Global epidemiology, ecology and control of soil-transmitted helminth infections.

Soil-transmitted helminth (STH) infections are among the most prevalent of chronic human infections worldwide. Based on the demonstrable impact on child development, there is a global commitment to finance and implement control strategies with a focus on school-based chemotherapy programmes. The major obstacle to the implementation of cost-effective control is the lack of accurate descriptions of the geographical distribution of infection. In recent years, considerable progress has been made in the use of geographical information systems (GIS) and remote sensing (RS) to better understand helminth ecology and epidemiology, and to develop low-cost ways to identify target populations for treatment. This review explores how this information has been used practically to guide large-scale control programmes. The use of satellite-derived environmental data has yielded new insights into the ecology of infection at a geographical scale that has proven impossible to address using more traditional approaches, and has in turn allowed spatial distributions of infection prevalence to be predicted robustly by statistical approaches. GIS/RS have increasingly been used in the context of large-scale helminth control programmes, including not only STH infections but also those focusing on schistosomiasis, filariasis and onchocerciasis. The experience indicates that GIS/RS provides a cost-effective approach to designing and monitoring programmes at realistic scales. Importantly, the use of this approach has begun to transition from being a specialist approach of international vertical programmes to becoming a routine tool in developing public sector control programmes. GIS/RS is used here to describe the global distribution of STH infections and to estimate the number of infections in school-age children in sub-Saharan Africa (89.9 million) and the annual cost of providing a single anthelmintic treatment using a school-based approach (US$5.0-7.6 million). These are the first estimates at a continental scale to explicitly include the fine spatial distribution of infection prevalence and population, and suggest that traditional methods have overestimated the situation. The results suggest that continent-wide control of parasites is, from a financial perspective, an attainable goal.

Immuno-epidemiology of Ascaris lumbricoides infection in a high transmission community: antibody responses and their impact on current and future infection intensity.

The role of the humoral immune system in human infection with Ascaris lumbricoides remains unclear. This study documents an epidemiological investigation in a highly endemic community in Vietnam, whereby serum antibody levels were assessed before treatment and after a 6-month reinfection period. These data were examined by correlation with infection status using an age-structured approach in an attempt to help shed light on the role of the humoral immune response. The first part of this study characterized levels of all serum antibody isotypes from the community in response to antigens of both adult and larval A. lumbricoides. Data were assessed in terms of their relation to host age and infection intensity with the aim to provide a broadly detailed account of immune responses to the parasite. In the second part, antibody responses to both life-stages of A. lumbricoides in serum samples collected before anthelmintic chemotherapy were analysed in relation to intensity of re-infection with the parasite 6 months following treatment. The results suggest that antibody responses may not confer protection from current infection or re-infection with A. lumbricoides and may not serve as reliable indicators of future infection intensity. Our results thereby lend support to the theory that immunity to A. lumbricoides may not be based on the humoral immune system.

Sequence variation in the Trichuris trichiura beta-tubulin locus: implications for the development of benzimidazole resistance.

Benzimidazole resistance has evolved in a variety of organisms and typically results from mutations in the beta-tubulin locus at specific amino acid sites. Despite widespread treatment of human intestinal nematodes with benzimidazole drugs, there have been no unambiguous reports of resistance. However, since beta-tubulin mutations conferring resistance are generally recessive, frequencies of resistance alleles less than 30% would be difficult to detect on the basis of drug treatment failures. Here we investigate sequence variation in a 1079 bp segment of the beta-tubulin locus in the human whipworm Trichuris trichiura from 72 individual nematodes from seven countries. We did not observe any alleles with amino acid mutations indicative of resistance, and of 40 point mutations there were only four non-synonymous mutations all of which were singletons. Estimated effective population sizes are an order of magnitude lower than those from another nematode species in which benzimidazole resistance has developed (Haemonchus contortus). Both the lower diversity and reduced population sizes suggest that benzimidazole resistance is likely to evolve less rapidly in Trichuris than in trichostrongyle parasites of livestock. We observed moderate levels of population subdivision (Phi(ST)=0.26) comparable with that previously observed in Ascaris lumbricoides, and identical alleles were frequently found in parasites from different continents, suggestive of recent admixture. A particularly interesting feature of the data is the high nucleotide diversities observed in nematodes from the Caribbean. This genetic complexity may be a direct result of extensive admixture and complex history of human populations in this region of the world. These data should encourage (but not make complacent) those involved in large-scale benzimidazole treatment of human intestinal nematodes.

