Hepatic schistosomiasis, upper gastrointestinal bleeding, and health related quality of life measurements from the Albert Nile Basin.

BACKGROUND: Health related quality of life measurements are vital elements of public health surveillance that uncover unmet health needs and predict the success of health interventions. We described health related quality of life measurements using the EuroQoL 5-dimension (EQ-VAS/EQ-5D) instrument and associated factors among patients with upper gastrointestinal bleeding (UGIB) and hepatic schistosomiasis at a rural health facility in the Albert Nile Basin, Uganda. METHODS AND MATERIALS: This was a cross-sectional study at Pakwach Health Centre IV. Participants included adult inpatients and outpatients with a history of UGIB and ultrasound evidence of hepatic schistosomiasis. We evaluated and recorded each participant's medical history, physical examination, laboratory tests results, ultrasound results, and endoscopy findings. We also recorded health related quality of life measurements using the EuroQoL 5-dimension instrument and derived disability weights from EQ-VAS and EQ-5D measurements. These were our dependent variables. Descriptive and inferential statistics were generated summarizing our findings. RESULTS: We found 103 participants had a history of upper gastrointestinal bleeding and hepatosplenic schistosomiasis. Sixty percent were between the ages of 30-49 years, 59% were females, 74% were farmers, 92% had splenomegaly, 88% had varices at endoscopy, 22% were medical emergencies with acute variceal upper gastrointestinal bleeding, and 62% had anemia. Measures of the different dimensions of health from 101 participants with patient reported outcomes revealed 77 (76%) participants experienced problems in self-care, 89 (88%) participants reported anxiety or depression, and 89 (88%) participants experienced pain or discomfort. The median EQ-VAS derived disability weights and median EQ-5D index-derived disability weights were 0.3 and 0.34, respectively. Acute upper gastrointestinal bleeding, praziquantel drug treatment, and age by decade predicted higher EQ-VAS derived disability weights (p value < 0.05). Under weight (Body mass index ≤ 18.5), acute upper gastrointestinal bleeding, ascites, age by decade, female gender, and praziquantel drug treatment predicted higher EQ-5D index- derived disability weights (p value < 0.05). CONCLUSION: Adult patients with upper gastrointestinal bleeding and hepatic schistosomiasis from this primary health facility experience poor health and considerable health loss. Several factors predicted increased health loss. These factors probably represent key areas of health intervention towards mitigating increased health loss in this population.

Praziquantel and Upper Gastrointestinal Bleeding in Hepatic Schistosomiasis: A Quasi-Experimental Study.

BACKGROUND: There is a general consensus that widespread use of praziquantel in populations where schistosomiasis is endemic prevents development of hepatic schistosomiasis and its complications. However, a few studies have reported discordant findings linking praziquantel to the occurrence of upper gastrointestinal bleeding (UGIB) in some patients with hepatic schistosomiasis and varices. OBJECTIVE: We explored if there was any causal association between recent praziquantel use (rPZQ) and upper gastrointestinal bleeding in hepatic schistosomiasis in rural Africa. PATIENTS AND METHODS: A quasi-experimental, retrospective case-controlled study was performed. It involved adult patients with past or acute UGIB, varices, periportal fibrosis, and/or cirrhosis. Cases had acute variceal bleeding while controls did not. The outcome was the frequency of lifetime episodes of UGIB and exposure was rPZQ (received praziquantel in the last 11 months from the date of enrollment). The data analysis included 2 × 2 tables, logistic regression, and propensity-score matching. Odds ratios (ORs), average treatment effects (ATEs), and their 95% confidence intervals (CIs) were used for inference. RESULTS: Over 6 weeks, we enrolled 19 cases with 92 lifetime episodes of UGIB, and 66 controls with 192 lifetime episodes of UGIB. Cases were more likely to experience UGIB than controls following rPZQ (92% vs. 62%; OR 7.6; 95% CI 3.4-17). Factors predictive of more lifetime episodes of UGIB at multivariable analysis included rPZQ (adjusted OR 13; 95% CI 2.9-53), relative leukocytosis (adjusted OR 26; 95% CI 7.6-89), large varices (adjusted OR 5.0; 95% CI 1.7-15), a family member with hepatosplenic schistosomiasis (adjusted OR 19; 95% CI 7.4-51), advanced periportal fibrosis (adjusted OR 8.0; 95% CI 2.6-22), ascites (adjusted OR 14; 95% CI 4.3-47), and jaundice (adjusted OR 32; 95% CI 7.8-128). While the ATE following rPZQ among the treated was 0.40 (95% CI 0.33-0.48). CONCLUSIONS: Our findings suggest the presence of a plausible causal association between recent praziquantel use and increased frequency of UGIB in our study population.

