Narcis B. Kabatereine

Epidemiology and geography of Schistosoma mansoni in Uganda: implications for planning control

Intestinal schistosomiasis caused by infection with Schistosoma mansoni is a widespread public health problem in Uganda. Although long known to be endemic, its current distribution within the country requires updating of parasitological data to help guide planned control. We report such data collected between 1998 and 2002 from 201 schools and 68 communities across Uganda. In accordance with epidemiological expectation, prevalence and intensity increased with age, peaking at 10–20 years and thereafter declined moderately with age, whereas intensity declined more rapidly with age, and the prevalence of infection in a school was non‐linearly related to the mean intensity of infection. We used geographical information systems to map the distribution of infection and to overlay parasitological data with interpolated environmental surfaces. The derived maps indicate both a widespread occurrence of infection and a marked variability in infection prevalence, with prevalence typically highest near the lakeshore and along large rivers. No transmission occurred at altitudes >1400 m or where total annual rainfall was <900 mm; limits which can help estimate the population at risk of schistosomiasis. The results are discussed in reference to the ecology of infection and provide an epidemiological framework for the design and implementation of control efforts underway in Uganda.

Impact of a national helminth control programme on infection and morbidity in Ugandan schoolchildren

OBJECTIVE We aimed to assess the health impact of a national control programme targeting schistosomiasis and intestinal nematodes in Uganda, which has provided population-based anthelmintic chemotherapy since 2003. METHODS We conducted longitudinal surveys on infection status, haemoglobin concentration and clinical morbidity in 1871 randomly selected schoolchildren from 37 schools in eight districts across Uganda at three time points - before chemotherapy and after one year and two years of annual mass chemotherapy. FINDINGS Mass treatment with praziquantel and albendazole led to a significant decrease in the intensity of Schistosoma mansoni - 70% (95% confidence interval (CI): 66-73%) after one year and 82% (95% CI: 80-85%) after two years of treatment. Intensity of hookworm infection also decreased (75% and 93%; unadjusted). There was a significant increase in haemoglobin concentration after one (0.135 g/dL (95% CI: 0.126-0.144)) and two years (0.303 g/dL (95% CI: 0.293-0.312)) of treatment, and a significant decrease in signs of early clinical morbidity. The impact of intervention on S. mansoni prevalence and intensity was similar to that predicted by mathematical models of the impact of chemotherapy on human schistosomiasis. Improvements in haemoglobin concentration were greatest among children who were anaemic or harbouring heavy S. mansoni infection at baseline. CONCLUSION Anthelmintic treatment delivered as part of a national helminth control programme can decrease infection and morbidity among schoolchildren and improve haemoglobin concentration.

Periportal fibrosis in human Schistosoma mansoni infection is associated with low IL-10, low IFN-gamma, high TNF-alpha, or low RANTES, depending on age and gender.

Schistosoma mansoni infection is highly endemic in parts of Uganda, and periportal fibrosis is common in communities along the shore of Lake Albert. In this study, we have identified cellular immune responses associated with fibrosis. A cohort of 199 individuals aged 6–50, resident in the village for at least 10 years or since birth, were examined for evidence of periportal fibrosis by ultrasound using the Niamey protocol. Whole-blood samples were assayed for levels of nine cellular immune molecules (IL-3, IL-4, IL-5, IL-10, IL-13, TNF-α, IFN-γ, IL-1β, and RANTES) in the absence of in vitro Ag stimulation, and after stimulation with egg and worm Ags. A lack of Ag specificity allowed the number of variables in the analysis to be reduced by factor analysis. The resulting factor scores were then entered into a risk analysis using a classification tree algorithm. Children, adult males, and adult females had different factors associated with fibrosis. Most cases of fibrosis in children (eight of nine) were associated with low (<47th percentile) IL-10 factor scores. Adult females at lowest risk had relatively high IFN-γ factor scores (>83rd percentile), whereas those at highest risk had a combination of intermediate (32nd to 83rd percentile) IFN-γ and relatively high (>60th percentile) TNF-α factor scores. Adult males at lowest risk of fibrosis had moderate TNF-α factor scores (55th to 82nd percentile), and a high risk was associated with either high TNF-α factor scores (>82nd percentile), or intermediate TNF-α combined with low RANTES factor scores (<58th percentile). These results demonstrate that periportal fibrosis is associated with cytokine production profiles that vary with both age and gender.

Adult resistance to schistosomiasis mansoni: age-dependence of reinfection remains constant in communities with diverse exposure patterns.

In a fishing community on Lake Albert in Uganda the pattern of intensity of Schistosoma mansoni infection 6 months after treatment with praziquantel was found to be very similar to reinfection patterns seen in previously studied endemic communities: the profile peaks sharply at around the age of 10 years falling away rapidly to much lower levels in adults. This is in stark contrast to the patterns of water contact, which differ greatly between fishing and non-fishing communities. On Lake Albert, adults appear to be more heavily exposed than children. From these observations we conclude that adults are physiologically (perhaps immunologically) more resistant to infection after treatment than children.