Heavy schistosomiasis associated with poor short-term memory and slower reaction times in Tanzanian schoolchildren.

Cross-sectional studies of the relationship between helminth infection and cognitive function can be informative in ways that treatment studies cannot. However, interpretation of results of many previous studies has been complicated by the failure to control for many potentially confounding variables. We gave Tanzanian schoolchildren aged 9-14 a battery of 11 cognitive and three educational tests and assessed their level of helminth infection. We also took measurements of an extensive range of potentially confounding or mediating factors such as socioeconomic and educational factors, anthropometric and other biomedical measures. A total of 272 children were moderately or heavily infected with Schistosoma haematobium, hookworm or both helminth species and 117 were uninfected with either species. Multiple regression analyses, controlling for all confounding and mediating variables, revealed that children with a heavy S. haematobium infection had significantly lower scores than uninfected children on two tests of verbal short-term memory and two reaction time tasks. In one of these tests the effect was greatest for children with poor nutritional status. There was no association between infection and educational achievement, nor between moderate infection with either species of helminth and performance on the cognitive tests. We conclude that children with heavy worm burdens and poor nutritional status are most likely to suffer cognitive impairment, and the domains of verbal short-term memory and speed of information processing are those most likely to be affected.

Predicting the distribution of urinary schistosomiasis in Tanzania using satellite sensor data.

In this paper, remotely sensed (RS) satellite sensor environmental data, using logistic regression, are used to develop prediction maps of the probability of having infection prevalence exceeding 50%, and warranting mass treatment according to World Health Organization (WHO) guidelines. The model was developed using data from one area of coastal Tanzania and validated with independent data from different areas of the country. Receiver operating characteristic (ROC) analysis was used to evaluate the model's predictive performance. The model allows reasonable discrimination between high and low prevalence schools, at least within those geographical areas in which they were originally developed, and performs reasonably well in other coastal areas, but performs poorly by comparison in the Great Lakes area of Tanzania. These results may be explained by reference to an ecological zone map based on RS-derived environmental data. This map suggests that areas where the model reliably predicts a high prevalence of schistosomiasis fall within the same ecological zone, which has common intermediate-host snail species responsible for transmission. By contrast, the model's performance is poor near Lake Victoria, which is in a different ecological zone with different snail species. The ecological map can potentially define a template for those areas where existing models can be applied, and highlight areas where further data and models are required. The developed model was then used to provide estimates of the number of schoolchildren at risk of high prevalence and associated programme costs.

Community perception of school-based delivery of anthelmintics in Ghana and Tanzania.

This paper presents the results of an evaluation of community perception of two large-scale, government-run, school-based health programmes delivering anthelmintic drugs to primary school children, in Ghana (80 442 children in 577 schools) and Tanzania (110 000 children in 352 schools). Most teachers (96% in Ghana and 98% in Tanzania) were positive about their role in the programme, including administration of anthelmintic drugs, and parents and children fully accepted their taking on this role. The benefits of the programme were apparent to teachers, parents and children in terms of improved health and well-being of the children. Over 90% of parents in both Ghana and Tanzania indicated a willingness to pay for the continuation of drug treatment. The evaluation also highlighted areas that are critical to programme effectiveness, such as communication between schools and parents, the issue of collaboration between the health and education sectors, parents' perception of the importance of helminth infection as a serious and chronic health problem (compared with more acute and life threatening illnesses such as malaria), and who should pay for treatment of side-effects.

