RSV is the most important viral cause of pneumonia and bronchiolitis in children worldwide and has been associated with significant disease burden. With the renewed interest in RSV vaccines, we provide realistic estimates on duration, and influencing factors on RSV shedding which are required to better understand the impact of vaccination on the virus transmission dynamics. The data arise from a prospective study of 47 households (493 individuals) in rural Kenya, followed through a 6-month period of an RSV seasonal outbreak. Deep nasopharyngeal swabs were collected twice each week from all household members, irrespective of symptoms, and tested for RSV by multiplex PCR. The RSV G gene was sequenced. A total of 205 RSV infection episodes were detected in 179 individuals from 40 different households. The infection data were interval censored and assuming a random event time between observations, the average duration of virus shedding was 11·2 (95% confidence interval 10·1–12·3) days. The shedding durations were longer than previous estimates (3·9–7·4 days) based on immunofluorescence antigen detection or viral culture, and were shown to be strongly associated with age, severity of infection, and revealed potential interaction with other respiratory viruses. These findings are key to our understanding of the spread of this important virus and are relevant in the design of control programmes.

A mathematical model that describes the transmission dynamics of Theileria annulata is proposed that consists of 2 host components: the Hyalomma tick population and a compartmental model of T. annulata infection in the cattle population. The model was parameterized using data describing tick infestation and the infection status of cattle in Turkey from 2006 to 2008. The tick attachment rates are highly seasonal and because of the temporal separation of infectious and susceptible ticks virtually all ticks are infected by carrier cattle, so that annual peaks of disease in cattle do not impact on infection in the Hyalomma tick population. The impact of intervention measures that target the tick population both on the host and in the environment and their impact on the transmission of T. annulata were investigated. Interventions that have a limited ‘one-off’ impact and interventions that have a more permanent impact were both considered. The results from the model show the importance of targeting ticks during the period when they have left their first host as nymphs but have yet to feed on their second host.

A meta-analysis was performed using all published and one unpublished long-term infection-challenge experiments to quantify the age- and dose-dependence of early and late shedding of Mycobacterium avium subsp. paratuberculosis (MAP) in cattle. There were 194 animals from 17 studies that fulfilled the inclusion criteria, of which 173 received a known dose of MAP and 21 were exposed naturally. Results from parametric time-to-event models indicated that challenging older calves or using multiple-exposure experimental systems resulted in a smaller proportion and shorter duration of early shedding as well as slower transition to late shedding from latent compartments. Calves exposed naturally showed variable infection progression rates, not dissimilar to other infection routes. The log-normal distribution was most appropriate for modelling infection-progression events. The infection pattern revealed by the modelling allowed better understanding of low-grade endemicity of MAP in cattle, and the parameter estimates are the basis for future transmission dynamics modelling.

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 rate 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.

Mathematical models are potentially useful tools to aid in the design of control programmes for parasitic diseases. In this paper, a fully age structured epidemiological model of human schistosomiasis is developed and parameterized, and used to predict trends in infection prevalence, intensity and prevalence of heavy infections over age and time during several rounds of mass and age targeted treatment. The model is validated against data from a Schistosoma mansoni control programme in Kenya.

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.

The relationship between paired hookworm prevalence and mean intensity of infection data from geographically defined communities was examined. The results show that, in spite of major socio-economic and environmental differences between communities, the relationship is consistent and non-linear. A generalized value of k (the exponent of the negative binomial distribution) for hookworms was estimated to be 0.34, which is consonant with previous estimates from cross-sectional data. Maximum likelihood analysis indicates that the severity of hookworm aggregation in humans has an inverse relationship to mean worm burden which is less marked than for Ascaris lumbricoides. A simple model, based on published estimates of hookworm burdens associated with hookworm anaemia, was used to predict prevalence of morbidity from prevalence of infection data for Tanzania, Kenya and Zambia. Predictions correspond to the observation that hookworm anaemia is highly focal, and largely coastal, in distribution. These analyses suggest that locality-targeting of chemotherapy is particularly appropriate for the control of hookworm morbidity.

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.

