Epidemiological evidence of higher susceptibility to vCJD in the young

BACKGROUND: The strikingly young age of new variant Creutzfeldt-Jacob disease (vCJD) cases remains unexplained. Age dependent susceptibility to infection has been put forward, but differential dietary exposure to contaminated food products in the UK population according to age and sex during the bovine spongiform encephalopathy (BSE) epidemic may provide a simpler explanation. METHODS: Using recently published estimates of dietary exposure in mathematical models of the epidemiology of the new variant Creutzfeldt Jacob disease (vCJD), we examine whether the age characteristics of vCJD cases may be reproduced. RESULTS: The susceptibility/exposure risk function has likely peaked in adolescents and was followed by a sharp decrease with age, evocative of the profile of exposure to bovine material consumption according to age. However, assuming that the risk of contamination was proportional to exposure, with no age dependent susceptibility, the model failed to reproduce the observed age characteristics of the vCJD cases: The predicted cumulated proportion of cases over 40 years was 48%, in strong disagreement with the observed 10%. Incorporating age dependent susceptibility led to a cumulated proportion of cases over 40 years old of 12%. CONCLUSIONS: This analysis provides evidence that differential dietary exposure alone fails to explain the pattern of age in vCJD cases. Decreasing age related susceptibility is required to reproduce the characteristics of the age distribution of vCJD cases

Effect of Vaccines and Antivirals during the Major 2009 A(H1N1) Pandemic Wave in Norway – And the Influence of Vaccination Timing

To evaluate the impact of mass vaccination with adjuvanted vaccines (eventually 40% population coverage) and antivirals during the 2009 influenza pandemic in Norway, we fitted an age-structured SEIR model using data on vaccinations and sales of antivirals in 2009/10 in Norway to Norwegian ILI surveillance data from 5 October 2009 to 4 January 2010. We estimate a clinical attack rate of approximately 30% (28.7–29.8%), with highest disease rates among children 0–14 years (43–44%). Vaccination started in week 43 and came too late to have a strong influence on the pandemic in Norway. Our results indicate that the countermeasures prevented approximately 11–12% of potential cases relative to an unmitigated pandemic. Vaccination was found responsible for roughly 3 in 4 of the avoided infections. An estimated 50% reduction in the clinical attack rate would have resulted from vaccination alone, had the campaign started 6 weeks earlier. Had vaccination been prioritized for children first, the intervention should have commenced approximately 5 weeks earlier in order to achieve the same 50% reduction. In comparison, we estimate that a non-adjuvanted vaccination program should have started 8 weeks earlier to lower the clinical attack rate by 50%

Hospitalizations for varicella in children and adolescents in a referral hospital in Hong Kong, 2004 to 2008: A time series study

Background: Varicella accounts for significant morbidities and remains a public health issue worldwide. Climatic factors have been shown to associate with the incidence and transmission of various infectious diseases. We describe the epidemiology of varicella in paediatric patients hospitalized at a tertiary referral hospital in Hong Kong from 2004 to 2008, and to explore the possible association between the occurrence of varicella infection and various climatic factors. Methods. The hospital discharge database of Princess Margaret Hospital was retrospectively analyzed for admissions associated with varicella from 2004 to 2008. Meteorological data were obtained from the monthly meteorological reports from the Hong Kong Observatory website. Time series analysis was performed with Poisson regression using a Generalized Estimating Equation (GEE) approach. Results: During the study period, 598 children were hospitalized for varicella. The mean age on admission was 57.6 months, and the mean duration of hospitalization was 3.7 days. The overall complication rate was 47%. The mean monthly relative humidity, especially in cool seasons, was inversely correlated with the monthly varicella cases of the same month. Conclusions: Varicella can lead to serious complications and prolonged hospitalization, even in previously healthy children. Lower relative humidity in cool seasons is associated with higher number of paediatric varicella hospital admissions. These findings are useful for a better understanding of the pattern of paediatric varicella hospitalization in Hong Kong. © 2011 Chan et al; licensee BioMed Central Ltd.link_to_subscribed_fulltex

A Comparison of the Epidemiology and Clinical Presentation of Seasonal Influenza A and 2009 Pandemic Influenza A (H1N1) in Guatemala

A new influenza A (H1N1) virus was first found in April 2009 and proceeded to cause a global pandemic. We compare the epidemiology and clinical presentation of seasonal influenza A (H1N1 and H3N2) and 2009 pandemic influenza A (H1N1) (pH1N1) using a prospective surveillance system for acute respiratory disease in Guatemala.Patients admitted to two public hospitals in Guatemala in 2008-2009 who met a pneumonia case definition, and ambulatory patients with influenza-like illness (ILI) at 10 ambulatory clinics were invited to participate. Data were collected through patient interview, chart abstraction and standardized physical and radiological exams. Nasopharyngeal swabs were taken from all enrolled patients for laboratory diagnosis of influenza A virus infection with real-time reverse transcription polymerase chain reaction. We identified 1,744 eligible, hospitalized pneumonia patients, enrolled 1,666 (96%) and tested samples from 1,601 (96%); 138 (9%) had influenza A virus infection. Surveillance for ILI found 899 eligible patients, enrolled 801 (89%) and tested samples from 793 (99%); influenza A virus infection was identified in 246 (31%). The age distribution of hospitalized pneumonia patients was similar between seasonal H1N1 and pH1N1 (P = 0.21); the proportion of pneumonia patients <1 year old with seasonal H1N1 (39%) and pH1N1 (37%) were similar (P = 0.42). The clinical presentation of pH1N1 and seasonal influenza A was similar for both hospitalized pneumonia and ILI patients. Although signs of severity (admission to an intensive care unit, mechanical ventilation and death) were higher among cases of pH1N1 than seasonal H1N1, none of the differences was statistically significant.Small sample sizes may limit the power of this study to find significant differences between seasonal influenza A and pH1N1. In Guatemala, influenza, whether seasonal or pH1N1, appears to cause severe disease mainly in infants; targeted vaccination of children should be considered

