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Biomedical subjects

M E Woolhouse

Publications and source records attributed to M E Woolhouse.

At least 19 recordsLinked to original sources
PubMed2001

Dynamics of the 2001 UK foot and mouth epidemic: stochastic dispersal in a heterogeneous landscape.

Foot-and-mouth is one of the world's most economically important livestock diseases. We developed an individual farm-based stochastic model of the current UK epidemic. The fine grain of the epidemiological data reveals the infection dynamics at an unusually high spatiotemporal resolution. We show that the spatial distribution, size, and species composition of farms all influence the observed pattern and regional variability of outbreaks. The other key dynamical component is long-tailed stochastic dispersal of infection, combining frequent local movements with occasional long jumps. We assess the history and possible duration of the epidemic, the performance of control strategies, and general implications for disease dynamics in space and time.

Animal Husbandry↗
PubMed2001

The origins of a new Trypanosoma brucei rhodesiense sleeping sickness outbreak in eastern Uganda.

BACKGROUND: Sleeping sickness, caused by two trypanosome subspecies, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, is a parasitic disease transmitted by the tsetse fly in sub-Saharan Africa. We report on a recent outbreak of T b rhodesiense sleeping sickness outside the established south-east Ugandan focus, in Soroti District where the disease had previously been absent. Soroti District has been the subject of large-scale livestock restocking activities and, because domestic cattle are important reservoirs of T b rhodesiense, we investigated the role of cattle in the origins of the outbreak. METHODS: We identified the origins of cattle entering the outbreak area in the 4 years preceding the outbreak. A matched case-control study was conducted to assess whether the distance of villages from the main market involved with restocking was a risk factor for sleeping sickness. We investigated the spatial clustering of sleeping sickness cases at the start of the outbreak. FINDINGS: Over 50% (1510 of 2796) of cattle traded at the market were reported to have originated from endemic sleeping sickness areas. The case-control study revealed that distance to the cattle market was a highly significant risk factor for sleeping sickness (p<0.001) and that there was a significant clustering of cases (27 of 28) close to the market at the start of the outbreak (p<0.001). As the outbreak progressed, the average distance of cases moved away from the cattle market (0.014 km per day, 95% CI 0.008-0.020 km per day, p<0.001). INTERPRETATIONS: The results are consistent with the disease being introduced by cattle infected with T b rhodesiense imported to the market from the endemic sleeping sickness focus. The subsequent spread of the disease away from the market suggests that sleeping sickness is becoming established in this new focus. Public health measures directed at controlling the infection in the animal reservoir should be considered to prevent the spread of sleeping sickness.

Adult↗
PubMed2001

Risk factors for human disease emergence.

A comprehensive literature review identifies 1415 species of infectious organism known to be pathogenic to humans, including 217 viruses and prions, 538 bacteria and rickettsia, 307 fungi, 66 protozoa and 287 helminths. Out of these, 868 (61%) are zoonotic, that is, they can be transmitted between humans and animals, and 175 pathogenic species are associated with diseases considered to be 'emerging'. We test the hypothesis that zoonotic pathogens are more likely to be associated with emerging diseases than non-emerging ones. Out of the emerging pathogens, 132 (75%) are zoonotic, and overall, zoonotic pathogens are twice as likely to be associated with emerging diseases than non-zoonotic pathogens. However, the result varies among taxa, with protozoa and viruses particularly likely to emerge, and helminths particularly unlikely to do so, irrespective of their zoonotic status. No association between transmission route and emergence was found. This study represents the first quantitative analysis identifying risk factors for human disease emergence.

Animals↗
PubMed2001

Population biology of multihost pathogens.

The majority of pathogens, including many of medical and veterinary importance, can infect more than one species of host. Population biology has yet to explain why perceived evolutionary advantages of pathogen specialization are, in practice, outweighed by those of generalization. Factors that predispose pathogens to generalism include high levels of genetic diversity and abundant opportunities for cross-species transmission, and the taxonomic distributions of generalists and specialists appear to reflect these factors. Generalism also has consequences for the evolution of virulence and for pathogen epidemiology, making both much less predictable. The evolutionary advantages and disadvantages of generalism are so finely balanced that even closely related pathogens can have very different host range sizes.

Animals↗
PubMed2001

Endemic stability--a veterinary idea applied to human public health.

Endemic stability is an epidemiological state of a population, in which clinical disease is scarce despite high level of infection. The notion was developed to describe patterns of tick-borne disease in cattle. However, we propose a general model of endemic stability that is applicable to a broader range of diseases that are important in public health, including malaria, rubella, and mumps. We postulate that endemic stability requires only that (1) the probability, or severity, of clinical disease after infection increases with age, and (2) after one infection, the probability that subsequent infections result in disease is reduced. We present these criteria in simple mathematical terms. Our hypothesis predicts that partial disease control activities might, under certain circumstances, lead to an increase in disease incidence. We discuss the implications for public health interventions.

