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Biomedical subjects

M E Woolhouse

Publications and source records attributed to M E Woolhouse.

At least 55 records · Page 3Linked to original sources
PubMed1998

Patterns in parasite epidemiology: the peak shift.

A characteristic relationship between infection and host age, with levels of infection reaching a peak in particular age classes, has been reported for many parasites. However, several field studies have shown that this relationship is not invariant: if age-infection data are compared across host populations, the peak level of infection is higher and occurs at a younger age when the transmission rate is high, and is lower and occurs at an older age when it is low. This pattern is called the ;peak shift'. Here, Mark Woolhouse reviews the evidence for and the implications of the peak shift. The peak shift is consistent with the predictions of mathematical models that assume gradually acquired protective immunity, and this interpretation is supported by experimental studies using animals. This agreement between theory, experimental evidence and field studies strongly suggests that acquired immunity has a major impact on epidemiological patterns not only for parasites such as malaria, where the importance of acquired immunity is not in doubt, but also for many parasitic helminths, where the role of acquired immunity is less widely accepted.

Journal Article↗
PubMed1998

On the interpretation of age-prevalence curves for trypanosome infections of tsetse flies.

Epidemiological models are used to analyse 8 published data sets reporting age-prevalence curves for trypanosome infections of the tsetse fly Glossina pallidipes. A model assuming a fixed maturation period and a rate of infection which is independent of fly age is adequate for Trypanosoma vivax-type infections, explaining 98% of observed variance in prevalence by site and age, allowing that the rate of infection may be site dependent. This model is not adequate for T. congolense-type infections and the fit can be improved by allowing (i) the rates of infection to decline with age (although non-teneral flies remain susceptible), (ii) a fraction of resistant flies, which may vary between sites, (iii) increased mortality of infected flies and (iv) variation in the maturation period. Models with these features can explain up to 97% of observed variance. Parameter estimates from published experimental data suggest that all may contribute in practice but that (i) and/or (ii) are likely to be the most important.

Animals↗
PubMed1998

Heterogeneities in schistosome transmission dynamics and control.

We review the theoretical framework for exploring the impact of individual and spatial heterogeneities in patterns of exposure and contamination and on the basic reproduction number, R0, for human schistosomes. Analysis of water contact data for 5 communities in Zimbabwe and Mali suggests that the impact is substantial, increasing R0 by factors of up to 6.5, mostly due to highly overdispersed distributions of contact rates among individuals. Several practical conclusions emerge: concentration of contacts at a single site should be avoided; the impact of control targeted at certain sites cannot be predicted without knowledge of how individuals' contacts are distributed among sites; control programmes targeted at individuals or sites contributing most to transmission can be very efficient but, conversely, will be ineffective if any of these individuals or sites are missed.

Animals↗
PubMed1998

Changes in specific anti-egg antibody levels following treatment with praziquantel for Schistosoma haematobium infection in children.

Fifty-seven children 6-15 years old resident in a Schistosoma haematobium endemic area in eastern Zimbabwe were treated with praziquantel at 40 mg/kg body weight. Levels of IgA, IgE, IgG1, IgG2, IgG3, IgG4, and IgM antibodies against soluble egg antigen (SEA) were assayed by ELISA before treatment and at 18 and 36 weeks following treatment. Prevalence of infection (as determined by urine egg counts) was 65% before treatment, all children were confirmed egg negative six weeks after treatment, and reinfection prevalence was 4% at 18 weeks and 21% at 36 weeks after treatment. At 18 weeks after treatment, there was a massive increase in IgG1 levels and significant increases in IgE and IgG4 levels and significant decreases in IgA and IgG2 levels. Similar patterns occurred at 36 weeks after treatment. Egg positive children showed a more marked increase in IgG1 and (for older children) a more marked decrease in IgG2 levels. There were no other effects of age or sex. IgA and IgG1 levels fell significantly between 18 and 36 weeks following treatment but not to pretreatment levels. The results show that specific anti-egg antibody responses are highly sensitive to the effects of praziquantel treatment. A possible consequence is that the susceptibility of children to infection with S. haematobium is altered by chemotherapy; this requires further investigation.

