Antonio Montresor

The global status of schistosomiasis and its control

Schistosomiasis is being successfully controlled in many countries but remains a major public health problem, with an estimated 200 million people infected, mostly in Africa. Few countries in this region have undertaken successful and sustainable control programmes. The construction of water schemes to meet the power and agricultural requirements for development have lead to increasing transmission, especially of Schistosoma mansoni. Increasing population and movement have contributed to increased transmission and introduction of schistosomiasis to new areas. Most endemic countries are among the least developed whose health systems face difficulties to provide basic care at the primary health level. Constraints to control include, the lack of political commitment and infrastructure for public health interventions. Another constraint is that available anti-schistosomal drugs are expensive and the cost of individual treatment is a high proportion of the per capita drug budgets. There is need for increased support for schistosomiasis control in the most severely affected countries.

The global epidemiological situation of schistosomiasis and new approaches to control and research

While the distribution of schistosomiasis has changed over the last 50 years and there have been successful control programmes, the number of people estimated to be infected or at risk of infection has not been reduced. Today, 85% of the number of infected people are estimated to be on the African continent where few control efforts are made. In terms of disease burden, there is therefore a growing discrepancy between sub-Saharan Africa and the rest of the world. WHO has now developed a dual strategy for the control of schistosomiasis: a strategy for morbidity control adapted to the public health context in high burden areas, and a strategy to consolidate control in areas where a low endemic level has been reached and elimination may be feasible. Related to this new vision, some research needs are pointed out.

Effects of iron supplementation and anthelmintic treatment on motor and language development of preschool children in Zanzibar: double blind, placebo controlled study

Abstract Objective: To measure the effects of iron supplementation and anthelmintic treatment on iron status, anaemia, growth, morbidity, and development of children aged 6–59 months. Design: Double blind, placebo controlled randomised factorial trial of iron supplementation and anthelmintic treatment. Setting: Community in Pemba Island, Zanzibar. Participants: 614 preschool children aged 6–59 months. Main outcome measures: Development of language and motor skills assessed by parental interview before and after treatment in age appropriate subgroups. Results: Before intervention, anaemia was prevalent and severe, and geohelminth infections were prevalent and light—Plasmodium falciparum infection was nearly universal. Iron supplementation significantly improved iron status, but not haemoglobin status. Iron supplementation improved language development by 0.8 (95% confidence interval 0.2 to 1.4) points on the 20 point scale. Iron supplementation also improved motor development, but this effect was modified by baseline haemoglobin concentrations (P=0.015 for interaction term) and was apparent only in children with baseline haemoglobin concentrations <90 g/l. In children with a baseline haemoglobin concentration of 68 g/l (one standard deviation below the mean value), iron treatment increased scores by 1.1 (0.1 to 2.1) points on the 18 point motor scale. Mebendazole significantly reduced the number and severity of infections caused by Ascaris lumbricoides and Trichuris trichiura, but not by hookworms. Mebendazole increased development scores by 0.4 (−0.3 to 1.1) points on the motor scale and 0.3 (−0.3 to 0.9) points on the language scale. Conclusions: Iron supplementation improved motor and language development of preschool children in rural Africa. The effects of iron on motor development were limited to children with more severe anaemia (baseline haemoglobin concentration <90 g/l). Mebendazole had a positive effect on motor and language development, but this was not statistically significant. What is already known on this topic Iron is needed for development and functioning of the human brain Anaemic children show developmental delays, but it is not yet clear whether iron deficiency causes these deficits or whether iron supplementation can reverse them Helminth infections in schoolchildren are associated with cognitive deficits, but few studies have been made of helminth infection and early child development What this study adds Low doses of oral iron supplementation given daily improved language development in children aged 1–4 years in Zanzibar Iron supplementation improved motor development, but only in children with initial haemoglobin concentrations below 90 g/l The effects of routine anthelmintic treatment on motor and language milestones were positive, but non-significant, with our sample size

Efficacy of mebendazole and levamisole alone or in combination against intestinal nematode infections after repeated targeted mebendazole treatment in Zanzibar