Development and validation of a 'tablet pole' for the administration of praziquantel in sub-Saharan Africa.

A pole estimating, for each individual, the number of praziquantel tablets needed for treatment according to height was tested in 20 data sets (n = 25,688). In more than 98% of the cases the indicated dose was within the range that has proven efficacious and safe (30 and 60 mg/kg).

Evaluation of efficacy of school-based anthelmintic treatments against anaemia in children in the United Republic of Tanzania.

OBJECTIVE: To determine the impact of deworming on anaemia as part of a large-scale school-based anthelmintic treatment programme in the Tanga Region of the United Republic of Tanzania. METHODS: Both the reduction in the prevalence of anaemia and the cost per case prevented were taken into consideration. Cross-sectional studies involved parasitological examination and anaemia evaluation before and at 10 months and 15 months after schoolchildren were dewormed. FINDINGS: Baseline studies indicated that the prevalence of anaemia (haemoglobin < 110 g/l) was high (54%) among schoolchildren, particularly those with high intensities of hookworm and schistosomiasis. Attributable fraction analysis suggested that hookworm and schistosomiasis were responsible for 6% and 15% of anaemia cases, respectively. Fifteen months after deworming with albendazole and praziquantel the prevalence of anaemia was reduced by a quarter and that of moderate-to-severe anaemia (haemoglobin <90 g/l) was reduced by nearly a half. The delivery of these anthelmintics through the school system was achieved at the relatively low cost of US$ 1 per treated child. The cost per anaemia case prevented by deworming schoolchildren was in the range US$ 6-8, depending on the haemoglobin threshold used. CONCLUSIONS: The results suggested that deworming programmes should be included in public health strategies for the control of anaemia in schoolchildren where there are high prevalences of hookworm and schistosomiasis.

An association between chronic undernutrition and educational test scores in Vietnamese children.

OBJECTIVE: To examine the association between results of educational tests and the anthropometric status of schoolchildren. DESIGN: Cross-sectional data collected during the baseline survey of a randomised trial. SETTING: Eighty-one primary schools in three districts of northern Vietnam. SUBJECTS: A total of 3055 schoolchildren enrolled in class 3 and born in 1990. MAIN OUTCOME MEASURES: Tests of mathematics and Vietnamese language developed not to show floor or ceiling effects, and Z-scores of height-for-age, weight-for-age and weight-for-height. RESULTS: After controlling for age, sex, district and school the results of test scores in both mathematics and Vietnamese were significantly negatively correlated with Z-scores of height-for-age (P<0.001) and weight-for-age (P<0.001), but not with weight-for-height (P=0.75). CONCLUSIONS: A cross-sectional negative association was observed in Vietnamese primary school children between indicators of chronic undernutrition and tests of educational achievement. SPONSORSHIP: The study was funded by donors to the Partnership for Child Development including the Rockefeller Foundation and the World Bank.

Placebo-controlled community trial of four cycles of single-dose diethylcarbamazine or ivermectin against Wuchereria bancrofti infection and transmission in India.