Age Distribution↗
PubMed2001

Population dynamics of a scrapie outbreak.

A detailed analysis of a scrapie outbreak in a flock of Cheviot sheep is described. A total of 33 cases of 1473 sheep born to the flock were reported between 1985 and 1994. The epidemiology of scrapie can only be understood with reference to sheep demography, the population genetics of susceptibility to scrapie, pathogenesis during a long incubation period, and the rate of transmission (by both horizontal and vertical routes), all of which interact in complex ways. In recent work a mathematical model incorporating these elements was developed and successfully reproduced key features of an earlier outbreak of scrapie in this flock. Here an application of the model to the second outbreak is described. The model accurately reproduces observed allele frequencies and total numbers of susceptible animals remaining at the end of the outbreak. A major difference between the two outbreaks is the very much lower force of infection in the second outbreak. This provided additional information which suggested two ways in which our existing assumptions be refined; firstly, older animals have reduced susceptibility to scrapie and secondly, homozygous and heterozygous susceptibles have different incubation periods.

Animals↗
PubMed2001

A centuries-long epidemic of scrapie in British sheep?

The apparent persistence of scrapie in British sheep for more than 250 years is difficult to explain. Susceptibility to scrapie is associated with particular alleles at a single locus, the PrP gene. As the only known effect of these alleles is to confer susceptibility to a fatal disease, natural selection is expected to reduce their frequency, as has been observed in practice during scrapie outbreaks in single sheep flocks. Susceptibility alleles, and hence scrapie itself, are therefore expected to become rare, yet the disease remains widespread. We suggest that the paradox of scrapie's persistence can be explained by the exceptionally long time-scales inherent in the epidemiology of the disease. It is proposed that scrapie should be regarded as epidemic in British sheep but, unlike more familiar epidemics, which have time-scales of months or years, the scrapie epidemic has a time-scale of centuries. This interpretation implies that scrapie should eventually disappear from the sheep population.

Animals↗
PubMed2001

Cytokine responses to mitogen and Schistosoma haematobium antigens are different in children with distinct infection histories.

Prevalence of Schistosoma haematobium infection in children from two neighbouring villages in Zimbabwe was 77.1% and 40.3%, respectively. The age-intensity data indicated peak intensities of infection at a lower age in the high prevalence village. This study investigated whether the difference in infection histories was reflected in a difference in cytokine profiles between children resident in these two villages. Blood samples were taken to assay for cytokine secretion 1 year after treatment for schistosomiasis. They were cultured with phytohaemagglutinin (PHA), schistosome egg antigens (SEA) or cultured without stimulant and tested for the presence of interleukin (IL)-4, IL-5, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IFN-gamma. Blood samples from children from the low prevalence village were more likely to produce IL-4 (P < 0.0001) and produced higher levels of IFN-gamma (P < 0.02) and GM-CSF (P < 0.03) when cultured with PHA for 24 h. Residence in the high prevalence village was associated with production of IL-10 (P < 0.006) and GM-CSF (P < 0.04) in response to culture with SEA and IL-5 (P < 0.02) with PHA for 48 h. The interaction between age and village was not significant for these results; however, there was a significant interaction between age and village for IL-5 detected in blood samples cultured with PHA for 24 h (P < 0.01). These results concur with previous observations that major patterns of cytokine production can be related to immunosuppression, but also indicate an underlying pattern which reflects the importance of history of infection to the immune response.

Adolescent↗
PubMed2001

Population genetics of the schistosome intermediate host Biomphalaria pfeifferi in the Zimbabwean highveld: implications for co-evolutionary theory.

Co-evolutionary theory proposes that polymorphisms in co-evolved traits may be maintained through differential selection in spatially heterogeneous environments. Spatial heterogeneity of the schistosome intermediate host, Biomphalaria pfeifferi, was investigated here, using RAPD markers. Overall, 256 individuals, collected at 32 sites on 13 rivers in the Chiweshe region of Zimbabwe, were analysed. Significant genetic differentiation was demonstrated, both between populations from the different rivers and between populations collected at different sites on each of several of the rivers investigated. However, the presence of spatial differentiation between populations from individual rivers varied with river type. It was not apparent in permanent, deep, fast-flowing rivers, where high levels of migration, through passive dispersal along the rivers, are likely. The snails collected from shallow, semi-permanent rivers not only showed relatively high levels of population subdivision but also high levels of within-site genetic diversity, consistent with the existence of 'co-evolutionary hot-spots' where schistosome infection may be prevalent. These results are discussed with reference to the population biology of B. pfeifferi and to host-parasite co-evolution.

Analysis of Variance↗
PubMed2001

Spatio-temporal genetic variability in the schistosome intermediate host Biomphalaria pfeifferi.