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 design of mass and targetted community-based chemotherapy programmes for the control of the major helminth infections of man is discussed in relation to the population and transmission dynamics of the parasites. Rapid reinfection following a single mass or targetted anthelmintic application is shown to be a universal feature of helminth transmission, as a consequence of the regulatory or feed-back mechanisms controlling population abundance within both individuals and the community as a whole. Control of reinfection requires repeated community treatment where the intensity of application and the interval between treatments are dependent on the reproductive life-expectancy of the adult worm, the net force of transmission prior to control (the basic reproductive rate) and the factors which create aggregation in the distribution of parasite loads within the population. Selective or targetted treatment is shown to be most effective for the control of morbidity as opposed to the control of transmission. The impact of targetted treatment depends critically on the factors that generate heterogeneity in parasite burdens and on whether or not selectivity is based on a single or repeated identification of the ‘wormy’ fraction of the community. Monte Carlo simulation studies are employed to assess the likely impacts of different control strategies on average parasite abundance/person and the distributions of parasite loads within populations. Future epidemiological research needs are discussed in relation to theoretical work and recent field studies of predisposition to heavy infection.

Epidemiological modelling can be a useful tool for the evaluation of parasite control strategies. An age-structured epidemiological model of intestinal helminth dynamics is developed. This model includes the explicit representation of changing worm distributions between hosts as a result of treatment, and estimates the morbidity due to heavy infections. The model is used to evaluate the effectiveness of different programmes of age-targeted community chemotherapy in reducing the amount of morbidity due to helminth infection. The magnitude of age-related heterogeneities is found to be very important in determining the results of age-targeted treatment programmes. The model was verified using field data from control programmes for Ascaris lumbricoides and Trichuris trichiura, and was found to provide accurate predictions of prevalence and mean intensities of infection during and following different control regimes.

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, hetero geneous between hosts, and both age and infection dose dependent, but has yet to be convincingly shown to be protective. Since the immune response is 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 immuno epidemiological study.

The transmission success of Onchocerca volvulus is thought to be influenced by a variety of regulatory or density-dependent processes that act at various points in the two-host life-cycle. This paper examines one component of the life-cycle, namely, the ingestion of microfilariae by the simuliid vector, to assess the relationship between intake of larvae and the density of parasites in the skin of the human host. Analysis is based on data from three areas in which onchocerciasis is endemic and includes published information as well as new data collected in field studies. The three areas are: Guatemala (Simulium ochraceum sl.), West and Central Africa (savanna members of the S. damnosum complex), and South Venezuela (S. guianense). The data record experimental studies of parasite uptake by flies captured in the field and fed to repletion on locally infected subjects who harboured varying intensities of dermal microfilarial infection. Regression analyses of log transformed counts of parasite burdens ingested by the flies plotted against log transformed counts of microfilariae per mg of skin revealed little evidence for saturation in parasite uptake by the flies as the intensity in the human host increased. There was a positive and highly significant rank correlation between both variables for the three blackfly species. In an alternative analysis a model was fitted to data on prevalence of flies with ingested microfilariae (mff) versus dermal mean intensities. The model assumed an overdispersed distribution of the number of mff/fly and a given functional relationship between intake and skin load. The results of both approaches were consistent. It is concluded that parasite ingestiossssn by the vector host is not strongly density dependent in the three geographical areas and ranges of dermal loads examined. It therefore appears that this transmission process is of reduced importance as a regulatory mechanism in the dynamics of parasite population growth.

There is growing emphasis on the use of community treatment to reduce the level of morbidity caused by helminth infection. The design of chemotherapy programmes, in terms of frequency of treatment and proportion of the community treated, would be assisted by a quantitative framework which enabled the morbidity reduction achieved by different approaches to be compared. The present study describes a model developed for this purpose which embodies two innovative features. First, a quantitative score of morbidity (the proportion of individuals harbouring an intense infection) is used to rate the success of a programme and, second, the distribution of helminths in the host population is generated by a mechanism that allows the distribution to change dynamically as a function of both treatment and reinfection. The model behaviour, using values typical of Ascaris lumbricoides, indicates that the benefit derived from community chemo- therapy increases non-linearly with the coverage and efficacy of treatment.

