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Biomedical subjects

G F Medley

Publications and source records attributed to G F Medley.

At least 55 records · Page 3Linked to original sources
PubMed1999

Free leptin, bound leptin, and soluble leptin receptor in normal and diabetic pregnancies.

We measured serum levels of free leptin, bound leptin, and soluble leptin receptor by specific RIA methods in 20 normal and 19 insulin-dependent diabetes mellitus subjects at 20 and 30 weeks gestation and postpartum, and analyzed the data using hierarchical statistical models. Total leptin levels rise from 20-30 weeks gestation (688 +/- 58 to 785 +/- 62 pmol/L, mean +/- SEM; P = 0.009). There is a significant postpartum fall to 445 +/- 47 pmol/L (P < 0.001). This rise is caused by the rise in the bound leptin levels, as there is no significant change in free leptin levels between 20 and 30 weeks (P = 0.17). There is a significant postpartum fall in free leptin levels (P < 0.001). Insulin requirements rise in the third trimester, but despite this there was no significant difference in free or bound leptin levels between the normal and diabetic subjects at any stage [free leptin, 223 +/- 35 and 266 +/- 24, 237 +/- 45 and 223 +/- 27, and 109 +/- 16 and 104 +/- 24 (P = 0.34); bound leptin, 410 +/- 73 and 428 +/- 54, 501 +/- 78 and 562 +/- 71, and 330 +/- 47 and 271 +/- 46 (P = 0.84); for normals and diabetics at 20 and 30 weeks gestation and postpartum, respectively]. Diabetic subjects, however, had significantly higher soluble leptin receptor levels at all stages (P << 0.001), which rose further in the third trimester from 3742 +/- 268 (mean +/- SEM) to 4134 +/- 239 pmol/L, whereas in the normal group there was a fall from 3149 +/- 169 to 2712 +/- 123 (P = 0.05). There is a linear relationship between the soluble leptin receptor levels and the body mass index in the diabetic group only. We conclude that there is no significant difference in free or bound leptin levels between the normal and insulin-dependent diabetic subjects either during pregnancy or postpartum, but female insulin-dependent diabetic subjects have significantly higher soluble leptin receptor levels. We speculate that high soluble leptin receptor levels might be implicated in the development of the leptin resistance in this group.

Adult↗
PubMed1998

Microparasite population dynamics and continuous immunity.

A mathematical model is presented for the transmission of a microparasite where the hosts occupy one of two states, uninfected or infected. In each state, the hosts are distributed over a continuous range of immunity. The immune levels vary within hosts due to the processes of waning of immunity (when uninfected), and increasing immunity (when infected), eventually resulting in recovery. Immunity level also influences the host's ability to infect or be infected. Thus the proposed model incorporates both inter- and intra-host dynamics. It is shown from equilibrium results that this model is a general form of the susceptible-infected-resistant (SIR) and susceptible-infected-susceptible (SIS) family of models, a development that is useful for exploring multistrain pathogen transmission and use of vaccines which confer temporary protection.

Animals↗
PubMed1998

Seroepidemiological study of respiratory syncytial virus in São Paulo state, Brazil.

Transmission of respiratory syncytial virus is thought to be highly seasonal based on reported clinical cases, although transmission resulting in mild disease in all age groups has been little studied. This has been investigated in a seroepidemiological survey using sera from São Paulo, Brazil. Seroprevalence was found to increase rapidly with age, reaching over 90% by three years of age. This is typical of viral infections, which produce life-long immunity following primary infection. One-hundred percent seropositivity was attained by five years of age and maintained throughout adulthood, whereas mean antibody titers continued to increase with age. The mean duration of maternal antibodies was estimated to be 3.3 months with antibody decay demonstrated in paired samples from infants. The results are discussed in relation to possible mechanisms generating such a profile.

Adolescent↗
PubMed1998

Vector competence of 7 rhipicephalid tick stocks in transmitting 2 Theileria parva parasite stocks from Kenya and Zimbabwe.

