Prevalence of strongyloidiasis in Latin America: a systematic review of the literature.

Strongyloides stercoralis is rarely recognized as a major public health issue, probably because its burden is largely underestimated. We reviewed the literature (both PubMed and 'grey' literature) about the prevalence of strongyloidiasis in Latin America, an area of presumable high endemicity. There were finally 88 papers involved in the analysis, covering the period between 1981 and 2011. Studies were heterogeneous in several aspects, such as the populations screened and the diagnostic methods used. Most of the studies relied on direct coproparasitological examination, which has low sensitivity for the detection of S. stercoralis larvae. The following countries presented areas of high prevalence (>20%): Argentina, Ecuador, Venezuela, Peru and Brazil. Globally, for most of the included countries it was not possible to define reliable data because of paucity and/or inadequacy of studies. S. stercoralis requires specific diagnostic methods for its detection; therefore, surveys should be specifically designed in order to avoid underestimation of the infection.

Comparison of the Kato-Katz method and ether-concentration technique for the diagnosis of soil-transmitted helminth infections in the framework of a randomised controlled trial.

Soil-transmitted helminth infections are a major public health problem. An accurate diagnosis is important in order to identify individuals and communities in need of intervention, and for monitoring drug efficacy and potential emergence of resistance. We compared the accuracy of the Kato-Katz method and ether-concentration technique for the diagnosis of soil-transmitted helminth infections within a randomised controlled trial. Quadruplicate Kato-Katz thick smears (duplicate Kato-Katz from two stool samples each) were examined before (baseline) and 3 weeks after treatment (follow-up). Additionally, at baseline and follow-up, the first stool sample was subjected to an ether-concentration method. We determined the prevalence, sensitivity, negative predictive value, diagnostic agreement and cure rates for single and duplicate Kato-Katz thick smears from the first stool sample, quadruplicate Kato-Katz thick smears produced from two stool samples and single ether-concentration as compared to our 'gold' standard (i.e. quadruplicate Kato-Katz plus ether-concentration). Quadruplicate Kato-Katz revealed a higher sensitivity than single ether-concentration for Trichuris trichiura at baseline (94.3 % vs. 88.5 %, p = 0.002) and follow-up (93.8 % vs. 83.5 %, p < 0.001). In contrary, at follow-up, ether-concentration showed a higher sensitivity than quadruplicate Kato-Katz for Ascaris lumbricoides diagnosis (86.7 % vs. 46.7 %, p = 0.012). The ether-concentration method showed similar or slightly higher sensitivity than the Kato-Katz technique based on a single stool sample for all soil-transmitted helminth infections. The estimated cure rates were heavily dependent on the diagnostic technique and sampling effort. In conclusion, data on the prevalence of soil-transmitted helminth infections and the efficacy of anthelminthics are greatly influenced by the diagnostic method and sampling effort. The ether-concentration technique is a valuable alternative to the Kato-Katz method for helminth diagnosis.

Praziquantel efficacy and long-term appraisal of schistosomiasis control in Pemba Island.

OBJECTIVE: To determine whether praziquantel (PZQ) has retained its efficacy against Schistosoma haematobium on Pemba Island after 20 years of mass administration--albeit discontinuous--and to analyse retrospectively the performance of schistosomiasis control programmes. METHODS: A sample of Pemba schoolchildren was examined before and after PZQ treatment by urine filtration, macro- and micro-haematuria and viability of excreted eggs. RESULTS: Although 5% of treated children continued to pass some eggs in the urine up to the seventh week after PZQ administration, none of these eggs was viable, indicating an effective schistosomicidal activity followed by a slow release of dead eggs from host tissues. CONCLUSION: No signs of PZQ resistance could be detected in the population under study. An overall retrospective analysis of schistosomiasis control activities in Pemba Island revealed that mass drug administration is clearly effective in reducing infection prevalence, but soon after interruption of drug distribution prevalence returns rapidly to pre-intervention levels.

Monitoring the efficacy of drugs for neglected tropical diseases controlled by preventive chemotherapy.

