Longitudinal Assessment of Systemic and Genital Tract Inflammatory Markers and Endogenous Genital Tract E. coli Inhibitory Activity in HIV-Infected and Uninfected Women.

PROBLEM: Stability over time of systemic and mucosal immunity and their associations with bacterial vaginosis (BV) and HIV-specific parameters were assessed. METHOD OF STUDY: Immune mediators and HIV viral load in plasma and cervicovaginal lavage (CVL), E. coli inhibition, and Nugent score were measured at three semiannual visits among 94 participants in the Women's Interagency HIV Study. Mixed models identified the factors associated with immune mediators. RESULTS: There was higher E. coli inhibition and lower inflammation over time in the genital tract and systemically. BV was consistently associated with higher CVL inflammatory mediators and lower CVL E. coli inhibition. HIV-infected women with higher CD4 counts had lower systemic and genital inflammatory mediators, and genital HIV shedding was associated with higher CVL inflammatory mediators. Use of antiretroviral therapy (ART) was associated with lower plasma and CVL mediators, but higher E. coli inhibition. CONCLUSION: HIV and BV are linked to inflammation, and ART may be associated with improved vaginal health.

Assessment of the protective effect of Imvamune and Acam2000 vaccines against aerosolized monkeypox virus in cynomolgus macaques.

To support the licensure of a new and safer vaccine to protect people against smallpox, a monkeypox model of infection in cynomolgus macaques, which simulates smallpox in humans, was used to evaluate two vaccines, Acam2000 and Imvamune, for protection against disease. Animals vaccinated with a single immunization of Imvamune were not protected completely from severe and/or lethal infection, whereas those receiving either a prime and boost of Imvamune or a single immunization with Acam2000 were protected completely. Additional parameters, including clinical observations, radiographs, viral load in blood, throat swabs, and selected tissues, vaccinia virus-specific antibody responses, immunophenotyping, extracellular cytokine levels, and histopathology were assessed. There was no significant difference (P > 0.05) between the levels of neutralizing antibody in animals vaccinated with a single immunization of Acam2000 (132 U/ml) and the prime-boost Imvamune regime (69 U/ml) prior to challenge with monkeypox virus. After challenge, there was evidence of viral excretion from the throats of 2 of 6 animals in the prime-boost Imvamune group, whereas there was no confirmation of excreted live virus in the Acam2000 group. This evaluation of different human smallpox vaccines in cynomolgus macaques helps to provide information about optimal vaccine strategies in the absence of human challenge studies.

Influenza in the elderly: a mini-review.

Influenza is an important cause of morbidity and mortality in the elderly population each year. The often subtle clinical manifestations in the frail geriatric patients may not be recognized initially, impeding timely administration of antiviral treatment. The effectiveness of current influenza vaccines in the elderly population is often diminished by immune senescence. Increasing immunization rates among health-care workers and elderly caregivers, and finding more effective vaccines for the elderly people are likely to significantly improve disease prevention in this population at risk.

Multiple imputation for interval censored data with auxiliary variables.

We propose a non-parametric multiple imputation scheme, NPMLE imputation, for the analysis of interval censored survival data. Features of the method are that it converts interval-censored data problems to complete data or right censored data problems to which many standard approaches can be used, and that measures of uncertainty are easily obtained. In addition to the event time of primary interest, there are frequently other auxiliary variables that are associated with the event time. For the goal of estimating the marginal survival distribution, these auxiliary variables may provide some additional information about the event time for the interval censored observations. We extend the imputation methods to incorporate information from auxiliary variables with potentially complex structures. To conduct the imputation, we use a working failure-time proportional hazards model to define an imputing risk set for each censored observation. The imputation schemes consist of using the data in the imputing risk sets to create an exact event time for each interval censored observation. In simulation studies we show that the use of multiple imputation methods can improve the efficiency of estimators and reduce the effect of missing visits when compared to simpler approaches. We apply the approach to cytomegalovirus shedding data from an AIDS clinical trial, in which CD4 count is the auxiliary variable.