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BackgroundBrazil has the second highest annual number of new leprosy cases. The aim of this study is to formally compare predictions of future new case detection rate (NCDR) trends and the annual probability of NCDR falling below 10/100,000 of four different modelling approaches in four states of Brazil: Rio Grande do Norte, Amazonas, Ceará, Tocantins.MethodsA linear mixed model, a back-calculation approach, a deterministic compartmental model and an individual-based model were used. All models were fitted to leprosy data obtained from the Brazilian national database (SINAN). First, models were fitted to the data up to 2011, and predictions were made for NCDR for 2012-2014. Second, data up to 2014 were considered and forecasts of NCDR were generated for each year from 2015 to 2040. The resulting distributions of NCDR and the probability of NCDR being below 10/100,000 of the population for each year were then compared between approaches.ResultsEach model performed well in model fitting and the short-term forecasting of future NCDR. Long-term forecasting of NCDR and the probability of NCDR falling below 10/100,000 differed between models. All agree that the trend of NCDR will continue to decrease in all states until 2040. Reaching a NCDR of less than 10/100,000 by 2020 was only likely in Rio Grande do Norte. Prediction until 2040 showed that the target was also achieved in Amazonas, while in Ceará and Tocantins the NCDR most likely remain (far) above 10/100,000.ConclusionsAll models agree that, while incidence is likely to decline, achieving a NCDR below 10/100,000 by 2020 is unlikely in some states. Long-term prediction showed a downward trend with more variation between models, but highlights the need for further control measures to reduce the incidence of new infections if leprosy is to be eliminated.

Background: Visceral leishmaniasis has been targeted for elimination as a public health problem (less than 1 case per 10,000 people per year) in the Indian sub-continent by 2017. However, there is still a high degree of uncertainty about the natural history of the disease, in particular about the duration of asymptomatic infection and the proportion of asymptomatically infected individuals that develop clinical visceral leishmaniasis. Quantifying these aspects of the disease is key for guiding efforts to eliminate visceral leishmaniasis and maintaining elimination once it is reached. Methods: Data from a detailed epidemiological study in Bangladesh in 2002-2004 was analysed to estimate key epidemiological parameters. The role of diagnostics in determining the probability and rate of progression to clinical disease was estimated by fitting Cox proportional hazards models. A multi-state Markov model of the natural history of visceral leishmaniasis was fitted to the data to estimate the asymptomatic infection period and the proportion of asymptomatic individuals going on to develop clinical symptoms. Results: At the time of the study, individuals were taking several months to be diagnosed with visceral leishmaniasis, leading to many opportunities for ongoing transmission. The probability of progression to clinical disease was strongly associated with initial seropositivity and even more strongly with seroconversion, with most clinical symptoms developing within a year. The estimated average durations of asymptomatic infection and symptomatic infection for our model of the natural history are 147 days (95 % CI 130-166) and 140 days (95 % CI 123-160), respectively, and are significantly longer than previously reported estimates. We estimate from the data that 14.7 % (95 % CI 12.6-20.0 %) of asymptomatic individuals develop clinical symptoms-a greater proportion than previously estimated. Conclusions: Extended periods of asymptomatic infection could be important for visceral leishmaniasis transmission, but this depends critically on the relative infectivity of asymptomatic and symptomatic individuals to sandflies. These estimates could be informed by similar analysis of other datasets. Our results highlight the importance of reducing times from onset of symptoms to diagnosis and treatment to reduce opportunities for transmission. [ABSTRACT FROM AUTHOR]

The article suggests a shift to a dose-dimension paradigm in the development of vaccines for infectious diseases. Topics covered include a model of pathogen transmission for exploring population effects of protection by a vaccine against infection, dose-infectivity curves, and classification of beta distribution shapes based on polarization.

Abstract: Dichelobacter nodosus, a Gram-negative anaerobic bacterium, is the essential causative agent of footrot in sheep. Currently, depending on the clinical presentation in the field, footrot is described as benign or virulent; D. nodosus strains have also been classified as benign or virulent, but this designation is not always consistent with clinical disease. The aim of this study was to determine the diversity of the pgr gene, which encodes a putative proline-glycine repeat protein (Pgr). The pgr gene was present in all 100 isolates of D. nodosus that were examined and, based on sequence analysis had two variants, pgrA and pgrB. In pgrA, there were two coding tandem repeat regions, R1 and R2: different strains had variable numbers of repeats within these regions. The R1 and R2 were absent from pgrB. Both variants were present in strains from Australia, Sweden and the UK, however, only pgrB was detected in isolates from Western Australia. The pgrA gene was detected in D. nodosus from tissue samples from two flocks in the UK with virulent footrot and only pgrB from a flock with no virulent or benign footrot for >10 years. Bioinformatic analysis of the putative PgrA protein indicated that it contained a collagen-like cell surface anchor motif. These results suggest that the pgr gene may be a useful molecular marker for epidemiological studies. [ABSTRACT FROM AUTHOR]

The SIR (susceptible–infectious–resistant) and SIS (susceptible–infectious–susceptible) frameworks for infectious disease have been extensively studied and successfully applied. They implicitly assume the upper and lower limits of the range of possibilities for host immune response. However, the majority of infections do not fall into either of these extreme categories. We combine two general avenues that straddle this range: temporary immune protection (immunity wanes over time since infection), and partial immune protection (immunity is not fully protective but reduces the risk of reinfection). We present a systematic analysis of the dynamics and equilibrium properties of these models in comparison to SIR and SIS, and analyse the outcome of vaccination programmes. We describe how the waning of immunity shortens inter-epidemic periods, and poses major difficulties to disease eradication. We identify a “reinfection threshold” in transmission when partial immunity is included. Below the reinfection threshold primary infection dominates, levels of infection are low, and vaccination is highly effective (approximately an SIR model). Above the reinfection threshold reinfection dominates, levels of infection are high, and vaccination fails to protect (approximately an SIS situation). This association between high prevalence of infection and vaccine failure emphasizes the problems of controlling recurrent infections in high-burden regions. However, vaccines that induce a better protection than natural infection have the potential to increase the reinfection threshold, and therefore constitute interventions with a surprisingly high capacity to reduce infection where reduction is most needed. [Copyright &y& Elsevier]

