Graham F. Medley

Isolation measures in the hospital management of methicillin resistant Staphylococcus aureus (MRSA): systematic review of the literature

Abstract Objective To evaluate the evidence for the effectiveness of isolation measures in reducing the incidence of methicillin resistant Staphylococcus aureus (MRSA) colonisation and infection in hospital inpatients. Design Systematic review of published articles. Data sources Medline, Embase, CINAHL, Cochrane Library, System for Information on Grey Literature in Europe (SIGLE), and citation lists (1966-2000). Review methods Articles reporting MRSA related outcomes and describing an isolation policy were selected. No quality restrictions were imposed on studies using isolation wards or nurse cohorting. Other studies were included if they were prospective or employed planned comparisons of retrospective data. Results 46 studies were accepted; 18 used isolation wards, nine used nurse cohorting, and 19 used other isolation policies. Most were interrupted time series, with few planned formal prospective studies. All but one reported multiple interventions. Consideration of potential confounders, measures to prevent bias, and appropriate statistical analysis were mostly lacking. No conclusions could be drawn in a third of studies. Most others provided evidence consistent with a reduction of MRSA acquisition. Six long interrupted time series provided the strongest evidence. Four of these provided evidence that intensive control measures including patient isolation were effective in controlling MRSA. In two others, isolation wards failed to prevent endemic MRSA. Conclusion Major methodological weaknesses and inadequate reporting in published research mean that many plausible alternative explanations for reductions in MRSA acquisition associated with interventions cannot be excluded. No well designed studies exist that allow the role of isolation measures alone to be assessed. None the less, there is evidence that concerted efforts that include isolation can reduce MRSA even in endemic settings. Current isolation measures recommended in national guidelines should continue to be applied until further research establishes otherwise.

The evaluation of potential global morbidity attributable to intestinal nematode infections

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

The Influence of Age on the Development of the Hepatitis B Carrier State

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

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.

Multilocus Sequence Typing of Intercontinental Bovine Staphylococcus aureus Isolates

ABSTRACT A total of 258 bovine-associated Staphylococcus aureus isolates from the United States, Chile, and the United Kingdom, plus the reference isolate S. aureus Newbould 305 (NCIMB 702892), were analyzed by multilocus sequence typing (MLST). A collection of previously characterized United Kingdom isolates were also included in the analysis. The results demonstrated that MLST is suitable for the differentiation of bovine S. aureus isolates from various sites (milk, teat skin, milking machine unit liners, hands, and bedding) and countries. The theory of the host specificity of S. aureus is supported by the detection of a previously undescribed clonal complex that comprised 87.4% of the isolates studied, with representatives from all geographic locations investigated. This suggests that a single clonal group has achieved a widespread distribution and is responsible for the majority of infections. Some sequence types (STs; ST25, ST115, ST124, and ST126) demonstrated site specificity, as they were significantly (P < 0.05) associated with milk or teat skin.

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 (Spearmans 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.

Respiratory Syncytial Virus Infection and Disease in Infants and Young Children Observed from Birth in Kilifi District, Kenya

BACKGROUND In developing countries, there are few data that characterize the disease burden attributable to respiratory syncytial virus (RSV) and clearly define which age group to target for vaccine intervention. METHODS Six hundred thirty-five children, recruited during the period 2002-2003, were intensively monitored until each experienced 3 epidemics of RSV infection. RSV infection was diagnosed using immunofluorescence of nasal washing specimens collected at each episode of acute respiratory infection. Incidence estimates were adjusted for seasonality of RSV exposure. RESULTS For 1187 child-years of observation (CYO), a total of 409 (365 primary and 82 repeat) episodes of RSV infection were identified. Adjusted incidence estimates of lower respiratory tract infection (LRTI), severe LRTI, and hospital admission were 90 cases per 1000 CYO, 43 cases per 1000 CYO, and 10 cases per 1000 CYO, respectively, and corresponding estimates among infants were 104 cases per 1000 CYO, 66 cases per 1000 CYO, and 13 cases per 1000 CYO, respectively. The proportion of cases of all-cause LRTI, and severe LRTI and hospitalizations attributable to RSV in the cohort was 13%, 19%, and 5%, respectively. Fifty-five percent to 65% of RSV-associated LRTI and severe LRTI occurred in children aged >6 months. The risk of RSV disease following primary symptomatic infection remained significant beyond the first year of life, and one-quarter of all reinfections were associated with LRTI. CONCLUSIONS RSV accounts for a substantial proportion of the total respiratory disease in this rural population; we estimate that 85,000 cases of severe LRTI per year occur in infants in Kenya. The majority of this morbidity occurs during late infancy and early childhood--ages at which the risk of disease following infection remains significant. Disease resulting from reinfection is common. Our results inform the debate on the target age group and effectiveness of a vaccine.

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

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

Heterogeneity in patterns of malarial oocyst infections in the mosquito vector

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

The relationship between the frequency distribution of Ascaris lumbricoides and the prevalence and intensity of infection in human communities.

Observed field data from a range of geographically distinct human communities suggest a consistent non-linear relationship between prevalence and mean intensity of Ascaris lumbricoides infection. Utilizing the negative binomial distribution as a description of observed aggregation, maximum-likelihood analysis reveals that the degree of aggregation is a negative linear function of mean worm burden. The factors responsible for this relationship in human populations require further study but may involve some combination of (i) density-dependent reduction in worm numbers within individuals, (ii) density-dependent parasite-induced host mortality or (iii) self-treatment by heavily infected hosts. Variability in the degree of aggregation appears dependent on the level of infection in a community and independent of geographical differences in the host or parasite populations.