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1.  Persistence of the efficacy of copper oxide wire particles against Haemonchus contortus in grazing South African goats 
Veterinary Parasitology  2012;190(1-2):159-166.
A study was conducted to examine the duration of anthelmintic effect of copper oxide wire particles (COWP) in grazing goats, as data for the persistence of efficacy of COWP in this host species is limited. Forty-eight indigenous male goats were infected naturally by grazing them on Haemonchus contortus-infected pasture. When the faecal egg count (FEC) in the goats was 3179 ± 540 eggs per gram of faeces (mean ± standard error), half the animals were treated with 4 g COWP (day 0; mean live weight = 25.5 ± 0.8 kg). Eight treated (COWP) and eight non-treated (CONTROL) goats were removed from the pasture on each of days 7, 28 and 56, maintained for 27 or 29 days in concrete pens and then humanely slaughtered for nematode recovery. Mean liver copper levels were in the high range in the goats removed from pasture at day 7 (treated: 191 ± 19.7 ppm; untreated: 120 ± 19.7 ppm; P = 0.022), but had dropped to normal levels at days 28 and 56. The mean H. contortus burdens of the treated versus the non-treated goats were, respectively, 184 ± 48 and 645 ± 152 for the goats removed from pasture at day 7 (71% reduction; P = 0.004), 207 ± 42 and 331 ± 156 at day 28 (37% reduction; P = 0.945) and 336 ± 89 and 225 ± 53 at day 56 (−49% reduction; P = 0.665). Weekly monitoring of FECs after treatment until slaughter indicated that the COWP-treated goats had lower FECs than the controls, the treatment main effect being significant at days 7, 28 and 56 (P < 0.01). The day main effect and the treatment × day interaction were only significant for the goats removed from pasture at day 28 (P ≤ 0.001). Packed cell volumes increased during the course of the experiment (day, P < 0.001), but the treatment main effect was significant only for the goats removed from pasture at day 28 (CONTROL 28 d, 28.65 ± 0.52% < COWP 28 d, 31.31 ± 0.52%; P < 0.001). No differences in live weight between groups were considered to be of any practical significance. The study indicated that persistence of efficacy of COWP is limited in goats, extending at most to 28 days after treatment. However, repeated COWP administration at three-month intervals may be safe, given that liver copper levels return to normal two to three months after COWP treatment.
doi:10.1016/j.vetpar.2012.06.018
PMCID: PMC3477318  PMID: 22789299
Anthelmintic resistance; Copper oxide wire particles (COWP); Goats; Haemonchus contortus; Persistent efficacy
2.  The Natural History of Respiratory Syncytial Virus in a Birth Cohort: The Influence of Age and Previous Infection on Reinfection and Disease 
American Journal of Epidemiology  2012;176(9):794-802.
This study aimed to quantify the effect of age, time since last infection, and infection history on the rate of respiratory syncytial virus infection and the effect of age and infection history on the risk of respiratory syncytial virus disease. A birth cohort of 635 children in Kilifi, Kenya, was monitored for respiratory syncytial virus infections from January 31, 2002, to April 22, 2005. Predictors of infection were examined by Cox regression and disease risk by binomial regression. A total of 598 respiratory syncytial virus infections were identified (411 primary, 187 repeat), with 409 determined by antigen assay and 189 by antibody alone (using a “most pragmatic” serologic definition). The incidence decreased by 70% following a primary infection (adjusted hazard ratio = 0.30, 95% confidence interval: 0.21, 0.42; P < 0.001) and by 59% following a secondary infection (hazard ratio = 0.41, 95% confidence interval: 0.22, 0.73; P = 0.003), for a period lasting 6 months. Relative to the age group <6 months, all ages exhibited a higher incidence of infection. A lower risk of severe disease following infection was independently associated with increasing age (P < 0.001) but not reinfection. In conclusion, observed respiratory syncytial virus incidence was lowest in the first 6 months of life, immunity to reinfection was partial and short lived, and disease risk was age related.
doi:10.1093/aje/kws257
PMCID: PMC3481264  PMID: 23059788
birth cohort; estimation; incidence; reinfection; respiratory syncytial virus; risk
3.  Tactical treatment with copper oxide wire particles and symptomatic levamisole treatment using the FAMACHA© system in indigenous goats in South Africa 
Veterinary Parasitology  2012;184(1):48-58.