OBJECTIVE To evaluate the efficacy of and resistance to mebendazole (500 mg) and levamisole (40 or 80 mg), alone or in combination, for the treatment of Ascaris lumbricoides, Trichuris trichiura and hookworm infections on Pemba Island - an area exposed to periodic school-based mebendazole treatment since 1994. METHODS A randomized, placebo-controlled trial was carried out in 914 children enrolled from the first and fifth grades of primary schools. Stool samples collected at baseline and 21 days after treatment were examined by the Kato-Katz technique to assess the prevalence and intensity of helminth infection. FINDINGS Efficacies of mebendazole and levamisole as single treatments against intestinal nematode infections were comparable with those in previous trials, but mebendazole treatment of hookworm infections gave significantly lower cure (7.6%) and egg reduction (52.1%) rates than reported in a study undertaken before the beginning of periodic chemotherapy (cure rate, 22.4%; egg reduction rate, 82.4%). Combined treatment with mebendazole and levamisole had a significantly higher efficacy against hookworm infections (cure rate, 26.1%; egg reduction rate, 88.7%) than either drug given alone. No difference in mebendazole efficacy was found in children who had been treated repeatedly compared with those who had not been treated previously. CONCLUSION The overall efficacy of mebendazole against hookworm infections after periodic chemotherapy is reduced. The efficacy of benzimidazoles in chemotherapy-based control programmes should be monitored closely. Combined treatment with mebendazole and levamisole may be useful as a tool to delay the development of benzimidazole resistance.

Assessment of the anthelmintic efficacy of albendazole in school children in seven countries where soil-transmitted helminths are endemic.

Background The three major soil-transmitted helminths (STH) Ascaris lumbricoides, Trichuris trichiura and Necator americanus/Ancylostoma duodenale are among the most widespread parasites worldwide. Despite the global expansion of preventive anthelmintic treatment, standard operating procedures to monitor anthelmintic drug efficacy are lacking. The objective of this study, therefore, was to define the efficacy of a single 400 milligram dose of albendazole (ALB) against these three STH using a standardized protocol. Methodology/Principal Findings Seven trials were undertaken among school children in Brazil, Cameroon, Cambodia, Ethiopia, India, Tanzania and Vietnam. Efficacy was assessed by the Cure Rate (CR) and the Fecal Egg Count Reduction (FECR) using the McMaster egg counting technique to determine fecal egg counts (FEC). Overall, the highest CRs were observed for A. lumbricoides (98.2%) followed by hookworms (87.8%) and T. trichiura (46.6%). There was considerable variation in the CR for the three parasites across trials (country), by age or the pre-intervention FEC (pre-treatment). The latter is probably the most important as it had a considerable effect on the CR of all three STH. Therapeutic efficacies, as reflected by the FECRs, were very high for A. lumbricoides (99.5%) and hookworms (94.8%) but significantly lower for T. trichiura (50.8%), and were affected to different extents among the 3 species by the pre-intervention FEC counts and trial (country), but not by sex or age. Conclusions/Significance Our findings suggest that a FECR (based on arithmetic means) of >95% for A. lumbricoides and >90% for hookworms should be the expected minimum in all future surveys, and that therapeutic efficacy below this level following a single dose of ALB should be viewed with concern in light of potential drug resistance. A standard threshold for efficacy against T. trichiura has yet to be established, as a single-dose of ALB is unlikely to be satisfactory for this parasite. Trial Registration ClinicalTrials.gov NCT01087099

Schistosomiasis and soil-transmitted helminth infections: forging control efforts

et al., 1992). After gradual intensification of efforts over the ensuing 10 years, the WHO and its member states and partners are implementing a combined strategy for the control of schistosomiasis and soil-transmitted helminths, integrated into ongoing health and education initiatives (WHO, in nrenaration, a). This strategy is summarized-in the World Health Assemblv (WHA) resolution of Mav 2001 KVHA. 200 1). ~l?re resolution urges member .states to ‘ensure access to essential drugs against schistosomiasis and soil-transmitted helminthiasis in all health services in endemic areas for the treatment of clinical cases and groups at high risk of morbidity such as women and children, with the goal of attaining a minimum target of regular administration of chemotherapy to at least 75% and up to 100% of all school-age children at risk of morbidity by 20 10. This policy is based on the evidence that morbidity can be controlled by periodical treatment of high-risk groups with anthelminthics. The burden of disease

Is anthelmintic resistance a concern for the control of human soil-transmitted helminths?