Modelling the Effects of Population Structure on Childhood Disease: The Case of Varicella

Realistic, individual-based models based on detailed census data are increasingly used to study disease transmission. Whether the rich structure of such models improves predictions is debated. This is studied here for the spread of varicella, a childhood disease, in a realistic population of children where infection occurs in the household, at school, or in the community at large. A methodology is first presented for simulating households with births and aging. Transmission probabilities were fitted for schools and community, which reproduced the overall cumulative incidence of varicella over the age range of 0–11 years old

Seasonal transmission potential and activity peaks of the new influenza A(H1N1): a Monte Carlo likelihood analysis based on human mobility

On 11 June the World Health Organization officially raised the phase of pandemic alert (with regard to the new H1N1 influenza strain) to level 6. We use a global structured metapopulation model integrating mobility and transportation data worldwide in order to estimate the transmission potential and the relevant model parameters we used the data on the chronology of the 2009 novel influenza A(H1N1). The method is based on the maximum likelihood analysis of the arrival time distribution generated by the model in 12 countries seeded by Mexico by using 1M computationally simulated epidemics. An extended chronology including 93 countries worldwide seeded before 18 June was used to ascertain the seasonality effects. We found the best estimate R0 = 1.75 (95% CI 1.64 to 1.88) for the basic reproductive number. Correlation analysis allows the selection of the most probable seasonal behavior based on the observed pattern, leading to the identification of plausible scenarios for the future unfolding of the pandemic and the estimate of pandemic activity peaks in the different hemispheres. We provide estimates for the number of hospitalizations and the attack rate for the next wave as well as an extensive sensitivity analysis on the disease parameter values. We also studied the effect of systematic therapeutic use of antiviral drugs on the epidemic timeline. The analysis shows the potential for an early epidemic peak occurring in October/November in the Northern hemisphere, likely before large-scale vaccination campaigns could be carried out. We suggest that the planning of additional mitigation policies such as systematic antiviral treatments might be the key to delay the activity peak inorder to restore the effectiveness of the vaccination programs.Comment: Paper: 29 Pages, 3 Figures and 5 Tables. Supplementary Information: 29 Pages, 5 Figures and 7 Tables. Print version: http://www.biomedcentral.com/1741-7015/7/4

Theoretical basis to measure the impact of short-lasting control of an infectious disease on the epidemic peak

Background. While many pandemic preparedness plans have promoted disease control effort to lower and delay an epidemic peak, analytical methods for determining the required control effort and making statistical inferences have yet to be sought. As a first step to address this issue, we present a theoretical basis on which to assess the impact of an early intervention on the epidemic peak, employing a simple epidemic model. Methods. We focus on estimating the impact of an early control effort (e.g. unsuccessful containment), assuming that the transmission rate abruptly increases when control is discontinued. We provide analytical expressions for magnitude and time of the epidemic peak, employing approximate logistic and logarithmic-form solutions for the latter. Empirical influenza data (H1N1-2009) in Japan are analyzed to estimate the effect of the summer holiday period in lowering and delaying the peak in 2009. Results. Our model estimates that the epidemic peak of the 2009 pandemic was delayed for 21 days due to summer holiday. Decline in peak appears to be a nonlinear function of control-associated reduction in the reproduction number. Peak delay is shown to critically depend on the fraction of initially immune individuals. Conclusions. The proposed modeling approaches offer methodological avenues to assess empirical data and to objectively estimate required control effort to lower and delay an epidemic peak. Analytical findings support a critical need to conduct population-wide serological survey as a prior requirement for estimating the time of peak. © 2011 Omori and Nishiura; licensee BioMed Central Ltd.published_or_final_versio

Characterizing the Epidemiology of the 2009 Influenza A/H1N1 Pandemic in Mexico

Gerardo Chowell and colleagues address whether school closures and other social distancing strategies were successful in reducing pandemic flu transmission in Mexico by analyzing the age- and state-specific incidence of influenza morbidity and mortality in 32 Mexican states

Repetitive Immunization Enhances the Susceptibility of Mice to Peripherally Administered Prions

The susceptibility of humans and animals to prion infections is determined by the virulence of the infectious agent, by genetic modifiers, and by hitherto unknown host and environmental risk factors. While little is known about the latter two, the activation state of the immune system was surmised to influence prion susceptibility. Here we administered prions to mice that were repeatedly immunized by two initial injections of CpG oligodeoxynucleotides followed by repeated injections of bovine serum albumin/alum. Immunization greatly reduced the required dosage of peripherally administered prion inoculum necessary to induce scrapie in 50% of mice. No difference in susceptibility was observed following intracerebral prion challenge. Due to its profound impact onto scrapie susceptibility, the host immune status may determine disease penetrance after low-dose prion exposure, including those that may give rise to iatrogenic and variant Creutzfeldt-Jakob disease