The diagnostic accuracy of routine clinical findings for detection of esophageal varices in rural sub-Saharan Africa where schistosomiasis is endemic.

BACKGROUND: Variceal upper gastrointestinal bleeding (UGIB) is common in sub-Saharan Africa (SSA). However, poor access to endoscopy services precludes the diagnosis of varices. OBJECTIVES: We determined the diagnostic accuracy of routine clinical findings for detection of esophageal varices among patients with UGIB in rural SSA where schistosomiasis is endemic. METHODS: We studied patients with a history of UGIB. The index tests included routine clinical findings and the reference test was diagnostic endoscopy. Multivariable regression with post-estimation provided measures of association and diagnostic accuracy. RESULTS: We studied 107 participants with UGIB and 21% had active bleeding. One hundred and three (96%) had liver disease and 86(80%) varices. Factors associated with varices (p-value <0.05) were ≥ 4 lifetime episodes of UGIB, prior blood transfusion, splenomegaly, liver fibrosis, thrombocytopenia, platelet count spleen diameter ratio <909, and a dilated portal vein. Two models showed an overall diagnostic accuracy of > 90% in detection of varices with a number needed to misdiagnose of 13(number of patients who needed to be tested in order for one to be misdiagnosed by the test). CONCLUSION: Where access to endoscopy is limited, routine clinical findings could improve the diagnosis of patients with UGIB in Africa.The diagnostic accuracy of routine clinical findings for detection of esophageal varices in rural sub-Saharan Africa where schistosomiasis is endemic.

Profiling lifetime episodes of upper gastrointestinal bleeding among patients from rural Sub-Saharan Africa where schistosoma mansoni is endemic.

INTRODUCTION: Severe chronic hepatic schistosomiasis is a common cause of episodes upper gastrointestinal bleeding (UGIB) in sub-Saharan Africa (SSA). However, there is paucity of data on clinical epidemiology of episodes of UGIB from rural Africa despite on going public health interventions to control and eliminate schistosomiasis. METHODS: Through a cross sectional study we profiled lifetime episodes of upper gastrointestinal bleeding and associated factors at a rural primary health facility in sub-Saharan Africa were schistosomiasis is endemic. The main outcome was number of lifetime episodes of UGIB analyzed as count data. RESULTS: From 107 enrolled participants, 323 lifetime episodes of UGIB were reported. Fifty-seven percent experienced ≥ 2 lifetime episodes of UGIB. Ninety-four percent had severe chronic hepatic schistosomiasis and 80% esophageal varices. Alcohol use and viral hepatitis was infrequent. Eighty-eight percent were previously treated with praziquantel and 70% had a history of blood transfusion. No patient had ever had an endoscopy or treatment for prevention of recurrent variceal bleeding. Multivariable analysis identified a cluster of eight clinical factor variables (age ≥ 40, female sex, history of blood transfusion, abdominal collaterals, esophageal varices, pattern x periportal fibrosis, anemia, and thrombocytopenia) significantly associated (P-value < 0.05) with increased probability of experiencing two or more lifetime episodes of UGIB in our study. CONCLUSION: Upper gastrointestinal bleeding is a common health problem in this part of rural SSA where schistosomiasis is endemic. The clinical profile described is unique and is important for improved case management, and for future research.

Treatment of intestinal schistosomiasis in Ugandan preschool children: best diagnosis, treatment efficacy and side-effects, and an extended praziquantel dosing pole.

