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G F Medley

Publications and source records attributed to G F Medley.

At least 73 records · Page 4Linked to original sources
PubMed1996

Dynamic modeling of epidemiologic patterns of schistosomiasis morbidity.

This paper uses preliminary mathematical models to examine how the dynamic relationship between schistosomiasis infection and disease is altered by chemotherapy. Two types of morbidity are examined: an acute form that is proportional to current infection intensity and that resolves after treatment, and a chronic form that represents accumulated experience of infection and that does not resolve after treatment, or resolves according to some delay function. The analyses indicate that nonlinearities in the age and frequency distributions of infection intensity have a marked impact on the patterns of morbidity. They also suggest that treatment close to the age of maximum infection intensity (i.e., children of schoolage) is most effective in controlling morbidity in the community as a whole. These models are preliminary, and their further development to include more realistic assumptions in relation to field data is discussed.

Acute Disease↗
PubMed1996

Dynamic models of schistosomiasis morbidity.

Previous attempts to assess the health impact of schistosomiasis control programs on community morbidity have been limited by a lack of a theoretical framework that describes the dynamic relationships between infection and morbidity. In this paper, a model of schistosomal morbidity is developed and parameterized. Morbidity is divided into that due to current heavy infection, and early and late stages of chronic disease. The model was parameterized using data showing resolution of disease after treatment, correlations between prevalence of disease and intensity of infection and using age-morbidity profiles. The fitted parameters suggest that early manifestations of disease such as hepatomegaly in Schistosoma mansoni and S. japonicum infections would resolve relatively quickly following treatment whereas later forms of disease such as liver fibrosis resolve very slowly or not at all. Similar general conclusions were obtained with data on early and late forms of urinary tract morbidity in S. haematobium.

Adolescent↗
PubMed1995

Density-dependent processes in the transmission of human onchocerciasis: relationship between the numbers of microfilariae ingested and successful larval development in the simuliid vector.

A previous paper reported that the intake of Onchocerca volvulus microfilariae (mff) by different species of Simulium is essentially proportional to the parasite load in the skin of infected carriers. This paper examines the fate of the ingested mff in susceptible vectors to assess the relationship between parasite intake and infective larval output in blackfly species with and without well-developed cibarial armatures. Analysis is based on data from 3 onchocerciasis endemic areas: Guatemala (S. ochraceum s.l.), West Africa (S. damnosum s.l./S. sirbanum) and the Amazonian focus between South Venezuela and Northern Brazil (S. guianense and S. oyapockense s.l.). The data, which include published and unedited information collected in the field, record experimental studies of parasite uptake by wild flies maintained in captivity until the completion of the extrinsic incubation period. The relationship between L3 output (measured as the mean number of successful larvae/fly or, as the proportion of flies with infective larvae) and average microfilarial intake, was strongly non-linear. This non-linearity was best represented by a sigmoid function in case of armed simuliids (S. ochraceum s.l., S. oyapockense s.l.), or by a hyperbolic expression in that of unarmed flies (S. damnosum s.l., S. guianense). These results are compatible, respectively, with the patterns of 'initial facilitation' and 'limitation' described in culicid vectors of lymphatic filariases. A maximum mean number of 1-3 L3/fly was observed in all 4 vectors. It is concluded that O. volvulus larval development to the infective stage is regulated by density-dependent mechanisms acting at the early phase of microfilarial migration out of the blackfly's bloodmeal. Damage by the bucco-pharyngeal armature may also be density dependent. A hypothesis, based on this density dependence is forwarded to explain initial facilitation, so far only recorded in vectors with well-developed cibarial teeth. Our results provide quantitative support for the conjecture that chemotherapy alone is likely to have a greater impact on reducing onchocerciasis transmission in endemic areas where the main vector has a toothed fore-gut than in foci where the vectors have unarmed cibaria.

Africa, Western↗
PubMed1995

The development of an age structured model for schistosomiasis transmission dynamics and control and its validation for Schistosoma mansoni.

Mathematical models are potentially useful tools to aid in the design of control programmes for parasitic diseases. In this paper, a fully age structured epidemiological model of human schistosomiasis is developed and parameterized, and used to predict trends in infection prevalence, intensity and prevalence of heavy infections over age and time during several rounds of mass and age targeted treatment. The model is validated against data from a Schistosoma mansoni control programme in Kenya.

Adolescent↗
PubMed1994

Estimates of disease incidence in women based on antenatal or neonatal seroprevalence data: HIV in New York City.

