Biomedical subjects
C Lengeler
Publications and source records attributed to C Lengeler.
Oral artemether for prevention of Schistosoma mansoni infection: randomised controlled trial.
BACKGROUND: Chemotherapy with praziquantel is the current strategy of choice to control schistosomiasis. However, in view of concern about praziquantel tolerance or resistance, new drugs are needed. Artemether, a derivative of the antimalarial drug artemisinin, kills immature schistosomes of Schistosoma japonicum, and reduces the incidence of infection in field trials. Laboratory studies have also showed activity by this drug against S. mansoni. We report a randomised double-blind placebo-controlled clinical trial of artemether to prevent S. mansoni infection. METHODS: The trial was done in an area of western Côte d'Ivoire endemic for S. mansoni. 354 schoolchildren were enrolled. Stool specimens were screened over four consecutive days, followed by two mass treatments with praziquantel 4 weeks apart. All S. mansoni negative children were randomly assigned to placebo (n=151) or artemether 6 mg/kg (n=138) orally six times once every 3 weeks. Adverse events were assessed 24 h after treatment. Perceived illness episodes were recorded once a week by interviewing the children with a standardised questionnaire. 3 weeks after the final medication S. mansoni infections were assessed by screening stool samples. Blood samples were examined for Plasmodium falciparum before the first and after the last artemether treatment. FINDINGS: Oral artemether showed no adverse reactions. The group that received artemether had a significantly lower incidence of S. mansoni infection (31/128 versus 68/140, relative risk: 0.50 [95% CI 0.35-0.71], p=0.00006). The geometric mean egg output among positive children in the artemether group was significantly lower than in placebo recipients (19 vs 32 eggs/g stool, p=0.017). There was also a significant reduction in the prevalence of P. falciparum. INTERPRETATION: Oral artemether is safe and shows a prophylatic effect against S. mansoni. The use of artemether may be recommended in appropriated situations as an additional tool for more effective schistosomiasis control measures. However the application needs to be carefully assessed especially in view of the concern that it could select for resistant plasmodia.
Simple school questionnaires can map both Schistosoma mansoni and Schistosoma haematobium in the Democratic Republic of Congo.
The use of self-administered questionnaires has been shown in different African countries to be inexpensive and reliable for the rapid identification of communities at highest risk of urinary schistosomiasis. For intestinal schistosomiasis due to Schistosoma mansoni there is a clear need for a similar approach. We report the results from a large-scale study undertaken in the western part of the Democratic Republic of Congo (DRC, formerly Zaire). Within 4 weeks questionnaires were correctly completed in 136 out of 160 schools (85%). In 57 of these schools children were screened for infections with schistosomes and geohelminths. The prevalence of 'schistosomiasis' as reported in the questionnaires showed the best correlation with the prevalence of S. mansoni infections (r = 0.77, P < 0.0001). Calculations of the diagnostic performance of reported 'schistosomiasis' to detect schools with a high risk of intestinal schistosomiasis gave positive predictive values of 87 and 62%, and negative predictive values of 74 and 87% for moderate and high infection thresholds, respectively. Reported 'blood in stool' was another useful indicator for intestinal schistosomiasis. Reported 'blood in urine' showed the best correlation with urinary schistosomiasis (r = 0.75, P < 0.001) and the positive predictive values were 81 and 50%, and the negative predictive values were 89 and 95% for moderate and high infection thresholds, respectively. We conclude that school children in DRC have a distinct perception of intestinal and urinary schistosomiasis and that questionnaires could be useful to identify high-risk schools for both parasites.
Insecticide-treated bednets and curtains for preventing malaria.
BACKGROUND: Malaria is an important cause of illness and death in many parts of the world, especially in Africa. There has been a renewed emphasis on preventive measures, both at community and at individual level. Insecticide treated bednets and curtains are a promising preventive measure. OBJECTIVES: The objective of this review was to assess the effects of insecticide-treated bednets or curtains in preventing malaria SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials register, Medline, Embase and the reference lists of articles. We handsearched journals, contacted researchers, funding agencies and net and insecticide manufacturers. SELECTION CRITERIA: Randomized and quasi-randomized trials of insecticide-treated bednets or curtains with a sufficient dose of a suitable insecticide compared with nets without insecticide or no nets at all. Studies including pregnant women were excluded. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data extracted by the reviewer. Trial inclusions/exclusions were reviewed by two independent individuals. MAIN RESULTS: Of 65 identified studies, 18 were included. Of these, 11 were randomized by cluster rather than individually. Mortality in children under five was measured in four trials. When impregnated nets were compared with plain nets or no nets, the summary relative risk was 0. 83. This translates to an estimate of protective efficacy of 17%. For treated nets compared with untreated nets, the relative risk of child mortality was 0.77. About six lives can be saved each year for every 1000 children protected with insecticide-treated nets. Insecticide-treated nets also reduced the incidence of mild malarial episodes by 48% (controls=no nets) and 34% (controls=untreated nets). REVIEWER'S CONCLUSIONS: Insecticide-treated nets appear to be effective in reducing childhood mortality and morbidity from malaria. Widespread access to insecticide-treated nets will require major financial, technical and operational inputs.