Haemonchosis is considered to be the most economically important gastrointestinal disease of small ruminants in the tropics and subtropics. However, chemical anthelmintics, which were the mainstay of control, have been compromised by a high prevalence of resistance worldwide. Copper oxide wire particles (COWP) have been shown to have anthelmintic effects, but few studies have examined their use under field conditions. The use of COWP was therefore evaluated as a tactical anthelmintic treatment in indigenous goats raised under communal farming conditions in Bergville, KwaZulu-Natal Province, South Africa. At the beginning of the summer rainfall season (October 2007), the faecal egg counts of 172 female goats belonging to 15 farmers were determined and this sampling continued every four weeks until the second week of January 2008. The goats within each of the 15 herds were ranked according to their faecal egg counts for this week. The goats were sequentially paired off within each ranking starting with those goats with the highest counts. One goat from each pair was randomly allocated to a treated or control group. Two weeks later, a 4 g COWP bolus was randomly administered to each goat in the treated group. Faecal egg counts were carried out on the goats two weeks following treatment, and the sampling of the goats then proceeded every four weeks until October 2008. Except for the six-week period prior to the administration of the COWP, the goats were examined according to the FAMACHA© system and symptomatically treated with 12 mg/kg levamisole when anaemic. The percentage reduction in faecal egg count due to the COWP treatment was 89.0%. Mean pre- and post-treatment faecal egg counts for the COWP-treated group (n = 73) were 2347 eggs per gram of faeces (epg) and 264 epg, respectively. The corresponding values for the untreated controls (n = 66) were 2652 epg and 2709 epg. The prevalence of Haemonchus spp. larvae in pre- and post-treatment faecal cultures was 72% and 46%, respectively. Symptomatic anthelmintic treatments in combination with mid-summer tactical treatments with COWP appear to be useful strategies for the control of Haemonchus contortus in indigenous goats in this farming system and this approach could have application in other similar agro-ecological zones.
doi:10.1016/j.vetpar.2011.08.003
PMCID: PMC3336207  PMID: 21880430
Copper oxide wire particles; FAMACHA©; Haemonchus contortus; Indigenous goats; Levamisole; Tactical treatment
4.  Bayesian analysis of a mastitis control plan to investigate the influence of veterinary prior beliefs on clinical interpretation 
Preventive Veterinary Medicine  2009;91(2-4):209-217.
The fundamental objective for health research is to determine whether changes should be made to clinical decisions. Decisions made by veterinary surgeons in the light of new research evidence are known to be influenced by their prior beliefs, especially their initial opinions about the plausibility of possible results. In this paper, clinical trial results for a bovine mastitis control plan were evaluated within a Bayesian context, to incorporate a community of prior distributions that represented a spectrum of clinical prior beliefs. The aim was to quantify the effect of veterinary surgeons’ initial viewpoints on the interpretation of the trial results.
A Bayesian analysis was conducted using Markov chain Monte Carlo procedures. Stochastic models included a financial cost attributed to a change in clinical mastitis following implementation of the control plan. Prior distributions were incorporated that covered a realistic range of possible clinical viewpoints, including scepticism, enthusiasm and uncertainty. Posterior distributions revealed important differences in the financial gain that clinicians with different starting viewpoints would anticipate from the mastitis control plan, given the actual research results. For example, a severe sceptic would ascribe a probability of 0.50 for a return of <£5 per cow in an average herd that implemented the plan, whereas an enthusiast would ascribe this probability for a return of >£20 per cow. Simulations using increased trial sizes indicated that if the original study was four times as large, an initial sceptic would be more convinced about the efficacy of the control plan but would still anticipate less financial return than an initial enthusiast would anticipate after the original study. In conclusion, it is possible to estimate how clinicians’ prior beliefs influence their interpretation of research evidence. Further research on the extent to which different interpretations of evidence result in changes to clinical practice would be worthwhile.
doi:10.1016/j.prevetmed.2009.05.029
PMCID: PMC2729300  PMID: 19576643
Prior distribution; Clinical decision making; Bayesian analysis; Mastitis
5.  Bayesian analysis of a mastitis control plan to investigate the influence of veterinary prior beliefs on clinical interpretation 
Preventive veterinary medicine  2009;91(2-4):209-217.
The fundamental objective for health research is to determine whether changes should be made to clinical decisions. Decisions made by veterinary surgeons in the light of new research evidence are known to be influenced by their prior beliefs, especially their initial opinions about the plausibility of possible results. In this paper, clinical trial results for a bovine mastitis control plan were evaluated within a Bayesian context, to incorporate a community of prior distributions that represented a spectrum of clinical prior beliefs. The aim was to quantify the effect of veterinary surgeons’ initial viewpoints on the interpretation of the trial results.