In the last decade, pharmaceutical companies, governments and global health organisations under the leadership of the World Health Organization (WHO) have pledged large-scale donations of anthelmintic drugs, including ivermectin (IVM), praziquantel (PZQ), albendazole (ALB) and mebendazole (MEB). This worldwide scale-up in drug donations calls for strong monitoring systems to detect any changes in anthelmintic drug efficacy. This review reports on the outcome of the WHO Global Working Group on Monitoring of Neglected Tropical Diseases Drug Efficacy, which consists of three subgroups: (i) soil-transmitted helminthiases (ALB and MEB); (ii) onchocerciasis and lymphatic filariasis (IVM); and (iii) schistosomiasis (PZQ). Progress of ongoing work, challenges and research needs for each of the four main drugs used in helminthic preventive chemotherapy (PC) are reported, laying the ground for appropriate implementation of drug efficacy monitoring programmes under the co-ordination and guidelines of the WHO. Best practices for monitoring drug efficacy should be made available and capacity built as an integral part of neglected tropical disease (NTD) programme monitoring. Development of a disease-specific model to predict the impact of PC programmes, to detect outliers and to solicit responses is essential. Research studies on genetic polymorphisms in relation to low-efficacy phenotypes should be carried out to identify markers of putative resistance against all NTD drugs and ultimately to develop diagnostic assays. Development of combination and co-administration of NTD drugs as well as of new drug entities to boost the armamentarium of the few drugs available for NTD control and elimination should be pursued in parallel.

Epidemiology of iron deficiency anemia in Zanzibari schoolchildren: the importance of hookworms.

Anemia is estimated to affect one-half of school-age children in developing countries. The school years are an opportune time to intervene, and interventions must be based on sound epidemiologic understanding of the problem in this age group. We report on the distribution of iron deficiency and anemia across age, sex, anthropometric indexes, and parasitic infections in a representative sample of 3595 schoolchildren from Pemba Island, Zanzibar. Iron status was assessed by hemoglobin, erythrocyte protoporphyrin (EP), and serum ferritin concentrations from a venous blood sample. Overall, 62.3% of children were anemic (hemoglobin < 110 g/L), and 82.7% of anemia was associated with iron deficiency. The overall prevalence of iron-deficient erythropoiesis (EP > 90 mumol/mol heme) was 48.5%, and the prevalence of exhausted iron stores (serum ferritin < 12 micrograms/L) was 41.3%. In bivariate analyses, iron status was slightly better in girls than in boys, and was better in children aged 7-11 y than in those older or younger. Hemoglobin but not EP or serum ferritin concentrations were lower in stunted children. Infection with malaria, Trichuris trichiura, Ascaris lumbricoides, and hookworms were all associated with worse iron status; the association with hookworms was strongest by far. In multivariate analyses, hookworm infection intensity was the strongest explanatory variable for hemoglobin, EP, and serum ferritin. Sex, malarial parasitemia, A. lumbricoides infection, and stunting were also retained in the multivariate model for hemoglobin. Twenty-five percent of all anemia, 35% of iron deficiency anemia, and 73% of severe anemia were attributable to hookworm infection; < 10% of anemia was attributable to A. lumbricoides, malaria infection, or stunting. We conclude that anthelminthic therapy is an essential component of anemia control in schoolchildren in whom hookworms are endemic, and should be complemented with school-based iron supplementation.

Effects of the Zanzibar school-based deworming program on iron status of children.

We evaluated the effects of the Zanzibar school-based deworming program on the iron status of primary school children. Parasitologic and nutritional assessments were carried out at baseline, 6 mo, and 12 mo in 4 nonprogram schools (n = 1002), 4 schools in which students received twice-yearly deworming (n = 952), and 4 schools in which students received thrice-yearly deworming (n = 970) with 500 mg generic mebendazole. Schools were randomly selected for evaluation and allocated to program groups. Relative to no treatment, thrice-yearly deworming caused significant decreases in protoporphyrin concentrations and both deworming regimens caused marginally significant increases in serum ferritin concentrations. The average annual changes in protoporphyrin concentrations were -5.9 and -23.5 micromol/mol heme in the control and thrice-yearly deworming groups, respectively (P < 0.001). The average changes in ferritin concentration were 2.8 and 4.5 microg/L, respectively (P = 0.07). Deworming had no effect on annual hemoglobin change or prevalence of anemia. However, the relative risk of severe anemia (hemoglobin < 70 g/L) was 0.77 (95% confidence limits: 0.39, 1.51) in the twice-yearly deworming group and 0.45 (0.19, 1.08) in the thrice-yearly deworming group. The effects on prevalence of high protoporphyrin values and incidence of moderate-to-severe anemia (hemoglobin < 90 g/L) were significantly greater in children with > 2000 hookworm eggs/g feces at baseline. We estimate that this deworming program prevented 1260 cases of moderate-to-severe anemia and 276 cases of severe anemia in a population of 30,000 schoolchildren in 1 y. Where hookworm is heavily endemic, deworming programs can improve iron status and prevent moderate and severe anemia, but deworming may be needed at least twice yearly.