Efficacy of praziquantel against Schistosoma mansoni with particular consideration for intensity of infection.
Chemotherapy with praziquantel is the cornerstone of schistosomiasis control. In view of recent concern about tolerance or resistance to praziquantel, monitoring its efficacy in different epidemiological settings is required. We report a study among 253 schoolchildren in an area highly endemic for Schistosoma mansoni in western Côte d'Ivoire. After examining four consecutive stool specimens from each child, the first praziquantel treatment at 60 mg/kg divided into two doses was administered. Four weeks later, stool specimens were again screened over 4 consecutive days and revealed a cure rate of 71.6% and an egg reduction rate of 79.9%. There was a significant association between cure rate and intensity of infection prior to treatment with highest cure rates observed in light infections (P < 0.01). Praziquantel, at a single dose of 40 mg/kg, was again administered 35 days after the first treatment. The overall cure and egg reduction rates increased considerably. The association between cure rate and intensity of infection prior to the second treatment was significant but less pronounced. Twenty-two children remained S. mansoni positive after the two chemotherapy campaigns, and interestingly, many of these were only identified after repeated stool examinations. We argue that pre-patent infections may account for some of these 'treatment failures'. However, further studies in other endemic settings are needed, with parasitological diagnoses having a high sensitivity.
Simple anamnestic questions and recalled water-contact patterns for self-diagnosis of Schistosoma mansoni infection among schoolchildren in western Côte d'Ivoire.
A study to determine the diagnostic performance of simple anamnestic questions and recalled water-contact patterns for self-diagnosis of Schistosoma mansoni infection was carried out in western C te d'Ivoire. A total of 322 schoolchildren were screened over four consecutive days with the Kato-Katz technique to assess S. mansoni and concurrent geohelminth infections. Children were individually interviewed by teachers using a standardized questionnaire asking about symptoms, reported diseases, and water-contact patterns. The cumulative infection prevalence of S. mansoni was 76.4%. Univariate statistics revealed a significant association between the level of S. mansoni infection and three recalled water contact patterns: (1) fishing with nets, (2) swimming/bathing and (3) crossing rivers, but no significant association with reported symptoms and/or reported diseases. Multivariate analysis revealed significant adjusted odds ratios (OR) for crossing the river Tchéorbour (OR = 3.90, P = 0.007), crossing the river Sonbour (OR = 3.90, P = 0.008) and swimming/bathing in the latter (OR = 3.28, P = 0.017). The diagnostic performance of these water-contact patterns was characterized by high specificities but low sensitivities, hence negative predictive values. In the village studied here, recalled water-contact patterns were more useful variables than anamnestic questions for schoolchildren's self-diagnosis of S. mansoni infection, but no generalization of these findings beyond this population is possible at this time.
Rapid screening for Schistosoma mansoni in western Côte d'Ivoire using a simple school questionnaire.
The distribution of schistosomiasis is focal, so if the resources available for control are to be used most effectively, they need to be directed towards the individuals and/or communities at highest risk of morbidity from schistosomiasis. Rapid and inexpensive ways of doing this are needed, such as simple school questionnaires. The present study used such questionnaires in an area of western Côte d'Ivoire where Schistosoma mansoni is endemic; correctly completed questionnaires were returned from 121 out of 134 schools (90.3%), with 12,227 children interviewed individually. The presence of S. mansoni was verified by microscopic examination in 60 randomly selected schools, where 5047 schoolchildren provided two consecutive stool samples for Kato-Katz thick smears. For all samples it was found that 54.4% of individuals were infected with S. mansoni. Moreover, individuals infected with S. mansoni reported "bloody diarrhoea", "blood in stools" and "schistosomiasis" significantly more often than uninfected children. At the school level, Spearman rank correlation analysis showed that the prevalence of S. mansoni significantly correlated with the prevalence of reported bloody diarrhoea (P = 0.002), reported blood in stools (P = 0.014) and reported schistosomiasis (P = 0.011). Reported bloody diarrhoea and reported blood in stools had the best diagnostic performance (sensitivity: 88.2%, specificity: 57.7%, positive predictive value: 73.2%, negative predictive value: 78.9%). The study, which is probably the largest of its kind ever undertaken in Africa, revealed a moderate diagnostic performance of questionnaires for identifying individuals and/or communities at high risk from S. mansoni.