The Ugandan national control programme for schistosomiasis has no clear policy for inclusion of preschool-children (

Epidemiology and control of intestinal schistosomiasis on the Sesse Islands, Uganda: integrating malacology and parasitology to tailor local treatment recommendations.

BACKGROUND: Intestinal schistosomiasis is often widespread among the populations living around Lake Victoria and on its islands. The Sesse Island group (containing some 84 islands), however, is typically assumed to be a low prevalence zone, with limited transmission, but has never been surveyed in detail. Here, we present a rapid mapping assessment, bringing together snail and parasite information, at 23 sites for the presence of intermediate host snails and at 61 sites for the prevalence of intestinal schistosomiasis in school-aged children (N = 905). Two different diagnostic tools were used and compared at 45 of these sites: Kato-Katz thick faecal smears and circulating cathodic antigen (CCA) urine dipsticks. RESULTS: Biomphalaria snails were found at 11 sites but in low numbers; none was found shedding schistosome cercariae. At 22 out of the 45 sites, local prevalence by urine and/or stool diagnostics was in excess of 50%, although mean prevalence of intestinal schistosomiasis overall was 34.6% (95% confidence intervals (CI) = 31.0-38.3%) by Kato-Katz and 46.5% (95% CI = 42.7-50.4%) by CCA if 'trace' reactions were considered infection-positive (if considered infection-negative, mean prevalence was 28.1% (95% CI = 24.7-31.7%)). Diagnostic congruence between CCA and Kato-Katz was poor and significant discordance in estimated prevalence by location was found, with each often inferring different mass drug administration regimes. CONCLUSIONS: Accurate estimation of schistosome prevalence is important for determining present and future treatment needs with praziquantel; the wide range of schistosome prevalence across the Sesse Island group requires a treatment regime largely tailored to each island. In high prevalence locations, further malacological sampling is required to confirm the extent of local transmission, especially on the northern islands within the group. The observation that different diagnostic tests can provide varying results in terms of estimating prevalence by location, and hence change treatment recommendations, suggests that care must be taken in interpreting raw prevalence data. In particular, further research into the reasons for the differences in the poorer performance of the CCA test should be pursued.

Intestinal schistosomiasis and soil-transmitted helminthiasis in Ugandan schoolchildren: a rapid mapping assessment.

Even with a national control programme in place, intestinal schistosomiasis continues to be a major public health problem in school-aged children and other community members in Uganda. This is especially the case in the environments around the Great Lakes, where disease transmission is high, such as Lake Victoria. Moreover, in the most remote areas, some schools might periodically miss large-scale drug administrations owing to inaccessibility. To provide contemporary monitoring and surveillance data, 27 schools along the lakeshore were surveyed with a rapid assessment protocol to determine both prevalence and intensity of Schistosoma mansoni and soil-transmitted helminth infections. In total, 25 (92.6%) of schools were positive for S. mansoni, with an average prevalence across the surveyed children of 42% and average infection intensity of 634 eggs per gram of faeces. Mean prevalence of Trichuris trichiura, Ascaris lumbricoides and hookworm was 12.9%, 9.3% and 2.4%, respectively. Results from questionnaire data revealed a high level of itinerancy among the children, and a total of 38.2% reported to have never received treatment for schistosomiasis, despite 96% living in districts targeted by the national control programme. A birthplace outside of Uganda was a significant predictor for increased risk of schistosomiasis infection (odds ratio (OR) = 9.6), and being resident at a school for less than a year was significantly associated with absence of praziquantel treatment (OR = 0.3). Univariate regression analysis showed a trend of increasing schistosomiasis towards the eastern region of Uganda, while semivariograms of infection prevalence demonstrated a range of spatial autocorrelation of ~78 km. Soil-transmitted helminth infections were more common in the Western region. Our results emphasise how social and demographic variables such as migration may affect epidemiological trends and confound the impact of existing treatment regimes.

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

BACKGROUND: Schistosomiasis 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. METHODS: The 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. RESULTS: Two 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. CONCLUSION: Annual 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.

