A P Plaisier

Erasmus Universiteit Rotterdam, Rotterdam, South Holland, Netherlands

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Publications (28)128.12 Total impact

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    ABSTRACT: 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.
    No preview · Article · Jun 2004 · Parasitology
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    ABSTRACT: To elucidate the conditions in which mass treatment with ivermectin reduces the transmission of Onchocerca volvulus sufficiently to eliminate infection from an African community. ONCHOSIM, a microsimulation model for onchocerciasis transmission, was used to explore the implications of different treatment intervals, coverage levels and precontrol endemicities for the likelihood of elimination. Simulations suggested that control strategies based exclusively on ivermectin mass treatments could eliminate onchocerciasis. The duration of treatment required to eliminate infection depended heavily on the treatment programme and precontrol endemicity. In areas with medium to high levels of infection, annual mass treatments with 65% coverage for at least 25 years were necessary. Model predictions suggested that durations exceeding 35 years would be required if there were much heterogeneity in exposure to vector bites and, consequently, wide individual variation in microfilaria counts. If the treatment interval were reduced from 12 to 6 months the time for completion of the programme could be more than halved and elimination could be accomplished in areas of hyperendemicity, provided that the effects of each treatment would be the same as with annual treatments. However, it was doubtful whether high coverage levels could be sustained long enough to achieve worldwide eradication. Elimination of onchocerciasis from most endemic foci in Africa appears to be possible. However, the requirements in terms of duration, coverage, and frequency of treatment may be prohibitive in highly endemic areas.
    Preview · Article · Feb 2002 · Bulletin of the World Health Organisation
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    ABSTRACT: Background In most endemic parts of the world, onchocerciasis (river blindness) control relies, or will soon rely, exclusively on mass treatment with the microfilaricide ivermectin. Worldwide eradication of the parasite by means of this drug is unlikely. Macrofilaricidal drugs are currently being developed for human use. Methods We used ONCHOSIM, a microsimulation mathematical model of the dynamics of onchocerciasis transmission, to explore the potentials of a hypothetical macrofilaricidal drug for the elimination of onchocerciasis under different epidemiological conditions, as characterized by previous intervention strategies, vectorial capacity and levels of coverage. Results With a high vector biting rate and poor coverage, a very effective macrofilaricide would appear to have a substantially higher potential for achieving elimination of the parasite than does ivermectin. Conclusions Macrofilaricides have a substantially higher potential for achieving onchocerciasis elimination than ivermectin, but high coverage levels are still key. When these drugs become available, onchocerciasis elimination strategies should be reconsidered. In view of the impact of control efforts preceding the introduction of macrofilaricides on the success of elimination, it is important to sustain current control efforts.
    Full-text · Article · Nov 2001 · BMC Public Health
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    ABSTRACT: The outcome of Helicobacter pylori infection has been associated with specific virulence-associated bacterial genotypes. The present study aimed to investigate the gastric histopathology in Portuguese and Colombian patients infected with H. pylori and to assess its relationship with bacterial virulence-associated vacA, cagA, and iceA genotypes. A total of 370 patients from Portugal (n = 192) and Colombia (n = 178) were studied. Corpus and antrum biopsy specimens were collected from each individual. Histopathological features were recorded and graded according to the updated Sydney system. H. pylori vacA, cagA, and iceA genes were directly genotyped in the gastric biopsy specimens by polymerase chain reaction and reverse hybridization. Despite the significant differences between the Portuguese and Colombian patient groups, highly similar results were observed with respect to the relation between H. pylori genotypes and histopathology. H. pylori vacA s1, vacA m1, cagA+ genotypes were significantly associated with a higher H. pylori density, higher degrees of lymphocytic and neutrophilic infiltrates, atrophy, the type of intestinal metaplasia, and presence of epithelial damage. The iceA1 genotype was only associated with epithelial damage in Portuguese patients. These findings show that distinct H. pylori genotypes are strongly associated with histopathological findings in the stomach, confirming their relevance for the development of H. pylori-associated gastric pathology.
    Full-text · Article · Mar 2001 · American Journal Of Pathology
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    ABSTRACT: Using estimates for the anthelmintic efficacy of a single dose of ivermectin in the treatment of lymphatic filariasis patients, Anton Plaisier, Wilma Stolk, Gerrit van Oortmarssen and Dik Habbema here present and discuss model predictions of the impact of a five-year programme of annual community treatment on the intensity of infection. They show that the effectiveness of such programmes in terms of reductions in the microfilarial density depends critically on the treatment coverage and the pattern of attendance at repeated mass administrations. Improving these factors will possibly be more important than improving the efficacy of ivermectin by increasing its dosage or by adding other drugs.
