Jürg Utzinger

Schistosomiasis and soil-transmitted helminthiasis: common drugs for treatment and control.

Schistosomiasis is a disease caused by parasitic trematode worms (schistosomes) that currently affects 200 million people living in tropical and subtropical environments. It is a chronic disease and the latest estimates for sub-Saharan Africa are that it kills > 200,000 people every year. Soil-transmitted helminthiasis (STH) is caused by intestinal nematodes. More than 2 billion people are infected worldwide and the disease burden might approach that of malaria. Recognising the enormous public health significance of schistosomiasis and STH, particularly among the poor, and in view of readily available drugs that are safe, efficacious and inexpensive, the World Health Assembly recently set forth a resolution for a combined approach for morbidity control of both diseases. This review briefly summarises the geographical distribution, life cycle and global burden of schistosomiasis and STH. The current arsenal of drugs available for morbidity control, including discovery, chemistry, pharmacological properties and aspects of therapeutic efficacy and adverse events in clinical human use is then discussed. The emphasis is on praziquantel, oxamniquine and artemisinin derivatives (against schistosomes) and albendazole, mebendazole, levamisole, pyrantel pamoate and other compounds (against intestinal nematodes). The experience gained with combination chemotherapy in schistosomiasis and STH is briefly discussed. Finally, current research needs and the critical importance for development of novel anthelmintic drugs, so that chemotherapy can continue to serve as the backbone of integrated and sustainable control of schistosomiasis and STH, is highlighted.

Efficacy and cost-effectiveness of environmental management for malaria control.

Roll back malaria (RBM) aims at halving the current burden of the disease by the year 2010. The focus is on sub‐Saharan Africa, and it is proposed to implement efficacious and cost‐effective control strategies. But the evidence base of such information is scarce, and a notable missing element is the discussion of the potential of environmental management. We reviewed the literature and identified multiple malaria control programmes that incorporated environmental management as the central feature. Prominent among them are programmes launched in 1929 and implemented for two decades at copper mining communities in Zambia. The full package of control measures consisted of vegetation clearance, modification of river boundaries, draining swamps, oil application to open water bodies and house screening. Part of the population also was given quinine and was sleeping under mosquito nets. Monthly malaria incidence rates and vector densities were used for surveillance and adaptive tuning of the environmental management strategies to achieve a high level of performance. Within 3–5u2003years, malaria‐related mortality, morbidity and incidence rates were reduced by 70–95%. Over the entire 20u2003years of implementation, the programme had averted an estimated 4173 deaths and 161u2003205 malaria attacks. The estimated costs per death and malaria attack averted were US

The influence of sampling effort and the performance of the Kato-Katz technique in diagnosing Schistosoma mansoni and hookworm co-infections in rural Côte d'Ivoire

858 and US

Relative contribution of day-to-day and intra-specimen variation in faecal egg counts of Schistosoma mansoni before and after treatment with praziquantel.

22.20, respectively. Over the initial 3–5u2003years start‐up period, analogous to the short‐duration of cost‐effectiveness analyses of current studies, we estimated that the costs per disability adjusted life year (DALY) averted were US

Sustainable schistosomiasis control—the way forward

524–591. However, the strategy has a track record of becoming cost‐effective in the longer term, as maintenance costs were much lower: US

The potential of artemether for the control of schistosomiasis

22–92 per DALY averted. In view of fewer adverse ecological effects, increased sustainability and better uses of local resources and knowledge, environmental management – integrated with pharmacological, insecticidal and bednet interventions – could substantially increase the chances of rolling back malaria.

Recent investigations of artemether, a novel agent for the prevention of schistosomiasis japonica, mansoni and haematobia☆