The competence of 7 different stocks of Rhipicephalus appendiculatus and R. zambeziensis to transmit 2 different stocks of Theileria parva was compared by feeding nymphae of each tick stock simultaneously on infected cattle and assessing the infections in the salivary glands of the resultant adult ticks. There were significant differences in the patterns of infection of the 2 stocks (T. parva Muguga and T. parva Boleni) in the different stocks of ticks, and these differences were shown to be reproducible. The Muguga tick stock from Kenya and the Zambia tick stock from Eastern Province had the highest infections of T. parva Muguga and T. parva Boleni respectively. The Zambia Southern Province tick stock and the Zimbabwe Mashonaland West tick stock had the lowest infections of T. parva Muguga and T. parva Boleni respectively. The difference in mean abundance of infection between the most and least efficient vector for T. parva Muguga was 63.3 while that for T. parva Boleni was 54.4 infected acini. The implications of these results for laboratory transmission of T. parva and for the epidemiology of theileriosis are discussed.

Age Factors↗
PubMed1998

Investigating the epidemiology of heartwater (Cowdria ruminantium infection) by means of a transmission dynamics model.

A mathematical model of the transmission dynamics of Cowdria ruminantium by the ixodid tick Amblyomma hebraeum in the bovine host is developed and used to investigate the epidemiology of heartwater across a range of vector challenge. The processes described are supported by empirical data. The pattern of outcome measures (incidence, case-fatality and proportion of infected hosts) predicted agrees with those described anecdotally from field experience and empirical observation, and demonstrates the concept of endemic stability. The underlying theory is explored and it is shown that endemic stability may be due principally to the protection of calves against disease by either innate or maternally derived factors. The role of vertical infection in the establishment and maintenance of endemic stability is also investigated. Although increasing the vertical infection proportion results in endemic stability occurring at progressively lower levels of tick challenge, the concomitant reduction in incidence and case-fatality predictions across the range of tick challenge means the endemically stable state simultaneously becomes less discernible. Model limitations and future developments are discussed. The essential role of a transmission dynamics model in assessing the impact of new vaccines in conjunction with vector control programmes is highlighted.

Africa South of the Sahara↗
PubMed1998

Distribution of Ascaris suum in experimentally and naturally infected pigs and comparison with Ascaris lumbricoides infections in humans.

This paper describes the distribution of Ascaris suum in experimentally and naturally infected pigs, and offers a comparison with A. lumbricoides infections in humans. In the first study, worms were recovered post-mortem from a group of 38 pigs that had been trickle inoculated with 10,000 infective A. suum eggs twice weekly for 12 weeks. In the second study, worms were collected from a group of 49 pigs that had been kept on a pasture contaminated with infective A. suum eggs for 10 weeks, after which they received treatment with an anthelmintic; they then were turned out on the same pasture for a second 10-week period before slaughter. The worm burdens of the naturally infected pigs were recorded both at treatment and post-mortem. Mean worm counts were similar at all occasions but the prevalence of infection was higher in the trickle infected and naturally reinfected pigs. Furthermore, the prevalence in naturally infected pigs increased significantly over the study period. Worm burden distributions in all groups were heavily overdispersed, but the distribution patterns differed significantly between groups: lower exposure (initial natural infection) gave a low prevalence and an almost uniform distribution of worm burdens among infected hosts. Continued or higher exposure (trickle and natural reinfection) resulted in increased prevalence and a reduction in the proportion of hosts with increasing worm load. A positive correlation was found between initial and reinfection worm burdens in the naturally infected pig population, suggesting that individual pigs are predisposed to a high or low intensity of infection. The prevalence and intensity as well as the distribution observed for A. suum infection in pigs were comparable to those reported for A. lumbricoides in endemic areas, and there is evidence for predisposition to A. suum in pigs, with an estimated correlation coefficient similar to that found in humans. It is concluded that A. suum infections in pigs are a suitable model to study the population dynamics of A. lumbricoides in human populations.

Administration, Oral↗
PubMed1998

Seroepidemiology of group A rotavirus in suburban São Paulo, Brazil.