    No preview · Article · Aug 2000 · Parasitology Today
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    ABSTRACT: Virulence factors of Helicobacter pylori are associated with peptic ulcer disease and may be also associated with the efficacy of treatment. To determine the relation between the vacA and the cagA status of H pylori, clinical disease, and treatment outcome. 121 patients with H pylori infection and peptic ulcer disease or functional dyspepsia were treated by quadruple antibiotic therapy in two groups for one and two days, respectively. DNA was isolated from gastric antral biopsy specimens, taken before and after treatment, and the vacA and cagA status was determined by polymerase chain reaction and reverse hybridisation. Peptic ulcer disease was significantly associated with the vacA s1 type, and cagA positivity, but not with the vacA m type. Treatment efficacy was significantly higher in patients with peptic ulcer disease, or infected with cagA+/vacA s1 strains. The strong association between the cagA and vacA status and peptic ulcer disease was confirmed. Cure rates seem to be higher for patients with cagA+/vacA s1 H pylori strains, which is consistent with the higher cure rate observed among ulcer patients compared with functional dyspepsia patients. Therefore, treatment studies may require stratification for presence of ulcers as well as H pylori genotypes.
    Preview · Article · Apr 2000 · Gut
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    ABSTRACT: BACKGROUND Virulence factors ofHelicobacter pylori are associated with peptic ulcer disease and may be also associated with the efficacy of treatment.AIMSTo determine the relation between the vacA and thecagA status of H pylori, clinical disease, and treatment outcome.PATIENTS121 patients withH pylori infection and peptic ulcer disease or functional dyspepsia were treated by quadruple antibiotic therapy in two groups for one and two days, respectively.METHODSDNA was isolated from gastric antral biopsy specimens, taken before and after treatment, and the vacA and cagAstatus was determined by polymerase chain reaction and reverse hybridisation.RESULTSPeptic ulcer disease was significantly associated with the vacA s1 type, and cagA positivity, but not with thevacA m type. Treatment efficacy was significantly higher in patients with peptic ulcer disease, or infected with cagA+/vacAs1 strains.CONCLUSIONS The strong association between the cagA andvacA status and peptic ulcer disease was confirmed. Cure rates seem to be higher for patients withcagA+/vacA s1H pylori strains, which is consistent with the higher cure rate observed among ulcer patients compared with functional dyspepsia patients. Therefore, treatment studies may require stratification for presence of ulcers as well as H pylori genotypes.
    No preview · Article · Jan 2000 · Gut
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    ABSTRACT: Ivermectin is a promising drug for the treatment of lymphatic filariasis. A meta-analysis of trials investigating the effects of a single treatment suggested a dose-dependent effect on the production of microfilariae (mf) by adult Wuchereria bancrofti parasites. A mathematical model that describes the parasite dynamics in the human host and the impact of ivermectin treatment is presented and its outputs compared with these trials. The calculated trend in mf density after treatment appears to be particularly sensitive to the assumption about the mean life-span of mf. Adopting 0.5-2 years as a range of plausible values for this mf life-span, the model is used to estimate the impact of treatment on the parasite. It is found that irrespective of dosage, ivermectin eliminates 100% of the blood mf from a patient. Furthermore, at a dosage level of 400 micrograms/kg a single treatment irreversibly reduces the mf production of the adult parasites by at least 65%. For a dosage of 200 micrograms/kg this reduction is at least 35%. No such effect can be concluded from the results of trials using lower dosages.
    No preview · Article · Nov 1999 · Parasitology
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    ABSTRACT: Clinical outcome of Helicobacter pylori infection may be associated with specific virulence-associated bacterial genotypes. The aim of this study was to assess the relationships between H. pylori cagA, vacA, and iceA status and severity of disease. Gastric biopsy specimens from 94 patients in The Netherlands were analyzed by polymerase chain reaction and reverse hybridization. cagA was present in 63 (67%) of 94 cases and was associated with peptic ulcer disease (P = 0.0019). vacA geno-types s1a/m1, s1b/m2, s1b/m1, s1b/m2, and s2/m2 were found in 36.2%, 23.4%, 2.1%, 5.3%, and 20.2%, respectively. Ten isolates (10.6%) contained multiple vacA genotypes. The presence of peptic ulcers was associated with type s1 strains (P = 0.0006) but not with the m type (P = 0.2035). cagA and vacA s1 were strongly associated (P < 10(-5)). iceA1 was found in 53 (56.4%) and iceA2 in 25 (26.6%) of the 94 cases. In 14 isolates (14.9%), both iceA alleles were found, and 2 (2.1%) were negative for both iceA1 and iceA2. iceA1 was also associated with peptic ulcer disease (P = 0.0042). The iceA allelic type was independent of the cagA and vacA status. vacA s1, cagA, and iceA1 are markers of H. pylori strains that are more likely to lead to ulcer disease.
