Biomedical subjects

Thomas Smith

Publications and source records attributed to Thomas Smith.

At least 19 recordsLinked to original sources

PubMed2006

Risk factors for surgical site infection in a Tanzanian district hospital: a challenge for the traditional National Nosocomial Infections Surveillance system index.

The incidence of surgical site infections (SSIs) was 24% in a district hospital in Tanzania. Wound classification was not an independent risk factor for SSI, indicating that risk scores developed in industrialized countries may require adjustments for nonindustrialized countries. The National Nosocomial Infections Surveillance system score required adjustments to reliably predict SSI, probably to account for improper hygiene and the lack of adjustment for the duration of surgery (defined as the 75th percentile of the duration for each type of operative procedure) to reflect local circumstances. Multidrug-resistant pathogens, such as methicillin-resistant Staphylococcus aureus and gram-negative pathogens expressing broad-spectrum beta-lactamases, have already emerged.

Adult↗

PubMed2006

El Niño Southern Oscillation (ENSO) and annual malaria incidence in Southern Africa.

We evaluated the association between annual malaria incidence and El Niño Southern Oscillation (ENSO) as measured by the Southern Oscillation Index (SOI) in five countries in Southern Africa from 1988 to 1999. Below normal incidence of malaria synchronised with a negative SOI (El Niño) and above normal incidence with a positive SOI (La Niña), which lead to dry and wet weather conditions, respectively. In most countries there was a positive relationship between SOI and annual malaria incidence, especially where Anopheles arabiensis is a major vector. This mosquito breeds in temporary rain pools and is highly sensitive to fluctuations in weather conditions. South Africa and Swaziland have the most reliable data and showed the strongest associations, but the picture there may also be compounded by the moderating effect of other oscillatory systems in the Indian Ocean. The impact of ENSO also varies over time within countries, depending on existing malaria control efforts and response capacity. There remains a need for quantitative studies that at the same time consider both ENSO-driven climate anomalies and non-ENSO factors influencing epidemic risk potential to assess their relative importance in order to provide an empirical basis for malaria epidemic forecasting models.

Africa, Southern↗

PubMed2006

Spatio-temporal analysis of the role of climate in inter-annual variation of malaria incidence in Zimbabwe.

BACKGROUND: On the fringes of endemic zones climate is a major determinant of inter-annual variation in malaria incidence. Quantitative description of the space-time effect of this association has practical implications for the development of operational malaria early warning system (MEWS) and malaria control. We used Bayesian negative binomial models for spatio-temporal analysis of the relationship between annual malaria incidence and selected climatic covariates at a district level in Zimbabwe from 1988-1999. RESULTS: Considerable inter-annual variations were observed in the timing and intensity of malaria incidence. Annual mean values of average temperature, rainfall and vapour pressure were strong positive predictors of increased annual incidence whereas maximum and minimum temperature had the opposite effects. Our modelling approach adjusted for unmeasured space-time varying risk factors and showed that while year to year variation in malaria incidence is driven mainly by climate, the resultant spatial risk pattern may to large extent be influenced by other risk factors except during high and low risk years following the occurrence of extremely wet and dry conditions, respectively. CONCLUSION: Our model revealed a spatially varying risk pattern that is not attributable only to climate. We postulate that only years characterized by extreme climatic conditions may be important for developing climate based MEWS and for delineating areas prone to climate driven epidemics. However, the predictive value of climatic risk factors identified in this study still needs to be evaluated.

Bayes Theorem↗

PubMed2006

Reduced top-down influences in contour detection in schizophrenia.

INTRODUCTION: Chronic schizophrenia patients have previously demonstrated performance deficits in contour integration tasks. The purpose of this study was to investigate whether schizophrenia patients, spanning a range of illness severity, would demonstrate responsiveness to manipulations that recruit top-down processing strategies involving learning and sequencing effects in a contour integration task. METHODS: We administered a contour integration test over four consecutive days and in two different presentation conditions each day. In one condition, the stimuli were administered in order of increasing difficulty, and in the other they were presented in random order. The order in which these two conditions were presented was counterbalanced across days and participants. In addition, a nonschizophrenia psychotic disorders control group was included to determine if past findings of a contour integration deficit in schizophrenia could be replicated in the presence of a symptomatically similar control group. RESULTS: All groups demonstrated similar learning curves across the four days and generally similar overall levels of performance, with the exception of the group of the most chronic schizophrenia patients. In addition, the order in which the stimuli were presented to subjects affected their performance, with higher scores achieved for all groups in the condition where the stimuli were presented in increasing order of difficulty. Interaction effects revealed that the effects of order presentation were greater for nonpatient than for psychotic patients. CONCLUSIONS: These data are further evidence that perceptual organization impairments in schizophrenia are illness severity-related, and that schizophrenia patients as a whole are less sensitive to top-down manipulations in this type of task.

Adult↗

PubMed2006

The impact of diet and betel nut use on skin lesions associated with drinking-water arsenic in Pabna, Bangladesh.