Adolescent↗
PubMed1998

Extensive genetic variation revealed in adjacent populations of the schistosome intermediate host Biomphalaria pfeifferi from a single river system.

Random amplified polymorphic DNA (RAPD) analysis was used to study genetic variation among schistosome hosts of the species Biomphalaria pfeifferi. The analysed snails came from 15 sites along a 6-km stretch of a Zimbabwean river, providing data on genetic-geographical relationships over, probably, the smallest scale yet studied for any snail intermediate host species. Only 6% of the DNA fragments were common to all snails, and snail populations as geographically close as 100 m were genetically distinct. The most genetically polymorphic snail populations were those collected within and downstream from human water-contact sites.

Animals↗
PubMed1998

Chemotherapy accelerates the development of acquired immune responses to Schistosoma haematobium infection.

Treatment of 41 Schistosoma haematobium-infected children, 5-16 years old, with the drug praziquantel induced a switch from a predominantly IgA-specific antibody response to a predominantly IgG1 response within 12 weeks. A cross-sectional survey suggests that the same switch occurs naturally, but over several years, as children age (n = 251). The switch may be driven by alterations in cytokine levels in response to the release of antigens by dead or damaged parasites. Adults are more resistant to schistosome infection than children, and the switch to an "adult" response suggests that praziquantel treatment may have an immunizing effect, with benefits extending beyond a transient reduction in levels of infection.

Adolescent↗
PubMed1997

A genetic interpretation of heightened risk of BSE in offspring of affected dams.

An analysis is presented of the results of a cohort study designed to test whether or not the aetiological agent of bovine spongiform encephalopathy (BSE) in cattle can be transmitted maternally (vertically) from dam offspring. Various genetic models are fitted to the data under the assumption that the results could be explained entirely by genetic predisposition to disease (as opposed to maternal transmission) given exposure of offspring of diseased and unaffected dams to contaminated cattle feed. The analyses suggest that the results could be explained by the hypothesis of genetic predisposition, provided a large difference exists in the susceptibility of resistant and susceptible hosts, and explore the range of genotypic parameters and frequencies consistent with the limited currently available data. The results presented are broadly robust, even under the scenario that a portion of the observed maternally enhanced risk of BSE is due to a low level of maternal transmission in late incubation stage dams.

Alleles↗
PubMed1997

The epidemiology of BSE in cattle herds in Great Britain. I. Epidemiological processes, demography of cattle and approaches to control by culling.

This paper explores the key epidemiological processes and demographic factors that determined the pattern of transmission of the aetiological agent of bovine spongiform encephalopathy (BSE) in cattle herds in Great Britain (GB). The analyses presented utilize data from published and unpublished experimental studies and from the GB central database of confirmed BSE cases. We review the experimental and epidemiological evidence that has both confirmed indirect horizontal transmission via the consumption of infectious material as the major transmission route and provided information on the duration and variability of the dose-dependent incubation period of BSE in cattle. The epidemiological and genetic data pertaining to the possible existence of maternal transmission and/or genetically variable susceptibility to infection is discussed. The demography of British cattle is characterized and the impacts of key demographic features on the observed epidemic profile are discussed. In the main BSE case database, analyses reveal that BSE cases cluster significantly at both the holding and county scale. Furthermore, analysis of longitudinal patterns reveal substantial temporal within-holding correlation. Such clustering of cases suggests a highly heterogeneous infection process. The paper ends with a discussion of how analyses of spatio-temporal clustering inform the design of targeted culling programmes aimed at reducing future disease incidence. We show how the retrospective implementation of culling policies on the BSE case database allows the qualitative evaluation of policy performance, but that model predictions of future trends in case incidence are required to estimate the precise impact of any current or future programme.

Age Factors↗
PubMed1997

The epidemiology of BSE in cattle herds in Great Britain. II. Model construction and analysis of transmission dynamics.

Mathematical model that describe the key processes determining the pattern of the bovine spongiform encephalopathy (BSE) epidemic in British cattle are derived that allow for infection from feed as well as maternal and direct horizontal transmission. Heterogeneous susceptibility classes are also incorporated into the analysis. Maximum likelihood methods are used to estimate parameters and to obtain confidence intervals from available experimental and epidemiological data. A comprehensive sensitivity analysis of all model parameters and distributional assumptions is presented. Additional validation is provided by fitting the model to independent data collected in Northern Ireland. Model estimates and predictions based on BSE case data for Great Britain and Northern Ireland, together with their implications, are reviewed, and future research priorities discussed.