Control strategies for human intestinal nematode infections.

In recent years significant progress has been made in understanding the ecology, epidemiology and related morbidity and development of new tools for the control of soil-transmitted helminths. Such knowledge has recognized the impact of helminth infections on the health of infected groups and has created a rational basis for their control. Schoolchildren harbour some of the most intense helminthic infections, which produce adverse effects on health, growth and scholastic performance. However, although great effort has been put into targeting school-age children, women of child-bearing age and pre-school children are two other groups at high risk of morbidity due to intestinal nematode infections. Highly effective and safety-tested, single-dose anthelminthic drugs are now available, permitting periodical deworming of schoolchildren and other high-risk groups at affordable prices. Four anthelminthics against all intestinal nematodes are included in the WHO Essential Drug List (albendazole, levamisole, mebendazole and pyrantel). Recently ivermectin has also been registered for use against Strongyloides stercoralis in humans. Several well-monitored country experiences have shown that chemotherapy-based control of morbidity due to soil-transmitted helminths is possible and highly cost-effective.

A controlled evaluation of two school-based anthelminthic chemotherapy regimens on intensity of intestinal helminth infections.

BACKGROUND: School-based deworming programmes have been promoted as a cost-effective strategy for control of nematode infection in developing countries. While numerous efficacy studies have been conducted, there is little information on actual programme effectiveness in areas of intense transmission. METHODS: A randomized trial of a school-based deworming programme was conducted in 12 primary schools on Pemba Island, Zanzibar. Four schools each were randomized to control, twice a year deworming with single dose mebendazole or three times a year deworming. Baseline and 12-month follow-up data on helminth infection using the Kato-Katz technique, demographic information and nutritional status were collected on 3028 children from March 1994 to May 1995. RESULTS: Intensity of infection measured as eggs per gram of faeces (epg) declined significantly for Ascaris lumbricoides, Trichuris trichiura and hookworm infections in both treatment groups. A. lumbricoides infection intensity declined 63.1% and 96.7% in the twice and three times per year treatment groups compared to the controls. T. trichiura infection intensity declined 40.4% and 75.9% respectively and hookworm intensity declined 35.3% and 57.2% respectively compared to control schools. CONCLUSIONS: These results suggest that school-based programmes can be a cost-effective approach for controlling the intensity of intestinal helminth infection even in environments where transmission is high.

Epidemiological evidence for a differential effect of hookworm species, Ancylostoma duodenale or Necator americanus, on iron status of children.

BACKGROUND: The hookworms, Ancylostoma duodenale and Necator americanus, cause significant gastrointestinal blood loss. In clinical studies, greater blood losses have been reported with A. duodenale. However, there has been no evidence that endemic A. duodenale infection has greater impact than N. americanus infection on the iron status of populations. METHODS: In a sample of 525 school children in Pemba Island, Tanzania, we compared the degree of anaemia and iron deficiency associated with the two hookworm species at the individual and community (i.e. school) levels. Multiple regression was used to control for infection intensities and other child characteristics. RESULTS: In the 492 children with hookworm positive faecal cultures, haemoglobin and ferritin concentrations decreased with increasing proportions of A. duodenale. Among children with only N. americanus larvae, the prevalence of anaemia was 60.5 % and the prevalence of ferritin <12 microg/l was 33.1%, while in children with > or =50% A. duodenale larvae, the respective prevalences were 80.6% and 58.9%. When children were grouped by the prevalence of A. duodenale at the school level, children from high prevalence (> or =20%) schools had significantly worse iron deficiency and anaemia than children from low prevalence schools. CONCLUSIONS: The species of hookworm being transmitted in a community influences the burden of iron deficiency anaemia in the community, and should be considered in prioritizing and planning programmes for hookworm and anaemia control.