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 the 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. In determining the impact of transmission blocking mechanisms we predict that under conditions where high oocyst intensities prevail, large reductions in intensity will be required before a reduction in prevalence can be expected i.e. here it will be necessary to measure intensity of infection. Conversely, under conditions where low oocyst intensities prevail, a rapid reduction in prevalence will occur with little concurrent reduction in intensity i.e. prevalence determination will be the more sensitive estimate.

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 infection levels produced in the various instars and sexes. While the process of sporogony in 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.

Two mathematical models are developed that investigate the transmission dynamics of Theileria parva by the ixodid tickRhipicephalus appendiculatus to cattle in endemically stable areas. A method of estimating the rate of infection to cattle ofT. parva at the endemically stable state is given. Empirical estimates of ail the parameters in the model are available. The degree to which animals that have recovered from theileriosis (the ‘carrier’ state) are able to transmit the infection to tick nymphs or larvae is a crucial determinant of the dynamics of infection in a herd. Two control methods influencing the transmission of infection are considered – infection and treatment immunization and the reduction in tick feeding by acaricide application. The impact of each method on the transmission of infection is evaluated. Future developments and the data required to predict the dynamics of T. parva infections in cattle and ticks are discussed.

A previous paper reported that the intake of Onchocerca volvulus microfilariae (mff) by different species of Simulium is essentially proportional to the parasite load in the skin of infected carriers. This paper examines the fate of the ingested mff in susceptible vectors to assess the relationship between parasite intake and infective larval output in blackfly species with and without well-developed cibarial armatures. Analysis is based on data from 3 onchocerciasis endemic areas: Guatemala (S. ochraceum s.l.), West Africa (S. damnosum s.l./S. sirbanum) and the Amazonian focus between South Venezuela and Northern Brazil (S. guianense and S. oyapockense s.l.). The data, which include published and unedited information collected in the field, record experimental studies of parasite uptake by wild flies maintained in captivity until the completion of the extrinsic incubation period. The relationship between L3 output (measured as the mean number of successful larvae/fly or, as the proportion of flies with infective larvae) and average microfilarial intake, was strongly non-linear. This non-linearity was best represented by a sigmoid function in case of armed simuliids (S. ochraceum s.l., S. oyapockense s.l.), or by a hyperbolic expression in that of unarmed flies (S. damnosum s.l., S. guianense). These results are compatible, respectively, with the patterns of ‘initial facilitation’ and ‘limitation’ described in culicid vectors of lymphatic filariases. A maximum mean number of 1–3 L3/fly was observed in all 4 vectors. It is concluded that O. volvulus larval development to the infective stage is regulated by density-dependent mechanisms acting at the early phase of microfilarial migration out of the blackfly's bloodmeal. Damage by the bucco-pharyngeal armature may also be density dependent. A hypothesis, based on this density dependence is forwarded to explain initial facilitation, so far only recorded in vectors with well-developed cibarial teeth. Our results provide quantitative support for the conjecture that chemotherapy alone is likely to have a greater impact on reducing onchocerciasis transmission in endemic areas where the main vector has a toothed fore-gut than in foci where the vectors have unarmed cibaria.

With reports of hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) continuing to increase and therapeutic options decrease, infection control methods are of increasing importance. Here we investigate the relationship between surveillance and infection control. Surveillance plays two roles with respect to control: it allows detection of infected/colonized individuals necessary for their removal from the general population, and it allows quantification of control success. We develop a stochastic model of MRSA transmission dynamics exploring the effects of two screening strategies in an epidemic setting: random and on admission. We consider both hospital and community populations and include control and surveillance in a single framework. Random screening was more efficient at hospital surveillance and allowed nosocomial control, which also prevented epidemic behaviour in the community. Therefore, random screening was the more effective control strategy for both the hospital and community populations in this setting. Surveillance strategies have significant impact on both ascertainment of infection prevalence and its control.

Objectives: This study reviewed the evidence for the effectiveness of different isolation policies and screening practices in reducing the incidence of methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection in hospital inpatients in an effort to develop transmission models to study the effectiveness and cost-effectiveness of isolation policies in controlling MRSA.