An established exposure-response relationship exists between water arsenic levels and skin lesions. Results of previous studies with limited historical exposure data, and laboratory animal studies suggest that diet may modify arsenic metabolism and toxicity. In this study, we evaluated the effect of diet on the risk of arsenic-related skin lesions in Pabna, Bangladesh. Six hundred cases and 600 controls loosely matched on age and sex were enrolled at Dhaka Community Hospital, Bangladesh, in 2001-2002. Diet, demographic data, and water samples were collected. Water samples were analyzed for arsenic using inductively coupled plasma mass spectroscopy. Betel nut use was associated with a greater risk of skin lesions in a multivariate model [odds ratio (OR) = 1.67; 95% confidence interval (CI), 1.18-2.36]. Modest decreases in risk of skin lesions were associated with fruit intake 1-3 times/month (OR = 0.68; 95%CI, 0.51-0.89) and canned goods at least 1 time/month (OR = 0.41; 95% CI, 0.20-0.86). Bean intake at least 1 time/day (OR = 1.89; 95% CI, 1.11-3.22) was associated with increased odds of skin lesions. Betel nut use appears to be associated with increased risk of developing skin lesions in Bangladesh. Increased intake of fruit and canned goods may be associated with reduced risk of lesions. Increased intake of beans may be associated with an increased risk of skin lesions. The results of this study do not provide clear support for a protective effect of vegetable and overall protein consumption against the development of skin lesions, but a modest benefit cannot be excluded.

Adult↗

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

Predictions of the epidemiologic impact of introducing a pre-erythrocytic vaccine into the expanded program on immunization in sub-Saharan Africa.

We predict the effects of introduction of a pre-erythrocytic vaccine against Plasmodium falciparum into a malaria-endemic population in Africa. We use a stochastic simulation model that includes components of transmission, parasitology, and clinical epidemiology of malaria and was validated using the results of field trials of the RTS,S/AS02A vaccine. The results suggest that vaccines with efficacy similar to that of RTS,S/AS02A have a substantial impact on malaria morbidity and mortality during the first decade after their introduction, but have negligible effects on malaria transmission at levels of endemicity typical for sub-Saharan Africa. The main benefits result from prevention of morbidity and mortality in the first years of life. Vaccines with very short half-life or low efficacy may have little overall effect on incidence of severe malaria. A similar approach can be used to make predictions for other strategies for deployment of the vaccine and to other types of malaria vaccines and interventions.

Adolescent↗

PubMed2006

A model for natural immunity to asexual blood stages of Plasmodium falciparum malaria in endemic areas.

Most mathematical models for acquired immunity to Plasmodium falciparum consider effects of immunity on duration of infection and infectiousness, but do not consider the most evident effect of immunity, which is to reduce parasite densities. Few attempts have been made to fit such models to field data. We propose a stochastic simulation model to predict the distributions of P. falciparum parasite densities in endemic areas, in which acquired immunity acts by reducing parasite densities. We have fitted this model to age-specific prevalence and geometric mean densities from settings in Ghana, Nigeria, and Tanzania. The model appears to reproduce reasonably well the parasitologic patterns seen in malariologic surveys in endemic areas and is appropriate for predicting the impact of interventions such as vaccination in the context of continual exposure to P. falciparum.

Adolescent↗

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

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↗

PubMed2006

Infectiousness of malaria-endemic human populations to vectors.

Despite its key role in determining the stability and intensity of malaria transmission, the infectiousness of human populations to mosquitoes has rarely been estimated. Field-based analyses of malaria transmission have frequently relied on the prevalence of asexual parasites or gametocytes as proxies for infectiousness. We now summarize empirical data on human infectiousness from Africa and Papua New Guinea. Over a wide range of transmission intensities there is little relationship between the infectiousness of human populations to vector mosquitoes and mosquito-to-human transmission intensity. We compare these data with the predictions of a stochastic simulation model of Plasmodium falciparum epidemiology. This model predicted little variation in the infectiousness of the human population for entomologic inoculation rates (EIRs) greater than approximately 10 infectious bites per year, demonstrating that the lack of relationship between the EIR and the infectious reservoir can be explained without invoking any effects of acquired transmission-blocking immunity. The near absence of field data from areas with an EIR < 10 per year precluded validation of the model predictions for low EIR values. These results suggest that interventions reducing mosquito-to-human transmission will have little or no effect on human infectiousness at the levels of transmission found in most rural areas of sub-Saharan Africa. Unless very large reductions in transmission can be achieved, measures to prevent mosquito-to-human transmission need to be complemented with interventions that reduce the density or infectiousness of blood stage parasites.

Animals↗

PubMed2006

Relationships between host infectivity to mosquitoes and asexual parasite density in Plasmodium falciparum.