Rapid mapping of schistosomiasis and other neglected tropical diseases in the context of integrated control programmes in Africa

There is growing interest and commitment to the control of schistosomiasis and other so-called neglected tropical diseases (NTDs). Resources for control are inevitably limited, necessitating assessment methods that can rapidly and accurately identify and map high-risk communities so that interventions can be targeted in a spatially-explicit and cost-effective manner. Here, we review progress made with (1) mapping schistosomiasis across Africa using available epidemiological data and, more recently, climate-based risk prediction; (2) the development and use of morbidity questionnaires for rapid identification of high-risk communities of urinary schistosomiasis; and (3) innovative sampling-based approaches for intestinal schistosomiasis, using the lot quality assurance sampling technique. Experiences are also presented for the rapid mapping of other NTDs, including onchocerciasis, loiasis and lymphatic filariasis. Future directions for an integrated rapid mapping approach targeting multiple NTDs simultaneously are outlined, including potential challenges in developing an integrated survey tool. The lessons from the mapping of human helminth infections may also be relevant for the rapid mapping of malaria as its control efforts are intensified.

An updated atlas of human helminth infections: the example of East Africa

BackgroundReliable and updated maps of helminth (worm) infection distributions are essential to target control strategies to those populations in greatest need. Although many surveys have been conducted in endemic countries, the data are rarely available in a form that is accessible to policy makers and the managers of public health programmes. This is especially true in sub-Saharan Africa, where empirical data are seldom in the public domain. In an attempt to address the paucity of geographical information on helminth risk, this article describes the development of an updated global atlas of human helminth infection, showing the example of East Africa.MethodsEmpirical, cross-sectional estimates of infection prevalence conducted since 1980 were identified using electronic and manual search strategies of published and unpublished sources. A number of inclusion criteria were imposed for identified information, which was extracted into a standardized database. Details of survey population, diagnostic methods, sample size and numbers infected with schistosomes and soil-transmitted helminths were recorded. A unique identifier linked each record to an electronic copy of the source document, in portable document format. An attempt was made to identify the geographical location of each record using standardized geolocation procedures and the assembled data were incorporated into a geographical information system.ResultsAt the time of writing, over 2,748 prevalence surveys were identified through multiple search strategies. Of these, 2,612 were able to be geolocated and mapped. More than half (58%) of included surveys were from grey literature or unpublished sources, underlining the importance of reviewing in-country sources. 66% of all surveys were conducted since 2000. Comprehensive, countrywide data are available for Burundi, Rwanda and Uganda. In contrast, information for Kenya and Tanzania is typically clustered in specific regions of the country, with few records from areas with very low population density and/or environmental conditions which are unfavourable for helminth transmission. Information is presented on the prevalence and geographical distribution for the major helminth species.ConclusionFor all five countries, the information assembled in the current atlas provides the most reliable, up-to-date and comprehensive source of data on the distribution of common helminth infections to guide the rational implementation of control efforts.

Efficacy and side effects of praziquantel treatment in a highly endemic Schistosoma mansoni focus at Lake Albert, Uganda

The aim of the study was to assess the efficacy and side effects following single and repeated (6 weeks apart) praziquantel treatment (40 mg/kg) in a Schistosoma mansoni-endemic focus with long-standing transmission at Lake Albert in Uganda between December 1996 and January 1997. The results were based on 482 individuals, randomly representing all age and both gender groups. The cure rate following the first and second treatments was 41.9% and 69.1%, respectively. The cure rate was higher in adults than in children, irrespective of intensity of infection. In addition, the cure rate declined markedly with increasing intensity of infection. The reduction in intensity of infection was marked, being 97.7% and 99.6% after the first and second treatments, respectively. A pre- and post-treatment symptom questionnaire revealed a broad range of side effects, including abdominal pain and diarrhoea. However, no serious or long-lasting complications affecting compliance were observed. The marked reductions in faecal egg excretion and the acceptable level of side effects point to a single praziquantel treatment (40mg/kg) as the strategy of choice in such a highly endemic S. mansoni focus.

Parasitological impact of 2-year preventive chemotherapy on schistosomiasis and soil-transmitted helminthiasis in Uganda