From Rio to Iragua--sustainability versus efficiency and equity for preventive health interventions.
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Short report: lack of specificity of Beilstein test in detecting pyrethroid insecticide on coloured mosquito nets.
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Relative versus absolute risk of dying reduction after using insecticide-treated nets for malaria control in Africa.
Four recently completed large-scale randomized controlled trials have assessed the impact of insecticide-treated bednets and curtains on overall child mortality in Africa. These results have sparked numerous discussions among implementing agency representatives and researchers about the public health significance of the results. For the interpretation of impact, most of the arguments have been based on the observed decrease in protective efficacy (a relative measure of impact) with increasing malaria transmission (range: 14-29%, regression for trend: F = 245 on 1,2 DF, P < 0.003). However, an analysis of the absolute measure of impact (the risk difference) showed a different pattern. The impact ranges from 3.8 to 6.9 lives saved per 1000 children protected per year, without a significant trend (F = 2.8 on 1,2 DF, P = 0.2) and with equally high values in both low and high transmission sites. When assessing the public health importance of an intervention, both relative and absolute decrease in risk should be considered.
Schistosoma mansoni, intestinal parasites and perceived morbidity indicators in schoolchildren in a rural endemic area of western Côte d'Ivoire.
There is a great need for rapid and low-cost identification of communities at high risk of intestinal schistosomiasis. We report the development of a questionnaire approach that may do so. In the first phase, 209 schoolchildren from 3 neighbouring villages in a rural area endemic for intestinal schistosomiasis in western Côte d'Ivoire were screened for Schistosoma mansoni and other helminths on 4 consecutive days using Kato-Katz thick smears. Daily infection prevalences of S. mansoni were high (60%-71%) and the cumulative infection prevalence was 92.3%. Infections with hookworms and Ascaris lumbricoides were also frequent, with cumulative prevalences of 60.8% and 38.3%, respectively. On day 3, the presence of Entamoeba histolytica/E. dispar and Giardia lamblia was assessed by a faecal concentration procedure. In the second phase, focus group discussions (FGD) were conducted: in each village one FGD with heavily infected children and one FGD with lightly or S. mansoni-uninfected schoolchildren to assess their perception of morbidity. The aim was to establish local terms indicating S. mansoni infections. 'Diarrhoea', 'blood in the stools', 'stomach disorders' and 4 terms in the local Yacouba/Dioula languages were frequently used by infected children. A simple questionnaire was then developed and the headteachers interviewed all schoolchildren individually. 'Blood in stools', gnon and toto were reported significantly more frequently among moderately and heavily S. mansoni-infected children than by those not or only lightly infected. The term gloujeu indicated borderline significance. The best diagnostic performance was found for 'blood in stool' (sensitivity: 47%; specificity: 76%; positive predictive value: 66%; negative predictive value: 60%). All schistosomiasis infections were treated with a single oral dose of praziquantel (40 mg/kg body weight) and the same questionnaire was re-administered 6 weeks post-treatment. Statistically significantly less children reported having had 'blood in stool' and 'gloujeu' after treatment (McNemar's (chi2-test, P < 0.01). We conclude that 'blood in stool', 'gnon', 'toto' and 'gloujeu' are the most reliable reported symptoms for rapid and low-cost identification of communities that are at high risk of S. mansoni infections in Côte d'Ivoire.
[Use of a questionnaire for quick identification of the principal foci of urinary bilharziasis in central Ivory Coast].
Simple questionnaires designed for use in schools have been used to identify communities at high risk for urinary schistosomiasis in several African countries but not in the Cote d'Ivoire. The primary purpose of this study was to assess the acceptance and feasibility of the school questionnaire approach in the Cote d'Ivoire. Questionnaires were distributed to 136 schools in central Cote d'Ivoire. Responses were obtained within 6 weeks from 124 schools (91.2%). A total of 12,479 school children were interviewed. At 60 schools, reagent stick tests were performed within two weeks to detect microhematuria by trained teachers. A biomedical team was sent to 14 selected schools to check results by reagent stick testing and urine filtration. Reagent stick tests showed high specificity (97%) and moderate sensitivity (67%). A strong statistical correlation was observed between responses to two key questions concerning "blood in urine" and "having had schistosomiasis" and the results of reagent stick testing (Spearman rank correlation, p < 0.0001). Our findings are in good agreement with previous reports. Using the data obtained, we were able to accurately map the distribution of urinary schistosomiasis in the study area. Use of this questionnaire for quick identification of high risk communities for urinary schistosomiasis was recommended as a preliminary step in the planned national control program and should allow better targeted of scarce resources.
