Many of the remaining challenges in infectious disease control involve pathogens that fail to elicit long-lasting immunity in their hosts. Antigenic variation is a common reason for this failure and a contributor to the complexity of vaccine design. Diversifying selection by the host immune system is commonly, and often correctly, invoked to explain antigenic variability in pathogens. However, there is a wide variety of patterns of antigenic variation across space and time, and within and between hosts, and we do not yet understand the determinants of these different patterns. This review describes five such patterns, taking as examples two bacteria (Streptococcus pneumoniae and Neisseria meningitidis), two viruses (influenza A and HIV-1), as well as the pathogens (taken as a group) for which antigenic variation is negligible. Pathogen-specific explanations for these patterns of diversity are critically evaluated, and the patterns are compared against predictions of theoretical models for antigenic diversity. Major remaining challenges are highlighted, including the identification of key protective antigens in bacteria, the design of vaccines to combat antigenic variability for viruses and the development of more systematic explanations for patterns of antigenic variation.

BackgroundDuring an influenza pandemic, a substantial proportion of transmission is thought to occur in households. We used data on influenza progression in individuals and their contacts collected by the City of Milwaukee Health Department (MHD) to study the transmission of pandemic influenza A/H1N1 virus in 362 households in Milwaukee, WI, and the effects of oseltamivir treatment and chemoprophylaxis.Methods135 households had chronological information on symptoms and oseltamivir usage for all household members. The effect of oseltamivir treatment and other factors on the household secondary attack rate was estimated using univariate and multivariate logistic regression with households as the unit of analysis. The effect of oseltamivir treatment and other factors on the individual secondary attack rate was estimated using univariate and multivariate logistic regression with individual household contacts as the unit of analysis, and a generalized estimating equations approach was used to fit the model to allow for clustering within households.ResultsOseltamivir index treatment on onset day or the following day (early treatment) was associated with a 42% reduction (OR: 0.58, 95% CI: 0.19, 1.73) in the odds of one or more secondary infections in a household and a 50% reduction (OR: 0.5, 95% CI: 0.17, 1.46) in the odds of a secondary infection in individual contacts. The confidence bounds are wide due to a small sample of households with early oseltamivir index usage - in 29 such households, 5 had a secondary attack. Younger household contacts were at higher risk of infection (OR: 2.79, 95% CI: 1.50-5.20).ConclusionsEarly oseltamivir treatment may be beneficial in preventing H1N1pdm influenza transmission; this may have relevance to future control measures for influenza pandemics. Larger randomized trials are needed to confirm this finding statistically.

BackgroundMany schools were temporarily closed in response to outbreaks of the recently emerged pandemic influenza A/H1N1 virus. The effectiveness of closing schools to reduce transmission depends largely on student/family behavior during the closure. We sought to improve our understanding of these behaviors.Methodology/Principal FindingsTo characterize this behavior, we surveyed students in grades 9–12 and parents of students in grades 5–8 about student activities during a weeklong closure of a school during the first months after the disease emerged. We found significant interaction with the community and other students–though less interaction with other students than during school–with the level of interaction increasing with grade.ConclusionsOur results are useful for the future design of social distancing policies and to improving the ability of modeling studies to accurately predict their impact.

Risks for disease in some population groups relative to others (relative risks) are usually considered to be consistent over time, though they are often modified by other, non-temporal factors. For infectious diseases, in which overall incidence often varies substantially over time, the patterns of temporal changes in relative risks can inform our understanding of basic epidemiologic questions. For example, recent work suggests that temporal changes in relative risks of infection over the course of an epidemic cycle can both be used to identify population groups that drive infectious disease outbreaks, and help elucidate differences in the effect of vaccination against infection (that is relevant to transmission control) compared with its effect against disease episodes (that reflects individual protection). Patterns of change in the in age groups affected over the course of seasonal outbreaks can provide clues to the types of pathogens that could be responsible for diseases for which an infectious cause is suspected. Changing apparent efficacy of vaccines during trials may provide clues to the vaccine's mode of action and/or indicate risk heterogeneity in the trial population. Declining importance of unusual behavioral risk factors may be a signal of increased local transmission of an infection. We review these developments and the related public health implications.