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Biomedical subjects

Marcel Tanner

Publications and source records attributed to Marcel Tanner.

At least 37 records · Page 2Linked to original sources

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↗

Predicting the cost-effectiveness of introducing a pre-erythrocytic malaria vaccine into the expanded program on immunization in Tanzania.

We model the cost-effectiveness of the introduction of a pre-erythrocytic malaria vaccine into the Expanded Program on Immunization. We use a dynamic stochastic simulation model of the epidemiology of Plasmodium falciparum in malaria-endemic areas and of case management in Tanzania. We consider a range of vaccine characteristics and a range of transmission settings. At low vaccine prices, the cost-effectiveness of such vaccines may be similar to that of other established preventative and curative interventions against malaria. The cost-effectiveness ratio increases rapidly and approximately linearly with vaccine cost per dose. The approach can be adopted for comparative analyses of the cost effectiveness of different vaccines and other intervention strategies.

Adolescent↗

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↗

Relationship between the entomologic inoculation rate and the force of infection for Plasmodium falciparum malaria.

We propose a stochastic model for the relationship between the entomologic inoculation rate (EIR) for Plasmodium falciparum malaria and the force of infection in endemic areas. The model incorporates effects of increased exposure to mosquito bites as a result of the growth in body surface area with the age of the host, naturally acquired pre-erythrocytic immunity, and the reduction in the proportion of entomologically assessed inoculations leading to infection, as the EIR increases. It is fitted to multiple datasets from field studies of the relationship between malaria infection and the EIR. We propose that this model can account for non-monotonic relationships between the age of the host and the parasite prevalence and incidence of disease. It provides a parsimonious explanation for the faster acquisition of natural immunity in adults than in children exposed to high EIRs. This forms one component of a new stochastic model for the entire transmission cycle of P. falciparum that we have derived to estimate the potential epidemiologic impact of malaria vaccines and other malaria control interventions.

Animals↗

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↗

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↗

Urban farming and malaria risk factors in a medium-sized town in Cote d'Ivoire.

Urbanization occurs at a rapid pace across Africa and Asia and affects people's health and well-being. A typical feature in urban settings of Africa is the maintenance of traditional livelihoods, including agriculture. The purpose of this study was to investigate malaria risk factors in urban farming communities in a medium-sized town in Côte d'Ivoire. Two cross-sectional surveys were carried out among 112 households from six agricultural zones. First, the heads of households were interviewed on agricultural land use, farming practices, water storage, sanitation facilities, and socioeconomic status. Second, a finger prick blood sample was taken from all household members and examined for the occurrence and density of Plasmodia. Geographic coordinates of houses, farming plots, and potential mosquito breeding sites were recorded and integrated into a geographic information system. Predictors of Plasmodium falciparum parasitemia were assessed using non-random and random effects Bayesian regression models. The overall prevalence of P. falciparum was 32.1%. In children < 15 years of age, risk factors for a P. falciparum infection included living in a specific agricultural zone, close proximity to permanent ponds and fish ponds, periodic stays overnight in temporary farm huts, and low socioeconomic status. Our findings indicate that specific crop systems and specific agricultural practices may increase the risk of malaria in urban settings of tropical Africa.

Agriculture↗

System level metabolic effects of a Schistosoma japonicum infection in the Syrian hamster.

A metabolic profiling strategy was used to investigate the metabolic responses of Syrian hamsters (SLAC) to a Schistosoma japonicum infection using high resolution 1H nuclear magnetic resonance (NMR) spectroscopy and pattern recognition. In two independent experiments, male hamsters were each infected with 100 S. japonicum cercariae. At days 34-36 post-infection, urine was obtained from hamsters housed individually in metabolism cages. At the same time, urine was collected from age- and sex-matched infection-free control hamsters. The main biochemical effects of a S. japonicum infection in the hamster consisted of reduced levels of urinary tricarboxylic acid cycle intermediates, including citrate and succinate and increased levels of pyruvate. In addition, a range of microbial-related metabolites, such as hippurate, p-cresol glucuronide, phenylacetylglycine and trimethylamine were also associated with a S. japonicum infection. Most of the observed biochemical effects were in common with those previously characterized for a S. mansoni infection in a mouse host. The major distinguishing consequence of a S. japonicum infection in the hamster was the inhibition of manufacture or utilization of short-chain fatty acids, when compared to a S. mansoni infection in the mouse.