Language bias in randomised controlled trials published in English and German.
BACKGROUND: Some randomised controlled trials (RCTs) done in German-speaking Europe are published in international English-language journals and others in national German-language journals. We assessed whether authors are more likely to report trials with statistically significant results in English than in German. METHODS: We studied pairs of RCT reports, matched for first author and time of publication, with one report published in German and the other in English. Pairs were identified from reports round in a manual search of five leading German-language journals and from reports published by the same authors in English found on Medline. Quality of methods and reporting were assessed with two different scales by two investigators who were unaware of authors' identities, affiliations, and other characteristics of trial reports. Main study endpoints were selected by two investigators who were unaware of trial results. Our main outcome was the number of pairs of studies in which the levels of significance (shown by p values) were discordant. FINDINGS: 62 eligible pairs of reports were identified but 19 (31%) were excluded because they were duplicate publications. A further three pairs (5%) were excluded because no p values were given. The remaining 40 pairs were analysed. Design characteristics and quality features were similar for reports in both languages. Only 35% of German-language articles, compared with 62% of English-language articles, reported significant (p < 0.05) differences in the main endpoint between study and control groups (p = 0.002 by McNemar's test). Logistic regression showed that the only characteristic that predicted publication in an English-language journal was a significant result. The odds ratio for publication of trials with significant results in English was 3.75 (95% CI 1.25-11.3). INTERPRETATION: Authors were more likely to publish RCTs in an English-language journal if the results were statistically significant. English language bias may, therefore, be introduced in reviews and meta-analyses if they include only trials reported in English. The effort of the Cochrane Collaboration to identify as many controlled trials as possible, through the manual search of many medical journals published in different languages will help to reduce such bias.
[Evidence-based medicine: approach to a more rational medicine. Arbeitsgemeinschaft Cochrane Collaboration Schweiz].
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Focus on the effect of bednets on malaria morbidity and mortality.
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Do insecticide-treated curtains reduce all-cause child mortality in Burkina Faso?
To evaluate whether insecticide-treated netting (ITN) reduces child mortality in different epidemiological settings, 4 large, randomized, controlled trials were conducted in Africa. Here we report the findings from the trial in Burkina Faso, in an area of hyperendemic and markedly seasonal malaria transmission. The trial involved 158 villages, with a total population of some 90,000, grouped into 16 geographical clusters. Ascertainment of mortality among children aged 6-59 months began in early 1993. In June/July 1994, 8 of the clusters, randomly selected, received permethrin-treated curtains. Follow-up of children and ascertainment of mortality continued until May 1996. A 15% reduction in all-cause mortality among children aged 6-59 months was observed over the 2-year period following the installation of the curtains (95% c.i. -4% to 30%). In the first year, post-intervention mortality was substantially lower in the clusters receiving curtains compared with the control clusters (rate ratio = 0.74; 95% c.i. 0.57, 0.95) but in the second year, there was no difference between mortality in the two groups (rate ratio = 0.99). The overall two-year impact of the intervention is consistent with the impacts observed in other trials which have demonstrated reductions in child mortality of from 17% to 33%. However, the year-by-year analysis raises some concerns about the long-term effect of ITN. Further follow-up of this population is warranted.
Insecticide-treated bednets reduce mortality and severe morbidity from malaria among children on the Kenyan coast.
New tools to prevent malaria morbidity and mortality are needed to improve child survival in sub-Saharan Africa. Insecticide treated bednets (ITBN) have been shown, in one setting (The Gambia, West Africa), to reduce childhood mortality. To assess the impact of ITBN on child survival under different epidemiological and cultural conditions we conducted a community randomized, controlled trial of permethrin treated bednets (0.5 g/m2) among a rural population on the Kenyan Coast. Between 1991 and 1993 continuous community-based demographic surveillance linked to hospital-based in-patient surveillance identified all mortality and severe malaria morbidity events during a 2-year period among a population of over 11000 children under 5 years of age. In July 1993, 28 randomly selected communities were issued ITBN, instructed in their use and the nets re-impregnated every 6 months. The remaining 28 communities served as contemporaneous controls for the following 2 years, during which continuous demographic and hospital surveillance was maintained until the end of July 1995. The introduction of ITBN led to significant reductions in childhood mortality (PE 33%, CI 7-51%) and severe, life-threatening malaria among children aged 1-59 months (PE 44%, CI 19-62). These findings confirm the value of ITBN in improving child survival and provide the first evidence of their specific role in reducing severe morbidity from malaria.