Piecewise constant incidence models were developed to estimate the force of infection in women from age- and time-specific antenatal or neonatal seroprevalence data. Differential inclusion of infected women in sero-surveys compared to uninfected women was taken into account, with respect to both changes in inclusion rate following infection, and changes in relative inclusion rate over calendar time. These models were applied to anonymous HIV seroprevalence data collected from neonates born to black and Hispanic women in New York City 1988-1992, with incidence and fertility parameters estimated by maximum likelihood. Estimates of inclusion rate parameters accorded well with what is known about the natural history of HIV. The data could not distinguish between additive and multiplicative combination of the effects of age and time on incidence. Incidence was strongly dependent on age with the highest incidence in women aged 20-34 years. There was strong evidence that incidence had been falling in Hispanic women since 1982-1984. The results illustrate the extent to which trends in incidence over time may be confounded by changes in the relative inclusion rate of infected and uninfected women.

Adolescent↗
PubMed1994

The evaluation of potential global morbidity attributable to intestinal nematode infections.

This paper presents a method of estimating the potential global morbidity due to human intestinal nematode infections (Ascaris lumbricoides, Trichuris trichiura and hookworms), based on the observed prevalence of infection. The method relies on the observed relationships between prevalence and intensity of infection, and between worm burden and potential morbidity. This approach is shown to be sensitive to the precision of the original prevalence estimates and, in particular, to the degree of spatial heterogeneity in levels of infection. The estimates presented here indicate that several tens of millions of children are likely to suffer developmental consequences from infection, and suggest that the global disease burden of geohelminthiasis may be significantly greater than was supposed.

Adolescent↗
PubMed1994

The development and validation of an age-structured model for the evaluation of disease control strategies for intestinal helminths.

Epidemiological modelling can be a useful tool for the evaluation of parasite control strategies. An age-structured epidemiological model of intestinal helminth dynamics is developed. This model includes the explicit representation of changing worm distributions between hosts as a result of treatment, and estimates the morbidity due to heavy infections. The model is used to evaluate the effectiveness of different programmes of age-targeted community chemotherapy in reducing the amount of morbidity due to helminth infection. The magnitude of age-related heterogeneities is found to be very important in determining the results of age-targeted treatment programmes. The model was verified using field data from control programmes for Ascaris lumbricoides and Trichuris trichiura, and was found to provide accurate predictions of prevalence and mean intensities of infection during and following different control regimes.

Adult↗
PubMed1994

Density-dependent processes in the transmission of human onchocerciasis: intensity of microfilariae in the skin and their uptake by the simuliid host.

The transmission success of Onchocerca volvulus is thought to be influenced by a variety of regulatory or density-dependent processes that act at various points in the two-host life-cycle. This paper examines one component of the life-cycle, namely, the ingestion of microfilariae by the simuliid vector, to assess the relationship between intake of larvae and the density of parasites in the skin of the human host. Analysis is based on data from three areas in which onchocerciasis is endemic and includes published information as well as new data collected in field studies. The three areas are: Guatemala (Simulium ochraceum s.l.), West and Central Africa (savanna members of the S. damnosum complex), and South Venezuela (S. guianense). The data record experimental studies of parasite uptake by flies captured in the field and fed to repletion on locally infected subjects who harboured varying intensities of dermal microfilarial infection. Regression analyses of log transformed counts of parasite burdens ingested by the flies plotted against log transformed counts of microfilariae per mg of skin revealed little evidence for saturation in parasite uptake by the flies as the intensity in the human host increased. There was a positive and highly significant rank correlation between both variables for the three blackfly species. In an alternative analysis a model was fitted to data on prevalence of flies with ingested microfilariae (mff) versus dermal mean intensities. The model assumed an overdispersed distribution of the number of mff/fly and a given functional relationship between intake and skin load. The results of both approaches were consistent. It is concluded that parasite ingestion by the vector host is not strongly density dependent in the three geographical areas and ranges of dermal loads examined. It therefore appears that this transmission process is of reduced importance as a regulatory mechanism in the dynamics of parasite population growth.

Africa, Central↗
PubMed1994

Relationship between prevalence and intensity of Plasmodium falciparum infection in natural populations of Anopheles mosquitoes.