Animals↗

Risk factors and spatial patterns of hookworm infection among schoolchildren in a rural area of western Côte d'Ivoire.

This study is aimed at investigating the risk factors for hookworm infection among schoolchildren in a rural area of western Côte d'Ivoire and predicting and mapping the spatial distribution of infection. We used demographic and socio-economic data from a cross-sectional survey of 6-16-year-old schoolchildren from 56 schools. Infection with hookworm was determined by microscopic examination of stool samples employing the Kato-Katz technique and an ether-concentration method. Environmental data were derived from satellite images and digitised maps. Bayesian variogram models were applied to investigate the variation of hookworm infection in relation to demographic, socio-economic and environmental factors. The overall hookworm infection prevalence, based on the pooled microscopic diagnoses, was 43.3% and ranged from 5.4 to 79.1% in the schools surveyed. Bivariate analyses showed that sex, age, socio-economic status, elevation, rainfall and land cover were significantly associated with the spatial distribution of hookworm infection. The final multivariate spatial model consisted of the covariates age, sex, socio-economic status, elevation and land cover. When assuming non-stationary underlying spatial dependency, the results of the model suggested that spatial correlation depended on the location only marginally. We conclude that, at the current resolution, it seems more reasonable to target interventions based on well-established epidemiologic risk factors, rather than on spatial factors.

Adolescent↗

Rapid urban malaria appraisal (RUMA) I: epidemiology of urban malaria in Ouagadougou.

BACKGROUND: Rapid urbanization in sub-Saharan Africa has a major impact on malaria epidemiology. While much is known about malaria in rural areas in Burkina Faso, the urban situation is less well understood. METHODS: An assessment of urban malaria was carried out in Ouagadougou in November -December, 2002 during which a rapid urban malaria appraisal (RUMA) was applied. RESULTS: The school parasitaemia prevalence was relatively high (48.3%) at the cold and dry season 2002. Routine malaria statistics indicated that seasonality of malaria transmission was marked. In the health facilities, the number of clinical cases diminished quickly at the start of the cold and dry season and the prevalence of parasitaemia detected in febrile and non-febrile cases was 21.1% and 22.0%, respectively. The health facilities were likely to overestimate the malaria incidence and the age-specific fractions of malaria-attributable fevers were low (0-0.13). Peak prevalence tended to occur in older children (aged 6-15 years). Mapping of Anopheles sp. breeding sites indicated a gradient of endemicity between the urban centre and the periphery of Ouagadougou. A remarkable link was found between urban agriculture activities, seasonal availability of water supply and the occurrence of malaria infections in this semi-arid area. The study also demonstrated that the usage of insecticide-treated nets and the education level of family caretakers played a key role in reducing malaria infection rates. CONCLUSION: These findings show that determining local endemicity and the rate of clinical malaria cases are urgently required in order to target control activities and avoid over-treatment with antimalarials. The case management needs to be tailored to the level of the prevailing endemicity.

Antimalarials↗

Rapid urban malaria appraisal (RUMA) in sub-Saharan Africa.