A Bayesian analysis was conducted using Markov chain Monte Carlo procedures. Stochastic models included a financial cost attributed to a change in clinical mastitis following implementation of the control plan. Prior distributions were incorporated that covered a realistic range of possible clinical viewpoints, including scepticism, enthusiasm and uncertainty. Posterior distributions revealed important differences in the financial gain that clinicians with different starting viewpoints would anticipate from the mastitis control plan, given the actual research results. For example, a severe sceptic would ascribe a probability of 0.50 for a return of <£5 per cow in an average herd that implemented the plan, whereas an enthusiast would ascribe this probability for a return of >£20 per cow. Simulations using increased trial sizes indicated that if the original study was four times as large, an initial sceptic would be more convinced about the efficacy of the control plan but would still anticipate less financial return than an initial enthusiast would anticipate after the original study. In conclusion, it is possible to estimate how clinicians’ prior beliefs influence their interpretation of research evidence. Further research on the extent to which different interpretations of evidence result in changes to clinical practice would be worthwhile.
doi:10.1016/j.prevetmed.2009.05.029
PMCID: PMC2729300  PMID: 19576643
Prior distribution; Clinical decision making; Bayesian analysis; Mastitis
6.  The potential to control Haemonchus contortus in indigenous South African goats with copper oxide wire particles 
Veterinary Parasitology  2009;162(3-4):306-313.
The high prevalence of resistance of Haemonchus contortus to all major anthelmintic groups has prompted investigations into alternative control methods in South Africa, including the use of copper oxide wire particle (COWP) boluses. To assess the efficacy of COWP against H. contortus in indigenous South African goats, 18 male faecal egg-count-negative goats were each given ca.1200 infective larvae of H. contortus three times per week during weeks 1 and 2 of the experiment. These animals made up an “established” infection group (ESTGRP). At the start of week 7, six goats were each given a 2-g COWP bolus orally; six goats received a 4-g COWP bolus each and six animals were not treated. A further 20 goats constituted a “developing” infection group (DEVGRP). At the beginning of week 1, seven of the DEVGRP goats were given a 2-g COWP bolus each; seven goats were treated with a 4-g COWP bolus each and no bolus was given to a further six animals. During weeks 1–6, each of these DEVGRP goats was given ca. 400 H. contortus larvae three times per week. All 38 goats were euthanized for worm recovery from the abomasa and small intestines in week 11. In the ESTGRP, the 2-g and 4-g COWP boluses reduced the worm burdens by 95% and 93%, respectively compared to controls (mean burden ± standard deviation, SD: 23 ± 33, 30 ± 56 and 442 ± 518 worms, P = 0.02). However, in the DEVGRP goats, both the 2-g and 4-g COWP treatments were ineffective in reducing the worm burdens relative to the controls (mean burdens ± SD: 1102 ± 841, 649 ± 855, 1051 ± 661 worms, P = 0.16). Mean liver copper levels did not differ between the ESTGRP goats treated with 2-g COWP, 4-g COWP or no COWP (mean ± standard error of the mean, SEM, in ppm: 93.7 ± 8.3; 101.5 ± 8.3; 71.8 ± 8.3, P = 0.07) nor did they differ between the DEVGRP goats (mean ± SEM, in ppm: 74.1 ± 9.1; 75.4 ± 9.1; 74.9 ± 10.0, P > 0.99). The copper values were considered adequate, but not high, for goats. The COWP boluses have the potential to be used in the place of conventional anthelmintics for the control of established H. contortus infections in indigenous South African goats, but their use as part of an integrated approach to control H. contortus in the field must be fully investigated.
doi:10.1016/j.vetpar.2009.03.005
PMCID: PMC2691795  PMID: 19346076
Anthelmintic resistance; Copper oxide; COWP; Goat; Haemonchus contortus
7.  Cow, Farm, and Herd Management Factors in the Dry Period Associated with Raised Somatic Cell Counts in Early Lactation 
Journal of dairy science  2008;91(4):1403-1415.