The major human soil-transmitted helminths (STH), Ascaris lumbricoides, hookworms (Necator americanus and Ancylostoma duodenale) and Trichuris trichiura have a marked impact on human health in many parts of the world. Current efforts to control these parasites rely predominantly on periodic mass administration of anthelmintic drugs to school age children and other at-risk groups. After many years of use of these same drugs for controlling roundworms in livestock, high levels of resistance have developed, threatening the sustainability of these livestock industries in some locations. Hence, the question arises as to whether this is likely to also occur in the human STH, thereby threatening our ability to control these parasites. This is particularly important because of the recent increase in mass control programmes, relying almost exclusively on benzimidazole anthelmintics. It will be important to ensure that resistance is detected as it emerges in order to allow the implementation of mitigation strategies, such as use of drug combinations, to ensure that the effectiveness of the few existing anthelmintic drugs is preserved. In this review we address these issues by firstly examining the efficacy of anthelmintics against the human STH, and assessing whether there are any indications to date that resistance has emerged. We then consider the factors that influence the effect of current drug-use patterns in selecting for resistant parasite populations. We describe the tools currently available for resistance monitoring (field-based coprological methods), and those under development (in vitro bioassays and molecular tests), and highlight confounding factors that need to be taken into account when interpreting such resistance-monitoring data. We then highlight means to ensure that the currently available tools are used correctly, particularly with regard to study design, and we set appropriate drug-efficacy thresholds. Finally, we make recommendations for monitoring drug efficacy in the field, as components of control programmes, in order to maximise the ability to detect drug resistance, and if it arises to change control strategy and prevent the spread of resistance.

Strongyloides stercoralis: a plea for action.

Strongyloidiasis remains an underestimated public health problem, just as it was at the dawn of last century.

A comparison of the sensitivity and fecal egg counts of the McMaster egg counting and Kato-Katz thick smear methods for soil-transmitted helminths

Background The Kato-Katz thick smear (Kato-Katz) is the diagnostic method recommended for monitoring large-scale treatment programs implemented for the control of soil-transmitted helminths (STH) in public health, yet it is difficult to standardize. A promising alternative is the McMaster egg counting method (McMaster), commonly used in veterinary parasitology, but rarely so for the detection of STH in human stool. Methodology/Principal Findings The Kato-Katz and McMaster methods were compared for the detection of STH in 1,543 subjects resident in five countries across Africa, Asia and South America. The consistency of the performance of both methods in different trials, the validity of the fixed multiplication factor employed in the Kato-Katz method and the accuracy of these methods for estimating ‘true’ drug efficacies were assessed. The Kato-Katz method detected significantly more Ascaris lumbricoides infections (88.1% vs. 75.6%, p<0.001), whereas the difference in sensitivity between the two methods was non-significant for hookworm (78.3% vs. 72.4%) and Trichuris trichiura (82.6% vs. 80.3%). The sensitivity of the methods varied significantly across trials and magnitude of fecal egg counts (FEC). Quantitative comparison revealed a significant correlation (Rs >0.32) in FEC between both methods, and indicated no significant difference in FEC, except for A. lumbricoides, where the Kato-Katz resulted in significantly higher FEC (14,197 eggs per gram of stool (EPG) vs. 5,982 EPG). For the Kato-Katz, the fixed multiplication factor resulted in significantly higher FEC than the multiplication factor adjusted for mass of feces examined for A. lumbricoides (16,538 EPG vs. 15,396 EPG) and T. trichiura (1,490 EPG vs. 1,363 EPG), but not for hookworm. The McMaster provided more accurate efficacy results (absolute difference to ‘true’ drug efficacy: 1.7% vs. 4.5%). Conclusions/Significance The McMaster is an alternative method for monitoring large-scale treatment programs. It is a robust (accurate multiplication factor) and accurate (reliable efficacy results) method, which can be easily standardized.

Control of schistosomiasis--a global picture.

The control of schistosomiasis has been a challenging task for most endemic countries. Thus, despite the concerted efforts to date, schistosomiasis remains a major public health concern, second only to malaria in the tropics and subtropics. In this review, Lorenzo Savioli and colleagues highlight changes in schistosomiasis prevalence and distribution over the past decades, discuss the success and limitations of the various control strategies, and present possible control initiatives for the future.