BACKGROUND: The rapid urban malaria appraisal (RUMA) methodology aims to provide a cost-effective tool to conduct rapid assessments of the malaria situation in urban sub-Saharan Africa and to improve the understanding of urban malaria epidemiology. METHODS: This work was done in Yopougon municipality (Abidjan), Cotonou, Dar es Salaam and Ouagadougou. The study design consists of six components: 1) a literature review, 2) the collection of available health statistics, 3) a risk mapping, 4) school parasitaemia surveys, 5) health facility-based surveys and 6) a brief description of the health care system. These formed the basis of a multi-country evaluation of RUMA's feasibility, consistency and usefulness. RESULTS: A substantial amount of literature (including unpublished theses and statistics) was found at each site, providing a good overview of the malaria situation. School and health facility-based surveys provided an overview of local endemicity and the overall malaria burden in different city areas. This helped to identify important problems for in-depth assessment, especially the extent to which malaria is over-diagnosed in health facilities. Mapping health facilities and breeding sites allowed the visualization of the complex interplay between population characteristics, health services and malaria risk. However, the latter task was very time-consuming and required special expertise. RUMA is inexpensive, costing around 8,500-13,000 USD for a six to ten-week period. CONCLUSION: RUMA was successfully implemented in four urban areas with different endemicity and proved to be a cost-effective first approach to study the features of urban malaria and provide an evidence basis for planning control measures.

Adolescent↗

A geographic information and remote sensing based model for prediction of Oncomelania hupensis habitats in the Poyang Lake area, China.

A model was developed using remote sensing and geographic information system technologies for habitat identification of Oncomelania hupensis, the intermediate host snail of Schistosoma japonicum, in the Poyang Lake area, China. In a first step, two multi-temporal Landsat TM 5 satellite images, one from the wet and the second from the dry season, were visually classified into different land-use types. Next, the normalized difference vegetation index was extracted from the images and the tasseled-cap transformation was employed to derive the wetness feature. Our model predicted an estimated 709 km2 of the marshlands in Poyang Lake as potential habitats for O. hupensis. Near-ground temperature measurements in April and August yielded a range of 22.8-24.2 degrees C, and pH values of 6.0-8.5 were derived from existing records. Both climatic features represent suitable breeding conditions for the snails. Preliminary validation of the model at 10 sites around Poyang Lake revealed an excellent accuracy for predicting the presence of O. hupensis. We used the predicted snail habitats as centroids and established buffer zones around them. Villages with an overall prevalence of S. japonicum below 3% were located more than 1200m away from the centroids. Furthermore, a gradient of high-to-low prevalence was observed with increasing distance from the centroids. In conclusion, the model holds promise for identifying high risk areas of schistosomiasis japonica and may become an important tool for the ongoing national schistosomiasis control programme. The model is of particular relevance for schistosome-affected regions that lack accurate surveillance capabilities and are large enough to be detected at most commercially available remote sensing scales.

Animals↗

Evaluation of the discriminatory power of variable number tandem repeat (VNTR) typing of Mycobacterium bovis strains.

The discriminatory power of variable number tandem repeat (VNTR) typing based on 16 known loci (12 MIRUs, 3 ETRs and VNTR 3232) was assessed for Mycobacterium bovis strains collected sequentially at the slaughterhouse of N'Djaména, Chad. Of 67 M. bovis strains analyzed, 67% were clustered. In this study, VNTR typing was highly discriminative with an overall allelic diversity (h(oa)) of 0.922. We defined five loci (ETR A, B, C and MIRU 26, 27) as highly (h>0.25), two loci (MIRU 4, and VNTR 3232) as moderately (0.11<h<0.25) and three loci (MIRU 16, 20, 31) as poorly (0.01<h<0.11) discriminative. Six loci (MIRU 2, 10, 23, 24, 39, and 40) showed no polymorphism at all. VNTR typing of the five highly discriminative loci (h=0.917) proved to be most appropriate for first line typing of M. bovis strains of Chad and superior than spoligotyping (h(sp)=0.789). In contrast to Mycobacterium tuberculosis strains, a consensus on VNTR loci needs to be found for M. bovis strains. The selection of a generally agreed set of VNTR loci for molecular discrimination of M. bovis in different geographical settings is discussed.

Alleles↗

A review of geographic information system and remote sensing with applications to the epidemiology and control of schistosomiasis in China.