This study investigated cow characteristics, farm facilities, and herd management strategies during the dry period to examine their joint influence on somatic cell counts (SCC) in early lactation. Data from 52 commercial dairy farms throughout England and Wales were collected over a 2-yr period. For the purpose of analysis, cows were separated into those housed for the dry period (6,419 cow-dry periods) and those at pasture (7,425 cow-dry periods). Bayesian multilevel models were specified with 2 response variables: ln SCC (continuous) and SCC >199,000 cells/mL (binary), both within 30 d of calving. Cow factors associated with an increased SCC after calving were parity, an SCC >199,000 cells/mL in the 60 d before drying off, increasing milk yield 0 to 30 d before drying off, and reduced DIM after calving at the time of SCC estimation. Herd management factors associated with an increased SCC after calving included procedures at drying off, aspects of bedding management, stocking density, and method of pasture grazing. Posterior predictions were used for model assessment, and these indicated that model fit was generally good. The research demonstrated that specific dry-period management strategies have an important influence on SCC in early lactation.
doi:10.3168/jds.2007-0621
PMCID: PMC2605244  PMID: 18349232
mastitis; somatic cell count; dry period; Bayesian multilevel model
8.  Rotavirus within day care centres in Oxfordshire, UK: characterization of partial immunity 
Repeated measures data for rotavirus infection in children within 14 day care centres (DCCs) in the Oxfordshire area, UK, are used to explore aspects of rotavirus transmission and immunity. A biologically realistic model for the transmission of infection is presented as a set of probability models suitable for application to the data. Two transition events are modelled separately: incidence and recovery. The complexity of the underlying mechanistic model is reflected in the choice of the fixed variables in the probability models. Parameter estimation was carried out using a Bayesian Markov chain Monte Carlo method. We use the parameter estimates obtained to build a profile of the natural history of rotavirus reinfection in an individual child. We infer that rotavirus transmission in children in DCCs is dependent on the DCC prevalence, with symptomatic infection of longer duration, but no more infectious per day of infectious period, than asymptomatic infection. There was evidence that a recent previous infection reduces the risk of disease and, to a lesser extent, reinfection, but not duration of infection. The results provide evidence that partial immunity to rotavirus infection develops over several time scales.
doi:10.1098/rsif.2008.0115
PMCID: PMC2475553  PMID: 18477541
rotavirus; partial immunity; transmission dynamics; Markov chain Monte Carlo; DCC; day care centre; MCMC; Markov chain Monte Carlo; DIC; deviance information criterion
9.  Blind sampling is superior to anoscope guided sampling for screening for anal intraepithelial neoplasia 
Sexually Transmitted Infections  2005;81(5):415-418.
Objectives: Anal cytology smears are either collected "blind" (swab inserted 4 cm into anal canal and rotated) or guided through an anoscope (transformation zone visualised and then sampled). We compared these smear techniques with respect to sample quality and patient acceptability.
Methods: Using a paired, random sequence clinical trial, 151 homosexual men (n = 95 HIV positive) underwent both smear techniques at a single visit; smear order was randomised and specimens were read blind. Both techniques utilised a Dacron swab, with water lubrication. Cytological specimens were prepared using a liquid based collection method (ThinPrep). The outcome measures were cytological specimen adequacy, cytological classification, presence of rectal columnar, squamous and metaplastic cells, contamination, patient comfort and acceptability, and volume of fluid that remained after the ThinPrep procedure.
Results: Regardless of smear order, guided smears were less likely to detect higher grade abnormalities than blind smears (15 v 27 cases, p = 0.001). Controlling for smear order, guided smears were more likely to be assessed as "unsatisfactory" for cytological assessment (OR 6.93, 95% CI 1.92 to 24.94), and contain fewer squamous (OR 0.20, 95% CI 0.04 to 0.94) and metaplastic cells (OR 0.12, 95% CI 0.03 to 0.54) than blind smears; there were no other statistically significant differences between techniques. Regardless of smear technique, first performed smears were more likely to detect a higher grade abnormality than second performed smears (23 v eight cases, p<0.001).
Conclusions: Blind cytology smears are superior to anoscope guided smears for screening for anal neoplasia in homosexual men.
doi:10.1136/sti.2004.014407
PMCID: PMC1745038  PMID: 16199742
10.  Understanding the transmission dynamics of respiratory syncytial virus using multiple time series and nested models 
Mathematical Biosciences  2007;209(1):222-239.