Genetic variation among temporally and spatially defined populations of the schistosome intermediate host, Biomphalaria pfeifferi, was analysed using RAPD markers. Snails were collected from each of eight sites that were 1-20 km apart, on four occasions, over a 2-year period. High levels of genetic variability were found within populations, between populations and between collections. Spatial differentiation and intrapopulation similarity were highest during periods of drought and were lowest following heavy rainfall. Temporal variability, consistent with founder effects, genetic drift and/or differential parasite pressure, was of similar or greater magnitude to that of the spatial variability. The results not only demonstrate that spatio-temporal sampling is necessary to understand the population genetics of short-lived species in variable habitats, but also provide empirical data to support current theoretical models of host-parasite co-evolution.

Analysis of Variance↗
PubMed2001

T cell clones from Schistosoma haematobium infected and exposed individuals lacking distinct cytokine profiles for Th1/Th2 polarisation.

T cell clones were derived from peripheral blood mononuclear cells of Schistosoma haematobium infected and uninfected individuals living in an endemic area. The clones were stimulated with S. haematobium worm and egg antigens and purified protein derivative. Attempts were made to classify the T cell clones according to production of the cytokines IL-4, IL-5 and IFN-gamma. All the T cell clones derived were observed to produce cytokines used as markers for the classification of Th1/Th2 subsets. However, the 'signature' cytokines marking each subset were produced at different levels. The classification depended on the dominating cytokine type, which was having either Th0/1 or Th0/2 subsets. The results indicated that no distinct cytokine profiles for polarisation of Th1/Th2 subsets were detected in these S. haematobium infected humans. The balance in the profiles of cytokines marking each subset were related to infection and re-infection status after treatment with praziquantel. In the present study, as judged by the changes in infection status with time, the T cell responses appeared to be less stable and more dynamic, suggesting that small quantitative changes in the balance of the cytokines response could result in either susceptibility or resistant to S. haematobium infection.

Animals↗
PubMed2001

Trypanosoma evansi in Indonesian buffaloes: evaluation of simple models of natural immunity to infection.

Deterministic models were employed to investigate the biology of Trypanosoma evansi infection in the Indonesian buffalo. Models were fitted to two age-structured data sets of infection. The Susceptible-Infected-Susceptible (SIS) model was the best supported description of this infection, although the results of the analysis depended on the serological test used; the Tr7 Ag-ELISA was judged the most reliable indicator of infection. Estimated forces of infection increase with age from 1.2 to 2.0 acquisitions per buffalo per year. The buffaloes would clear infection in an estimated mean time period of 16.8 months (95% CIs: 12.5-25.9 months) since acquisition, either by drug treatment by owners or self-cure. A general discussion on the role of immunity in protozoan infections includes consideration that the fitted SIS model would be consistent with strain-specific immunity. The model may become a useful tool for the evaluation of control programmes.

Age Factors↗
PubMed2000

What is antibiotic resistance and how can we measure it?

Antibiotic resistance is being found with increasing frequency in both pathogenic and commensal bacteria of humans and animals. Quantifying resistance within and between bacterial and host populations presents scientists with complex challenges in terms of laboratory methodologies and sampling design. Here, we discuss, from an epidemiological perspective, how antibiotic resistance can be defined and measured and the limitations of current approaches.

Anti-Bacterial Agents↗
PubMed2000

Exposure, infection and immune responses to Schistosoma haematobium in young children.

Behavioural, parasitological and immunological data were obtained from 48 children up to 6 years old, resident in a Schistosoma haematobium endemic area in Zimbabwe. The children averaged more than 1 contact with infective water bodies every 3 days and all showed immunological evidence of exposure (an anti-cercarial and/or anti-egg antibody response). IgM was the dominant isotype and appeared in the youngest children, followed by IgA, IgE and IgG3. However, only 38 children showed evidence of infection (an anti-egg response or eggs in urine) and only 14 were excreting eggs. The best estimates from these data are that less than 1 in 100 contacts results in infection and less than 1 in 1000 result in egg output. This suggests that there may be substantial attrition of invading cercaria even in naïve individuals.

Animals↗
PubMed2000

Stochastic simulation and the detection of immunity to schistosome infections.

In this paper we address the question of detecting immunity to helminth infections from patterns of infection in endemic communities. We use stochastic simulations to investigate whether it would be possible to detect patterns predicted by theoretical models, using typical field data. Thus, our technique is to simulate a theoretical model, to generate the data that would be obtained in field surveys and then to analyse these data using methods usually employed for field data. The general behaviour of the model, and in particular the levels of variability of egg counts predicted, show that the model is capturing most of the variability present in field data. However, analysis of the data in detail suggests that detection of immunity patterns in real data may be very difficult even if the underlying patterns are present. Analysis of a real data set does show patterns consistent with acquired immunity and the implications of this are discussed.

Adolescent↗