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Biomedical subjects

Jürg Utzinger

Publications and source records attributed to Jürg Utzinger.

At least 55 records · Page 3Linked to original sources
PubMed2004

Multiple parasite infections and their relationship to self-reported morbidity in a community of rural Côte d'Ivoire.

BACKGROUND: Concomitant parasitic infections are common in the developing world, yet most studies focus on a single parasite in a narrow age group. We investigated the extent of polyparasitism and parasite associations, and related these findings to self-reported morbidity. METHODS: Inhabitants of 75 randomly selected households from a single village in western Côte d'Ivoire provided multiple faecal specimens and a single finger prick blood sample. The Kato-Katz technique and a formol-ether concentration method were employed to screen faecal samples for Schistosoma mansoni, soil-transmitted helminths and intestinal protozoa. Giemsa-stained blood smears were analysed for malaria parasites. A questionnaire was administered for collection of demographic information and self-reported morbidity indicators. RESULTS: Complete parasitological data were obtained for 500/561 (89.1%) participants, similarly distributed among sex, with an age range from 5 days to 91 years. The prevalences of Plasmodium falciparum, hookworms, Entamoeba histolytica/E. dispar, and S. mansoni were 76.4%, 45.0%, 42.2%, and 39.8%, respectively. Three-quarters of the population harboured three or more parasites concurrently. Multivariate analysis revealed significant associations between several pairs of parasites. Some parasitic infections and the total number of parasites were significantly associated with self-reported morbidity indicators. CONCLUSIONS: Our data confirm that polyparasitism is very common in rural Côte d'Ivoire and that people have clear perceptions about the morbidity caused by some of these parasitic infections. Our findings can be used for the design and implementation of sound intervention strategies to mitigate morbidity and co-morbidity.

Adolescent↗
PubMed2004

Representation of authors and editors from countries with different human development indexes in the leading literature on tropical medicine: survey of current evidence.

OBJECTIVE: To assess the current international representation of members of editorial and advisory boards and authors in the leading peer reviewed literature on tropical medicine. DESIGN: Systematic review. MAIN OUTCOME MEASURES: Country affiliations, as classified by the human development index, of editorial and advisory board members of all tropical medicine journals referenced by the Institute of Scientific Information (ISI) as of late 2003 and of all contributing authors of full articles published in the six leading journals on tropical medicine in 2000-2. RESULTS: Sixteen (5.1%) of the 315 editorial and advisory board members from the 12 ISI referenced journals on tropical medicine are affiliated to countries with a low human development index and 223 (70.8%) to countries with a high index. Examination of the 2384 full articles published in 2000-2 in the six highest ranking tropical medicine journals showed that 48.1% of contributing authors are affiliated to countries with a high human development index, whereas the percentage of authors from countries with a low index was 13.7%. Articles written exclusively by authors from low ranked countries accounted for 5.0%. Our data indicate that research collaborations between a country with a high human development index and one that has either a medium or a low index are common and account for 26.5% and 16.1% of all full articles, respectively. CONCLUSION: Current collaborations should be transformed into research partnerships, with the goals of mutual learning and institutional capacity strengthening in the developing world.

Advisory Committees↗
PubMed2004

Opportunities and limiting factors of intensive vegetable farming in malaria endemic Côte d'Ivoire.

