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Biomedical subjects

G F Medley

Publications and source records attributed to G F Medley.

At least 19 recordsLinked to original sources
PubMed2003

Serological survey of anti-group A rotavirus IgM in UK adults.

Rotaviral associated disease of infants in the UK is seasonal and infection in adults not uncommon but the relationship between these has been little explored. Adult sera collected monthly for one year from routine hospital samples were screened for the presence of anti-group A rotavirus immunoglobulin M class antibodies as a marker of recent infection. Anti-rotavirus IgM was seen in all age groups throughout the year with little obvious seasonal variation in the distribution of antibody levels. IgM concentrations and the proportion seropositive above a threshold both increased with age with high concentrations consistently observed in the elderly. Results suggest either high infection rates of rotavirus in adults, irrespective of seasonal disease incidence in infants, IgM persistence or IgM cross-reactivity. These results support recent evidence of differences between infant and adult rotavirus epidemiology and highlight the need for more extensive surveys to investigate age and time related infection and transmission of rotavirus.

Adolescent↗
PubMed2003

Survival of Theileria parva in its nymphal tick vector, Rhipicephalus appendiculatus, under laboratory and quasi natural conditions.

Groups of nymphal Rhipicephalus appendiculatus Muguga, having a mean of 1 or 9 Theileria parva Muguga-infected salivary gland acini per tick, were kept under quasi-natural conditions at an altitude of 1950 m or 20 degrees C at a relative humidity of 85% in the laboratory and their survival and infection prevalence and abundance determined over time. Theileria parva infections for both categories of ticks survived in the nymphal ticks for 50 or 26 weeks post salivary gland infection under quasi-natural or laboratory conditions respectively. There was a distinct decline in infections in the more heavily infected nymphae under both conditions of exposure, reflecting an apparent density dependence in parasite survival. Nymphal ticks having an average infection level of 1 infected salivary gland acinus per tick, survived for up to 69 or 65 weeks post-repletion under quasi-natural or the laboratory conditions respectively. Nymphae having an average infection level of 9 infected salivary gland acini per tick survived for a similar duration under each of the 2 conditions. The infection level of 9 infected salivary gland acini per tick did not seem to significantly affect the survival of the tick vector compared to those having an average of 1 infected salivary gland acinus per tick.

Animals↗
PubMed2002

The epidemiological consequences of optimisation of the individual host immune response.

We present a simple unscaled, quantitative framework that addresses the optimum use of resources throughout a host's lifetime based on continuous exposure to parasites (rather than evolutionary, genetically explicit trade-offs). The principal assumptions are that a host's investment of resources in growth increases its survival and reproduction, and that increasing parasite burden reduces survival. The host reproductive value is maximised for a given combination of rates of parasite exposure, host resource acquisition and pathogenicity, which results in an optimum parasite burden (for the host). Generally, results indicate that the optimum resource allocation is to tolerate some parasite infection. The lower the resource acquisition, the lower the proportion of resources that should be devoted to immunity, i.e. the higher the optimum parasite burden. Increases in pathogenicity result in reduced optimum parasite burdens, whereas increases in exposure result in increasing optimum parasite burdens. Simultaneous variation in resource acquisition, pathogenicity and exposure within a community of hosts results in overdispersed parasite burdens, with the degree of heterogeneity decreasing as mean burden increases. The relationships between host condition and parasite burden are complicated, and could potentially confound data analysis. Finally, the value of this approach for explaining epidemiological patterns, immunological processes and the possibilities for further work are discussed.

Adolescent↗
PubMed2002

Influence of dry period bacterial intramammary infection on clinical mastitis in dairy cows.

