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Jürg Utzinger

Publications and source records attributed to Jürg Utzinger.

At least 19 recordsLinked to original sources
PubMed2006

Effect of temperature on the development of Schistosoma japonicum within Oncomelania hupensis, and hibernation of O. hupensis.

The objectives of this investigation were to assess the effect of temperature on the development of Schistosoma japonicum harboured in Oncomelania hupensis and to determine the lowest temperature threshold at which the hibernation of O. hupensis occurs. In the first experiment, adult infection-free O. hupensis, collected from Jiangsu province in eastern China, were infected with S. japonicum miracidia and raised at different temperatures under laboratory conditions. The development of miracidia until the release of cercariae was monitored employing the cercarial shedding method. In the second experiment, batches of O. hupensis were kept at temperatures below 13 degrees C with the temperature gradually reduced. Snail activity was assessed by a pin puncture method. We found a positive relationship between the development of S. japonicum within O. hupensis and temperature. In snails kept at 15.3 degrees C, S. japonicum arrested their development, while the fastest development occurred at 30 degrees C. The temperature at which half of the snails were in hibernation (ET(50)) was 6.4 degrees C. Our results underscore the pivotal role temperature plays on the biological activity of O. hupensis and the development of S. japonicum within the intermediate host. These findings are likely to have implications for the transmission of schistosomiasis in a warmer future China.

Animals↗
PubMed2006

The synthetic peroxide OZ78 is effective against Echinostoma caproni and Fasciola hepatica.

OBJECTIVES: The trematocidal properties of a synthetic peroxide, 1,2,4-trioxolane (OZ78) were determined both in vivo and in vitro. METHODS: Two weeks post-infection Echinostoma caproni-infected mice were administered single oral doses of 400-1000 mg/kg OZ78. Fasciola hepatica-infected rats were treated orally with 50-400 mg/kg OZ78 3 and 8-9 weeks post-infection. Worm burden reductions were assessed against untreated control animals. Adult F. hepatica were observed by scanning electron microscopy (SEM) after recovery from the bile duct of a rat 3 days after administration of a single oral dose of 100 mg/kg OZ78 and after in vitro exposure to concentrations of 1, 10 and 100 microg/mL OZ78. RESULTS: In the E. caproni-mouse model 100% worm burden reductions were achieved with a single oral dose of 1000 mg/kg OZ78. A single dose of 100 mg/kg OZ78 resulted in worm burden reductions of 100% against juvenile and adult F. hepatica. F. hepatica recovered from rats 3 days post-treatment displayed feeble activity and some flukes had died. Typical features revealed by SEM included extensive blebbing and sloughing. Exposure of F. hepatica to 10-100 microg/mL OZ78 in vitro resulted in the death of all trematodes. F. hepatica showed focal blebbing and sloughing of the tegument at all concentrations investigated. CONCLUSIONS: Our data indicate that OZ78 is highly efficacious against F. hepatica and E. caproni and provide a sound platform for identification of a synthetic peroxide drug development candidate against major trematode infections.

Adamantane↗
PubMed2006

Effect of artesunate and artemether against Clonorchis sinensis and Opisthorchis viverrini in rodent models.

Food-borne trematodiasis is an emerging public health problem and there is a need to develop novel treatment options. We examined the in vivo efficacy of single oral doses of artesunate and artemether administered to rodents experimentally infected with either Clonorchis sinensis or Opisthorchis viverrini. Rats infected with adult C. sinensis were administered artesunate or artemether at doses of 75, 150 or 300 mg/kg. Hamsters infected with adult O. viverrini were administered artesunate or artemether at doses of 200, 400 or 600 mg/kg. Treatment efficacy was assessed according to reductions in worm burden compared with infected but untreated control animals. Worm burden reductions of 98.6-100% were found in C. sinensis-infected rats after a single dose of artesunate and artemether at 150 mg/kg. Administration of artesunate and artemether at a dose of 400mg/kg to O. viverrini-infected hamsters resulted in worm burden reductions of 77.6% and 65.5%, respectively. However, both drugs showed toxic effects when administered to O. viverrini-infected hamsters at a dose > or =400mg/kg. Our study demonstrates that artesunate and artemether possess excellent clonorchicidal activities in vivo. These findings provide a foundation for subsequent clinical trials. More laboratory investigations are warranted to investigate further the opisthorchicidal properties of the artemisinins.