The nature and role of re-infection and partial immunity are likely to be important determinants of the transmission dynamics of human respiratory syncytial virus (hRSV). We propose a single model structure that captures four possible host responses to infection and subsequent reinfection: partial susceptibility, altered infection duration, reduced infectiousness and temporary immunity (which might be partial). The magnitude of these responses is determined by four homotopy parameters, and by setting some of these parameters to extreme values we generate a set of eight nested, deterministic transmission models. In order to investigate hRSV transmission dynamics, we applied these models to incidence data from eight international locations. Seasonality is included as cyclic variation in transmission. Parameters associated with the natural history of the infection were assumed to be independent of geographic location, while others, such as those associated with seasonality, were assumed location specific. Models incorporating either of the two extreme assumptions for immunity (none or solid and lifelong) were unable to reproduce the observed dynamics. Model fits with either waning or partial immunity to disease or both were visually comparable. The best fitting structure was a lifelong partial immunity to both disease and infection. Observed patterns were reproduced by stochastic simulations using the parameter values estimated from the deterministic models.
doi:10.1016/j.mbs.2006.08.018
PMCID: PMC3724053  PMID: 17335858
Respiratory syncytial virus; Transmission model; Immunity; Seasonality; Hospital data; Infectiousness
11.  Cow, Farm, and Management Factors During the Dry Period that Determine the Rate of Clinical Mastitis After Calving 
Journal of dairy science  2007;90(8):3764-3776.
The purpose of the research was to investigate cow characteristics, farm facilities, and herd management strategies during the dry period to examine their joint influence on the rate of clinical mastitis after calving. Data were collected over a 2-yr period from 52 commercial dairy farms throughout England and Wales. Cows were separated for analysis into those housed for the dry period (8,710 cow-dry periods) and those at pasture (9,964 cow-dry periods). Multilevel models were used within a Bayesian framework with 2 response variables, the occurrence of a first case of clinical mastitis within the first 30 d of lactation and time to the first case of clinical mastitis during lactation. A variety of cow and herd management factors were identified as being associated with an increased rate of clinical mastitis and these were found to occur throughout the dry period. Significant cow factors were increased parity and at least one somatic cell count ≥200,000 cells/mL in the 90 d before drying off. A number of management factors related to hygiene were significantly associated with an increased rate of clinical mastitis. These included measures linked to the administration of dry-cow treatments and management of the early and late dry-period accommodation and calving areas. Other farm factors associated with a reduced rate of clinical mastitis were vaccination with a leptospirosis vaccine, selection of dry-cow treatments for individual cows within a herd rather than for the herd as a whole, routine body condition scoring of cows at drying off, and a pasture rotation policy of grazing dry cows for a maximum of 2 wk before allowing the pasture to remain nongrazed for a period of 4 wk. Models demonstrated a good ability to predict the farm incidence rate of clinical mastitis in a given year, with model predictions explaining over 85% of the variability in the observed data. The research indicates that specific dry-period management strategies have an important influence on the rate of clinical mastitis during the next lactation.
doi:10.3168/jds.2007-0107
PMCID: PMC1949869  PMID: 17638988
mastitis; dry period; dairy cow; Bayesian multilevel model
12.  Multilocus Sequence Typing of Intercontinental Bovine Staphylococcus aureus Isolates 
Journal of Clinical Microbiology  2005;43(9):4737-4743.
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.
doi:10.1128/JCM.43.9.4737-4743.2005
PMCID: PMC1234155  PMID: 16145135
13.  Multilocus Sequence Typing of Staphylococcus aureus Isolated from High-Somatic-Cell-Count Cows and the Environment of an Organic Dairy Farm in the United Kingdom 
Journal of Clinical Microbiology  2005;43(9):4731-4736.
An outbreak of Staphylococcus aureus intramammary infections on an organic dairy farm was monitored for 10 months. Environmental and milk samples were collected from a total of 26 cows and a group of 21 purchased heifers about to be introduced into the milking herd. There was variation in the rate of isolation of S. aureus (9.5 to 43.8%) from individual mammary quarters, although no S. aureus isolates were detected in the milk samples collected from the heifers. One hundred ninety-one S. aureus isolates were detected from cow milk samples (n = 182), milking machine clusters (n = 4), farm personnel (n = 4), and the environment (n = 1). Multilocus sequence typing (MLST) had a typeability of 100% when it was applied to the 191 isolates. Among the 191 isolates there was limited strain diversity, with seven sequence types (STs) dominated by two strains with closely related STs that differed at a single locus. Within individual mammary quarters there were naturally occurring dual infections, although this was identified in only 0.4% of milk samples. Different strains were associated with variable persistence within quarters. MLST is clearly a very suitable tool for the differentiation and analysis of S. aureus populations detected on dairy cattle farms.
doi:10.1128/JCM.43.9.4731-4736.2005
PMCID: PMC1234152  PMID: 16145134
14.  Isolation measures in the hospital management of methicillin resistant Staphylococcus aureus (MRSA): systematic review of the literature 
BMJ : British Medical Journal  2004;329(7465):533.