Poverty reduction policies guide development strategies. In economies that depend heavily on agriculture, in the face of rapid population growth, innovative approaches are required to satisfy food needs, increase household welfare and alleviate poverty. Irrigated agriculture is an important strategy to enhance crop production, but it must be well tailored to specific socio-ecological settings, as otherwise, it might increase the burden of water-related parasitic diseases and delay economic advance. The purpose of this study is to assess and quantify the effect of ill health, particularly malaria, on the performance of farm activity, with an emphasis on drip-irrigated vegetable farming in rural Côte d'Ivoire. Vegetable yields and revenues were monitored among 12 farmers and linked with longitudinal medical and entomological surveys. Over the course of 10 months, farmers were classified as sick, on average, for 14-15 days, with malaria accounting for 8-9 days (58%), confirming that malaria is the most important disease in this setting. There was a large heterogeneity among farmers, with malaria-related work losses ranging between 0 and 26 days. Work absenteeism correlated with overall yields and revenues. During a single cabbage production cycle, those farmers who were prescribed sick because of malaria for more than 2 days (mean: 4.2 days) had 47% lower yields and 53% lower revenues than farmers who missed a maximum of 2 days (mean: 0.3 days). This is consequential in an intensive cropping system, where substitutes for qualified workers are not readily available. We conclude that mitigating the burden of malaria is an important step towards reducing the vulnerability of people engaged in intensive agricultural production. This calls for targeted interventions to facilitate agriculture-based rural development that might spur social and economic development and reduce inequities in sub-Saharan Africa.

Adult↗
PubMed2004

Community health outreach program of the Chad-Cameroon petroleum development and pipeline project.

A critical appraisal has been presented of the CHOP for a large-scale energy infrastructure development project that was implemented in two of the world's poorest countries. The project is under close scrutiny from various independent monitoring groups, civil society organizations, and human rights groups. Reviewing the achievements and shortcomings permits the extraction of important lessons that will be critical for the future adoption of the CHOP in the current setting and for the implementation of additional CHOPs elsewhere in the developing world. The authors believe that the design must be flexible, efficient, and innovative so that a CHOP promptly can address pressing public health issues as they arise (eg, epidemic outbreak) and include the needs and demands of the concerned communities. An innovative feature of the current project is the high degree and mix of public-private partnerships. The project's CHOP also relies on partnerships. As elaborated elsewhere, public-private partnerships should be seen as a social experiment--they reveal promise but are not the solution for every problem. For this CHOP, the focus is on partnerships between a multinational consortium, government agencies, and international organizations. The partnerships also include civil society organizations for monitoring and evaluation and local NGOs designated for the implementation of the selected public health interventions within the CHOP. The governments and their respective health policies often form the umbrella under which the partnerships operate. With the increase in globalization, however, the importance and capacities of governments have diminished, and there is growing private-sector involvement. Private enterprise is seen as an efficient, innovative, pragmatic, and powerful means to achieve environmental and social sustainability. Experiences with the partnership configurations in the current CHOP are of importance for tackling grand challenges in global health by applying a systemic approach. Other innovations of the project in general, and the CHOP in particular, are the strong emphases on institutional-capacity building, integration, and sustainability. In countries like Chad and Cameroon, there are serious shortages of well-qualified health personnel. The CHOP described in this article provides leverage for initiating better healthcare that will reduce the high burden of disease in the developing world. Reducing mortality rates for infants and children younger than 5 years in sub-Saharan Africa requires massive scaling-up of malaria-control interventions (eg, large-scale distribution of ITNs to protect millions of African children), thereby approaching the Abuja targets (see Armstrong Schellenberg et al). The local NGOs that took a lead within the framework of the CHOP in the distribution of ITNs and accompanying health education messages can extend these activities to communities living outside the vicinity of the project area. Serious shortcomings of the current CHOP, consistently identified by the external monitoring groups, include the lack of a regional health plan, cumulative impact assessment, and provision of clean water and sanitation outside the narrowly defined project area. This point is of central importance, particularly for Chad, where access to clean water and improved sanitation facilities is low. Another limitation of the current CHOP is the insufficient amount of significance addressed to tuberculosis and the apparent lack of concerted control efforts against HIV infection, AIDS, and tuberculosis. These criticisms, however, must be balanced against the lack of clarity in international discourse about the proper extent of responsibility of the corporate sector for dealing with the health problems of countries in which they do business. In an elegant analysis, the environmental risk factor "unsafe water, sanitation and hygiene" was shown to be one of the major contributors to loss of healthy life, particularly in the developing world. Provision of clean water and sanitation is a key factor for sustainable control of schistosomiasis and soil-transmitted helminths. Reduction of helminth infections might have a beneficial effect on the HIV and AIDS pandemic. The question still remains: What is, or should be, the scope and limits of responsibility of the corporate sector in solving these problems? There is a critical need for the monitoring and evaluation of the long-term impact of a CHOP that develops in parallel with a large development project, emphasizing the broadest possible determinants of health and well-being. To become operational, it requires the establishment and running of a longitudinal demographic surveillance system in the area and in adjacent areas that are unlikely to be affected by the project. This approach, coupled with regular household surveys for in-depth appraisal of health-seeking and asset indices, is the most promising source of data for impact measurement of health, poverty, and equity-related issues. It will facilitate subtle monitoring and surveillance activities, fostering a truly systemic approach by inclusion of all stake holders on the basis of the existing but constantly evolving system.

