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Biomedical subjects

Marcel Tanner

Publications and source records attributed to Marcel Tanner.

At least 91 records · Page 5Linked to original sources

Recent investigations of artemether, a novel agent for the prevention of schistosomiasis japonica, mansoni and haematobia.

Two decades ago, a group of Chinese scientists discovered the antischistosomal properties of artemether, a derivative of the antimalarial drug artemisinin. However, it was only recently that the importance of this finding was recognized internationally, following a collaborative effort between Chinese, European and African scientists, who investigated the effects of artemether against the major human schistosome species. Laboratory studies revealed that artemether exhibits the highest activity against juvenile stages of the parasites, while adult worms are significantly less susceptible. There was no indication of neurotoxicity following repeated high doses of artemether given fortnightly for up to 5 months. Randomized controlled clinical trials confirmed that artemether, orally administered at a dose of 6 mg/kg once every 2-3 weeks, results in no drug-related adverse effects, and significantly reduces the incidence and intensity of schistosome infections. The risk that these treatment regimens might select for resistance, particularly for resistant-plasmodia, appears to be low. Combined treatment with artemether and praziquantel, given to animals harbouring juvenile and adult schistosome worms, resulted in significantly higher worm burden reductions than each drug administered singly. In conclusion, artemether-integrated with other control strategies-has considerable potential for reducing the current burden of schistosomiasis in different epidemiological settings.

Administration, Oral↗

Association between Schistosoma mansoni and hookworm infections among schoolchildren in Côte d'Ivoire.

Infections with Schistosoma mansoni and hookworms are widespread in sub-Saharan Africa and the burden of disease associated with both parasites is enormous. Although there is a large overlap in their geographic distribution, little is known about the association between S. mansoni and hookworm infections and the underlying mechanisms. We explored this association among 325 schoolchildren from Côte d'Ivoire, by screening multiple stool specimens over consecutive days. We found a highly significant positive association between S. mansoni and hookworm infections with an adjusted odds ratio of 2.25 (95% confidence interval: 1.31-3.85; P=0.003). Increasing infection intensity of S. mansoni was significantly correlated with an increased likelihood of concomitant hookworm infections (chi(2)=20.72; P<0.001). Egg counts in stool specimens derived from a single day did not consistently reveal the positive association between the two parasites, which underlines the importance of repeated stool examinations. Several self-reported water contact patterns were significantly associated either with S. mansoni, hookworm or concomitant infections. Our findings are of considerable importance for tailoring effective health education messages that are readily adapted to the local epidemiological setting. Complemented with other control interventions, these measures might significantly reduce the burden caused by S. mansoni and hookworm infections.

Adolescent↗

Schistosoma japonicum: effect of artemether on glutathione S-transferase and superoxide dismutase.

Glutathione S-transferase (GST) and superoxide dismutase (SOD) are major antioxidant enzymes of schistosomes that are involved in detoxification processes. To study the effect of artemether on these enzymes, mice infected with adult Schistosoma japonicum, were treated with artemether either at a subcurative (100 mg/kg) or a curative dose (300 mg/kg). Schistosomes were recovered 24-72 h post-treatment separated by sex and used for GST and SOD activity measurements. Female worms showed consistently higher GST inhibitions than males. For instance, 24 h after administration of 100 mg/kg artemether, GST activities of female worms were inhibited by 23.3%, as compared to 12.7% in males. Both activities were significantly lower when compared to worms recovered from untreated mice. Slightly higher inhibitions were observed at the higher dose of artemether, which gradually increased to levels of 52.5-55.1%, 72 h post-treatment. GST inhibitions could be reversed by application of 1,4-dithiothreitol at a concentration of 10 mmol/L. Adding L-cysteine also reduced GST inhibitions, but in female worms, GST activities remained significantly higher than in worms from untreated animals. Administration of 300 mg/kg artemether resulted in significant reductions of SOD activities in both sexes. In conclusion, these results suggest that the inhibition of GST and, to a lesser extent also SOD enzymes, could lead to increased schistosome susceptibility to oxidant attacks and might be linked with the antischistosomal action of artemether.

Animals↗

Reduction in the prevalence and intensity of hookworm infections after praziquantel treatment for schistosomiasis infection.