Milk samples were taken from 1920 quarters (480 cows, six herds) on four occasions to examine the relationship between quarter level intramammary infection (IMI) during the dry period and clinical mastitis in the next lactation. All quarters were sampled at drying off and within 1 wk of calving, and two quarters from each cow were sampled both 0 to 7 and 8 to 14 d before calving. Milk samples were collected from all cases of clinical mastitis during the following lactation. Logistic regression models were developed to investigate the associations between IMI present during the sampling period and clinical mastitis. The probability of a quarter succumbing to clinical mastitis increased when Streptococcus dysgalactiae, Streptococcus faecalis, Escherichia coli, or Enterobacter spp. were cultured at drying off and when Escherichia coli, coagulase-positive staphylococcus, Serratia spp., or Streptococcus faecalis were cultured in two out of three late dry and post-calving samples. Quarters from which Corynebacterium spp. were isolated at drying off were at an increased risk of clinical mastitis, whereas the presence of Corynebacterium spp. in the late dry and post-calving samples was associated with a reduction in the risk of clinical mastitis. The risk of mastitis for specific pathogens increased if the same species of bacteria that had caused mastitis was isolated at least twice in the late dry and post-calving samples. Kaplan-Meier survival plots indicated that clinical mastitis associated with dry period infections was more likely to occur earlier in lactation than clinical mastitis not associated with dry period infections. There was evidence of quarter susceptibility to IMI or the possibility that infection with one organism led to clinical mastitis with another.

Animals↗
PubMed2001

The structural identifiability and parameter estimation of a multispecies model for the transmission of mastitis in dairy cows.

A structural identifiability analysis is performed on a mathematical model for the coupled transmission of two classes of pathogen. The pathogens, classified as major and minor, are aetiological agents of mastitis in dairy cows that interact directly and via the immunological reaction in their hosts. Parameter estimates are available from experimental data for all but four of the parameters in the model. Data from a longitudinal study of infection are used to estimate these unknown parameters. A novel approach and application of structural identifiability analysis is combined in this paper with the estimation of cross-protection parameters using epidemiological data.

Animals↗
PubMed2001

A multispecies model for the transmission and control of mastitis in dairy cows.

Mastitis in dairy cows is a significant economic and animal welfare issue in the dairy industry. The bacterial pathogens responsible for infection of the mammary gland may be split into two main categories: major and minor pathogens. Infection with major pathogens generally results in clinical illness or strong inflammatory responses and reduced milk yields, whereas minor pathogen infection is usually subclinical. Previous investigations have considered the transmission of these pathogens independently. Experimental evidence has shown cross-protection between species of pathogens. In this study a mathematical model for the coupled transmission of major and minor pathogens along with their interaction via the host was developed in order to consider various methods for controlling the incidence of major pathogen infection. A stability analysis of the model equilibria provides explanations for observed phenomena and previous decoupled modelling results. This multispecies model structure has provided a basis for quantifying the extent of cross-protection between species and assessing possible control strategies against the disease.

Animals↗
PubMed2001

Population-based evaluation of the Ehrlichia ruminantium MAP 1B indirect ELISA.

The indirect MAP 1B ELISA based on the recombinant MAP 1B fragment of the immunodominant MAP I protein of Ehrlichia ruminantium is considered to be the most sensitive and specific assay for the serodiagnosis of heartwater. In this study, we evaluated its reliability in detecting exposure to E. ruminantium in field populations of domestic ruminants in Zimbabwe. Cattle and goat herds in endemically stable areas with high infection pressure and an expected close to 100% prevalence of E. ruminantium exposure were sampled. Bovine sera (858) and caprine sera (706) collected at seven locations representative of the two main production systems (communal lands and large scale commercial farms) in the two main agroecological zones of Zimbabwe (highveld and lowveld) were analysed. The prevalence of MAP 1B-specific antibodies in goats was similar and high, ranging from 67 to 100%, at all except one site (43%). Age-specific differences in goats (1, 2, 3, 4, 5 years) were not observed. In contrast, MAP 1B seroprevalence in cattle was significantly lower (P < 0.001), ranging from 46 to 61% in the lowveld communal area and from 24 to 33% in the remaining areas (P < 0.001). Age-specific differences in seroprevalence (1, 2, 3, 4, 5-7 + years) were similarly not evident in cattle (P < 0.15). Hence, the indirect MAP 1B ELISA may be an unreliable indicator of past exposure to heartwater in field-infected cattle in Zimbabwe. Although the reasons for this low response in field cattle are not fully understood, this study illustrates the need for field validation of the performance of new diagnostic tests prior to their use for epidemiological purposes.