The Klato-Katz method is widely used for diagnosing helminth infections in epidemiological surveys, but is known to have a low sensitivity. In the case of Schistosoma mansoni, statistical methods have been developed to compensate for the poor sensitivity, but the same is not true of any other helminth parasite, or infections with multiple-helminth species. We screened 101 schoolchildren from a rural area of Côte dIvoire over 5 consecutive days and made 5 Kato-Katz readings from each stool specimen. We estimated single and dual-species infections with S. mansoni and hookworm based on raw egg count data and after developing a latent-class model. The cumulative prevalence of co-infections was estimated at 9.9% after reading slides on the first day, and 57.0% after reading all 25 slides per person. The latent class model yielded a co-infection prevalence estimate of 79.6%, with marginal prevalence estimates for hookworm and S. mansoni infections of 83.9% and 91.6% respectively. The sensitivities of a single Kato-Katz thick smear for detection of S. mansoni alone, hookworms alone, or S. mansoni plus hookworms were 22.4%, 8.0% and 17.7%, respectively. In the current setting this could be attributable to low infection intensities of both parasites, combined with intra-specimen and day-to-day variation in egg output. If confirmed in other settings, these findings have implications for estimating the prevalence of multiple species helminth infections, and hence the design and implementation of efficacious and cost-effective control programmes.

Disparities in parasitic infections, perceived ill health and access to health care among poorer and less poor schoolchildren of rural Côte d'Ivoire

There is evidence that faecal egg counts of Schistosoma mansoni vary considerably from day to day, which results in poor sensitivity of single stool readings. Intra-specimen variation of S. mansoni egg counts may also be considerable, but has previously been considered as the less important component. We quantified the relative contribution of these two sources of variation among 96 schoolchildren from an area in Cĵte dIvoire highly endemic for S. mansoni. Stool specimens were collected over 5 consecutive days, and 5 egg-counts were made in each specimen by the Kato-Katz technique. The point prevalence of the first sample was 42.7% and the cumulative prevalence after the maximum sampling effort was 88.5%. Using generalized linear mixed models we found that the presence of S. mansoni eggs in a stool sample varied much more between days than within specimens, indicating that stool sample examination over multiple days is required for accurate prevalence estimates. However, using the same approach, we found that among infected children intra-specimen variation in egg counts was 4.3 times higher than day-to-day variation. After praziquantel administration, day-to-day variation was more important than before, since most infections were very light and thus likely to be missed altogether by stool examination on a single day. We conclude that diagnostic sensitivity in high transmission areas is maximized by making several stool readings on several days, but examining 1 stool specimen several times can make reasonable estimates of infection intensity.

Efficacy of praziquantel against Schistosoma mansoni with particular consideration for intensity of infection.

Schistosomiasis a chronic and debilitating disease is draining the economic and social development in much of the tropics especially in sub-Saharan Africa where 85% of its global burden is concentrated. An estimated 200 million people are infected and more than 600 million live in endemic areas. Sustained heavy infection leads to morbidity contributes to anaemia and often results in retarded growth and reduced physical and cognitive function in children. Recent estimates suggest that the yearly death rate of schistosomiasis in sub-Saharan Africa exceeds 200 000 which is largely attributable to renal failure or haematemesis. WHO has proposed a dual strategy to control schistosomiasis. The strategy rests on morbidity control in high-burden regions and consolidation of control measures where the endemicity has been greatly reduced.23 Safe effective single-dose antischistosomal drugs—eg praziquantel—have been available for 25 years. The large reduction in cost to less than US

The economic payoffs of integrated malaria control in the Zambian copperbelt between 1930 and 1950

0·30 per treatment3 has been the leverage for chemotherapy-based morbidity control. However a serious limitation of chemotherapy alone is its indefinite dependence (dependence for an unlimited period of time) on praziquantel potentially reducing the useful life-span of this drug. Preventive measures focused on clean water adequate sanitation and health education are essential features of any long-term strategy for reduction and elimination of schistosomiasis.78 The absence of such measures in many past programmes stems from a severe lack of resources plus inadequate capacity and political commitment to emphasise clean water and sanitation as a basic human need. We are now witnessing a sea of change in the political landscape that should facilitate provision of clean water and sanitation. High priority has been given to this task in the United Nations Millennium Development Goals embodied in the Millennium Declaration set forth in September 2000. Further it was one of the top priorities at the World Summit on Sustainable Development held in September 2002 in Johannesburg South Africa and during the 3rd World Water Forum convened in Japan in March 2003. The specific provision is to halve the number of people without access to clean water supply and sanitation by 2015.910 Linking schistosomiasis control to these initiatives has the potential to ensure long-term control and in many instances elimination of the disease. (authors)