Biomedical subjects

Jürg Utzinger

Publications and source records attributed to Jürg Utzinger.

66 records · Page 4Linked to original sources

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

The economic payoffs of integrated malaria control in the Zambian copperbelt between 1930 and 1950.

It has long been suggested that malaria is delaying the economic development of countries that are most severely affected by the disease. Several studies have documented the economic consequences of malaria at the household level, primarily in communities engaged in subsistence farming. A missing element is the appraisal of the economic impact of malaria on the industrial and service sectors that will probably become the backbone of many developing economies. We estimate the economic effects of integrated malaria control implemented during the colonial period and sustained for 20 years in four copper mining communities of the former Northern Rhodesia (now Zambia). Integrated malaria control was characterized by strong emphasis on environmental management, while part of the mining communities also benefited from rapid diagnosis and treatment and the use of bednets. The programmes were highly successful as an estimated 14,122 deaths, 517,284 malaria attacks and 942,347 work shift losses were averted. Overall, 127,226 disability adjusted life years (DALYs) were averted per 3-year incremental period. The cumulative costs of malaria control interventions were 11,169,472 US dollars (in 1995 US dollars). Because the control programmes were so effective, the mining companies attracted a large reservoir of migrant labourers and sustained healthy work forces. The programmes averted an estimated 796,622 US dollars in direct treatment costs and 5,678,745 US dollars in indirect costs as a result of reduced work absenteeism. Within a few years of programme initiation, Northern Rhodesia became the leading copper producer in Africa, and mining generated the dominant share of national income. Copper production and revenues, which increased dramatically during malaria control interventions, amounted to the equivalent of 7.1 billion US dollars (in 1995 US dollars). Integrated malaria control in copper mining communities was a sound investment. It had payoff for public and occupational health, generally, and without it copper extraction and social and economic development would have been impossible.

Absenteeism↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

The potential of intermittent irrigation for increasing rice yields, lowering water consumption, reducing methane emissions, and controlling malaria in African rice fields.

Rice production in sub-Saharan Africa has more than doubled in the last 3 decades and the potential to further develop rice-harvested areas is considerable. Several studies have demonstrated that the transformation of arable land into rice irrigation might create suitable habitats for large populations of disease vectors. Prominent among those are anopheline mosquitoes responsible for transmission of malaria. The method of irrigation on an intermittent basis during the rice-cropping calendar has gained renewed interest as a potentially effective malaria control strategy since the early 1980s. We review the experiences of the past 80 years with intermittent irrigation in the cultivation of rice. This method has been shown to reduce significantly the density of malaria vectors by curtailing their larval development. Furthermore, reduced methane emissions and water savings with at least equal yields were achieved in intermittently irrigated rice fields. We explore and discuss under what conditions intermittent irrigation might be beneficial in new rice-growing areas and identify steps that have to be taken to expand such programs in the future.

Africa South of the Sahara↗

PubMedDate not supplied

Conquering schistosomiasis in China: the long march.

The last half-century of schistosomiasis control activities in China have brought down the overall prevalence of human infection with Schistosoma japonicum to less than 10% of the level initially documented in the mid 1950s. Importantly, this reduction is not only, or even mainly, due to the advent of praziquantel in the 1970s and its subsequent dramatic fall in price. Instead, it is the result of a sustained, multifaceted national strategy, adapted to different eco-epidemiological settings, which has been versatile enough to permit subtle adjustments over time as the nature of the challenge changed. Consequently, prevalence has been falling relatively smoothly over the whole period rather than suddenly dropping when mass chemotherapy became feasible. Thus, early recognition of the huge public health and economic significance of the disease, and the corresponding political will to do something about it,underpinned this success. In addition, intersectoral collaboration and community participation played important roles in forming a sustained commitment to a working control strategy based on local resources. The unfolding story is presented from the early years' strong focus on snail control, by means of environmental management, to the last period of praziquantel-based morbidity control carried out under the 10-year World Bank Loan Project (WBLP). An important legacy of the WBLP is the understanding that a research component would sustain control measures and enable future progress. We are now witnessing the payoffs of this forward thinking in the form of a new promising class of drugs, improved diagnostics, and budding vaccine development in addition to novel ways of disease risk prediction and transmission control using satellite-based remote sensing. Different aspects of social and economic approaches are also covered and the importance of health promotion and education is emphasized. Issuing from the review is a set of recommendations, which might further consolidate current control activities, with the ultimate aim to eliminate schistosomiasis from the Chinese mainland.

Animals↗

PubMedDate not supplied

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↗