Animals↗
PubMed2001

Hepatitis-B virus endemicity: heterogeneity, catastrophic dynamics and control.

Hepatitis-B virus infection is globally ubiquitous, but its distribution is very heterogeneous, with prevalence of serological markers in various nations ranging from less than 1% to more than 90%. We propose an explanation for this diversity using a mathematical model of hepatitis-B virus transmission dynamics that shows, for the first time, 'catastrophic' behavior using realistic epidemiological processes and parameters. Our major conclusion is that the prevalence of infection is largely determined by a feedback mechanism that relates the rate of transmission, average age at infection and age-related probability of developing carriage following infection. Using the model we identify possible, highly non-linear, consequences of chemotherapy and immunization interventions, for which the starting prevalence of carriers is the most influential, predictive quantity. Taken together, our results demand a re-evaluation of public health policy towards hepatitis-B.

Carrier State↗
PubMed2001

Effects of insulin and glucocorticoids on the leptin system are mediated through free leptin.

OBJECTIVE: Insulin and glucocorticoids are known to increase total leptin levels. However, the effects of insulin and glucocorticoids on the components of the leptin system - free leptin (FL), bound leptin (BL) and soluble leptin receptor (SR) - have not been elucidated. The aim of this study was to determine if there is a differential effect of insulin and glucocorticoids on the leptin system. MATERIAL AND METHODS: In the first of two studies (study 1), we measured free leptin (FL), bound leptin (BL), a soluble leptin receptor (SR) and insulin, by specific RIA methods, in six healthy subjects on a control day, and subsequently during a hyperinsulinaemic euglycaemic clamp study. In the second study (study 2) we measured the same parameters in six healthy subjects, before (day 1) and during administration of dexamethasone over 3 consecutive days. RESULTS: In study 1, on the control day FL levels rose over the 16 h monitoring period (P = 0.057) and SR levels declined (P < 0.001), but there was no change of BL levels. Even after accounting for diurnal variation, FL levels increased even more substantially over 12 h of insulin infusion than observed on the control day (P < 0.001). In study 2, mean FL concentration doubled from day 1 to day 2 (P = 0.01) and remained elevated subsequently. In contrast to FL, BL and SR levels remained unchanged during the study. Fasting insulin levels (pmol/l) increased from day 1 to day 2, but this rise only approached significance on day 4 (P = 0.05). CONCLUSION: We conclude that insulin and dexamethasone increase free leptin levels, but do not change the concentrations of bound leptin and soluble leptin receptor. Furthermore, the dexamethasone-induced rise in leptin levels is (at least partially) independent of the effects of glucocorticoid-induced hyperinsulinaemia.

Adult↗
PubMed1999

Evaluating the cost-effectiveness of vaccination programmes: a dynamic perspective.

Although there are many models which are used to calculate the health benefits (and thus the cost-effectiveness) of vaccination programmes, they can be divided into two groups: those which assume a constant force of infection, that is a constant per-susceptible rate of infection; and those which assume that the force of infection (at time t) is a function of the number of infectious individuals in the population at that time (dynamic models). In constant force of infection models the per-susceptible rate of infection is not altered, whereas in dynamic models mass immunization results in fewer infectious individuals in the community and thus a lower force of infection acting on those who were not immunized. We take an example of each of these types of model, examine their underlying assumptions and compare their predictions of the cost-effectiveness of a mass immunization programme against a hypothetical close contact infection, such as measles. We show that if cases of infection are the outcome of interest then the constant force of infection model will always underestimate the cost-effectiveness of the immunization programme except at the extremes when no one or everyone is immunized. However, unlike the constant force of infection model, the dynamic model predicts an increase in the average age at infection after immunization which could impact on the estimate of the cost-effectiveness of the programme if the risk of developing serious disease is a function of the age at infection (as, for instance, is the case for congenital rubella syndrome). Taking cases of infection as the outcome measure and using the dynamic model, the undiscounted cost-effectiveness ratio will tend to decline over time and approach a constant value, as the system moves from pre- to post-immunization equilibrium. We go on to show how the cost-effectiveness of a fixed-term immunization programme might change over time, and discuss why, under most circumstances, decision makers should not assume that elimination (permitting termination of mass immunization) will occur.