We describe a statistical model for the relationship between asexual parasite densities of Plasmodium falciparum and the infectivity of the host to mosquitoes. The model takes into account the delay between asexual parasitemia and infectivity resulting from the time course of gametocytemia. It also allows for the need for the blood meal to contain gametocytes of both sexes if infection is to take place. We show that by fitting this model to data from malariatherapy patients it can explain observed patterns of infectiousness of the human host and is consistent with distributions of gametocyte densities in malariatherapy patients. By integrating this model into an individual-based simulation of human populations exposed to endemic P. falciparum transmission, we are able to predict the contributions of different host age groups to the infectious reservoir. Comparison of model predictions with published estimates of this quantity confirms that infected adults hosts are likely to make a significant contribution to the reservoir of transmission, and points to the need for improved population-based estimates of this age-dependence in infectivity of humans in endemic areas.

Animals↗

PubMed2006

An epidemiologic model of the incidence of acute illness in Plasmodium falciparum malaria.

We propose a stochastic model for simulating malaria tolerance. The model relates the probability of a clinical attack of malaria to the peripheral parasite densities via a pyrogenic threshold that itself responds dynamically to the parasite load. The parameters of the model have been estimated by fitting it to the relationship between incidence of clinical episodes and the entomologic inoculation rate, using age-specific incidence data from two villages in Senegal and one village in Tanzania. The model reproduces the shifts in age distribution of clinical episodes associated with variation in transmission intensity, and in keeping with the data, predicts a slightly higher lifetime number of episodes in the mesoendemic village of Ndiop than in the holoendemic village of Dielmo. This model provides a parsimonious explanation of counter-intuitive relationships between the overall incidence of clinical malaria and transmission intensity. In contrast to the theory of endemic stability, recently proposed to apply to P. falciparum, it does not assume any intrinsic age dependence in the outcome of infection. This model can be used to explore the consequences for predictions of the effects of different anti-malarial interventions on the incidence of clinical malaria.

Acute Disease↗

PubMed2006

An epidemiologic model of severe morbidity and mortality caused by Plasmodium falciparum.

The intensity of Plasmodium falciparum transmission has multifarious and sometimes counter-intuitive effects on age-specific rates of severe morbidity and mortality in endemic areas. This has led to conflicting speculations about the likely impact of malaria control interventions. We propose a quantitative framework to reconcile the various apparently contradictory observations relating morbidity and mortality rates to malaria transmission. Our model considers two sub-categories of severe malaria episodes. These comprise episodes with extremely high parasite densities in hosts with little previous exposure, and acute malaria episodes accompanied by co-morbidity or other risk factors enhancing susceptibility. In addition to direct malaria mortality from severe malaria episodes, the model also considers the enhanced risk of indirect mortality following acute episodes accompanied by co-morbidity after the parasites have been cleared. We fit this model to summaries of field data from endemic areas of Africa, and show that it can account for the observed age- and exposure-specific patterns of pediatric severe malaria and malaria-associated mortality in children. This model will allow us to make predictions of the long-term impact of potential malaria interventions. Predictions for children will be more reliable than those for older people because there is a paucity of epidemiologic studies of adults and adolescents.

Animals↗

PubMed2006

The effect of malaria transmission intensity on neonatal mortality in endemic areas.

Estimates of the impact of Plasmodium falciparum infections during pregnancy on neonatal mortality have not taken into account how this varies with the level of malaria endemicity and thus do not indicate the possible effects of malaria control strategies that reduce transmission. We now review the relevant literature, and propose a mathematical model for the association between P. falciparum transmission and neonatal death. The excess risk of neonatal mortality in malaria-endemic areas appears to be insensitive to the intensity of P. falciparum transmission over a wide range of endemicity. Moderate reductions in the overall level of malaria transmission in endemic areas are therefore unlikely to significantly reduce neonatal mortality. The magnitude of the excess risk is very uncertain because existing estimates are heavily dependent on the questionable assumption that the effects are mediated by birth weight. Accurate prediction of the impact of malaria control measures targeted at pregnant women requires direct estimates of malaria-attributable neonatal mortality rates.

Endemic Diseases↗

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↗

PubMed2004

Comparing excess costs across multiple corporate populations.

The purpose of this study was to examine the relationship of health risk level to charged medical costs and determine the excess cost of higher risk individuals compared to low risk. Two years of medical claims from six corporations were used to determine costs of health risk assessment (HRA) participants and nonparticipants. A total of 165,770 employees, 21,124 of which took an HRA, were used for the study. Costs increased as risk level increased. There were no significant differences within a risk level between companies for the cost ratio. Percent of medical costs due to excess risk ranged from 15.0-30.8% for HRA participants and 23.8-38.3% for the study population. Cost patterns were consistent across companies. Excess cost as the result of increased risk level accounted for a substantial portion of the cost at each company. These results can be used to justify the need for a health-promotion program and to estimate potential savings as the result of excess risk. Even without the use of an HRA, health practitioners should feel confident stating that excess risk accounts for at least 25% to 30% of medical costs per year across a wide variety of companies, regardless of industry or demographics. The numbers can be used as a realistic estimate for any health promotion program financial proposal.

Adult↗