PIP: Hookworms infect 1.3 billion people annually. Iron-deficiency anemia caused or exacerbated by intestinal blood loss is the major feature of hookworm infection, with such loss caused by the feeding of hookworms upon the intestinal mucosa. The hookworms Ancylostoma duodenale and Necator americanus cause major gastrointestinal blood loss. While relatively greater blood loss has been reported in clinical studies due to infection with A. duodenale, there has been no evidence that endemic A. duodenale infection has a greater impact than N. americanus infection upon the iron status of populations. The authors compared the degree of anemia and iron deficiency associated with these 2 hookworm species at the individual and community levels using a sample of 525 school children in grades 1-4 in Pemba Island, Tanzania, and controlling for infection intensities and other child characteristics through multiple regression. In the 492 children with hookworm-positive fecal cultures, hemoglobin and ferritin concentrations decreased with increasing proportions of A. duodenale. Among children with only N. americanus larvae, the prevalence of anemia was 60.5% and the prevalence of ferritin under 12 mcg/l was 33.1%. In children with 50% or higher proportions of A. duodenale larvae, the respective prevalences were 80.6% and 58.9%. Children from schools with high prevalences of A. duodenale infection had significantly worse iron deficiency and anemia than did children from low prevalence schools.

Hookworm control as a strategy to prevent iron deficiency.

The hookworms Necator americanus and Ancylostoma duodenale infect approximately 1 billion people worldwide. The prevalence of hookworm infection increases with age in children, typically reaching a plateau in late adolescence, whereas the intensity of infection may continue to increase throughout adulthood. Hookworms cause intestinal blood loss in amounts proportional to the number of adult worms in the gut. The relationship between hookworm infection intensity and hemoglobin concentration is evident in epidemiologic studies, but may be apparent only above a threshold worm burden that is related to the iron stores of the population. Current hookworm control efforts are focused on reducing infection load and transmission potential through periodic anthelminthic chemotherapy. Several controlled trials have demonstrated a positive impact of anthelminthic treatment on hemoglobin levels, with best results obtained in settings where iron intakes were also increased. Evidence suggests that anthelminthic programs will have modest impacts on iron deficiency anemia in the short term, with greater impacts on more severe anemia. Hookworms are an important cause of anemia in women, who are often overlooked by current helminth control programs. Current WHO recommendations for use of anthelminthics in schoolchildren and women are reviewed. There is a need to clarify whether hookworms are an important etiology of iron deficiency anemia in preschool children.

Hemoquant determination of hookworm-related blood loss and its role in iron deficiency in African children.

Iron deficiency remains the most prevalent form of human malnutrition, and current interventions to control it have not decreased the global prevalence. Hookworm control activities are becoming more widely implemented, but the importance of these efforts to prevent anemia in populations is not well-defined. We studied the relationships among hookworm infection, intestinal blood loss, and iron status of 203 Zanzibari school children. Helminth infection intensity was quantified by fecal egg counts, and iron deficiency anemia was defined by low hemoglobin and serum ferritin concentrations. Intestinal blood loss was quantified by measuring fecal heme and heme breakdown products as porphyrin, a noninvasive method that has not been used previously to assess hookworm blood loss. Intestinal blood loss was strongly and linearly related to hookworm egg counts. The degree of degradation of fecal heme indicated that blood loss occurred in the upper gastrointestinal tract, compatible with the behavior of hookworms. Trichuris trichiura and Ascaris lumbricoides infections were also common, but did not contribute significantly to intestinal blood loss in this population. The prevalence of iron deficiency anemia increased steadily as hookworm infection intensity and intestinal blood loss increased. In the context of a poor diet, as exists in Zanzibar and many tropical countries, hookworm-related blood loss contributes dramatically to anemia. In such contexts, hookworm control is a feasible and essential component of anemia control. Determination of fecal heme is relatively simple and noninvasive and may be a useful tool for measuring the impact of hookworm control activities.

A randomized controlled trial comparing mebendazole and albendazole against Ascaris, Trichuris and hookworm infections.