Age-specific patterns of rotavirus infection were investigated using a randomly selected and representative sample of sera from a suburban community of São Paulo, Brazil screened for class-specific antibodies to group A rotavirus. Age-serology of anti-rotavirus IgG showed primary infection predominant in young infants with a median age of around 18 months consistent with IgM serology suggesting highest rates of recent infection between ages 4 and 48 months. Anti-rotavirus serum IgA prevalence increased gradually with age. Paired samples from infants, collected 1 month apart, indicated high exposure rates with seroconversion occurring in several infants during the reported low transmission season. Between 5 and 10% of adults had elevated IgM levels indicative of recent infection and, potentially, of an important contribution adults may play to rotavirus transmission. Further understanding of the dynamics of rotavirus transmission within populations, at group and serotype level, would benefit the design and monitoring of future immunization programmes.

Adolescent↗
PubMed1998

Distributions of the vectors of heartwater, Amblyomma hebraeum and Amblyomma variegatum (Acari: Ixodidae), in Zimbabwe.

The tick vectors of heartwater (Cowdria ruminantium infection) in Zimbabwe, Amblyomma hebraeum and Amblyomma variegatum, historically were believed to be confined to the low-lying regions of the south and north-west of the country. However, country-wide surveys performed in 1975-1980 and 1988-1991 demonstrated that both species were also established in western parts of the highveld plateau and had started to encroach on the predominantly heartwater-free central and eastern highveld regions. To determine the current distributions of both the vectors and evaluate the potential threat of heartwater to animals in the highveld, a survey of ticks infesting cattle was performed in 1996 at 2994 locations in small-holder and large-scale commercial farming areas throughout Zimbabwe. Amblyomma hebraeum was collected at 1329 locations, A. variegatum at 72 locations and both A. hebraeum and A. variegatum at 13 locations. The results demonstrated that A. hebraeum was present, as previously recorded, throughout the southern half of the country and appeared to have undergone further limited spread into the central and eastern highveld regions. Only the northern-most region of the country appeared to be free of this species. Amblyomma variegatum was collected mainly in the north-west, as previously recorded, but was also found at isolated locations across the central highveld region and along the eastern border with Mozambique. This species was, however, still absent from the southern half and the northern-most regions of the country. An overlap of the distributions of the two species existed within a zone along the southern and eastern regions of the distribution of A. variegatum. These results suggest that the vectors of heartwater are spreading and threaten to introduce heartwater into intensive livestock-producing regions of the country.

Animals↗
PubMed1998

Infection with group C rotavirus in a suburban community in Brazil.

Group C rotaviruses are associated with sporadic outbreaks of gastroenteritis worldwide. Age-specific seroprevalence of group C rotavirus antibodies was investigated in sera, randomly collected and representative of a suburban community in Brazil which had previously been screened for group A rotavirus antibodies. Antibody prevalence to group C rotavirus was low in children under 5 years and increased slowly with age to 36% seropositivity in adults, reflecting continuous exposure to primary infection in all age groups. This suggests a higher incidence of infection than disease might predict. Adult antibody prevalence was similar to that in other geographical settings. No obvious patterns of infection with group A and group C rotavirus were found within individuals, which suggests independent transmission. However, further epidemiological studies are required to understand group C rotavirus dynamics and possible interactions with group A rotavirus transmission and immunity.

Adolescent↗
PubMed1998

Cross immunity and vaccination against multiple microparasite strains.