Animals↗
PubMed2006

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

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

Abdomen↗
PubMed2006

A blueprint for success: integration of neglected tropical disease control programmes.

The rapid expansion of chemotherapy-based control programmes for neglected tropical diseases has been catalysed by funding from the Bill and Melinda Gates Foundation, donations of several drugs from pharmaceutical manufacturers, and the reduced price of the drug praziquantel. Focussing on lymphatic filariasis, schistosomiasis and soil-transmitted helminthiasis, we review here the progress made to date with the implementation and integration of large-scale control programmes. Unresolved issues include a means for rapid identification of communities at highest risk of co-morbidity, cost-effective approaches for integrating the technical interventions into setting-specific packages, and determination of the most appropriate and sustainable delivery systems.

Animals↗
PubMed2006

Effect of artemether administered alone or in combination with praziquantel to mice infected with Plasmodium berghei or Schistosoma mansoni or both.

The artemisinins have become key drugs for the treatment and control of malaria, particularly within artemisinin-based combination therapies. Since the artemisinins also exhibit antischistosomal properties, their use in areas where malaria and schistosomiasis are co-endemic may have an effect on both diseases and co-infection might alter drug efficacy. We assessed the antimalarial and antischistosomal efficacies of artemether in mice infected with Plasmodium berghei or Schistosoma mansoni or both parasites concurrently. Three oral doses of 400 mg/kg artemether at 14-day intervals reduced total and female S. mansoni worm burdens by 98.7-100%, regardless of a concurrent P. berghei infection. When four daily doses of 55 mg/kg artemether were administered, which is a standard treatment schedule to cure P. berghei-infected mice, significantly lower total and female S. mansoni worm burden reductions were observed (73.1-89.2%). Artemether, administered at both of the above-mentioned treatment schemes, showed excellent antimalarial efficacy with no indications of delayed clearance of P. berghei or recrudescence, also in mice co-infected with S. mansoni. Co-infection with P. berghei had no effect on S. mansoni worm burden reductions following artemether-praziquantel combinations. Our findings point to the need for epidemiological studies in areas where malaria and schistosomiasis co-exist and where artemisinin-based combination therapies are introduced, since artemisinin-based combination therapies as part of a malaria control package may have ancillary benefits against schistosomiasis.

Animals↗
PubMed2006

An integrated approach for risk profiling and spatial prediction of Schistosoma mansoni-hookworm coinfection.

Multiple-species parasitic infections are pervasive in the developing world, yet resources for their control are scarce. We present an integrated approach for risk profiling and spatial prediction of coinfection with Schistosoma mansoni and hookworm for western Côte d'Ivoire. Our approach combines demographic, environmental, and socioeconomic data; incorporates them into a geographic information system; and employs spatial statistics. Demographic and socioeconomic data were obtained from education registries and from a questionnaire administered to schoolchildren. Environmental data were derived from remotely sensed satellite images and digitized ground maps. Parasitologic data, obtained from fecal examination by using two different diagnostic approaches, served as the outcome measure. Bayesian variogram models were used to assess risk factors and spatial variation of S. mansoni-hookworm coinfection in relation to demographic, environmental, and socioeconomic variables. Coinfections were found in 680 of 3,578 schoolchildren (19.0%) with complete data records. The prevalence of monoinfections with either hookworm or S. mansoni was 24.3% and 24.1%, respectively. Multinomial Bayesian spatial models showed that age, sex, socioeconomic status, and elevation were good predictors for the spatial distribution of S. mansoni-hookworm coinfection. We conclude that our integrated approach, employing a diversity of data sources, geographic information system and remote sensing technologies, and Bayesian spatial statistics, is a powerful tool for risk profiling and spatial prediction of S. mansoni-hookworm coinfection. More generally, this approach facilitates risk mapping and prediction of other parasite combinations and multiparasitism, and hence can guide integrated disease control programs in resource-constrained settings.