The efficacies and side effects of single dose treatments with 500 mg mebendazole (Janssen Pharmaceutica) and 400 mg albendazole (SmithKline Beecham) against intestinal nematodes were compared in a single-blind, randomized controlled trial among 2294 children aged 6 to 12 years on Pemba Island, Zanzibar, among whom infections with Ascaris, hookworms and Trichuris were highly prevalent. Both drugs were highly effective against Ascaris, with cure rates of over 97%. The cure rates for Trichuris were low, but mebendazole was significantly better than albendazole and produced a greater reduction in the geometric mean egg count. Mebendazole was inferior to albendazole in curing hookworm infections and in reducing the geometric mean egg count. There was no difference in the frequency of side effects reported by heavily infected children treated with either drug. In a trial on 402 children, 500 mg mebendazole (Janssen) was compared with a generic version of the drug, 500 mg mebendazole (Pharmamed). No difference was apparent in the efficacies of the 2 treatments against any of the 3 parasites studied.

Rate of reinfection with intestinal nematodes after treatment of children with mebendazole or albendazole in a highly endemic area.

The comparative efficacy of albendazole and mebendazole in the treatment of intestinal nematode infections were compared 3 weeks after treatment in a randomized trial among schoolchildren on Pemba Island, Tanzania. Egg counts were compared 3 weeks, 4 months and 6 months after treatment of 731 children seen on each occasion. Differences in the efficacies were apparent with some nematodes 21 d after treatment, but these were no longer apparent 4 months after treatment, and by 6 months intensities of infection were similar to pre-treatment levels. These findings suggest that treatment of schoolchildren every 4 months may be necessary in this highly endemic area in order to have an impact on the intensity of intestinal nematode infections sufficient to be likely to reduce morbidity.

Methods to sustain drug efficacy in helminth control programmes.

Assessment of the efficacy of anthelminthic treatment in public health is a broad concept, which goes beyond parasitological methods and should be clearly defined according to several indicators of morbidity. Several factors may influence the efficacy of anthelminthic drugs. The quality of drug is an issue of great importance, especially when produced locally as a generic product and used in large-scale chemotherapy-based control programmes. Other factors include the drug-patient interaction, the host-parasite relationship, the diagnostic method used, genetic variations between parasite strains and induced drug resistance. Veterinary scientists have warned that drug resistance can be selected through frequent mass treatment of sheep and goats and have developed a body of knowledge on evaluation of efficacy and detection of resistance in nematodes of veterinary importance. In soil-transmitted nematodes infections of humans, the egg reduction rate (ERR), the egg hatch assay (EHA) and novel molecular biological techniques may be used to monitor drug efficacy in helminth control programmes and to detect early occurrence of resistance. Evidence of reduced drug efficacy of some anthelminthics has been suggested by recent studies and strategies to prevent or delay the emergence of drug resistance in human soil-transmitted nematodes.

Progress in the prevention and control of schistosomiasis and soil-transmitted helminthiasis.

In the last two decades important progress has been made in the understanding the epidemiology and the disease burden of schistosomiasis and soil-transmitted nematodes infection. In addition, practical tools for disease control have been developed and a strategy for the prevention and control of morbidy of schistosomaisis and soil-transmitted nematodes infection has been endorsed by the World Health Organization. This paper presents the recent progress in the prevention and control of these infections: the estimates of chronic and subtle morbidity in high risk groups and the evidence that these chronic and severe sequelae of infections can be reversed by appropriate treatment; the use of anthelminthic drugs during pregnancy and lactation; the relevance to control morbidity due to these infections also in pre-school children; the efficacy of anthelminthic drugs and the possible threat of drug resistance; price, quality and accessibility of treatment by delivering drugs through the school system and ways of reaching also non-enrolled school-age children. Finally, the strategy, targets and recommendations of the World Health Organization for the control of schistosomiasis and soil-transmitted nematodes infection are described.

Ancylostoma duodenale is responsible for hookworm infections among pregnant women in the rural plains of Nepal.

Fecal specimens from 292 pregnant women (ages 15-40 yr) and 129 infants (ages 10-20 wk) were examined for helminth eggs by the Kato-Katz method and cultured for helminth larvae identification using a modified Harada Mori method. These specimens were collected from June 1995 through July 1996 in Sarlahi District in the southern rural plains of Nepal. Among pregnant women, the prevalence of helminth infection by the Kato-Katz method was 78.8%, 56.2%, and 7.9% for hookworm, Ascaris lumbricoides, and Trichuris trichiura, respectively. Using the modified Harada-Mori method, 66.1% and 2.0% of women's fecal cultures were positive for hookworm and Strongyloides stercoralis, respectively. All of the cultured hookworm larvae were identified as Ancylostoma duodenale. Among infants, 1 specimen was positive for hookworm and 1 for A. lumbricoides using the Kato-Katz method. The modified Harada Mori method detected no larvae in specimens from infants. There was 81.8% agreement between the 2 methods for the detection of hookworm infection. Ancylostoma duodenale is endemic in this study population and highly prevalent in pregnant women.