Abstract: Footrot is an infectious bacterial disease of sheep that causes lameness. The causal agent is Dichelobacter nodosus. There is debate regarding the role of Fusobacterium necrophorum in disease initiation. This research used an observational longitudinal study of footrot, together with quantitative PCR (qPCR) of bacterial load of D. nodosus and F. necrophorum, to elucidate the roles of each species in the development of disease. All feet of 18 a priori selected sheep were monitored for five weeks assessing disease severity (healthy, interdigital dermatitis (ID) and severe footrot (SFR)) and bacterial load. A multinomial model was used to analyse these data. Key unadjusted results were that D. nodosus was detected more frequently on feet with ID, whereas F. necrophorum was detected more frequently on feet with SFR. In the multinomial model, ID was associated with increasing log10 load of D. nodosus the week of observation (OR=1.28 (95% CI=1.08–1.53)) and the week prior to development of ID (OR=1.20 (95% CI=1.01–1.42). There was no association between log10 load2 of F. necrophorum and presence of ID (OR=0.99 (95% CI=0.96–1.02))). SFR was associated with increasing log10 load of D. nodosus the week before disease onset (OR=1.42 (95% CI=1.02–1.96)) but not once SFR had occurred. SFR was positively associated with log10 load2 of F. necrophorum once disease was present (OR=1.06 (95% CI=1.01–1.11)). In summary, there was an increased risk of increasing D. nodosus load the week prior to development of ID and SFR and during an episode of ID. In contrast, F. necrophorum load was not associated with ID before or during an episode, and was only associated with SFR once present. These results contribute to our understanding of the epidemiology of footrot and highlight that D. nodosus load plays the primary role in disease initiation and progression, with F. necrophorum load playing a secondary role. Further studies in more flocks and climates would be useful to confirm these findings. This study identifies that D. nodosus load is highest during ID. This supports previous epidemiological findings, which demonstrate that controlling ID is the most effective management strategy to prevent new cases of ID and SFR. [Copyright &y& Elsevier]

Abstract: Between December 2002 and April 2006, 114 cattle farms in the south west of England were visited at least once, with 100 farms visited three times. A total of 29,782 serum samples were collected from 15,736 individually identified cattle. The sera were tested for the presence of antibodies against Mycobacterium avium subsp. paratuberculosis (MAP) using an indirect enzyme-linked immunosorbent assay (ELISA). The mean seroprevalence in herds sampled three times was 7.1%; 10.1% of cattle had at least one positive result. There were 78%, 75% and 75% dairy herds with at least one positive bovine at the first, second and third routine visits, respectively. In comparison, 44%, 42% and 46% suckler herds had at least one positive bovine for the first, second and third routine visits, respectively. In most herds (>90%), within herd seroprevalence of MAP remained stable over time. Markov chain Monte Carlo (MCMC) simulation methods were used to re-estimate the test sensitivity and specificity. The sensitivity results were 33.3% (95% CI, 28.8–37.8%), 34.5% (95% CI, 30.3–38.8%) and 34.8% (95% CI, 30.8–38.9%) for the first, second and third routine visits and the specificity results were 99.7% (95% CI, 99.3–99.9%), 99.8% (95% CI, 99.4–99.9%) and 99.7% (95% CI, 99.3–99.9%) for the first, second and third routine visits, respectively. The expected true prevalence was also estimated, 11 (21.1%) suckler herds and 1 (2.1%) dairy herd were predicted to be truly free from infection during the study period. The seroprevalence of antibodies against MAP increased with cattle age. There was a significantly higher seroprevalence of MAP in dairy breeds of cattle compared with suckler breeds of cattle. This was more pronounced in Channel Island breeds. Smaller dairy herds (<100 cattle) had a relatively lower seroprevalence of MAP than dairy herds with ≥100 cattle. In 8 (42%) of the 19 herds with ≥100 cattle born into the same herd, seropositive cattle were clustered by birth month whilst in the remaining herds clustering was not apparent. Daughters were significantly more likely to be MAP seropositive when born to a seropositive dam. [Copyright &y& Elsevier]

Summary: The quality of research in hospital epidemiology (infection control) must be improved to be robust enough to influence policy and practice. In order to raise the standards of research and publication, a CONSORT equivalent for these largely quasi-experimental studies has been prepared by the authors of two relevant systematic reviews, following consultation with learned societies, editors of journals, and researchers. The ORION (Outbreak Reports and Intervention Studies Of Nosocomial infection) statement consists of a 22 item checklist, and a summary table. The emphasis is on transparency to improve the quality of reporting and on the use of appropriate statistical techniques. The statement has been endorsed by a number of professional special interest groups and societies. Like CONSORT, ORION should be considered a “work in progress”, which requires ongoing dialogue for successful promotion and dissemination. The statement is therefore offered for further public discussion. Journals and research councils are strongly recommended to incorporate it into their submission and reviewing processes. Feedback to the authors is encouraged and the statement will be revised in 2 years. [Copyright &y& Elsevier]