BackgroundSchistosomiasis and soil-transmitted helminthiasis (STH) are among the neglected tropical diseases in Africa. A national control program for these diseases was initiated in Uganda during March 2003. Annual treatment with praziquantel and albendazole was given to schoolchildren in endemic areas and to adults in selected communities where local prevalence of Schistosoma mansoni in schoolchildren was high.MethodsThe impact of the treatment program was monitored through cohorts of schoolchildren and adults. Their infection status with S. mansoni and STH was determined by parasitological examinations at baseline and at annual follow-ups. The prevalence and intensity of S. mansoni and STH before and after treatment were analyzed.ResultsTwo rounds of treatment significantly reduced the prevalence of S. mansoni infection in schoolchildren across three regions in the country from 33.4–49.3% to 9.7–29.6%, and intensity of infection from 105.7–386.8 eggs per gram of faeces (epg) to 11.6–84.1 epg. The prevalence of hookworm infection was reduced from 41.2–57.9% to 5.5–16.1%, and intensity of infection from 186.9–416.8 epg to 3.7–36.9 epg. The proportion of children with heavy S. mansoni infection was significantly reduced from 15% (95% CI 13.4–16.8%) to 2.3% (95% CI 1.6–3.0%). In adults, significant reduction in the prevalence and intensity of S. mansoni and hookworm infections was also observed. More importantly, the prevalence and intensity of both S. mansoni and hookworm infections in the cohorts of newly-recruited 6-year-olds who had never previously received treatment decreased significantly over 2 years: 34.9% (95% CI 31.9–37.8%) to 22.6% (95% CI 19.9–25.2%) and 171.1 epg (95% CI 141.5–200.7) to 72.0 epg (95% CI 50.9–93.1) for S. mansoni; and 48.4% (95% CI 45.4–51.5) to 15.9% (95% CI 13.6–18.2) and 232.7 epg (95% CI 188.4–276.9) to 51.4 epg (95% CI 33.4–69.5) for hookworms, suggesting a general decline in environmental transmission levels.ConclusionAnnual anthelminthic treatment delivered to schoolchildren and to adults at high risk in Uganda can significantly reduce the prevalence and intensity of infection for schistosomiasis and STH, and potentially also significantly reduce levels of environmental transmission of infection.

Schistosoma mansoni in infants (aged ,3 years) along the Ugandan shoreline of Lake Victoria

Abstract In two complementary epidemiological surveys of villages on the Ugandan shoreline of Lake Victoria, the putative occurrence of intestinal schistosomiasis in the local infants (children aged <3 years) was investigated. When, during the first survey, 136 mother-and-infant pairs from a total of 12 villages were studied, only 7% of the infants but 45% of the mothers were found to be egg-patent for Schistosoma mansoni infection. The use of dipstick tests for urine-circulating cathodic antigen indicated, however, a much higher prevalence, of approximately 40%, among the infants. In the second survey, urine samples and multiple, not single, stool samples were collected from another 19 mother-and-infant pairs in two of the 12 study villages (Bugoto and Bwondha), and a standardized questionnaire was implemented. The prevalence of egg-patent infection was then found to be markedly higher in the study infants from Bugoto (86%) than in those from Bwondha (25%). A greater level of mother-and-infant water contact, a higher abundance of (infected) Biomphalaria choanomphala, and an unusual lakeshore topology may explain why S. mansoni infection was so much more common in the Bugoto subjects than in the Bwondha. All but one of the infants studied in the second survey were found to be anaemic (with <110 g haemoglobin/litre). Taken together, these children were less likely to be found infected with hookworm (16%), Hymenolepis nana (11%) or Trichuris trichiura (5%) than with S. mansoni (47%). Infection with the parasites causing intestinal schistosomiasis can be common among the infants living in these lakeshore villages. Although the immediate and later-life clinical impacts of such infection have yet to be elucidated, such infants would probably benefit from regular de-worming. Mothers should be strongly encouraged to visit the nearest health-services clinic, with their infants, for any necessary anthelmintic treatment.

The impact of helminths on the response to immunization and on the incidence of infection and disease in childhood in Uganda: design of a randomized, double-blind, placebo-controlled, factorial trial of deworming interventions delivered in pregnancy and early childhood [ISRCTN32849447]

Background Helminths have profound effects on the immune response, allowing long-term survival of parasites with minimal damage to the host. Some of these effects “spill-over”, altering responses to non-helminth antigens or allergens. It is suggested that this may lead to impaired responses to immunizations and infections, while conferring benefits against inflammatory responses in allergic and autoimmune disease. These effects might develop in utero, through exposure to maternal helminth infections, or through direct exposure in later life. Purpose To determine the effects of helminths and their treatment in pregnancy and in young children on immunological and disease outcomes in childhood. Methods The trial has three randomized, double-blind, placebo-controlled interventions at two times, in two people: a pregnant woman and her child. Pregnant women are randomized to albendazole or placebo and praziquantel or placebo. At age 15 months their children are randomized to three-monthly albendazole or placebo, to continue to age five years. The proposed designation for this sequence of interventions is a 2 × 2(×2) factorial design. Children are immunized with BCG and against polio, Diphtheria, tetanus, Pertussis, Haemophilus, hepatitis B and measles. Primary immunological outcomes are responses to BCG antigens and tetanus toxoid in whole blood cytokine assays and antibody assays at one, three and five years of age. Primary disease outcomes are incidence of malaria, pneumonia, diarrhoea, tuberculosis, measles, vertical HIV transmission, and atopic disease episodes, measured at clinic visits and twice-monthly home visits. Effects on anaemia, growth and intellectual development are also assessed. Conclusion This trial, with a novel design comprising related interventions in pregnant women and their offspring, is the first to examine effects of helminths and their treatment in pregnancy and early childhood on immunological, infectious disease and allergic disease outcomes. The results will enhance understanding of both detrimental and beneficial effects of helminth infection and inform policy.