Adolescent↗
PubMed2006

Artesunate and artemether are effective fasciolicides in the rat model and in vitro.

OBJECTIVES: To study the fasciocidal properties of artesunate and artemether in the rat model and in vitro. METHODS: Adult Fasciola hepatica were exposed in vitro to 1, 10 and 100 microg/mL of artesunate, artemether and dihydroartemisinin for 72 h. Female Wistar rats were administered a single oral dose of artesunate and artemether (100-400 mg/kg) commencing 3 or 10-14 weeks post-infection and worm burden reductions were assessed against infected but untreated control rats. F. hepatica were also observed by scanning electron microscopy (SEM) after recovery from bile ducts of rats given a single oral dose of 200 mg/kg artesunate 24 and 72 h post-treatment. RESULTS: F. hepatica exposed for 72 h to 10 microg/mL of artesunate, artemether and dihydroartemisinin in vitro showed poor mobility, swelling of the worm body, roughness, damage of the tegument and blebbing. Exposure to drug concentrations of 100 microg/mL resulted in the death of all F. hepatica by 72 h. One hundred per cent worm burden reductions were achieved in rats infected with adult F. hepatica after treatment with artesunate and artemether at 400 and 200 mg/kg, respectively. Administration of artesunate and artemether at a dose of 200 mg/kg to rats harbouring juvenile F. hepatica resulted in worm burden reductions of 46% and 82%, respectively. F. hepatica recovered from rats' bile ducts 24 h after administration of 200 mg/kg artesunate showed normal activity and SEM observations revealed that there was no visible damage. Seventy-two hours post-treatment F. hepatica displayed very poor mobility and there was focal swelling of the tegument and spines. CONCLUSIONS: Artesunate and artemether exhibit promising fasciocidal activities, with the latter showing better tolerability by the hosts.

Animals↗
PubMed2006

Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk.

An estimated 779 million people are at risk of schistosomiasis, of whom 106 million (13.6%) live in irrigation schemes or in close proximity to large dam reservoirs. We identified 58 studies that examined the relation between water resources development projects and schistosomiasis, primarily in African settings. We present a systematic literature review and meta-analysis with the following objectives: (1) to update at-risk populations of schistosomiasis and number of people infected in endemic countries, and (2) to quantify the risk of water resources development and management on schistosomiasis. Using 35 datasets from 24 African studies, our meta-analysis showed pooled random risk ratios of 2.4 and 2.6 for urinary and intestinal schistosomiasis, respectively, among people living adjacent to dam reservoirs. The risk ratio estimate for studies evaluating the effect of irrigation on urinary schistosomiasis was in the range 0.02-7.3 (summary estimate 1.1) and that on intestinal schistosomiasis in the range 0.49-23.0 (summary estimate 4.7). Geographic stratification showed important spatial differences, idiosyncratic to the type of water resources development. We conclude that the development and management of water resources is an important risk factor for schistosomiasis, and hence strategies to mitigate negative effects should become integral parts in the planning, implementation, and operation of future water projects.

Africa↗
PubMed2006

Trematocidal activity of praziquantel and artemisinin derivatives: in vitro and in vivo investigations with adult Echinostoma caproni.

We examined the effects of praziquantel and the artemisinins on adult Echinostoma caproni. In vitro, both praziquantel and the artemisinins exhibited exposure-response relationships. In vivo, worm burden reductions of 100% were achieved with single oral doses of praziquantel, artesunate, and artemether at 50, 700, and 1,100 mg/kg of body weight, respectively.

Animals↗
PubMed2006

Effect of tribendimidine on adult Echinostoma caproni harbored in mice, including scanning electron microscopic observations.