Geographic information system (GIS) and remote sensing (RS) technologies offer new opportunities for rapid assessment of endemic areas, provision of reliable estimates of populations at risk, prediction of disease distributions in areas that lack baseline data and are difficult to access, and guidance of intervention strategies, so that scarce resources can be allocated in a cost-effective manner. Here, we focus on the epidemiology and control of schistosomiasis in China and review GIS and RS applications to date. These include mapping prevalence and intensity data of Schistosoma japonicum at a large scale, and identifying and predicting suitable habitats for Oncomelania hupensis, the intermediate host snail of S. japonicum, at a small scale. Other prominent applications have been the prediction of infection risk due to ecological transformations, particularly those induced by floods and water resource developments, and the potential impact of climate change. We also discuss the limitations of the previous work, and outline potential new applications of GIS and RS techniques, namely quantitative GIS, WebGIS, and utilization of emerging satellite information, as they hold promise to further enhance infection risk mapping and disease prediction. Finally, we stress current research needs to overcome some of the remaining challenges of GIS and RS applications for schistosomiasis, so that further and sustained progress can be made to control this disease in China and elsewhere.

Animals↗

Diagnosis and management of tuberculosis by private practitioners in Manila, Philippines.

SETTING: Private for-profit health care providers are prominent in the health system of the Philippines. OBJECTIVES: To examine the practices of the private practitioners in Malabon, Metropolitan Manila, Philippines, concerning diagnosis and treatment of tuberculosis (TB). DESIGN: Forty-five private practitioners of Malabon who treat adult TB patients were interviewed. RESULTS: For diagnosis, most private practitioners relied on the clinical presentation and result of an X-ray. Only 13% of the respondents routinely also asked for sputum examination. Ninety-six percent used X-ray as a tool to monitor treatment. Sixty percent of the respondents prescribed a regimen consisting of isoniazid, rifampicin, pyrazinamide, and ethambutol. Except for rifampicin, over-dosage was common. For re-treatment cases, none prescribed the WHO-recommended re-treatment regimen. The private practitioners perceived the main reasons for patient non-adherence to be the patients' lack of finances to buy drugs and patients' perceived well being after a certain period of treatment. Patients' lack of money was seen as the main obstacle to compliance. The only case holding mechanism mentioned was occasional clinic appointments of the TB patients. CONCLUSION: Private practices for diagnosis and treatment of TB typically deviate from guidelines. The quality of care among private practitioners needs improvement. Innovative strategies are required.

Adult↗

Habitat characterization and spatial distribution of Anopheles sp. mosquito larvae in Dar es Salaam (Tanzania) during an extended dry period.

INTRODUCTION: By 2030, more than 50% of the African population will live in urban areas. Controlling malaria reduces the disease burden and further improves economic development. As a complement to treated nets and prompt access to treatment, measures targeted against the larval stage of Anopheles sp. mosquitoes are a promising strategy for urban areas. However, a precise knowledge of the geographic location and potentially of ecological characteristics of breeding sites is of major importance for such interventions. METHODS: In total 151 km2 of central Dar es Salaam, the biggest city of Tanzania, were systematically searched for open mosquito breeding sites. Ecologic parameters, mosquito larvae density and geographic location were recorded for each site. Logistic regression analysis was used to determine the key ecological factors explaining the different densities of mosquito larvae. RESULTS: A total of 405 potential open breeding sites were examined. Large drains, swamps and puddles were associated with no or low Anopheles sp. larvae density. The probability of Anopheles sp. larvae to be present was reduced when water was identified as "turbid". Small breeding sites were more commonly colonized by Anopheles sp. larvae. Further, Anopheles gambiae s.l. larvae were found in highly organically polluted habitats. CONCLUSIONS: Clear ecological characteristics of the breeding requirements of Anopheles sp. larvae could not be identified in this setting. Hence, every stagnant open water body, including very polluted ones, have to be considered as potential malaria vector breeding sites.

Animals↗