Praziquantel exhibits activity against all major human schistosome parasites and has become the cornerstone for treatment and morbidity control of schistosomiasis. Praziquantel is also active against a wide range of trematodes, human and veterinary cestodes and displays cysticidal effects. To the best of our knowledge anthelminthic properties have never been documented. Here, we report a study among 96 schoolchildren from an area highly endemic for Schistosoma mansoni and hookworm infection, and place particular emphasis on the effect of praziquantel on the prevalence and intensity of hookworm infections. Stool specimens were screened over several consecutive days prior and 4 weeks after systematic administration of praziquantel. We found a significant reduction in the prevalence of hookworm infection from 75.0 to 40.6% (odds ratio (OR)=0.21; 95% confidence interval (CI): 0.11-0.40). Infection intensities, expressed by geometric mean egg counts of all children, were also reduced significantly from 10.7 to 2.0 eggs per gram stool (paired t-test=7.78, P<0.001). If these findings are confirmed in other epidemiological settings - following a similarly sensitive diagnostic approach - they might become of considerable relevance. In areas where both schistosome and hookworm coexist, and praziquantel is being recommended for schistosomiasis control, large-scale application of this drug might also reduce the burden of hookworms.

Adolescent↗

Medical syncretism with reference to malaria in a Tanzanian community.

What happens when new health information is introduced into a community? We have explored this question in a semi-rural community of Southeastern Tanzania whose population has been in contact with biomedicine for many decades. With the example of malaria, we illustrate how biomedical knowledge transmitted in health messages coexists, interacts and merges with local pre-existing ideas and logics. The results are syncretic models, which may deviate considerably from what health promoters intended to transmit. Some of those may have implications for treatment of malaria, which may include delay in seeking treatment and non-compliance with therapy. Analysing this medical syncretism clearly demonstrates that even if comprehension of health messages is accurate, the way in which people interpret these messages may not be. Disentangling syncretic processes permits us to understand the dynamics of how information is processed by the recipients, and provides orientations for health promoters for adapting messages to the local context.

Female↗

Screening for schistosomiasis with questionnaires.

New schistosomiasis control initiatives have been launched to reduce significantly the current global burden of this disease, mainly through regular administration of praziquantel to schoolchildren living in endemic areas. Because schistosomiasis is distributed focally, epidemiological tools for rapid and inexpensive identification of communities at highest risk of morbidity are required to target praziquantel most efficiently. This article outlines the development and validation of simple questionnaires for screening of Schistosoma haematobium and Schistosoma mansoni in sub-Saharan Africa.

Africa South of the Sahara↗

Serum retinol of Chadian nomadic pastoralist women in relation to their livestocks' milk retinol and beta-carotene content.

Human serum retinol and livestock milk retinol levels were assessed as part of a study on the health status of Chadian nomadic pastoralists and their livestock in close partnership between Chadian public health and livestock institutions. Of the examined women (n = 99), 43% were moderately retinol-deficient (0.35 mol/L < x < 0.7 mol/L 95% CI; 33-54%), and 17% severely retinol-deficient (< 0.35 mol/L 95% CI; 10-26%). None of the interviewed women (n = 87) reported the consumption of fruit, and only two of fresh vegetables were reported consumed in the past 24 hours. Milk is the almost exclusive source of vitamin A for these populations. Goats (n = 6) had the highest average milk retinol level (329 +/- 84 micrograms/kg [mean +/- SEM]), followed by cattle (n = 25; 247 +/- 32 micrograms/kg), and camels (n = 12; 120 +/- 18 micrograms/kg). Milk retinol levels did not differ between the rainy and dry seasons. Human serum retinol depends significantly on livestock milk retinol levels (partial slope 0.23; 95% CI: 0.008-0.47). Our study supports the use of goat and cow milk as an important source of vitamin A in pastoral nomadic settings. However, the levels still require to be complemented further by promoting green leafy vegetables, fruits, and supplements.

Animals↗

Risk factors for child mortality in rural Tanzania.