Age Distribution↗
PubMed1997

Heterogeneities in the transmission of infectious agents: implications for the design of control programs.

From an analysis of the distributions of measures of transmission rates among hosts, we identify an empirical relationship suggesting that, typically, 20% of the host population contributes at least 80% of the net transmission potential, as measured by the basic reproduction number, R0. This is an example of a statistical pattern known as the 20/80 rule. The rule applies to a variety of disease systems, including vector-borne parasites and sexually transmitted pathogens. The rule implies that control programs targeted at the "core" 20% group are potentially highly effective and, conversely, that programs that fail to reach all of this group will be much less effective than expected in reducing levels of infection in the population as a whole.

Animals↗
PubMed1997

Human schistosomiasis: potential long-term consequences of vaccination programmes.

Fields trials of new schistosomiasis vaccines are anticipated within the next few years, but there remains great uncertainty regarding the optimal design of vaccination programmes. Mathematical models are used here to explore the potential long-term consequences of vaccination, assuming that the vaccines provide partial protection for a limited period. The analysis suggests that vaccines acting to reduce infection rates or egg output will have a similar impact on levels of infection, that this impact may be highly sensitive to the duration as well as the degree of protection, that it may take several decades for the full impact to become apparent, and that one consequence will be peak levels of infection occurring in older age classes. In terms of lowering levels of infection there may be advantages in delaying vaccination until children reach school age, especially if the vaccine gives short-lived protection, or to repeat vaccination. The short-term advantages can be greatly increased by combining the introduction of a vaccination programme with initial mass chemotherapy. Continuous combined vaccination and chemotherapy programmes may also be more effective than either intervention alone. More research is needed on the consequences of vaccinating previously vaccinated, infected, and infected and treated individuals and the importance of natural boosting of vaccine-induced immunity.

Adolescent↗
PubMed1997

Simulation studies of vaccination strategies in African horse sickness.

A simulation model including two hosts (horses and donkeys) and one vector (Culicoides imicola) for African horse sickness in Spain is extended to consider vaccination strategies. If hosts were protected prior to virus introduction, elimination of simulated epidemics was related nonlinearly to the fraction protected. Protecting donkeys as well as horses increased the effectiveness of vaccination. Prevention of 50% of epidemics required 75% coverage of horses and donkeys or 90% coverage of horses only. Protection after the introduction of the virus was rarely successful in preventing outbreaks. If horses alone were protected, the number of donkeys was the most significant factor determining the level of protection needed to prevent an epidemic. If both hosts were protected, the abundance of other hosts for vector blood meals was the most significant factor. These results suggest that prophylactic vaccination of both horses and donkeys with high coverage is necessary to prevent outbreaks of African horse sickness in Spain.

African Horse Sickness↗
PubMed1997

The design of veterinary vaccination programmes.

The optimal design of a veterinary vaccination programme depends on both the characteristics of the vaccine and the epidemiology of the pathogen or parasite. Relevant vaccine characteristics are the proportion of those vaccinated that are initially protected, the duration of protection and the coverage achieved by the vaccination programme. The most important epidemiological parameter is the basic reproduction number, R0. Mathematical theory can integrate this information to address such questions as: whether it is possible to eliminate an infection; what proportion of hosts must be vaccinated to achieve this: what age should hosts first be vaccinated; and at what interval should hosts be revaccinated? Examples of rabies in foxes and foot-and-mouth disease in cattle suggest that theory can be used to guide the design of vaccination programmes.

Animals↗
PubMed1997

Schistosoma mansoni infection in a natural population of olive baboons (Papio cynocephalus anubis) in Gombe Stream National Park, Tanzania.