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.
PMCID: PMC516101  PMID: 15345626
15.  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.
PMCID: PMC1689474  PMID: 9821363
16.  Epidemiological patterns of hepatitis B virus (HBV) in highly endemic areas. 
Epidemiology and Infection  1996;117(2):313-325.
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.
PMCID: PMC2271713  PMID: 8870629
17.  The transmission dynamics of hepatitis B in the UK: a mathematical model for evaluating costs and effectiveness of immunization programmes. 
Epidemiology and Infection  1996;116(1):71-89.
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.
PMCID: PMC2271247  PMID: 8626006
18.  The development of an age structured model for schistosomiasis transmission dynamics and control and its validation for Schistosoma mansoni. 
Epidemiology and Infection  1995;115(2):325-344.
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.
Images
PMCID: PMC2271402  PMID: 7589272
19.  Cervical cytology reported as negative and risk of adenocarcinoma of the cervix: no strong evidence of benefit. 
British Journal of Cancer  1995;71(4):894-897.
The relationship between negative cervical cytology reports and risk of adenocarcinoma of the cervix was evaluated in a case-control study of 113 cases and 452 controls. All cases and controls had received at least two negative cytology reports. There was no significant difference between the cases and controls in the number of negative cytology reports or in history of cervical abnormality; while a test for trend in the time since last negative cytology report was significant (P < 0.001), the estimated benefit was very modest. Although the estimates of relative protection were higher in women aged less than 35 years than in women aged 35-69 years, this difference was not statistically significant. These results suggest that cervical screening as practised in the 1970s and 1980s was much less effective in preventing adenocarcinoma than squamous carcinoma of the cervix.
PMCID: PMC2033741  PMID: 7710961
20.  Short-term predictions of HIV prevalence and AIDS incidence. 
Epidemiology and Infection  1992;109(1):149-160.
Reports of AIDS cases in Amsterdam up to February 1990 were used to make predictions of future cases up to 1993. Two published methods were applied, which make extrapolations from current cases and simultaneously estimate the extent of delay in reporting. The choice of the exact model greatly influenced the predictions, as did predictions for distinct transmission groups. We present results for the homo/bisexual male group, and the total population of Amsterdam. The AIDS case predictions are used to predict the HIV prevalence using the ratio of HIV prevalence to AIDS incidence and through 'back calculation'. We suggest that the ratio is a simple technique that may be used to estimate HIV prevalence. The estimated number of cumulative HIV infected homo/bisexual males in Amsterdam in January 1990 was between 2100 and 4100 in a total of 2200-4600 infected people.
PMCID: PMC2272225  PMID: 1499669
21.  A new approach to morbidity risk assessment in hookworm endemic communities. 
Epidemiology and Infection  1992;108(3):469-481.
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.
PMCID: PMC2272209  PMID: 1601081
22.  Cytological reporting of cervical abnormalities according to endocervical status. 
British Journal of Cancer  1993;67(3):585-588.
An analysis of cytology reporting within Victorian Cytology Service demonstrates that the proportion of Papanicolaou smears which were reported as including an endocervical component increased from approximately one half during 1987-89 to more than three quarters during 1990-91. The improvement coincided with the routine provision of special sampling instruments to all practitioners supplemented by an education program. Despite the increase in endocervical sampling, no increase in the rate of reporting of high-grade intraepithelial lesions of the cervix has occurred. An increase between the two time periods in the cytological reporting of adenocarcinoma, adenocarcinoma in situ and endocervical dyskaryosis has occurred, but does not reach statistical significance.
PMCID: PMC1968260  PMID: 8439508
24.  Cervical cancers diagnosed after negative results on cervical cytology: perspective in the 1980s. 
BMJ : British Medical Journal  1990;300(6740):1622-1626.