We conducted a community-based nested case-control study of post-neonatal deaths in children under 5 years, with frequency-matched controls chosen from a full sampling frame provided by a demographic surveillance system. Using a questionnaire, we studied treatment-seeking behaviour in fatal illness. In cases and controls we investigated demographic and socio-economic factors, health-seeking behaviour, the household environment including accessibility of health care, and individual child care factors. Half of the deaths (215/427) occurred at home, and one-third (146/427) at a health facility. Three-quarters (330/427) of the children who died had received treatment from a health facility in their fatal illness. Four independent risk factors for death were identified which were each associated with more than 5% of child mortality: not being carried on the back while the mother cooked [odds ratio (OR) 1.6: 1.3, 2.0], poor maternal education (OR 1.4: 95% CI 1.0, 1.9 for those with no education compared with those with complete primary education), lack of exclusive breastfeeding in the first 3 months of life (OR 1.4: 1.1, 1.8), and low socio-economic status (OR 1.3: 1.0, 1.6). The majority of children who died had sought treatment at a health facility during the fatal illness, which would lend support to interventions to improve case-management. The association between mothers carrying their children and child survival was unexpected and deserves further investigation.

Case-Control Studies↗

Polyparasitism with Schistosoma mansoni, geohelminths, and intestinal protozoa in rural Côte d'Ivoire.

Single species infections with schistosomes, geohelminths, and intestinal protozoans are common over large parts of sub-Saharan Africa, and it is expected that polyparasitism affects a considerable proportion of the population, hence posing a great toll on public health. However, few investigations have been carried out to quantify the extent of polyparasitism. Here, a detailed assessment is reported for the epidemiology of Schistosoma mansoni, geohelminths, and intestinal protozoan infections, with particular emphasis on polyparasitism among 260 community members in rural Cĵte d'Ivoire. Schistosoma mansoni, Entamoeba coli, and hookworm were the predominant species with prevalences of 71.5, 64.6, and 51.9%, respectively. Only 8 individuals displayed no infection, whereas two-thirds of the population harbored 3 or more parasites concurrently. There were a series of significant pairwise parasite co-occurrences, e.g., between S. mansoni and hookworms and between S. mansoni and E. coli. It is concluded that polyparasitism in the population studied here was very common, which is probably the case also in other areas of rural Cĵte d'Ivoire and elsewhere in sub-Saharan Africa. These findings call for integrated approaches to effectively control multiple parasitic and protozoan infections.

Adolescent↗

Potential long-term toxicity of repeated orally administered doses of artemether in rats.

Artemether, an efficacious antimalarial drug, effectively prevents patent schistosome infections and morbidity, as established in laboratory models and in clinical trials. In view of concern about the potential long-term toxicity, rats were treated orally with 80 mg/kg artemether once every 2 weeks for 5 months. After the final treatment, routine blood test results were normal except for reversible reductions of reticulocyte counts and reversible increases in hemoglobin levels. Liver and kidney function and histopathological examination showed no differences between treated and untreated rats. Administration of 400 mg/kg artemether resulted in transient focal vesicle degeneration of the liver or slight damage to the proprius layer lamina of intestinal villi. No damage to the central nervous system tissues, including cerebrum, cerebellum, midbrain, thalamus, pons, medulla oblongata, and spinal cord, was seen at either concentration. There were no alterations in electrocardiograms during the 6-month treatment period. We conclude that 80 mg/kg artemether administered once every 2 weeks is safe, and doses of 400 mg/kg do not result in evidence of neurotoxicology.

Administration, Oral↗

The safety and efficacy of sulfadoxine-pyrimethamine, amodiaquine, and their combination in the treatment of uncomplicated Plasmodium falciparum malaria.

The safety and efficacy of amodiaquine (AQ), sulfadoxine-pyrimethamine (SP), and coadministered AQ+SP was assessed in 351 Tanzanian children (age range, 6-59 months) with uncomplicated Plasmodium falciparum malaria. This open, randomized study followed the 28-day World Health Organization (WHO) protocol and evaluated safety using clinical and laboratory parameters. Children receiving SP were more likely to vomit during follow-up (32% vs. 17%: P = 0.03), and SP alone resulted in prolonged fever clearance times. Although Day 7 and Day 14 clinical and parasitological cure rates were similar, by Day 28 45% of children treated with AQ demonstrated R1 resistance and 27.5% were clinical failures compared with 25% and 6.3%, respectively, for SP alone. Coadministered AQ+SP was safe, combined the greater clinical (96.2%) and parasitological (64.2%) efficacy of SP with the more rapid symptom resolution of AQ, and reduced the incidence of gametocytemia during follow-up (AQ+SP 12.6% vs. SP 29.9%; P = 0.001). The level of R1 resistance to SP may herald a rapid decline in its efficacy as SP drug pressure increases. Coadministration of AQ+SP may delay this.

Amodiaquine↗

Questionnaires for rapid screening of schistosomiasis in sub-Saharan Africa.