Wild-caught Anopheles gambiae s. l. and An. funestus were dissected and their midguts were examined for the presence of Plasmodium falciparum oocyst infections. The mean intensity of infection and the prevalence of infected mosquitoes were determined for each sample, with one sample representing the mosquitoes caught in a single house at any given time. The patterns of infection were investigated using the relationships between prevalence, intensity, and variance within samples, and were found to be consistent with laboratory infections. The overall distribution of oocysts is characterized by a mixture of negative binomial distributions with means determined by the infectiousness of the human hosts, and a constant degree of aggregation (k = 0.0767) presumably determined by the development of oocysts within mosquitoes. The prevalence/intensity relationship was treated as a bivariate distribution to ascertain the effect of sample size on the accuracy of estimation, and to allow inference of intensity from prevalence. In mathematical models fitted to the collected data, sample size affected directly the minimum possible prevalence of infection, and the accuracy of both mean and prevalence estimations. Based on minimum possible positive prevalence rates, data from samples of less than 20-25 mosquitoes would provide unacceptable errors in prevalence estimations. However, natural oocyst rates are consistently higher than the minimum prevalence, and it is suggested that any interpretations from samples of less than approximately 40 mosquitoes must be treated with some caution. Such variation in natural samples means that prediction of intensity of infection from prevalence (or vice versa) is extremely inaccurate.

Animals↗
PubMed1993

The influence of age on the development of the hepatitis B carrier state.

The relation between the age at infection with hepatitis B virus (HBV) and the development of the carrier state is examined by using data from a number of published and unpublished surveys. A remarkably consistent relation was found. Infants infected perinatally (within the first 6 months of life) were found to have a high probability of becoming carriers (0.885; 95% C.L. 0.84-0.93). Over the infant and early childhood age classes there was found to be a sharp decrease in the proportion of infections which lead to the carrier state. By adulthood (over 15 years) the probability of developing the carrier status was found to be about 0.1. A model was fitted to the data by using maximum likelihood, which provides a good empirical description of the observed data and can be used to predict the expected probability of developing the carrier state given the age at infection. It is postulated that, as a result of this rapid decline in the probability of becoming a carrier during early childhood, a mass childhood immunization campaign, which will tend to postpone the average age at infection in the unvaccinated community, will have a disproportionately large impact on the rate of generation of new carriers.

Adolescent↗
PubMed1993

A quantitative framework for evaluating the effect of community treatment on the morbidity due to ascariasis.

There is growing emphasis on the use of community treatment to reduce the level of morbidity caused by helminth infection. The design of chemotherapy programmes, in terms of frequency of treatment and proportion of the community treated, would be assisted by a quantitative framework which enabled the morbidity reduction achieved by different approaches to be compared. The present study describes a model developed for this purpose which embodies two innovative features. First, a quantitative score of morbidity (the proportion of individuals harbouring an intense infection) is used to rate the success of a programme and, second, the distribution of helminths in the host population is generated by a mechanism that allows the distribution to change dynamically as a function of both treatment and reinfection. The model behaviour, using values typical of Ascaris lumbricoides, indicates that the benefit derived from community chemotherapy increases non-linearly with the coverage and efficacy of treatment.

Animals↗
PubMed1993

Preliminary analysis of the transmission dynamics of Theileria parva in eastern Africa.

Two mathematical models are developed that investigate the transmission dynamics of Theileria parva by the ixodid tick Rhipicephalus appendiculatus to cattle in endemically stable areas. A method of estimating the rate of infection to cattle of T. parva at the endemically stable state is given. Empirical estimates of all the parameters in the model are available. The degree to which animals that have recovered from theileriosis (the 'carrier' state) are able to transmit the infection to tick nymphs or larvae is a crucial determinant of the dynamics of infection in a herd. Two control methods influencing the transmission of infection are considered--infection and treatment immunization and the reduction in tick feeding by acaricide application. The impact of each method on the transmission of infection is evaluated. Future developments and the data required to predict the dynamics of T. parva infections in cattle and ticks are discussed.

Africa, Eastern↗
PubMed1993

Heterogeneity in patterns of malarial oocyst infections in the mosquito vector.