Cohort Studies↗
PubMed1999

Predicting the effect of vaccination on the transmission dynamics of heartwater (Cowdria ruminantium infection).

We used a mathematical description of the transmission dynamics of the tick-borne infection Cowdria ruminantium in commercial beef enterprises in Zimbabwe to consider the potential impact of a candidate vaccine to prevent heartwater. The important characteristics of the vaccine were (1) a delay in development of full protection, (2) prevention of clinical disease but not of infection and (3) a waning period of protection in the absence of challenge. We considered three different scenarios in which the vaccine might be used: prophylactically in susceptible cattle prior to the introduction of infection into a herd; in susceptible cattle in the face of an epidemic (i.e., when the infection is introduced and disease is first noticed); and at equilibrium (i.e., when parasite, vector and host have been co-existing for some time). The epidemic rise in infection was modelled assuming two different patterns (i.e., resulting from slow and fast increases in tick challenge). Vaccination (administered both in the face of an epidemic and prophylactically) reduced and delayed the peak of the epidemic. With insufficiently frequent revaccination, this can result in the epidemic occurring during a period of susceptibility, so that the benefit derived from a more-efficacious vaccine is lower than that from a less-efficacious vaccine. A vaccine of only 30% or 50% efficacy (if given to the whole herd) can have important effects on both morbidity and mortality if administered with sufficient frequency. However, a highly efficacious vaccine (e.g., 90%) can have only minimal effect if revaccination occurs too infrequently - especially if the epidemic of disease occurs when tick challenge is high and vaccination-related immunity has waned. There was a fairly consistent pattern of decreasing returns on increasing protection, although this was reversed in the situation of annual vaccination undertaken prophylactically combined with an epidemic of infection that occurred when the tick challenge was relatively low. Vaccination in equilibrium situations was most beneficial at low and intermediate tick challenges. There was very little effect of vaccination in high-transmission areas regardless of vaccine efficacy and/or frequency of revaccination because most animals were infected during periods of innate or maternally derived immunity (i.e., under endemic stability). Our results suggest that where relatively high tick challenge can be achieved and consistently maintained, vaccination may be used in susceptible herds to minimise losses in a policy of transition to endemic stability.

Animals↗
PubMed1999

Cowdria ruminantium infection in ticks in the Kruger National Park.

Adult Amblyomma hebraeum ticks, the principle vector of heartwater (cowdriosis) of domestic ruminants in southern Africa, were collected in pheromone traps placed in Kruger National Park, an exclusively wildlife sanctuary in South Africa. These ticks transmitted Cowdria ruminantium, the rickettsial agent causing heartwater, to a susceptible goat, resulting in acute, fatal disease. C ruminantium was isolated in bovine endothelial cell culture from the plasma of this animal during the febrile stage of the disease and transmitted to susceptible goats, causing fatal heartwater. The prevalence of C ruminantium infection in 292 ticks was determined by polymerase chain reaction (PCR) analysis to be 1.7 per cent (95 per cent confidence interval 0.71 to 4.0 per cent). A DNA probe analysis, which is less sensitive than PCR, detected infection in three of the five PCR-positive ticks. The remaining infections were below the detection limit of the DNA probe, which is approximately 70,000 organisms. This is the first evidence that a vector-wildlife cycle of transmission of C ruminantium can be maintained independently of domestic ruminants.

Animals↗
PubMed1999

An assessment of the economic impact of heartwater (Cowdria ruminantium infection) and its control in Zimbabwe.