New initiatives are aiming to reduce the global burden of schistosomiasis, mainly through the large-scale application of chemotherapy. To target chemotherapy effectively, rapid assessment procedures are needed for identifying high-risk communities that are foci for the disease. In this review, we examine the development and validation of simple school questionnaires for screening communities for Schistosoma haematobium and S. mansoni rapidly and inexpensively. The focus is on sub-Saharan Africa, where 85% of the current schistosomiasis burden is concentrated. For more than a decade, the questionnaire approach has been validated in 10 countries, with 133 880 children interviewed in 1282 schools, and with 54 996 children examined for S. haematobium. The questionnaires were well accepted, highly reliable, and of low cost. The success of the questionnaires is explained by the fact that S. haematobium infections were easily perceived through the presence of blood in urine. Evidence from 48 258 children interviewed in 545 schools indicated that reported blood in stools and bloody diarrhoea are valuable indicators for community diagnosis of S. mansoni. However, the diagnostic performance of the questionnaires for S. mansoni was weaker than for S. haematobium, and although these results are encouraging, the questionnaires need additional validation. Recently, questionnaires were extended from community to individual diagnosis and showed considerable promise. Questionnaires are now available for promptly defining the magnitude of schistosomiasis in a large area, which will allow limited resources for morbidity control to be allocated optimally.

Africa South of the Sahara↗

[Rapid identification of Oncomelania hupensis snail habitat in the Poyang Lake region by Geographic Information System (GIS) and Remote Sensing (RS)].

OBJECTIVE: To identify Oncomelania hupensis snail habitats and areas with high transmission potential by GIS/RS. METHODS: Marshland areas near high endemic villages of schistosomiasis in the Poyang Lake region were selected. Corresponding map was digitized and (Landsat 5 TM) image was corrected according to the digital map. The image in dry seasons was calculated by both normalized difference vegetation index (NDVI) and tasseled cap model. RESULTS: Result showed that snails spots were distributed in class 6, 7 and 8. Farther analysis of both NDVI and tasseled cap model showed that the snail habitats were mainly distributed in the areas where NDVI value was more than 110, and in tasseled cap wetness value between -10 to 3 with correction rate 94.93%. CONCLUSION: First step was to use unsupervised classification to define the class 6, 7 and 8 snail habitat environment. Second step was to extract the value by NDVI model, and to define a healthy vegetation as snail suspicious habitat when NDVI value was more than 110. Then the third step was to use tasseled cap wetness model to define the areas as snail habitats which value was between -10 to 3.

Animals↗

Cost-effectiveness analysis of the impacts on infection and morbidity attributable to three chemotherapy schemes against Schistosoma japonicum in hyperendemic areas of the Dongting Lake region, China.

A study was carried out in 8 villages endemic with S. japonicum in Hunan Province, China from 1998 to 2000 to evaluate the cost-effectiveness in preventing schistosome infection and related morbidity under three chemotherapy schemes: (1) 'clue' chemotherapy, consisting of treatment to those with contact with infected water and/or symptoms of infection; (2) 'mass' chemotherapy-treatment to all the villagers except those not able to take praziquantel; and (3) 'screen' chemotherapy-treatment prescribed to the stool egg positive cases after Kato-Katz examination. An itemized cost menu was used to estimate the cost incurred to each scheme, from the perspective of the health care provider. The numbers of cases prevented by chemotherapy schemes were estimated through standardized attributable fractions of the outcomes to absence of chemotherapy before intervention. The cost-effectiveness ratios were calculated using weighted ranks of unit costs of the four outcome measurements: the costs per case with infection, liver and spleen abnormality (as determined by ultrasonography) prevented and 1% reduction in intensity of infection (as estimated by egg per gram feces, EPG) after the two years of intervention. Sensitivity of total cost to changes in the costs of personnel, praziquantel and other key factors were analyzed. It is demonstrated that all the three schemes had a significant impacts on the prevalence and intensity of infection, but the overall effects on liver and spleen morbidity of the residents varied between schemes. Mass chemotherapy achieved the best cost-effectiveness ratio, with unit costs of preventing cases of infection, liver and spleen abnormality and 1% reduction of EPG being RMB yuan 161.2, 99.8, 219.3 and 176.3, respectively. However, clue and screen chemotherapy schemes did not show significant prevention of liver damages in the villagers. The unit costs per case prevented for the outcomes were RMB yuan 140.2, 602.7 and 169.3, respectively for clue chemotherapy, while RMB yuan 190.0, 448.4 and 145.0 respectively for screen chemotherapy. The study concluded that mass chemotherapy should still be the choice of preference in areas where prevalence of infection and frequencies of contact with infested water by residents are high, particularly if the drug cost could be further reduced. Clue chemotherapy could be an alternative to mass chemotherapy, especially when the frequency of water contact is not as high as 80% recorded in our study. Screen chemotherapy is the least favored option in the hyperendemic area of Hunan Province.