Microgeographical and tribal variations in water contact and Schistosoma mansoni exposure within a Ugandan fishing community.

OBJECTIVE: To explore patterns of water contact and Schistosoma mansoni exposure by age, sex, tribe and space within a single village. METHODS: For 10 months, we systematically observed water contacts made by the 800 inhabitants of a small Ugandan fishing village. In order to estimate cercarial exposure, times spent in water were weighted by snail infection levels, time of day and degree of immersion. RESULTS: There were marked differences in water contact patterns between the two main tribes, which inhabited geographically distinct ends of the village resulting in geographically distinct spatial patterns of water contact. The distributions of the intermediate hosts, Biomphalaria sudanica and Biomphalaria stanleyi, also appeared to differ over small distances. This led to quite different exposure patterns between the two tribes, particularly amongst females. CONCLUSIONS: Schistosoma mansoni exposure can vary markedly within a single village. Such non-homogenous patterns of exposure are likely to have wider implications for schistosomiasis control programmes and research studies.

The 434(G>C) polymorphism within the coding sequence of Eosinophil Cationic Protein (ECP) correlates with the natural course of Schistosoma mansoni infection.

Schistosomiasis is a chronic parasitic infection with over 200 million people infected worldwide. In Schistosoma mansoni infections, parasite-derived eggs get trapped in the liver, causing the formation of granulomas, which may develop into periportal fibrosis and portal hypertension, and thus severe morbidity. Eosinophil cationic protein (ECP) is a secretory protein of eosinophil granulocytes that efficiently kills the larval stage of S. mansoni, but also affects fibroblast functions. We have investigated the prevalence of the ECP gene polymorphism 434(G>C) in two African populations, from an S. mansoni endemic area in Uganda (n=297) and from a non-endemic area in Sudan (n=78), and also compared these with a Swedish population (n=209). The genotype frequencies in the Ugandan population differed significantly from both the Sudanese and Swedish populations (P<0.001). In the Ugandan population there was a significant association between genotype and prevalence of infection (P=0.03), with lower prevalence in subjects with the GG genotype compared with GC (P=0.02) and CC (P=0.03). There was also a trend towards an association with periportal fibrosis (P=0.08) in the Ugandan population. This suggested association was confirmed when the predominant tribe (n=212) was analysed separately (P=0.004). Our results suggest that ECP may be an important protein, both in the immune response against S. mansoni and in the development of periportal fibrosis. The results also suggest genetic selection towards the ECP 434CC genotype in populations living in S. mansoni endemic areas.

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.

Morbidity indicators of Schistosoma mansoni: relationship between infection and anemia in Ugandan schoolchildren before and after praziquantel and albendazole chemotherapy.

The potential relationship between Schistosoma mansoni and anemia was examined using data obtained by the Schistosomiasis Control Initiative (SCI) before (baseline) and 1 year after (follow-up) a chemotherapeutic treatment program in Uganda. Changes in hemoglobin (Hb) levels in 2,788 children in relation to their schistosomiasis and/or hookworm infection intensity category and baseline anemia status were analyzed. At baseline, significant predictors of childhood anemia were intensities of S. mansoni and hookworm infection. At follow-up, moderate or heavy hookworm as well as heavy S. mansoni infections were important. Children heavily infected with S. mansoni or hookworm had significantly lower Hb counts at baseline compared with those not infected. Among anemic children at the baseline survey, a significant increase in Hb counts of 0.834 g/dL after treatment was found. Our results suggest that anemia is associated with schistosomiasis and hookworm in Ugandan children and that such anemia shows a significant improvement after chemotherapy.

Morbidity due to Schistosoma mansoni: an epidemiological assessment of distended abdomen syndrome in Ugandan school children with observations before and 1-year after anthelminthic chemotherapy.