Heartwater, caused by the rickettsial organism Cowdria ruminantium, is a serious constraint to livestock development in much of sub-Saharan Africa. Traditionally, the disease has been controlled by the use of chemical acaricides to control the vector tick. The University of Florida/USAID-supported heartwater research project (based in Zimbabwe) is developing a new inactivated vaccine to control the disease. In order that the vaccine is used effectively, the project has been studying the epidemiology of the disease in different livestock production systems of Zimbabwe, and evaluating the economic impact of the disease and of its future control using a vaccine such as the one under development. Initially, field studies were conducted to characterise the communal and commercial livestock-productions systems at risk from heartwater and to understand the epidemiology of the disease. The data from these studies were then applied to an infection-dynamics model of heartwater, which was used to provide estimates of disease incidence and impact under various scenarios over a period of 10 yr. Two principal outputs of the epidemiological model (cumulative annual heartwater incidence and infection-fatality proportion) were key inputs into an economics model. The estimated total annual national losses amount to Z$ 61.3 million (US$ 5.6 million) in discounted value terms over 10 yr. Annual economic losses per animal in the commercial production system (Z$ 56 discounted values) are 25 times greater than the losses in the communal system (Z$ 2.2). The greatest component of economic loss is acaricide cost (76%), followed by milk loss (18%) and treatment cost (5%). Losses in outputs other than milk (beef, traction and manure) appear to be minimal. A new vaccine has the promise of a benefit: cost ratio of about 2.4:1 in the communal and 7.6:1 in the commercial system. A control strategy based on a new vaccine would yield additional non-financial benefits to farmers and the government resulting from reductions in the use of chemical acaricides.

Animals↗
PubMed1999

The control of heartwater on large-scale commercial and smallholder farms in Zimbabwe.

As part of a series of studies associated with the development of improved vaccines for heartwater (a tick-borne disease of ruminant livestock caused by Cowdria ruminantium), field surveys were carried out to assess losses associated with the disease and the costs associated with controlling it in the two main agro-ecological zones of Zimbabwe (lowveld and highveld) where heartwater is believed to be endemic and epidemic, respectively. In each zone, a cross-sectional study was performed in the main farming systems (smallholder (SH) and large-scale commercial (LSC) beef and dairy), followed by longitudinal studies in the same sectors to improve data accuracy for some parameters. Suspected heartwater-specific mortality in cattle was similar in all LSC sectors (p = 0.72) accounting for a median 1% mortality risk. Heartwater-specific mortality in SH areas was not assessed due to poor diagnostic ability of the farmers. Few LSC farms and SH households kept sheep; suspected heartwater-specific mortality in LSC sheep was 0.8% in the lowveld and 2.4% in the highveld. Goats were a major enterprise in SH areas but not on LSC farms. Suspected heartwater mortality in LSC goats was 0.8% at one site in the highveld and 17.5% on a farm in the lowveld. Application of acaricides was the major control method for heartwater and other tick-borne diseases on both SH and LSC farms. On LSC farms, plunge dipping was used most frequently and the number of acaricide applications ranged widely between 3 and 52 per year. The total cost of acaricides per head per annum was higher in highveld dairies than in highveld and lowveld beef enterprises (p = 0.03). In SH areas, cattle plunge dipping was conducted by the government with an average frequency of 8 +/- 2 (sd) immersions per annum in both the lowveld and highveld. The type of tick control on sheep and goats in all production systems was highly variable (ranging from none to hand removal or intensive acaricide treatment). Suspected heartwater cases on LSC farms were treated with tetracyclines; treatment was not reported in SH areas. Reported treatment costs were high (median Z$ 120) and highly variable (range Z$-833). Vaccination against heartwater with the live, blood-based vaccine was reported on only one LSC farm. LSC farms applying acaricide 30 or more times per year reported higher morbidity (p < 0.0001) and mortality (p < 0.0001) than farms applying acaricides less than 30 times a year. This finding supports the use of reduced tick control in the management of heartwater in Zimbabwe.