Cameroon↗
PubMed2004

Efficacy and side effects of praziquantel against Schistosoma mansoni in a community of western Côte d'Ivoire.

Praziquantel is efficacious against the adult stages of all human schistosome parasites, and has become the drug of choice for morbidity control of schistosomiasis. There is concern that resistance to praziquantel might develop or already exists, and could be further facilitated through new control initiatives relying on large-scale administration of praziquantel. Therefore, monitoring praziquantel efficacy in different epidemiological settings is required. We assessed the efficacy and side effects of praziquantel against Schistosoma mansoni in a rural community of western Côte d'Ivoire. Three consecutive stool specimens from 545 children and adults were examined by the Kato-Katz technique, revealing an overall prevalence of 40.9%. S. mansoni-infected individuals were treated with a single oral dose of praziquantel at 40 mg/kg. The most frequent side effects were abdominal pain, dizziness and diarrhoea. The overall cure rate, assessed 6 weeks post-treatment, was 60.9%. Moderate or heavy infections were only cleared in half or one-third of the individuals, respectively. The total egg count reduction was 61.4%. Infection intensity pre-treatment was significantly associated with age, cure rate, reported diarrhoea and dizziness. Our findings call for additional studies that rigorously evaluate the efficacy of praziquantel against different schistosome species in entire communities, using similarly sensitive diagnostic approaches as employed here.

Administration, Oral↗
PubMed2004

Schistosomiasis and soil-transmitted helminthiasis: common drugs for treatment and control.

Schistosomiasis is a disease caused by parasitic trematode worms (schistosomes) that currently affects 200 million people living in tropical and subtropical environments. It is a chronic disease and the latest estimates for sub-Saharan Africa are that it kills > 200000 people every year. Soil-transmitted helminthiasis (STH) is caused by intestinal nematodes. More than 2 billion people are infected worldwide and the disease burden might approach that of malaria. Recognising the enormous public health significance of schistosomiasis and STH, particularly among the poor, and in view of readily available drugs that are safe, efficacious and inexpensive, the World Health Assembly recently set forth a resolution for a combined approach for morbidity control of both diseases. This review briefly summarises the geographical distribution, life cycle and global burden of schistosomiasis and STH. The current arsenal of drugs available for morbidity control, including discovery, chemistry, pharmacological properties and aspects of therapeutic efficacy and adverse events in clinical human use is then discussed. The emphasis is on praziquantel, oxamniquine and artemisinin derivatives (against schistosomes) and albendazole, mebendazole, levamisole, pyrantel pamoate and other compounds (against intestinal nematodes). The experience gained with combination chemotherapy in schistosomiasis and STH is briefly discussed. Finally, current research needs and the critical importance for development of novel anthelmintic drugs, so that chemotherapy can continue to serve as the backbone of integrated and sustainable control of schistosomiasis and STH, is highlighted.

Animals↗
PubMed2004

Chemotherapy for major food-borne trematodes: a review.