A double-blind placebo-controlled trial was carried out in 1994-98 to compare the effects of 4 cycles of single-dose diethylcarbamazine (DEC) or ivermectin on prevalence and geometric mean intensity (GMI) of microfilaraemia in the human population, infection rates in the vector population, and transmission intensity of Culex-transmitted Wuchereria bancrofti in rural areas in Tamil Nadu state, south India. Fifteen villages (population approximately 26,800) were included in the study: 5 villages each were randomly assigned to community-wide treatment with DEC or ivermectin or placebo. People over 14 kg bodyweight received DEC 6 mg/kg, ivermectin 400 micrograms/kg or a placebo, all identically packaged. After 2 cycles of treatment at a 6-month interval, the code was broken and the study continued as an open trial, with third and fourth cycles of treatment at a 12-month interval; 54-77% of eligible people (20,872) received treatment during the 4 cycles. Microfilaraemia prevalence and GMI fell by 48% and 65% with DEC and 60% and 80% with ivermectin respectively after 4 cycles of treatment. There was no change in the incidence of acute adenolymphangitis. Infection in resting mosquitoes fell significantly in all arms: 82%, 78% and 42% in the ivermectin, DEC and placebo arm, respectively. Landing mosquitoes also showed the same trend. The decline in infectivity was significant for resting (P < 0.05) and landing mosquitoes (P < 0.05) with ivermectin and DEC (P < 0.05), and for neither in the placebo group (P > 0.05). Transmission intensity was reduced by 68% with ivermectin and 63% with DEC. Transmission was apparently interrupted in 1 village with ivermectin, but infected resting mosquitoes were consistently found in this village. Single-dose community-level treatment with DEC or ivermectin is effective in reducing W. bancrofti infection in humans and mosquitoes, and may result in total interruption of transmission after several years of control. There is an immediate need to define the role of vector, parasite and community factors that influence the elimination of lymphatic filariasis, particularly the duration of treatment vis-à-vis efficacy of drugs, treatment compliance and efficiency of vectors.

Multiple helminth infections in children: impact and control.

Parasitic worm infections are amongst the most widespread of all chronic human infections. It is estimated that there are more than 3 billion infections in the world today. In many low income countries it is often more common to be infected than not to be. Indeed, a child growing up in an endemic community can expect be infected soon after weaning, and to be infected and constantly reinfected for the rest of her or his life. Infection is most common amongst the poorest and most disadvantaged communities, and is typically most intense in children of school going age. As the risk of morbidity is directly related to intensity of infection, it follows that children are the most at risk from the morbid effects of disease. Multiparasite infections are also common in such communities and there is evidence that individuals harbouring such infections may suffer exacerbated morbidity, making children even more vulnerable. Thus, these infections pose a serious threat to the health and development of children in low income countries. For many years, the need to control these infections has lain uncontested, and with the advent of broad-spectrum anthelminthic drugs that are cheap, safe and simple to deliver, control has at last become a viable option for many communities. Furthermore, there is now increased emphasis being placed on a multispecies approach as a cost-effective mechanism to control the morbidity of virtually all the major helminthic infections of humans.

The potential of rapid screening methods for Schistosoma mansoni in western Kenya.

Data from 46 schools in western Kenya were used to investigate the performance of school-based questionnaires, on reported blood in stool and water-contact patterns, as indicators of the prevalence of human infection with Schistosoma mansoni. Prevalence of infection was associated with the prevalence of self-reported blood in stool, recent history of swimming and recent history of fishing. It was shown that use of a threshold of 30% of subjects reporting blood in stool would identify 42.9% of the 'high-prevalence' schools (i.e. prevalence > or = 50%) and 87.5% of the 'low-prevalence' schools (i.e. prevalence < 50%). A threshold of 25% reporting swimming would identify 57.1% and 93.7% of the high- and low-prevalence schools, respectively. Blood in stool appears to be too coarse an indicator to identify schools for mass treatment correctly. Although the use of multiple questions improved the diagnostic performance of the questionnaire in identifying the high-prevalence schools, it was unclear how questions can best be combined in other settings. However, there is a direct relationship between prevalence of S. mansoni infection and distance of the school from the lakeshore; analysis indicated that use of a threshold of 5 km from the lakeshore would correctly identify most (90%) of both the low- and high-prevalence schools. Distance to the lakeshore may therefore be used to screen schools in much of East Africa (i.e. those areas close to the Great Lakes where the infection is known to be prevalent and where much of the region's population is concentrated). In other areas of transmission, such as irrigation areas, further studies are still required.

Guidelines for the evaluation of soil - transmitted helminthiasis and schistosomiasis at community level

It provides guidelines for health planners at national, regional or district levels in the organization, management and evaluation of surveys on soil-transmitted helminthiasis andschistosomiasis for the development and implementation of control activities. Document in pdf format; Acrobat Reader needed.