    No preview · Article · Jul 1998 · Gastroenterology
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    ABSTRACT: The uptake of Wuchereria bancrofti microfilariae (Mf) by Culex quinquefasciatus and their development in relation to human Mf density were quantified by allowing a total of 1096 wild mosquitoes to feed on 13 volunteers sleeping under partially open bed-nets. For each volunteer, each hour between 18.00 and 06.00 h the Mf density in finger-prick blood was determined and engorged mosquitoes collected. Each hourly collection of mosquitoes was kept separately. Half of them was dissected within 18 h post-feeding for the presence of ingested Mf, the other half was reared for 12 days to allow for the development of L3 larvae. About 20% of the latter mosquitoes died during these 12 days and these harboured significantly more larvae than the surviving ones, which could be an indication of excess-mortality among heavily infected mosquitoes. Assuming that variability in Mf uptake and in the number of developed L3 larvae can be described by a negative binomial distribution, a maximum-likelihood procedure was applied to estimate the relationship between human Mf density and both the arithmetic mean Mf uptake and L3 development. Both were adequately described by a saturating hyperbolic function that significantly differed from linearity. The saturation level for Mf was estimated at 29 (CI: 20-54) and for L3 larvae at 6.6 (CI: 4.3-17.0). Next, the L3 yield was related to Mf uptake indicating that the W. bancrofti-C. quinquefasciatus complex shows 'limitation', i.e. a decreasing yield for an increasing uptake. Both the number of Mf ingested and the number of L3 larvae developing per mosquito were found to be highly aggregated, with the level of aggregation decreasing in a non-linear way with human Mf density.
    Full-text · Article · Mar 1998 · Parasitology
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    ABSTRACT: The uptake of Wuchereria bancrofti microfilariae (Mf) by Culex quinquefasciatus and their development in relation to human Mf density were quantified by allowing a total of 1096 wild mosquitoes to feed on 13 volunteers sleeping under partially open bed-nets. For each volunteer, each hour between 18.00 and 06.00 h the Mf density in finger-prick blood was determined and engorged mosquitoes collected. Each hourly collection of mosquitoes was kept separately. Half of them was dissected within 18 h post-feeding for the presence of ingested Mf, the other half was reared for 12 days to allow for the development of L3 larvae. About 20% of the latter mosquitoes died during these 12 days and these harboured significantly more larvae than the surviving ones, which could be an indication of excess-mortality among heavily infected mosquitoes. Assuming that variability in Mf uptake and in the number of developed L3 larvae can be described by a negative binomial distribution, a maximum-likelihood procedure was applied to estimate the relationship between human Mf density and both the arithmetic mean Mf uptake and L3 development. Both were adequately described by a saturating hyperbolic function that significantly differed from linearity. The saturation level for Mf was estimated at 29 (CI: 20–54) and for L3 larvae at 6·6 (CI: 4·3–17·0). Next, the L3 yield was related to Mf uptake indicating that the W. bancrofti–C. quinquefasciatus complex shows ‘limitation’, i.e. a decreasing yield for an increasing uptake. Both the number of Mf ingested and the number of L3 larvae developing per mosquito were found to be highly aggregated, with the level of aggregation decreasing in a non-linear way with human Mf density.
    No preview · Article · Feb 1998 · Parasitology

  • No preview · Article · Jan 1998 · Gastroenterology
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    ABSTRACT: The LYMFASIM modeling framework for the transmission and control of the tropical parasitic disease lymphatic filariasis is described and its use in the context of an endemic community in north-eastern Brazil is illustrated. Lymphatic filariasis is a disease with a complex natural history with many unknowns. This complicates decision making with respect to control strategies. With LYMFASIM, a variety of hypotheses can be tested about the life history of the parasite Wuchereria bancrofti, its transmission from man to man through mosquitoes, the role of the immune system in regulating parasite numbers, the development of disease symptoms, and the effects of control measures (drug treatment or mosquito control). The implications of alternative assumptions and uncertainty about the quantification of parameters for the effectiveness of control strategies can be investigated. Thanks to the use of stochastic microsimulation, LYMFASIM is highly flexible and can be adapted and extended as new knowledge emerges.
    Full-text · Article · Jan 1998 · Methods of Information in Medicine
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    ABSTRACT: Summary The efficacy and safety of ivermectin in the treatment of filariasis due to Wuchereria bancrofti was assessed by a meta-analysis of the results from 15 published clinical trials. Seven hundred and forty-eight microfilaraemic patients were enrolled in 7 dose-finding and 8 comparative studies. Administered as a single dose, ivermectin induced nearly complete clearance of microfilariae from the blood from the first day to 30 days post-treatment, followed by gradual recurrence of microfilaraemia and increase in its intensity. Higher doses of ivermectin showed greater clearance effects and maintained lower microfilaraemia levels for a longer time. The adverse reactions caused by the drug were flu-like, transient, generally mild and well tolerated by patients. The frequency and intensity of adverse reactions were strongly associated with pretreatment microfilaria counts in the blood, but independent of dose. The findings of the meta-analysis suggest that ivermectin given at a single annual dose of 200 μg/kg body weight or higher, whether or not in combination with DEC, has great potential for therapeutic strategies to control bancroftian filariasis.