The objectives of this study were to determine the prevalence and distribution of distended abdomens among Ugandan school children across a range of eco-epidemiological settings and to investigate the relationship between distended abdomens and helminth infections, in particular Schistosoma mansoni, before and 1-year after anthelminthic treatment. A cross-sectional survey was conducted on 4354 school children across eight districts, with a longitudinal 1-year follow-up of 2644 children (60.7%). On both occasions, parasitological, biometrical and clinical data were collected for each child. Baseline prevalence of S. mansoni and hookworms was 44.3% and 51.8%, respectively. Distended abdomens, defined as an abdominal circumference ratio (ACR) >1.05, were observed in 2.5% of the sampled children, several of whom presented with particularly severe distensions necessitating hospital referral. ACR scores were highly overdispersed between districts and schools. Multivariate regression analysis revealed that S. mansoni infection accounted for only a small fraction of ACR variation, suggesting that either single point prevalence and intensity measures failed to reflect this more chronically evolved morbidity and/or that other interacting factors were involved, e.g. malnutrition and malaria. At 1-year follow-up, ACR scores showed an overall trend of regression towards the mean, potentially indicative of amelioration following chemotherapy, but geographic overdispersion still remained.

Use of circulating cathodic antigen (CCA) dipsticks for detection of intestinal and urinary schistosomiasis.

An evaluation of a commercially available antigen capture dipstick that detects schistosome circulating cathodic antigen (CCA) in urine was conducted in representative endemic areas for intestinal and urinary schistosomiasis in Uganda and Zanzibar, respectively. Under field-based conditions, the sensitivity (SS) and specificity (SP) of the dipstick was 83 and 81% for detection of Schistosoma mansoni infections while positive predictive (PPV) and negative predictive values (NPV) were 84%. Light egg-positive infections were sometimes CCA-negative while CCA-positives included egg-negative children. A positive association between faecal egg output and intensity of CCA test band was observed. Estimating prevalence of intestinal schistosomiasis by school with dipsticks was highly correlated (r=0.95) with Kato-Katz stool examinations, typically within +/-8.5%. In Zanzibar, however, dipsticks totally failed to detect S. haematobium despite examining children with egg-patent schistosomiasis. This was also later corroborated by further surveys in Niger and Burkina Faso. Laboratory testing of dipsticks with aqueous adult worm lysates from several reference species showed correct functioning, however, dipsticks failed to detect CCA in urine from S. haematobium-infected hamsters. While CCA dipsticks are a good alternative, or complement, to stool microscopy for field diagnosis of intestinal schistosomiasis, they have no proven value for field diagnosis of urinary schistosomiasis. At approximately 2.6 US dollars per dipstick, they are presently too expensive to be cost-effective for wide scale use in disease mapping surveys unless Lot Quality Assurance Sampling (LQAS) strategies are developed.

Applied and basic research on the epidemiology, morbidity, and immunology of schistosomiasis in fishing communities on Lake Albert, Uganda.

We report multidisciplinary studies on schistosomiasis which have been ongoing in the fishing communities of Piida, Booma, Bugoigo and Walakuba, on Lake Albert, Uganda, since 1996. Schistosomiasis is the major health problem in this area, with high infection intensities and prevalence. In addition to generating basic data on the epidemiology, morbidity and immunology of human schistosomiasis, this research programme is providing important descriptive and methodological information, and has contributed to the increase in operational capacity within Uganda in recent years. Such information and operational capacity are needed to facilitate much needed schistosomiasis control programmes, such as the Schistosomiasis Control Initiative that was launched in Uganda in 2003.

Progress towards countrywide control of schistosomiasis and soil-transmitted helminthiasis in Uganda.

Schistosomiasis caused by infection with Schistosoma mansoni is a serious public health burden in 38 of the 56 districts of Uganda. This article reviews the initial experience of the national control programme. Launched in 2003, this started with a pilot phase with the main aim of utilizing the experience to formulate feasible and appropriate methods of drug delivery. Overall, 432,746 people were treated and coverage was 91.4% in schools and 64.7% in communities. The issues raised by independent evaluators included that most communities did not participate in the selection of community drug distributors (CDD) and that teachers and CDDs needed refresher training mainly on health education and the management of side effects. As a way forward, it is suggested that the Ministry of Health should integrate deworming into the existing health infrastructure so that every time a child is reached for any health service, the child is also de-wormed.