Food-borne trematode infections, caused by liver flukes (Clonorchis, Fasciola, Opisthorchis), lung flukes (Paragonimus) and intestinal flukes (Echinostoma, Fasciolopsis, heterophyids), are significant public health problems, most notably in Southeast Asia and the Western Pacific. Globally, it is estimated that > 40 million people are infected among the 750 million people who live in endemic areas. The epidemiology of food-borne trematodiasis has changed over the past few decades, and now presents a dual picture. On the one hand, increasing numbers of infections are reported from non-endemic areas, and endemic areas are expanding due to larger areas utilised for aquaculture, domestic migration, declining socioeconomic conditions, lack of improved sanitation, and increasing availability of aquatic foods through wider distribution networks often without proper food inspections. On the other hand, social and economic advances in many Asian countries, going hand-in-hand with urbanisation, use of chemical fertilisers and, above all, the administration of safe, efficacious and inexpensive drugs, have significantly reduced the prevalence of food-borne trematode infections. In this review, the taxonomy, life cycle, and geographical distribution of the major food-borne trematodes, including issues of diagnosis and clinical disease manifestations, is summarised. The discovery, chemistry, pharmacological properties, safety, therapeutic efficacy and adverse effects of the current drugs of choice, namely praziquantel and triclabendazole, is then discussed. Recent advances on other drugs and contemporary investigations on novel compounds that might become important players in chemotherapy are highlighted. Finally, the need for research and development of new trematocidal drugs that - employed in concert with health education, improved sanitation and enhanced food safety - are key factors for sustainable control of food-borne trematodiasis, is highlighted.

Animals↗
PubMed2004

Triggering of high-level resistance against Schistosoma mansoni reinfection by artemether in the mouse model.

Artemether, a methyl ether derivative of dihydroartemisinin, not only exhibits antimalarial properties, but also possesses strong activity against schistosomula, the immature stages of a parasitic worm that can cause schistosomiasis. To test if the effect would be similar to that of irradiation with respect to the induction of immunologic protective responses, groups of mice were infected with Schistosoma mansoni cercariae and treated with artemether at 1-3 weeks post-infection. Control mice were either infected with normal cercariae or with cercariae exposed to radiation that permitted early development but not maturation of the parasites. The mice were challenged six weeks after the initial infection, and the mean numbers of schistosomes recovered in the various groups were calculated upon dissection eight weeks post-challenge. The administration of artemether two weeks after the initial infection resulted in 58% protection, while giving the drug three weeks post-infection increased the level of protection to 81%. This level of protection is as high as that normally obtained by immunization with irradiated cercariae (84% in the present study) and is superior to the level of resistance obtained with any individual schistosome vaccine candidate antigen thus far reported.

Animals↗
PubMed2003

Selection and reversal of Plasmodium berghei resistance in the mouse model following repeated high doses of artemether.

Artemether, a derivative of artemisinin, is effectively used for the treatment of malaria without any clinically relevant resistance to date. Artemether has also been developed as an antischistosomal agent, exhibiting highest activity against immature parasites. Here, we employ a rodent model and investigate whether the proposed artemether treatment schedule to prevent schistosome-attributable morbidity might select for Plasmodium berghei resistance. Mice infected with an ANKA strain of P. berghei were treated with artemether at either 47 mg/kg or 300 mg/kg. Once every 7-10 days, parasitized erythrocytes were passed to the next group of mice, receiving the same doses of artemether, for 50 passages. Resistance development was slow but increased considerably over the final ten passages. At the higher dose of artemether, the indices of resistance were 4.8 and 8.8 after 40 and 50 passages, respectively. Importantly, resistance was unstable, since sensitivity reverted to near-normal after five passages without drug pressure. A moderate index of P. berghei resistance and no apparent reversibility was found in comparative experiments employing pyronaridine. In conclusion, the pace of resistance development in P. berghei to repeated high doses of artemether is slow and reversible.

