three species (60.5%) and the highest combination was six of the nine species recorded in the study. The patterns of between-year variations in the prevalence and abundance of infection were different for each of the six species for which sufficient quantitative data were available to enable statistical analysis. For H. polygyrus, the most important source of variation arose from between-year differences, host age and the interaction of these factors: abundance increased with host age but in 1995 the age pattern was markedly different from that in the remaining years. The abundance of C. vitta also varied significantly between years but additionally there was a strong independent age effect. For M. crenata, the year x age interaction was significant, indicating that abundance among different age cohorts varied from year to year but there was also a weak significant main effect of age arising from the youngest age cohort carrying no parasites and the oldest age cohort the heaviest infections. For P. strongyloides the only significant factor was between-year variation with 1995 being a year of exceptionally low prevalence and abundance of infection. No significant between-year variation was detected for S. stroma but there was a strong sex effect (males carrying heavier infections) and an age effect (older mice of both sexes carrying heavier infections). The abundance of Trichuris muris varied only in relation to host age, worm burdens growing in intensity with increasing age, but there was also a significant interaction between year and host sex with respect to prevalence. For the remaining three species, the prevalence of infections was too low (< 8.2%) to enable any meaningful interpretation. This analysis emphasizes the need for carefully controlled statistical procedures in aiding the interpretation and the prioritization of the factors affecting worm burdens in wild rodents.

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Helminth infections in Apodemus sylvaticus in southern England: interactive effects of host age, sex and year on the prevalence and abundance of infections.

Virtually all the important helminth infections in humans can be treated with one of 5 anthelmintics currently in use: albendazole, mebendazole, diethylcarbamazine, ivermectin and praziquantel. These drugs are vital not only for the treatment of individual infections, but also useful in controlling transmission of the more common infections. This article reviews briefly the pharmacology of these 5 drugs, and then discusses current issues in the use of anthelmintics in the treatment and/or control of soil-transmitted nematode infections, filariasis, onchocerciasis, schistosomiasis (and other trematode infections), neurocysticercosis and hydatidosis. Mebendazole and albendazole are most effective against intestinal nematodes, but are contraindicated during the first trimester of pregnancy. The efficacy of prolonged therapy with these 2 drugs for treatment of larval cestode infections has not yet been established. Diethylcarbamazine is widely used to treat and control lymphatic filariasis, but adverse effects related to death of microfilariae or damage to adult worms may be marked. While ivermectin has been used in the treatment of patients with onchocerciasis, it is also undergoing investigation against lymphatic filariae. Praziquantel, used to treat schistosome infections, is also effective in other trematode infections and adult cestode infections.

Anthelmintics. A comparative review of their clinical pharmacology.

Levels of intestinal nematode infections were assessed six months after a two year trial of ivermectin for efficacy against onchocerciasis had ended. In the trial the inhabitants of six villages in Sierra Leone were offered treatment with ivermectin or placebo at six monthly intervals for four rounds in total. Quantitative faecal egg counts were carried out on stool samples provided by 202 subjects, all of whom had received all four rounds of treatment, in two of the villages (Dodo and Mogibisi). These data were analysed by a novel procedure in which a 3-way ANOVA with negative binomial errors enabled village and host gender influences on the outcome of treatment to be identified. Necator americanus was the most common species showing an overall prevalence of 90% but a higher intensity in Mogibisi relative to Dodo, particularly among male subjects. Neither prevalence nor intensity of infection were altered in ivermectin-treated compared with placebo-treated subjects. Trichuris trichiura was the least common species with a prevalence of 15%. It was concluded that there was no significant protection from infection with this species among the ivermectin relative to the placebo-treated subjects. Ascaris lumbricoides, with an overall prevalence of 39%, was more common among female (50%) compared with male (27%) villagers. Prevalence was not significantly affected by ivermectin but the intensity of infection declined by 91.3% in Dodo whilst in Mogibisi intensity was only reduced by 14.6%. The results indicate that the long-term benefits of treatment of necatoriasis and trichuriasis with ivermectin are likely to be minimal whilst those of ascariasis will depend on the individual characteristics of local communities and may differ quite markedly within a limited geographical area. Possible explanations for the discrepancy in efficacy between villages are considered.

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J.R. Park

Papers

Effect of ivermectin on infection with gastro-intestinal nematodes in Sierra Leone