    Preview · Article · Mar 1997 · Tropical Medicine & International Health
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    ABSTRACT: In the extension areas of the Onchocerciasis Control Programme in West Africa, aerial larviciding is supplemented with annual ivermectin treatment, mainly to achieve better control of morbidity. The purpose of this study is to determine whether and to what extent the addition of annual ivermectin treatment permits earlier cessation of vector control than originally recommended. The effectiveness of combined ivermectin distribution and vector control was assessed using an epidemiological model. Model predictions suggest that, dependent on the pre-control endemicity of the area and the proportion of persons treated during each ivermectin round, large-scale annual treatment permits a considerable reduction in the duration of vector control. Taking into account uncertainty about the efficacy of ivermectin, our results indicate that, provided treatment coverage is at least 65% and there is no importation of infection from elsewhere, 12 years of combined control will be sufficient to reduce the risk of recrudescence to below 1% in even the most afflicted areas.
    Preview · Article · Feb 1997 · Bulletin of the World Health Organisation
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    ABSTRACT: 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.
    No preview · Article · Dec 1996 · The American journal of tropical medicine and hygiene
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    ABSTRACT: 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.
    No preview · Article · Dec 1996 · The American journal of tropical medicine and hygiene
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    A. P. Plaisier
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    ABSTRACT: In 1990 the World Health Organization (WHO) coordinated Onchocerciasis Control Programme in West Africa (OCP) used this slogan for evaluating fifteen years of control of the parasitic disease onchocerciasis and for expressing its optimism about the future. Based on the obvious success of OCP and on the availability of a safe and effective drug (ivermectin), the UNDP/World BanklWHO Special Programme for Research & Training in Tropical Diseases (TDR) has announced onchocerciasis to be one of the tropical diseases with good prospects for worldwide elimination, at least as a public health problem (the others being Chagas disease, Lymphatic filariasis, and Leprosy!). To judge slogans and statements like these, and in particular to determine under which circumstances and with what strategies they could become a realistic perspective, one should perform an integrated and detailed study of the dynamics of the disease and the impact of control. Such a study should preferably be embedded in a comprehensive quantitative approach. In the light of this, the objectives of the work reported in this thesis were (1) to develop, quantify, and validate a model for the transmission and control of onchocerciasis in West African savanna and (2) to use this model for aiding decision making in the OCP. Through achieving these objectives we have tried to contribute to a better understanding of the dynamics of the parasite that causes the illness and the impact of intervention measures, and to the as yet successful combat against the disease. In the general introduction an outline will be given of the epidemiology and control of onchocerciasis. Secondly, an overview of the achievements of the OCP in controlling the disease in West Africa will be provided. Finally, a short history will be presented of the role of quantitative modelling within OCP prior to the work reported in this thesis.
    Preview · Article · Jan 1996
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    ABSTRACT: 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 ∼30%/treatment. This result has important implications for public health strategies designed to eliminate onchocerciasis as a significant health hazard.
    No preview · Article · Aug 1995 · The Journal of Infectious Diseases
  • E S Alley · A.P. Plaisier · B.A. Boatin · K.Y. Dadzie · JHF Remme · G Zerbo · E M Samba
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    ABSTRACT: Following the registration of ivermectin (Mectizan) for human use in the treatment of onchocerciasis, in 1987 the Onchocerciasis Control Programme in West Africa (OCP) begun a series of trials in order to determine the safety of the drug when used on a large scale and its potential for morbidity control. This paper reports the changes in skin microfilarial loads during the first 5 years of annual treatment in the holoendemic focus of Asubende in Ghana, which was the largest trial area and which also had the longest series of follow-up surveys. The general observed pattern was a marked reduction of microfilarial loads shortly after each treatment followed by a steady repopulation of the skin until a subsequent treatment round. The overall reduction of microfilarial loads observed between the base line survey and one year after the last treatment was 90% for the total population examined and over 93% for a cohort which received the drug at all 5 treatment rounds. In contrast, there was only a very gradual decrease in the prevalence of infection in the population after subsequent treatments. The study further emphasizes that even a single treatment with ivermectin has a significant medium-term impact on microfilarial loads. Microfilarial counts barely increased after 14-16 months of treatment and stabilized around 55% of pre-treatment counts 2-4 years after a single treatment.
    No preview · Article · Sep 1994 · Transactions of the Royal Society of Tropical Medicine and Hygiene