Oocyst prevalence and intensity have been recorded in 349 laboratory infections of Anopheles stephensi with Plasmodium berghei. Intensity and prevalence of infection are shown to be predictably related. The structure and heterogeneity in the infections has been analysed with the objective of describing the biological mechanisms by which the observed negative binomial oocyst distributions are generated. The analysis has revealed that the most likely processes lie within the population dynamic events of malaria within the mosquito, namely gametogenesis, fertilization and mortality. The distribution is similar in all Plasmodium-mosquito combinations examined so far, whether they are of laboratory (P. gallinaceum in Aedes aegypti) or field (P. vivax in An. albimanus and P. falciparum in An. gambiae s.l. and An. funestus) origin. Further we conclude that there is competition between parasites in the vector. Oocyst frequency distribution analysis shows that under natural conditions of transmission intensity, and even under the best laboratory conditions, significant numbers (> 10%) of fully susceptible mosquitoes will not be infected under conditions where the mean infection is as high as 250 oocysts. Failure to infect is not therefore an absolute indicator of refractoriness. In assessing transmission data it is shown that sample sizes should not be less than 50, and ideally 100 mosquitoes, if reliable data are to be obtained. In field it is suggested that difficulties in determining the low natural intensity of oocyst infections indicate that prevalence estimates are a useful and accessible parameter to measure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aedes↗
PubMed1993

The treatment-free incubation period of AIDS in a cohort of homosexual men.

OBJECTIVE: The treatment-free incubation period distribution was estimated from data obtained from a cohort of homo/bisexual men in Amsterdam. DESIGN: Participants in a cohort study that started in Amsterdam at the end of 1984 were seen at 3- or 6-monthly intervals. The analysis excluded time since the start of zidovudine treatment (given to 27 individuals) and no cohort member received primary Pneumocystis carinii pneumonia prophylaxis (i.e., before AIDS diagnosis) before February 1990. METHODS: Both HIV-positive (n = 269) and HIV-seroconverted (n = 79) homosexual men were included in this study. Of these, 68 developed AIDS before February 1990. The unobserved dates of seroconversion were obtained by multiple imputation. The incubation period distribution was estimated from these data by direct Kaplan-Meier analysis and by using parametric Weibull and gamma distributions (including a parameter describing the probability of never progressing to AIDS). Our results are compared with published estimates of progression to AIDS from other homo/bisexual cohort studies. RESULTS: Both the Weibull and the gamma distributions provide equally good empirical descriptions of the incubation period distribution for up to 7 years postseroconversion, but the estimated gamma distribution (median, 9.2; mean, 10.2; percentage AIDS at 7 years, 33%) should be preferred beyond that time, due to a slowing of the hazard rate. There is insufficient information to be able to estimate accurately the probability of never progressing to AIDS. CONCLUSIONS: The time-dependent pattern of HIV incidence should be considered in the analysis of prevalent cohort studies. Our results are in agreement with other homo/bisexual cohort studies, and will be valuable for future comparison with and understanding of the epidemiological consequences of clinical treatment that delays the onset of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Immuno-epidemiology of human geohelminthiasis: ecological and immunological determinants of worm burden.

The morbidity and transmission dynamics of geohelminthiases are determined by the patterns of infection intensity in the community. Understanding the determinants of these patterns requires a combination of field, laboratory and theoretical study. Studies of age-specific reinfection, and of the phenomenon of predisposition, indicate that the major determinant of convex age-intensity profiles and of heterogeneity in infection intensity is the rate of establishment of infection, rather than the rate of adult worm mortality. The rate of establishment is, in turn, determined by exposure to, and protection from, infection. The evidence indicates that exposure, at least to the orally-transmitted geohelminths, varies with age and is highly heterogeneous between hosts. The immune response in geohelminthiasis is vigorous, parasite-specific, heterogeneous between hosts, and both age and infection dose dependent, but has yet to be convincingly shown to be protective. Since the immune response it itself a function of exposure, unravelling the interaction between ecology and immunology as determinants of geohelminth worm burden will require simultaneous assessment of both processes via immunoepidemiological study.

Age Factors↗
PubMed1992

A new approach to morbidity risk assessment in hookworm endemic communities.

The relationship between paired hookworm prevalence and mean intensity of infection data from geographically defined communities was examined. The results show that, in spite of major socio-economic and environmental differences between communities, the relationship is consistent and non-linear. A generalized value of k (the exponent of the negative binomial distribution) for hookworms was estimated to be 0.34, which is consonant with previous estimates from cross-sectional data. Maximum likelihood analysis indicates that the severity of hookworm aggregation in humans has an inverse relationship to mean worm burden which is less marked than for Ascaris lumbricoides. A simple model, based on published estimates of hookworm burdens associated with hookworm anaemia, was used to predict prevalence of morbidity from prevalence of infection data for Tanzania, Kenya and Zambia. Predictions correspond to the observation that hookworm anaemia is highly focal, and largely coastal, in distribution. These analyses suggest that locality-targeting of chemotherapy is particularly appropriate for the control of hookworm morbidity.

Ancylostomiasis↗