Agriculture↗
PubMed1999

Exposure of sows to Ascaris suum influences worm burden distributions in experimentally infected suckling piglets.

This paper reports on the influence of maternal exposure to Ascaris suum on worm burden distributions in experimentally infected piglets. In the first study, sows were inoculated before and during gestation (6 months, long-term exposure) with 10,000 A. suum eggs twice weekly. In a second study, sows were inoculated during gestation only (3 months, short-term exposure) with increasing doses of eggs (10,000-40,000 eggs twice weekly). Helminth-naive sows served as controls in both studies. The third study used the same design as the short-term exposure study, but piglets from exposed and control sows were cross-suckled within 4 h of birth before colostrum uptake. All piglets were inoculated 2 or 3 times with 50 A. suum eggs on days 4 and 7 (and 14) after birth, and left with the sows. At 10 weeks of age all piglets were necropsied, and liver lesions and worm burdens were recorded. Surprisingly, in piglets born to long-term exposed sows, the prevalence of A. suum infection and the mean worm burden were significantly higher than those in piglets from control sows. In contrast, neither worm burdens nor prevalence were significantly different between piglets from short-term exposed sows compared with their controls. In the cross-suckling experiment, 67% of piglets suckling control sows harboured worms at slaughter, compared with 15% of piglets suckling exposed sows. Maximum likelihood analysis of worm burden distribution and the degree of parasite aggregation showed 3 distinctly different types of overdispersed distributions: worm counts in piglets from control sows, in piglets from short-term exposed sows and in piglets from long-term exposed sows. When the worm burden data were analysed including the cross-suckled piglets by biological mother, it appeared that the control and short-term distributions converged and that only the long-term exposure was significantly different. Overall, the degree of parasite aggregation in piglets infected with A. suum decreased with exposure of the sows. A non-linear relationship was observed between prevalence of infection and mean worm burden, which was different for piglets from exposed and control sows, and similar to relationships of this type that previously have been found in human A. lumbricoides infections. It was concluded that in porcine A. suum infections maternal exposure alters the distribution of worms in their offspring, in which the duration of exposure appeared to be an important influence. The results of the cross-suckling further suggest that maternal factors, e.g. antibodies, are transferred via colostrum.

Animals↗
PubMed1999

Intestinal parasites in swine in the Nordic countries: multilevel modelling of Ascaris suum infections in relation to production factors.

In Denmark, Finland, Iceland, Norway and Sweden, 413 sow herds were randomly selected for sampling. Faeces from pigs of 7 age groups/categories were examined for helminth eggs (11,233 individual samples), and an accompanying questionnaire was completed at each visit. In total, 1138 pigs on 230 farms were found to be positive for Ascaris suum. Considerable differences in the occurrence of A. suum could be observed directly for several of 20 independent variables at the herd or category level. However, given that univariate analyses may be severely affected by confounding of covariates resulting in spurious inference, additional multivariate analyses were undertaken. An ordinary logistic regression on Ascaris positive/negative farms showed that Denmark had the highest frequency of infected herds, while Iceland and Finland had the lowest frequencies and that herds using 'late weaning' and 'Class 2' drugs (pyrantel, levamisole) were most often infected. Because many herds were found to be totally negative for A. suum, mixed hierarchical logistic-normal regression models (both the penalized quasi-likelihood and the Markov Chain Monte Carlo methods) were developed for both a full (all herds) and a reduced (the 230 infected herds) data set using either a cut-off of > 0 eggs per gram (epg) or > 200 epg to counter for false-positive egg counts. Estimates for identical models, but where the animal level variance was constrained to the binomial assumption, were also calculated. Significant covariates were robust to model development with 'Age group', 'Country', 'Weaning age', 'Water system' and simple interactions between the latter two and 'Age group' being significantly associated with the occurrence of A. suum, while all variables concerning anthelmintic drug, anthelmintic strategy, floor type, bedding, dung removal, washing and disinfection were not. These findings are discussed in the light of the complex relationship between A. suum and its pig host.

Age Factors↗