We explore the equilibrium properties of a series of compartmental, ODE models describing the interaction between different strains of pathogen. The interaction is conceptualized as acting through shared antigens: infection and recovery from one strain leaves the host with a primed immune response against subsequent strains. The models consider the effect of this priming on susceptibility (the ability to be infected) and transmission (the ability to infect) in an SIR model. In these models, the specific past history of infection is encapsulated in different susceptible compartments within the model. In a third, SIS, model, specific past history is not included, but strains have differential abilities to infect previously infected hosts. Equilibrium results include criteria for the coexistence of strains. For the SIR models, the region of coexistence defined by parameters shrinks as the effect of strains on each other (increased antigenic similarity) increases. For the SIS model, coexistence depends critically on the rate at which complete susceptibility is recovered following infection, and coexisting strains must have differential abilities to infect completely and partially susceptible hosts. Interestingly, this model provides analogies to commensalism (the first species gains from the presence of the second; the second neither gains nor loses from the interaction) and symbiosis (the presence of both species benefits the other). Additionally, we show that the maximum number of coexisting strains is two in this model. The effect of vaccination depends on the initial strain structure, the ability of vaccination to mount protection to both strains and the coverage. Vaccination may allow a previously excluded strain to coexist or exist alone, and may allow a previously rarer strain to become more common with the possibility of increasing incidence of disease. We discuss the dynamics of these models, compare model results to observed patterns and consider additional model structures. The importance of these results to specific multi-strain pathogens, in particular rotavirus, is considered.

Animals↗
PubMed1998

The distribution of heartwater in the highveld of Zimbabwe, 1980-1997.

Heartwater, the tick-borne disease caused by the rickettsia Cowdria ruminantium has historically been confined to the southern and western lowvelds of Zimbabwe. Since 1986, however, cases of heartwater have been diagnosed with increasing frequency in the central and eastern regions of the previously heartwater-free highveld plateau. During the same period, collections of the two major tick vectors of heartwater in Zimbabwe, Amblyomma hebraeum and Amblyomma variegatum, were made for the first time in these areas, suggesting that spread of these ticks was responsible for the changed distribution of the disease. The factors associated with this spread have not been determined, but increased cattle and wildlife movement and reduced intensity of dipping undoubtedly play important roles. Currently, the distribution of heartwater and its vectors in the highveld is still largely restricted to the central and eastern regions. The northern regions of the highveld appear to be predominantly uninfected, though it is likely that, eventually, heartwater will spread further with considerable impact on livestock production in Zimbabwe.

Animals↗
PubMed1996

The transmission dynamics and control of hepatitis B virus in The Gambia.

A deterministic, compartmental, mathematical model is used to describe the transmission dynamics of hepatitis B virus (HBV) in a high endemicity country. All three major transmission routes are included in the model, that is, perinatal, horizontal and sexual transmission. The model also reflects the demography of a typical developing country, and incorporates age-dependence in the rates of transmission and the probability of becoming a chronic carrier. Numerical simulations of the model are shown to capture the observed age-specific patterns of serological markers. The sensitivity of the model to age-specific heterogeneities and routes of transmission is investigated. The model is used in a preliminary study of the possible implications of mass infant immunization on HBV epidemiology, and the results suggest that eradication of HBV may be achieved by immunizing less than 70 per cent infants, which is relatively low compared to most childhood viral infections. This is due in part to the interaction between changes to the average age at infection under immunization, and the nature of age-dependence in the force of infection and the probability of becoming a carrier. However, numerical results also suggest that eradication may take many decades to be achieved, largely due to the presence of a pool of chronic carriers. Furthermore, there may be a significant lag between the implementation of mass infant immunization and a decline in the incidence of liver cancer.

Adolescent↗
PubMed1996

Dynamic aspects of morbidity and acquired immunity in schistosomiasis control.

In schistosomiasis control, rational planning of chemotherapy programmes is complicated by the dynamic interactions between treatment and levels of acquired immunity and morbidity in the community. In this paper, mathematical models that address the development of acquired immunity and the prevalence of morbidity are incorporated within an age-structured transmission framework to explore some of the dynamic complexities of long-term chemotherapy programmes. As well as illustrating some of the potential problems inherent in predicting the consequences of control measures, the model provides insights into the dynamics of schistosomiasis transmission and the parameters that need to be measured to further improve the design of community-based control programmes.

Humans↗
PubMed1996

Comparison of the transmission of Theileria parva between different instars of Rhipicephalus appendiculatus.