OBJECTIVES--To assess the magnitude of the problem of interval cancers of the cervix (those that are diagnosed within a short time after negative screening test results) in the 1980s, to compare the nature of interval cancers in younger women with that in older women, and, by reviewing negative cervical smears, to determine the proportion of interval cancers that might represent the development of malignancy anew compared with the proportion that might be associated with difficulties in sampling or errors in reporting. DESIGN--An audit of the interval cases of cervical cancer that had been diagnosed within 36 months of a smear having been reported as negative by the Victorian Cytology Gynaecological Service among women registered with cervical cancer during 1982-6. SETTING--The Victorian Cytology Gynaecological Service, a free public sector cytology laboratory in Victoria, Australia. SUBJECTS--138 Women, all of whom had had cervical cancer diagnosed during the 36 months after having had a negative cervical smear. Subjects were divided into two age groups: younger women, aged less than 35; older women, aged 35-69. INTERVENTIONS--Negative slides were reviewed for evidence of optimal sampling and for the presence of cellular abnormalities that had been missed at the time of the original reporting. MAIN OUTCOME MEASURES--The number of interval cases of cancer of the cervix registered during 1982-6. The proportion of interval cases occurring in younger women and the proportion occurring in older women. Division of women into three risk categories based on clinical history and screening history that broadly corresponded to the probability that a diagnosis of cervical cancer might be expected during the 36 months after the issuing of a negative smear report. RESULTS--138 Of 1044 (13.2%) women who had been registered with cervical cancer during 1982-6 had had one or more negative smears during the 36 months preceding the diagnosis of cancer. Interval cancers comprised a larger proportion of registrations of cervical cancer in women aged less than 35 years than in women aged 35-69 (21.1% v 11.0%, p less than 0.01). Women with interval cancer who had had at least three negative smears during the 10 years before the diagnosis of cancer were commoner in the younger age group than in the older age group (7.0% v 2.5%, p less than 0.01). When, however, the number of observed cases of squamous cell carcinoma was related to the number of expected cases in the absence of screening, no significant difference was found between the two age groups (6.8% v 4.8%, p greater than 0.10). The rate of diagnosis of interval cancer per 100,000 negative tests was lower among younger women than among older women (10/100,000 v 16/100,000). Review of the negative slides showed that 11.9% were again considered to be negative with an optimal sample having been obtained as evidenced by the presence of endocervical cells or metaplastic cells, or both. CONCLUSIONS--Interval cancers might comprise a larger proportion of all registered cases of cervical cancer among younger women owing to the larger proportion of such cancers being prevented in this age group. Among women with interval cancer review of the negative slides showed that most were accounted for by suboptimal sampling or by errors of reporting.
PMCID: PMC1663265  PMID: 2372641
25.  Adherence to recommendations for early repeat cervical smear tests. 
BMJ : British Medical Journal  1989;298(6688):1605-1607.
OBJECTIVE--To assess adherence to recommendations for an early repeat cervical smear test in women with reports of cytological abnormalities, and to evaluate the impact of reminder letters to medical practitioners when such smear tests are overdue. DESIGN--Observational study. SETTING--Cytology (gynaecological) service for Victoria, Australia. SUBJECTS--Two groups of women who had abnormal cervical smears during 1985. Women in group A had some evidence of an important dysplasia and were advised to have a repeat smear in three months' time whereas women in group B had a less serious abnormality and were advised to have a repeat smear test in six months' time. In all, 971 of the 1036 women in group A and 1401 of the 1464 women in group B were eligible to have a repeat smear analysed by the service. INTERVENTION--If a repeat smear had not been received within three months of the recommended date a reminder letter generated by the service's computer was sent to the medical practitioner who had taken the smear. END POINT--Thirty six months after the report on the abnormal smear was issued. MEASUREMENTS AND MAIN RESULTS--In all, 870 (90%) of the women in group A and 1154 (82%) of the women in group B had a repeat smear test. The mean time to a repeat test was 3.0 months (95% confidence interval 0.5 to 16.4) in group A and 6.0 months (1.2 to 30.3) in group B. The reminder letter to the practitioner potentially increased the rate of return for a repeat smear test by 18% in group A and 24% in group B. Adherence to the recommendation for a repeat test increased with increasing age. CONCLUSIONS--Achieving high rates of follow up smear tests and appropriate management in women with cytological abnormalities is critical to the impact of a screening programme for cervical cancer. The reminder system used in this study was not labour intensive or expensive and provided a fail safe mechanism for ensuring that reports of abnormal smears were not overlooked.
PMCID: PMC1836856  PMID: 2503146

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