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G J Van Oortmarssen

Publications and source records attributed to G J Van Oortmarssen.

12 recordsLinked to original sources

The dynamics of Wuchereria bancrofti infection: a model-based analysis of longitudinal data from Pondicherry, India.

This paper presents a model-based analysis of longitudinal data describing the impact of integrated vector management on the intensity of Wuchereria bancrofti infection in Pondicherry, India. The aims of this analysis were (1) to gain insight into the dynamics of infection, with emphasis on the possible role of immunity, and (2) to develop a model that can be used to predict the effects of control. Using the LYMFASIM computer simulation program, two models with different types of immunity (anti-L3 larvae or anti-adult worm fecundity) were compared with a model without immunity. Parameters were estimated by fitting the models to data from 5071 individuals with microfilaria-density measurement before and after cessation of a 5-year vector management programme. A good fit, in particular of the convex shape of the age-prevalence curve, required inclusion of anti-L3 or anti-fecundity immunity in the model. An individual's immune-responsiveness was found to halve in approximately 10 years after cessation of boosting. Explanation of the large variation in Mf-density required considerable variation between individuals in exposure and immune responsiveness. The mean life-span of the parasite was estimated at about 10 years. For the post-control period, the models predict a further decline in Mf prevalence, which agrees well with observations made 3 and 6 years after cessation of the integrated vector management programme.

Adolescent↗

Vector survival and parasite infection: the effect of Wuchereria bancrofti on its vector Culex quinquefasciatus.

This paper investigates a cohort of 2187 laboratory reared Culex quinquefasciatus fed on 69 human volunteers, including 59 persons with different levels of Wuchereria bancrofti microfilariae and 10 without microfilaria. Mosquitoes were followed until death. Mosquito survival was analysed in relation to the level of microfilaria in the human and larval count in the dead mosquito. Vector mortality during the extrinsic incubation period (12 days post-engorgement) was significantly higher in mosquitoes fed on microfilaraemic volunteers (50%) than in those fed on amicrofilaraemics (29%). Both the percentage infected and the geometric mean parasite density was significantly higher among mosquitoes which died before 13 days (45% infected and 10 larvae per infected mosquito) than those surviving beyond 13 days (39% and 2.2), suggesting a parasite loss of more than 80% during the extrinsic incubation period. A large proportion (62%) of the mosquitoes that died during the early of phase of parasite development were infected (36% in low, 26% in medium and 90% in high human Mf-density). Survival analysis showed that the parasite load in mosquitoes and the human Mf-density for a given parasite load are independent risk factors of vector survival. Overall, the hazard of dying was found to be 11-15 times higher among mosquitoes fed on microfilaraemic volunteers than those fed on amicrofilaraemics. The hazard doubles for every increase of about 60-70 parasites in the vector. As a consequence of the parasite-induced reduction in vector survival, the transmission success of the parasite is reduced. The implication of the results on control/elimination of lymphatic filariasis using mass-drug administration is discussed.

Animals↗

Meta-analysis of age-prevalence patterns in lymphatic filariasis: no decline in microfilaraemia prevalence in older age groups as predicted by models with acquired immunity.

The role of acquired immunity in lymphatic filariasis is uncertain. Assuming that immunity against new infections develops gradually with accumulated experience of infection, models predict a decline in prevalence after teenage or early adulthood. A strong indication for acquired immunity was found in longitudinal data from Pondicherry, India, where Mf prevalence was highest around the age of 20 and declined thereafter. We reviewed published studies from India and Subsaharan Africa to investigate whether their age-prevalence patterns support the models with acquired immunity. By comparing prevalence levels in 2 adult age groups we tested whether prevalence declined at older age. For India, comparison of age groups 20-39 and 40+ revealed a significant decline in only 6 out of 53 sites, whereas a significant increase occurred more often (10 sites). Comparison of older age groups provided no indication that a decline would start at a later age. Results from Africa were even more striking, with many more significant increases than declines, irrespective of the age groups compared. The occurrence of a decline was not related to the overall Mf prevalence and seems to be a chance finding. We conclude that there is no evidence of a general age-prevalence pattern that would correspond to the acquired immunity models. The Pondicherry study is an exceptional situation that may have guided us in the wrong direction.