Quantifying mosquito biting patterns on humans by DNA fingerprinting of bloodmeals.

A major debate in infectious disease epidemiology concerns the relative importance of exposure and host factors, such as sex and acquired immunity, in determining observed age patterns of parasitic infection in endemic communities. Nonhomogeneous contact between hosts and vectors is also expected to increase the reproductive rate, and hence transmission, of mosquito-borne infections. Resolution of these questions for human parasitic diseases has been frustrated by the lack of a quantitative tool for quantifying the exposure rate of people in communities. Here, we show that the polymerase chain reaction (PCR) technique for amplifying and fingerprinting human DNA from mosquito bloodmeals can address this problem for mosquito-borne diseases. Analysis of parallel human and mosquito (resting Culex quinquefasciatus) samples from the same households in an urban endemic focus for bancroftian filariasis in South India demonstrates that a 9-locus radioactive short-tandem repeat system is able to identify the source of human DNA within the bloodmeals of nearly 80% of mosquitoes. The results show that a person's exposure rate, and hence the age and sex patterns of exposure to bites in an endemic community, can be successfully quantified by this method. Out of 276 bloodmeal PCR fingerprints, we also found that on average, 27% of the mosquitoes caught resting within individual households had fed on people outside the household. Additionally, 13% of mosquitoes biting within households contained blood from at least 2 people, with the rate of multiple feeding depending on the density of humans in the household. These complex vector feeding behaviors may partly account for the discrepancies in estimates of the infection rates of mosquito-borne diseases calculated parasitologically and entomologically, and they underline the potential of this tool for investigating the transmission dynamics of infection.

The impact of weekly iron supplementation on the iron status and growth of adolescent girls in Tanzania.

We evaluated the effect of weekly doses of 400 mg of ferrous sulphate for 4 months on the iron status of adolescent girls in a controlled trial in Tanga, Tanzania. Supplementation led to a significantly greater increase in serum ferritin compared with the control group (+ 15.6 microg/l vs. 8.6 microg/l) (P = 0.002) but there was no significant difference in change in haemoglobin. Children given iron showed a significantly greater weight gain than controls (+ 2.4 kg vs. + 1.4 kg) (P = 0.03). Weekly iron supplementation may be an effective means of increasing iron stores and growth in children vulnerable to iron deficiency.

The health of enrolled and non enrolled children of school age in Tanga, Tanzania.

The health of 227 children enrolled at primary school was compared with that of 214 non enrolled children living in rural Tanga, Tanzania. No consistent difference was observed with respect to prevalence and intensity of parasitic infection (hookworm, T. trichiura, A. lumbricoides, S. haematobium and P. falciparum). Since enrolled children were as commonly and as heavily infected as non enrolled children, treatment of enrolled children would be effective in reducing transmission throughout the total population. Non enrolled children were more stunted (P=0.0001) and wasted (P=0.0001) than enrolled children and also tended to be more anaemic (P=0.080) showing that poor nutrition is not only associated with delayed enrolment but continues to be associated with non enrolment throughout the school age years. Given that treatment has the greatest impact on the most malnourished children, additional measures to extend treatment to non enrolled children would be justified.

EPIFIL: the development of an age-structured model for describing the transmission dynamics and control of lymphatic filariasis.

Mathematical models of transmission dynamics of infectious diseases provide a useful tool for investigating the impact of community based control measures. Previously, we used a dynamic (constant force-of-infection) model for lymphatic filariasis to describe observed patterns of infection and disease in endemic communities. In this paper, we expand the model to examine the effects of control options against filariasis by incorporating the impact of age structure of the human community and by addressing explicitly the dynamics of parasite transmission from and to the vector population. This model is tested using data for Wuchereria bancrofti transmitted by Culex quinquefasciatus in Pondicherry, South India. The results show that chemotherapy has a larger short-term impact than vector control but that the effects of vector control can last beyond the treatment period. In addition we compare rates of recrudescence for drugs with different macrofilaricidal effects.