Infection with Schistosoma mansoni was studied in 5 troops of olive baboons (Papio cynocephalus amubis) in Gombe Stream National Park, Tanzania. Three troops were infected with S. mansoni. An aggregated distribution of parasites was observed among hosts. Troop membership was found to be the most significant factor influencing parasite prevalence. Age and reproductive status had no significant effect, but there was a trend for males to acquire higher levels of infection. However, age-prevalence curves showed a high infection in young baboons declining in the older baboons. Behavioural components of exposure--as measured in water-contact pattern--may be related to parasite burden. A 'peak shift' between infection in different age-classes in the different troops was observed: troops with higher schistosome prevalences displayed an earlier peak in prevalence of infection. The baboon troop with the most contact with people showed highest prevalence of infection possibly due to longer exposure to the parasite than the other troops and/or higher host density.

Age Distribution↗
PubMed1997

Transmission and distribution of virus serotypes: African horse sickness in zebra.

The prevalence of African horse sickness (AHS) serotypes in zebra foals from the Kruger National Park, South Africa was examined for possible associations between serotypes and to estimate the basic reproduction number, R0. The distributions of serotypes between zebra were not independent in the 6- and 7-8-month-old age classes (P < 0.005). This does not necessarily imply biological interactions between serotypes, as heterogeneity in host-vector transmission rates can generate non-independent distributions of serotypes. Both age and month of capture were significant factors in the number of serotypes infecting each zebra (P < 0.0001). Pairwise, positive associations between non-cross-reacting serotypes were found in the 7-8-month-old class only. For AHS overall, estimates of R0 ranged from 31-68. Assuming serotypes are transmitted independently, estimates of R0 for individual serotypes ranged from 10 for serotype 1 to 23 for serotype 6. The wide range of estimates emphasizes the need for a better understanding of serotype transmission and interactions in AHS.

African Horse Sickness↗
PubMed1997

A comparison of humoral responses to Schistosoma haematobium in areas with low and high levels of infection.

Antibody responses to Schistosoma haematobium of 280 Zimbabweans were studied in two areas of differing infection levels. 133 of the subjects came from a low infection area with a prevalence of 33.8% and geometric mean infection intensity of 0.8 eggs per 10ml of urine, while 147 of the subjects came from a high infection area with a prevalence of 62.7% and geometric mean intensity of 3.2 eggs per 10 ml of urine. Both the age-prevalence and age-intensity curves exhibited a peak shift. IgA, IgE, IgG, IgG1, IgG2, IgG3, IgG4, and IgM antibody levels against soluble egg antigen (SEA) and whole worm homogenate (WWH) were assayed by ELISA. Females produced significantly more anti-SEA IgG1, IgG4, IgM, anti-WWH IgE and IgG1. People from the high infection area produced significantly more anti-SEA IgE, IgG3 and anti-WWH IgG3 and significantly lower levels of anti-SEA IgA, IgM and anti-WWH IgM when the effects of infection intensity, sex and age had been allowed for. The age profiles of anti-SEA IgA, IgG and anti-WWH IgA and IgM reflected current levels of infection while anti-WWH IgG1, IgG2 and anti-SEA IgG1 evolved more slowly with age, and anti-WWH IgE rose with age in both areas. Some antibody responses, anti-SEA/WWH IgM, anti-SEA IgG1 and possibly anti-SEA/ WWH IgA showed different age profiles in the two areas, with changes in antibody levels occurring at a younger age in the high infection area suggesting that immune responses are evolving more rapidly in residents of this area. This result clearly demonstrates that antibody levels are not a function of age alone.

Adolescent↗
PubMed1997

An analysis of foot-and-mouth-disease epidemics in the UK.

There was a major epidemic of the foot-and-mouth-disease virus among cattle herds in the UK in 1967-68 which showed a very rapid early spread, a much slower later spread, and eventually infected 12% of herds in the core epidemic area. A simple discrete-time version of a susceptible-latent-infectious-removed epidemiological model is used to generate a set of estimates of the transmission rate. This parameter has high values over the first few days, then the values are lower and they subsequently decline. The early high values are consistent with the view that unusual meteorological conditions produced exceptionally good conditions for wind-borne spread of the virus over the first few days. The corresponding basic reproduction number, Rzero, is estimated as 38.4. Subsequent low values of the transmission rate correspond to a value of Rzero of 2.0; this is within the range of estimates made from the observed ratio of secondary to primary outbreaks for 25 other epidemics. Prophylactic control measures, such as vaccination, would have to be extremely effective to prevent epidemics with the higher Rzero value.

Animals↗