Adolescent↗

Assessing density dependence in the transmission of lymphatic filariasis: uptake and development of Wuchereria bancrofti microfilariae in the vector mosquitoes.

Understanding density dependence in the transmission of lymphatic filariasis is essential for assessing the prospects of elimination. This study seeks to quantify the relationship between microfilaria (Mf) density in human blood and the number of third stage (L3) larvae developing in the mosquito vectors Aedes polynesiensis Marks and Culex quinquefasciatus Say (Diptera: Culicidae) after blood-feeding. Two types of curves are fitted to previously published data. Fitting a linearized power curve through the data allows for correction for measurement error in human Mf counts. Ignoring measurement error leads to overestimation of the strength of density dependence; the degree of overestimation depends on the accuracy of measurement of Mf density. For use in mathematical models of transmission of lymphatic filariasis, a hyperbolic saturating function is preferable. This curve explicitly estimates the Mf uptake and development at lowest Mf densities and the average maximum number of L3 that can develop in mosquitoes. This maximum was estimated at 23 and 4 for Ae. polynesiensis and Cx. quinquefasciatus, respectively.

Aedes↗

Regulation of anti-filarial IgE by infection pressure.

In lymphatic filariasis, specific IgG4 responses to the parasite and their relationship with infection have been studied extensively, but only a few studies have concentrated on anti-filarial and total IgE. Here we have investigated the role of filarial infection pressure on production of IgE by considering length of exposure (age), filarial endemicity and parasitological status. Antibody levels were determined in 366 individuals, who were resident in 3 villages in South-Sulawesi, Indonesia, with varying degrees of filarial transmission intensity, as indicated by the prevalence of Brugia malayi microfilaraemia (0.7%, 9% and 32%, respectively). Anti-filarial IgE levels were significantly lower in the low transmission village than in the areas with intermediate and high filarial transmission; however, in the latter village a remarkable suppression of specific IgE was found. Microfilaria-positive individuals showed elevated levels of total IgE, but suppression of specific IgE, which has been reported before. Taken together, these observations suggest that 2 opposing mechanisms regulate anti-parasite IgE expression: increasing experience of filarial infection stimulates specific IgE, but antibody levels become specifically suppressed when microfilariae or adult worms develop. Using a simple mathematical model, we illustrate how anti-filarial IgE increases with parasite antigen up to a threshold level, but levels off and becomes down-regulated after the threshold is exceeded.

Adolescent↗

Validation of a chart to estimate true Schistosoma mansoni prevalences from simple egg counts.

Schistosoma mansoni egg counts by faecal examination vary considerably and are not very sensitive, so prevalences are underestimated. The distribution of egg counts can adequately be described by a stochastic model which distinguishes variation in counts between persons and variation in repeated counts within a person. Based on this model a pocket chart has been developed which predicts the proportion of individuals harbouring at least 1 S. mansoni worm pair-the 'true prevalence'-from a simple single survey prevalence and geometric mean egg count (using common duplicate 25 mg Kato-Katz smears). The current paper describes the validation of this chart by comparing predicted true prevalences with prevalences observed after 5-7 repeated Kato-Katz faecal examinations (Burundi), by examination of a large quantity of stool using the Visser filter (Brazil) or a selective sedimentation-filtration method (Surinam). Because 5-7 repeated examinations do not suffice to measure all infections, predictions have been made of the cumulative proportion positives over 5-7 surveys-the 'approximate true prevalence'-as well. After dividing the data into age groups, 12 different subsets were considered for validation. In all 12 cases, predicted true prevalences (or approximate true prevalences for the Burundi data) agree well with those observed. The overall agreement depends only slightly on the assumed relationship between worm numbers and mean egg counts, with a good fit for a productivity between 0.8 and 4.4 eggs per gramme faeces (EPG) per worm pair (WP). This interval includes the most plausible value from the literature, i.e. 1.0 EPG/WP, which has been applied in the initial pocket chart. These findings support the validity of the chart to predict true prevalences for a wide range of productivity assumptions, and reinforces the applicability of its underlying stochastic model to describe egg count variation. However, as predictions appear to vary importantly when using only part of the data, it is also concluded that the pocket chart never compensates for limited validity of initial single survey prevalences and geometric means in consequence of small sample sizes.