Animals↗
PubMed2003

Schistosoma japonicum: In vitro effects of artemether combined with haemin depend on cultivation media and appraisal of artemether products appearing in the media.

We recently found that the exposure of schistosomes in vitro to artemether plus haemin can lead to parasite death, while exposure to each compound singly had no effect. Since these observations might be relevant to understanding the mechanism of action of artemether against schistosomes, we conducted additional experiments. First, we performed a comparative appraisal of Schistosoma japonicum survival after incubation in two media, namely Hanks' balanced salt solution (HBSS) and RPMI 1640, supplemented with inactivated calf serum, antibiotics and different concentrations of artemether and/or haemin. Worm mortalities were consistently higher and occurred faster in HBSS when compared to RPMI 1640. Second, we investigated the behaviour of artemether in different chemical systems, including reduced glutathione or cysteine, in the presence of haemin or ferrous sulfate. Cleavage of the endoperoxide bridge of artemether occurred in all experiments, consistently forming five different products, of which one has not been described previously. Third, RPMI 1640 and HBSS media were supplemented with artemether and haemin in the presence of S. japonicum. The consumption of artemether in RPMI 1640 was much faster than in HBSS. Trace amounts of artemether and five free radical reaction products of artemether could be detected in RPMI 1640 after 24-48 h. In contrast, large amounts of artemether remained without the formation of free radical products in HBSS under the same conditions. These findings coincide with significantly higher schistosome mortalities employing HBSS instead of RPMI 1640. Our results suggest that it is artemether or an active metabolite thereof (most likely a carbon-centred free radical), rather than any free radical reaction product that is harmful for the worms. We speculate that schistosomes ingest artemether and cleave it in their gut. This cleavage is induced by haemin or another iron-containing molecule. These findings might be a further step forward in elucidating the mechanism of action of artemether against schistosomes.

Animals↗
PubMed2003

Random spatial distribution of Schistosoma mansoni and hookworm infections among school children within a single village.

Schistosomes and soil-transmitted helminths currently infect a third of the world's human population. An important feature of these parasitic infections is their focal distribution, which has significant implications for control. Only a few studies have been carried out at the microepidemiological scale, comparing infection levels among individuals or households within a single village. In this study, data are presented from a cross-sectional survey, examining all children attending a primary school in rural Côte d'Ivoire over several consecutive days for Schistosoma mansoni, soil-transmitted helminths, and intestinal protozoa. All houses in the main village were mapped, and school children were linked to these households for small-area spatial analyses. Comparison between the 260 school children who live within the main village and the 89 children who reside in nearby settlements revealed significant differences in the overall prevalence and intensity of infections with S. mansoni and hookworm, confirming the focal nature of these 2 parasites. On the other hand, S. mansoni and hookworm infections exhibited random spatial patterns within the main village. The validity of these results is discussed in the context of this epidemiological setting, drawing attention to the issue of scale. Our findings have direct implications for intervention because they call for a uniform, community-wide approach to control schistosomiasis and soil-transmitted helminthiasis. Implementation can be relatively straightforward, and the proposed control approach might be cost-effective and prove sustainable.

Adolescent↗
PubMed2003

Randomized, double-blind, placebo-controlled trial of oral artemether for the prevention of patent Schistosoma haematobium infections.