Adolescent↗

Decentralizing EPI services and prospects for increasing coverage: the case of Tanzania.

Primary health Care (PHC) strategies were adopted widely in 1978 after the Alma Ata declaration to improve accessibility to health services and the health of the people. Of the strategies of PHC was the decentralization of health services to lower levels in order to enhance participation and responsiveness of the health system to local problems. While PHC was being promoted vertical programmes such as the expanded programme on immunization (EPI) were also being promoted and achieved substantial benefits. However, almost 25 years later many countries have not been able to achieve these health goals. This study addressed the question: Can we make the process of health care decentralization more likely to support health system and EPI goals? This study analysed the experience of EPI decentralization at national, regional and district levels. Several stakeholders were identified who were supportive and others who were non-supportive of the process. Community support to EPI measured by using willingness to pay (WTP) for kerosene (to keep vaccines cool) was low. It was significantly (p < 0.05) associated with whether providers in the nearest health facility properly attended the target population and whether the providers in the facility were available when needed. There was a substantial stakeholder support and opposition to the process of decentralization at the district level. Community support was not high possibly due to the perceived non-availability of the service providers and their lack of awareness of the population they serve. It was proposed that reforms should give priority to the involvement of communities and peripheral health facility providers in the process.

Delivery of Health Care↗

Comparative study of the effects of artemether and artesunate on juvenile and adult Schistosoma mansoni in experimentally infected mice.

Artemether and artesunate, derivatives of the antimalarial artemisinin, also exhibit antischistosomal properties. There is a need to assess comparatively the activity of both compounds against different developmental stages of schistosome parasites. Since artemisinin derivatives will be increasingly used to treat malaria, it is important to study the effects of 7-day monotherapy regimens on schistosome infections. We carried out experiments with mice, infected with juvenile or adult Schistosoma mansoni, and treated with artemether or artesunate at various doses and regimens including those currently used for monotherapy of malaria. Three doses of artemether, at concentrations of 150 or 300 mg/kg, administered to mice with juvenile S. mansoni resulted in worm reductions of 88-97%, which were significantly higher than the 67-77% obtained with artesunate (P < 0.05). Total concentrations of 600 or 800 mg/kg artemether, administered over 2 or 4 consecutive days to mice with adult S. mansoni, reduced the worm burden significantly by 46-51% (P < 0.05). The reduction of the worm burden observed with artesunate was considerably lower, 24-33%, and not significant when compared with untreated control mice. Seven-day monotherapy regimens of artemether or artesunate given at different concentrations to mice with adult S. mansoni showed total worm reductions of 53-61% or 34-49%, respectively. We conclude that artemether and artesunate are efficacious antischistosomal agents, with artemether displaying consistently higher activities. Our findings may contribute to the current strategic discussions on the effect and use of artemisinin derivatives against schistosomes when they are used in malaria chemotherapy in areas of co-endemicity of both parasites.

Animals↗

Intermittent preventive antimalarial treatment for Tanzanian infants: follow-up to age 2 years of a randomised, placebo-controlled trial.

Stopping antimalarial chemoprophylaxis can be followed by increased risk of malaria, suggesting that it interferes with the development of antimalarial immunity. We report analysis of extended follow-up until age 2 years of a randomised, placebo-controlled double-blind trial of intermittent preventive antimalarial treatment in infants. The rate of clinical malaria (events per person-year at risk, starting 1 month after final dose of intermittent treatment) was 0.28 in the sulfadoxine-pyrimethamine group and 0.43 in the placebo group (protective effect 36%, 95% CI 11-53). Intermittent treatment produced a sustained reduction in the risk of clinical malaria extending well beyond the duration of the pharmacological effects of the drugs, excluding a so-called rebound effect and suggesting that such treatment could facilitate development of immunity against Plasmodium falciparum.

Antimalarials↗