Adolescent↗

The microsimulation approach to epidemiologic modeling of helminthic infections, with special reference to schistosomiasis.

The microsimulation technique has been used since 1985 as a tool for epidemiologic modeling of helminthic infections. This technique is characterized by mimicking individual life histories, which makes it possible to include several relevant processes and mechanisms that have not so far been considered in applied modeling. Biological, epidemiologic, and social processes can be simulated in detail, which allows realistic prediction of the impact of control strategies. It is clear that careful quantification and validation of the many processes and parameters in the model requires close collaboration with experts working on control projects. In the development and application of a microsimulation model, we distinguish eight steps, ranging from the identification of questions the model will be designed to address, to the completion of a model that can be used as a routine decision-making tool in a control program.

Animals↗

SCHISTOSIM: a microsimulation model for the epidemiology and control of schistosomiasis.

A computer simulation model, SCHISTOSIM, has been developed for the epidemiology and control of schistosomiasis, based on the stochastic microsimulation technique. The eventual aim is to evaluate and predict the effects of different control strategies. In the current state of the model, human-, worm-, and infection-related aspects have been included. However, many others, including most transmission and transmission-related mechanisms, have yet to be modeled. By simulating a series of surveys and treatments in Burundi, short-term effects of this program were satisfactorily explained by the model. However, long-term predictions did not match the observed data. Possible extensions of the model to properly describe these effects are identified. The potential of SCHISTOSIM as a tool for the prediction of outcomes of alternative control strategies is illustrated and discussed.

Animals↗

Irreversible effects of ivermectin on adult parasites in onchocerciasis patients in the Onchocerciasis Control Programme in West Africa.

Ivermectin is an effective drug for the treatment of human onchocerciasis, a disease caused by the parasitic filarial nematode Onchocerca volvulus. When humans are treated, the microfilariae normally found in the skin are rapidly and very nearly completely eliminated. Nonetheless, after a delay, microfilariae gradually reappear in the skin. This study is concerned with the causes of this delay. Hypotheses are tested by comparing the results of model calculations with skin microfilaria counts collected from 114 patients during a trial of five annual treatments in the focus area of Asubende, Ghana. The results obtained strongly suggest that annual treatment with ivermectin causes an irreversible decline in microfilariae production of approximately 30%/treatment. This result has important implications for public health strategies designed to eliminate onchocerciasis as a significant health hazard.

Adult↗

A model for variations in single and repeated egg counts in Schistosoma mansoni infections.

Faecal egg counts are often used to measure Schistosoma mansoni infection, but the considerable variation between successive counts complicates their interpretation. The stochastic model described in this paper gives a description of observed egg counts in a population and can be used as a tool to gain an insight into the underlying worm load distribution. The model distinguishes between two sources of variation in egg counts: (1) variation caused by the difference in worm load between individuals, and (2) the variability of egg counts for an individual with a given worm load. Empirical data, single and repeated measurements, from surveys in five villages in Burundi and Zaire have been used to fit and validate the model. We have discussed possible mechanisms that explain the differences in estimated values between the villages. The model indicates that the expected number of eggs in a stool sample per S. mansoni worm pair is lower than suggested by autopsy data and that, possibly as a consequence of immunity, the inter-individual variation in worm loads decreases with age.

Adolescent↗