Control of epidemic malaria on the highlands of Madagascar.

The Malagashy national malaria control programme ('Programme National de Lutte contre le Paludisme', PNLP) has been developing, since 1996, an epidemiological early warning system for malaria epidemics in the Central Highlands with the support of the Italian Development Cooperation. The system is based on the monitoring of malaria morbidity (clinical diagnosis) in 536 peripheral health centres (CSB) of the Highlands. The intervention area corresponds to 27 districts of the Antananarivo and Fianarantsoa provinces (4.7 million inhabitants) and spans around 100,000 square km. For each CSB a monthly warning threshold, defined as the 1993-1996 monthly mean number of malaria cases plus two standard deviations, was established. Three levels of epidemic alert have been defined according to the number of times the cases of presumptive malaria surpassed the threshold and according to the reported presence of severe malaria cases. The surveillance system relies also on the monitoring, in district hospitals of the Highlands, of the Plasmodium falciparum infection rate among clinically diagnosed malaria cases. A total of 185,589 presumptive malaria cases, corresponding to a 42/1000 malaria incidence, were recorded in 1997 by the surveillance system. During the same year 184 alerts of 2nd degree were reported. During 1998 173,632 presumptive malaria cases corresponding to a 38/1000 incidence were reported and 207 alerts of 2nd degree were detected; 75 of these alerts were investigated with ad hoc surveys and 3 initial malaria epidemics identified and controlled. Out of 6884 presumptive malaria cases diagnosed in the district hospitals during 1997-1998, only 835 (12.1%) have been confirmed by microscopy (P. falciparum 81.7%, P. vivax 15.0%, P. malariae 2.5%, P. ovale 0.2%, mixed infections 0.6%); 22.4% of these infections were imported cases from coastal endemic areas. The efficiency of the system in monitoring the trend of malaria morbidity and in the rapid detection and response to malaria epidemics is still being evaluated.

Parasitic infections in Pemba Island school children.

Intestinal helminths, schistosomiasis and malaria have been recognised for decades to be major public health problems in Zanzibar, Tanzania. During the evaluation of the impact of the Zanzibar Helminth Control Programme, baseline parasitological data on 3,605 school children were collected in Pemba Island. Prevalence of intestinal helminth infections was 72%, 94% and 96% for Ascaris lumbricoides, Trichuris trichiura and hookworm, respectively. Thirty one percent of children tested positive for haematuria, a reliable indicator of urinary schistosomiasis in the study area. Malaria parasites were found in 61% of children. Hookworm infections and haematuria were more prevalent in boys. Sixty seven percent of the children were infected with all the three helminths, and 28% harboured double infection. No association was found between intestinal helminths and schistosomiasis or malaria. Children living in rural areas were more heavily infected with hookworms, schistosomiasis and malaria compared to children in towns. Results from this study provided relevant information for designing a "plan of action" for the integrated control of filariasis, intestinal helminths, malaria and schistosomiasis in Zanzibar.

Hookworm infection and disease: advances for control.

Advances in epidemiology and in control strategies of hookworm infection and associated disease were reviewed. Recent estimates indicate that hookworms infect approximately 1.3 billion people worldwide, and 96 million suffer from associated morbidity, including also insidious effects on nutritional status and on physical and intellectual development. Recent research studies on iron loss and iron-deficiency anaemia associated to hookworm infection were irondeficiency anemia associated to hookworm infection were reviewed. Recommendations for planning strategies for the control of hookworm infection were addressed and epidemiology, targets, chemotherapy, health education, sanitation, monitoring and evaluation in helminth control programmes were discussed. Special relevance was given to chemotherapy with new, single dose broad spectrum, safe anthelminthic drugs as the mainstay of control strategy to reduce intensity of infection, iron-deficiency anaemia and other morbidity indicators associated with hookworm infections. For the control of transmission of hookworm infection, periodic chemotherapy should be implemented in the context of ongoing improvement of sanitation and promotion of health education. These elements should be integrated into the prevailing system of primary health care and must be based on multisectoral collaboration to ensure sustainability of control programmes.

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

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.