The transmission of Theileria parva by nymphal and adult Rhipicephalus appendiculatus was compared by the assessment of salivary gland infections in tick batches fed on the same group of infected cattle at the same time. When larval and nymphal R. appendiculatus Muguga ticks were fed concurrently on cattle undergoing acute infection with T. parva Muguga, the resultant nymphae developed a slightly lower prevalence of infection than did the adult ticks. The abundance of infection was 5-20 times higher in the adult ticks than in the nymphae. When larval and nymphal R. appendiculatus Muguga and R. appendiculatus McIlwaine were fed to repletion on cattle infected with T. parva Boleni, a parasite causing subacute infection, resultant adult tick batches had a relatively high prevalence of infection, but infection was not detected in resultant nymphal batches. When cattle that were carriers of 2 stocks of T. parva, Marikebuni and Kiambu 5, were used as the source of infection, the infections developing in adult R. appendiculatus Muguga ticks were much higher than those developing in nymphae. The structure of salivary glands differed between nymphal ticks, adult males and adult females, and this is considered to be an important factor affecting the infection levels. The morphology of the type III acini, the target acini for sporogony, was similar, but the mean numbers of type III acini were different, with 87 in nymphae, 1346 in males and 1736 in females. This difference was correlated with the different tick instars and sexes was similar, the rate of sporogony was fastest in feeding nymphae, taking on average 2-3 days. compared to 3-4 days in females and an irregular period in the males. These results are discussed in relation to the epidemiology of T. parva.

Animals↗
PubMed1996

Epidemiological patterns of hepatitis B virus (HBV) in highly endemic areas.

This paper uses meta-analysis of published data and a deterministic mathematical model of hepatitis B virus (HBV) transmission to describe the patterns of HBV infection in high endemicity areas. We describe the association between the prevalence of carriers and a simple measure of the rate of infection, the age at which half the population have been infected (A50), and assess the contribution of horizontal and perinatal transmission to this association. We found that the two main hyper-endemic areas of sub-Saharan Africa and east Asia have similar prevalences of carriers and values of A50, and that there is a negative nonlinear relationship between A50 and the prevalence of carriers in high endemicity areas (Spearman's Rank, P = 0.0086). We quantified the risk of perinatal transmission and the age-dependent of infection to allow a comparison between the main hyper-endemic areas. East Asia was found to have higher prevalences of HBeAg positive mothers and a greater risk of perinatal transmission from HBeAg positive mothers than sub-Saharan Africa, though the differences were not statistically significant. However, the two areas have similar magnitudes and age-dependent rates of horizontal transmission. Results of a simple compartmental model suggest that similar rates of horizontal transmission are sufficient to generate the similar patterns between A50 and the prevalences of carriers. Interrupting horizontal transmission by mass immunization is expected to have a significant, nonlinear impact on the rate of acquisition of new carriers.

Adult↗
PubMed1996

The transmission dynamics of hepatitis B in the UK: a mathematical model for evaluating costs and effectiveness of immunization programmes.

Complex hepatitis B (HBV) epidemiology makes it difficult to evaluate and compare effectiveness of different immunization policies. A method for doing so is presented using a mathematical model of HBV transmission dynamics which can represent universal infant and adolescent vaccination strategies and those targeted at genito-urinary (GU) clinic attenders and infants born to infectious mothers. Model structure, epidemiological underpinning, and parameterization, are described. Data from the UK National Survey of Sexual Attitudes and Lifestyles is used to define patterns of sexual activity and GU clinic attendance; data deficiencies are discussed, in particular that of UK seroprevalence of HBV markers stratified by age, sex, and risk factors. General model predictions of endemic HBV marker prevalence in homosexual and heterosexual populations seem consistent with published UK data. The simulations exhibit non-linearities in the impact of different vaccination strategies. Estimated number of carriers prevented per vaccine dose for each strategy provides a measure of costs and benefits, varying temporally over the course of a programme, and with level of vaccine coverage. Screening before vaccination markedly increases payback per dose in homosexuals but not in heterosexuals; mass infant vaccination gives the poorest effectiveness ratio and vaccination of infants after antenatal screening the best; in general, increasing vaccine coverage yields lower pay-back per dose. The model provides a useful framework for evaluating costs and benefits of immunization programmes, but for precise quantitative comparison more UK epidemiological data is urgently needed.

Adolescent↗