Artemether is an efficacious antimalarial drug that also displays antischistosomal properties. Laboratory studies have found that artemether curtails the development of adult worms of Schistosoma japonicum, S. mansoni and S. haematobium, and thus prevents morbidity. These findings have been confirmed in clinical trials for the former two parasites; administered orally once every 2-3 weeks, artemether significantly reduced the incidence and intensity of patent infections. Here, we present the first randomized, double-blind, placebo-controlled trial of artemether against S. haematobium, done in a highly endemic area of Côte d'Ivoire. Urine specimens from 440 schoolchildren were examined over 4 consecutive days, followed by two systematic praziquantel treatments 4 weeks apart. S. haematobium-negative children were randomized to receive 6 mg/kg artemether (N = 161) or placebo (N = 161). Medication was administered orally for a total of six doses once every 4 weeks. Adverse events were assessed 72 hours after medication, and perceived illness episodes were monitored throughout the study period. Incidence and intensity of S. haematobium infections, and microhematuria and macrohematuria were assessed 3 weeks after the final dosing. We also monitored malaria parasitemia and treated positive cases with sulfadoxine-pyrimethamine (SP). Oral artemether was well tolerated. The incidence of patent S. haematobium infections in artemether recipients was significantly lower than in placebo recipients (49% versus 65%, protective efficacy: 0.25, 95% CI: 0.08-0.38, P = 0.007). The geometric mean infection intensity in the artemether group was less than half that of the placebo recipients (3.4 versus 7.4 eggs/10 mL urine, P < 0.001). Heavy S. haematobium infections, microhematuria and macrohematuria, and the incidence of malaria parasitemia were all significantly lower in artemether recipients. In conclusion, previous findings of efficacy of artemether against S. japonicum and S. mansoni were confirmed for S. haematobium, although the protective efficacy was considerably lower. These findings enlarge the scope and potential of artemether and further contribute to discussions of its role as an additional tool for integrated schistosomiasis control.

Administration, Oral↗
PubMed2002

Ultrastructural alterations in adult Schistosoma mansoni caused by artemether.

Progress has been made over the last decade with the development and clinical use of artemether as an agent against major human schistosome parasites. The tegument has been identified as a key target of artemether, implying detailed studies on ultrastructural damage induced by this compound. We performed a temporal examination, employing a transmission electron microscope to assess the pattern and extent of ultrastructural alterations in adult Schistosoma mansoni harboured in mice treated with a single dose of 400 mg/kg artemether. Eight hours post-treatment, damage to the tegument and subtegumental structures was seen. Tegumental alterations reached a peak 3 days after treatment and were characterized by swelling, fusion of distal cytoplasma, focal lysis of the tegumental matrix and vacuolisation. Tubercles and sensory organelles frequently degenerated or collapsed. Typical features of subtegumental alterations, including muscle fibres, syncytium and parenchyma tissues, were focal or extensive lysis, vacuolisation and degeneration of mitochondria. Severe alterations were also observed in gut epithelial cells and vitelline cells of female worms. Our findings of artemether-induced ultrastructural alterations in adult S. mansoni confirm previous results obtained with juvenile S. mansoni and S. japonicum of different ages.

Animals↗
PubMed2002

Transmission electron microscopic observations on ultrastructural damage in juvenile Schistosoma mansoni caused by artemether.

Artemether, a derivative of the antimalarial artemisinin, has been shown to induce rapid and extensive alteration to the tegument of juvenile Schistosoma japonicum, S. mansoni and S. haematobium. Less is known with regard to ultrastructural damage caused by artemether; therefore, the present work was designed to assess the damage in juvenile S. mansoni. Mice infected with S. mansoni were treated intragastrically with a single dose of 400 mg/kg artemether 21 days post-infection. Between 8 h and 14 days after treatment groups of two mice were sacrificed, and schistosomula recovered for transmission electron microscopic observations. Ultrastructural damage was seen in the tegument, subtegumental musculature, parenchymal tissues and gastrodermis. It was already apparent 8 h after drug administration and increased gradually to reach a peak, 7 days post-treatment. Tegumental alterations were characterised by swelling, vesiculation and degeneration of sensory structures. Damage in subtegumental musculature, parenchymal tissues and gastrodermis included swelling, focal or extensive lysis, and decrease in granular endoplasmatic reticulum. Fourteen days after treatment ultrastructural damage was still seen in most schistosomula, however, there was partial repair in some specimens. The ability of artemether to cause extensive ultrastructural damage to juvenile S. mansoni correlates with its schistosomicidal effects and confirms earlier findings with S. japonicum.

Animals↗