Food-borne trematodiasis is an emerging public health problem with more than 10% of the world's population at risk of infection, yet there are only 2 drugs available for treatment and morbidity control. We assessed the effect of a promising broad-spectrum anthelmintic drug, i.e., tribendimidine, with an experimental focus on adult Echinostoma caproni. Female NMRI mice were infected with 30 E. caproni for 2 wk and then administered single oral doses of tribendimidine ranging between 25 and 500 mg/kg. Three days post-treatment, mice were necropsied, and adult worms were recovered from their intestines. Worm burden reductions were assessed against untreated control mice. In addition, scanning electron microscopic observations were done on adult E. caproni recovered from mice given a single dose of 150 mg/kg tribendimidine intragastrically 2, 4, and 8 hr post-treatment. Worm burden reductions of 100% were achieved at doses of 125 mg/kg and above. Severe damage of the tegument, including extensive peeling, formation of blebs, and structural loss of the definition of collar and tegumentary spines already occurred within 2 hr after drug administration. Our findings call for further investigations using tribendimidine in other trematode-animal models, because this compound shows promising trematocidal activity.

Animals↗
PubMed2006

Modeling a field trial of the RTS,S/AS02A malaria vaccine.

A double-blind, phase IIb, randomized controlled trial of the malaria vaccine RTS,S/AS02A showed an efficacy of 45.0% in reducing the force of infection for Plasmodium falciparum and of 29.9% in reducing incidence of clinical malaria in children 1-4 years of age in Manhiça, Mozambique. We simulate this trial using a stochastic model of P. falciparum epidemiology, and the setting-specific seasonal pattern of entomologic inoculations as input. The simulated incidence curve for the control group was comparable with that observed in the trial. To reproduce the observed efficacy in extending time to first infection, the model needed to assume an efficacy of 52% in reducing the force of infection. This bias arises as a result of acquired partial immunity against blood stages, thus suggesting an explanation for the lower efficacy observed in a previous trial in semi-immune adult men in The Gambia. The shape of the incidence of infection curve for the vaccine cohort in Manhiça indicates that the vaccine provides incomplete protection to a large proportion of the vaccinees, rather than offering complete protection to some recipients and none to others. This behavior is compatible with a model of no decay in efficacy over the six-month surveillance period of the trial. The model accurately reproduced the lower efficacy against clinical disease than against infection. In the simulations this finding resulted from loss of acquired clinical immunity as a result of a reduction in the force of infection in the vaccinated cohort. The model also predicted greater efficacy against severe diseases than against clinical disease. The success of the simulation model in reproducing the results of the Manhiça trial encourages us to apply the same model to predict the potential public health and economic impact if RTS,S/AS02A were to be introduced into the existing expanded program on immunization.

Child, Preschool↗
PubMed2006

Mathematical modeling of the impact of malaria vaccines on the clinical epidemiology and natural history of Plasmodium falciparum malaria: Overview.

We report a major project to develop integrated mathematical models for predicting the epidemiologic and economic effects of malaria vaccines both at the individual and population level. The project has developed models of the within-host dynamics of Plasmodium falciparum that have been fitted to parasite density profiles from malaria therapy patients, and simulations of P. falciparum epidemiology fitted to field malariologic datasets from a large ensemble of settings across Africa. The models provide a unique platform for predicting both the short- and long-term effects of malaria vaccines on the burden of disease, allowing for the temporal dynamics of effects on immunity and transmission. We discuss how the models can be used to obtain robust cost-effectiveness estimates for a wide range of malaria vaccines and vaccination delivery strategies in different eco-epidemiologic settings. This paper outlines for a non-mathematical audience the approach we have taken and its underlying rationale.

Animals↗
PubMed2006

Modeling the relationship between the population prevalence of Plasmodium falciparum malaria and anemia.