Field evaluation of the Meade Readiview handheld microscope for diagnosis of intestinal schistosomiasis in Ugandan school children.

A novel, inexpensive handheld microscope, the Meade Readiview, was evaluated for field diagnosis of intestinal schistosomiasis by comparison of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) against conventional compound microscopy as part of a parasitologic survey in nine sentinel schools and a rapid mapping survey across 22 schools in Uganda. Fecal smears from 685 primary school children were examined and the overall prevalence of Schistosoma mansoni was 45%. However, prevalence by school ranged widely from 0% to 100%. For individual diagnosis the Readiview had a sensitivity of 85%, a specificity of 96%, a PPV of 95%, and an NPV of 88%. Due to the poorer movement control of the glass slide on the Readiview stage, fecal smears with less than four eggs could be overlooked. At the highest magnification (160x), egg-like objects could be confounding. Estimating prevalence by school was usually within +/- 7% of that of conventional microscopy. Since the Readiview is more robust and portable, both in size and weight, and one-tenth as expensive as the traditional compound microscope, a change in the logistics and costs associated with field infection surveillance is possible. This inexpensive microscope is a pragmatic alternative to the compound microscope. It could play an important role in the collection of prevalence data to better guide anthelmintic drug delivery and also empower the diagnostic capacity of peripheral health centers where compound microscopes are few or absent.

Origin and diversification of the human parasite Schistosoma mansoni.

Schistosoma mansoni is the most widespread of the human-infecting schistosomes, present in 54 countries, predominantly in Africa, but also in Madagascar, the Arabian Peninsula, and the Neotropics. Adult-stage parasites that infect humans are also occasionally recovered from baboons, rodents, and other mammals. Larval stages of the parasite are dependent upon certain species of freshwater snails in the genus Biomphalaria, which largely determine the parasite's geographical range. How S. mansoni genetic diversity is distributed geographically and among isolates using different hosts has never been examined with DNA sequence data. Here we describe the global phylogeography of S. mansoni using more than 2500 bp of mitochondrial DNA (mtDNA) from 143 parasites collected in 53 geographically widespread localities. Considerable within-species mtDNA diversity was found, with 85 unique haplotypes grouping into five distinct lineages. Geographical separation, and not host use, appears to be the most important factor in the diversification of the parasite. East African specimens showed a remarkable amount of variation, comprising three clades and basal members of a fourth, strongly suggesting an East African origin for the parasite 0.30-0.43 million years ago, a time frame that follows the arrival of its snail host. Less but still substantial variation was found in the rest of Africa. A recent colonization of the New World is supported by finding only seven closely related New World haplotypes which have West African affinities. All Brazilian isolates have nearly identical mtDNA haplotypes, suggesting a founder effect from the establishment and spread of the parasite in this large country.

Increases in human T helper 2 cytokine responses to Schistosoma mansoni worm and worm-tegument antigens are induced by treatment with praziquantel.

Levels of Schistosoma mansoni-induced interleukin (IL)-4 and IL-5 and posttreatment levels of immunoglobulin E recognizing the parasite's tegument (Teg) correlate with human resistance to subsequent reinfection after treatment. We measured changes in whole-blood cytokine production in response to soluble egg antigen (SEA), soluble worm antigen (SWA), or Teg after treatment with praziquantel (PZQ) in a cohort of 187 individuals living near Lake Albert, Uganda. Levels of SWA-induced IL-4, IL-5, IL-10, and IL-13 increased after treatment with PZQ, and the greatest relative increases were seen in the responses to Teg. Mean levels of Teg-specific IL-5 and IL-10 increased ~10-15-fold, and mean levels of IL-13 increased ~5-fold. Correlations between the changes in cytokines suggested that their production was positively coregulated by tegumentally derived antigens. Levels of SEA-, SWA-, and Teg-induced interferon- gamma were not significantly changed by treatment, and, with the exception of IL-10, which increased slightly, responses to SEA also remained largely unchanged. The changes in cytokines were not strongly influenced by age or intensity of infection and were not accompanied by corresponding increases in the numbers of circulating eosinophils or lymphocytes.