More than half of all young children and pregnant women are affected by anemia. Although its etiology is multi-factorial, malaria is likely to be a major contributor to chronic anemia in endemic areas. Recent reviews have examined the effect of community-based malaria control interventions on anemia. We analyze how the prevalence of anemia depends on that of Plasmodium falciparum malaria by developing models of the excess risk of anemia caused by malaria at a population level in 24 villages in northeastern Tanzania. In that setting, we estimated that the prevalence of a hemoglobin level < 8 g/dL attributable to malaria was 4.6% in infants, 4.1% in children one year of age, 2.7% in children two years of age, and 3.3% in women of childbearing age. Successful validation of our models in other malaria-endemic settings would enable their use for predicting the impact of malaria control interventions on anemia, and for long-term monitoring and surveillance of malaria.

Adolescent↗
PubMed2006

An approach to model the costs and effects of case management of Plasmodium falciparum malaria in sub-saharan Africa.

An important shortcoming of existing methods for estimating the cost-effectiveness of malaria control interventions is that the incidence of illness and transmission dynamics are assumed to be independent of the case management system. We have developed a model for case management and integrated it into a stochastic simulation of Plasmodium falciparum malaria dynamics. This allows us to predict the incidence of clinical episodes and of mortality while incorporating effects of case management on persistence of parasites and transmission. We make predictions for a range of different transmission intensities in sub-Saharan Africa and simulate a range of case management scenarios with different coverage rates. The model predicts that high treatment rates have a proportionately greater epidemiologic impact at low transmission levels. Further development is needed for models for health-seeking behavior and referral patterns. The current model is a first step towards useful predictions of the epidemiologic and economic consequences of introducing and/or scaling-up of malaria control interventions.

Adolescent↗
PubMed2006

Triclabendazole and its two main metabolites lack activity against Schistosoma mansoni in the mouse model.

Some have claimed that triclabendazole, a safe and efficacious drug for the treatment of fascioliasis, also exhibits antischistosomal properties, but results are conflicting. We assessed the effect of triclabendazole and its two main metabolites against two different strains of Schistosoma mansoni harbored in mice. Low worm burden reductions (18.6-35.9%) were observed in mice infected with an Egyptian strain of S. mansoni and treated with a single dose of 120 mg/kg 3 days before infection or single/double doses of 120-200 mg/kg 7 weeks after infection. Triclabendazole failed to significantly reduce hepatic and intestinal tissue egg loads, and eggs of all developmental stages were observed. Administration of 400 mg/kg of either triclabendazole, triclabendazole sulphone, or triclabendazole sulfphoxide to mice infected with a Liberian strain of S. mansoni resulted in worm burden reductions < 10%. In comparison, high worm burden reductions (82-100%) were observed in S. mansoni-infected mice treated with single oral doses of 400, 500, or 500 mg/kg twice a day praziquantel, regardless of the S. mansoni strain. We conclude that triclabendazole and its main metabolites display weak and inconsistent schistosomicidal activities.

Animals↗
PubMed2006

A growing degree-days based time-series analysis for prediction of Schistosoma japonicum transmission in Jiangsu province, China.

It has been suggested that global warming may alter the frequency and transmission dynamics of vector-borne diseases. To test this claim for schistosomiasis, we conducted a time-series analysis from 1972-2002 for 39 of the 70 counties of Jiangsu province, eastern China, where Schistosoma japonicum is partially endemic. We used a modeling approach to estimate the annual growing degree-days (AGDD), employing a lower temperature threshold of 15.3 degrees C. Our final model included both temporal and spatial components, the former consisting of second order polynomials in time plus a seasonality component, whereas the spatial trend was formed by second order polynomials of the coordinates plus the thin-plate smoothing splines. We found that temperature increased over the past 30 years in all observing stations. There were distinct temporal trends with seasonality and periodicities of 12, 6, and 3 months, whereas only marginal spatial variation was observed. The predicted AGDDs for 2006 and 2003 showed increases for the entire Jiangsu province, with the AGDDs difference between these two time points exhibiting an increase from north to south. Our data suggest that changes in temperature will alter the extent and level of schistosomiasis transmission, which is relevant for the control of S. japonicum in a future warmer China.

Animals↗