Immunopathogenesis and diagnosis of tuberculosis and tuberculosis-associated immune reconstitution inflammatory syndrome during early antiretroviral therapy.

BACKGROUND: In many settings, the benefits of antiretroviral therapy (ART) are reduced by the high early incidence of tuberculosis and tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS). METHODS: We used tuberculin skin testing and the QuantiFERON-TB Gold In-Tube assay to investigate cellular immune responses to purified protein derivative (PPD) and region of difference 1 (RD1) antigens during the first 24 weeks of ART. RESULTS: TB-IRIS and ART-associated tuberculosis occurred in 15 of 75 (20%) and 11 of 231 (4.8%) participants at risk, respectively. Greater increases in interferon gamma (IFN-gamma) and skin test responses to PPD were seen at week 24 and 12 in participants with TB-IRIS (P< or = .04), respectively. Raw IFN-gamma responses to RD1 antigens and PPD corrected for pre-ART CD4(+) T cell counts were higher at all time points in individuals with ART-associated tuberculosis (P<.001) and were associated with areas under receiver operator characteristic curves of 0.90 for RD1 (95% confidence interval [CI], 0.78-1.00) and 0.92 for PPD (95% CI, 0.83-1.00) for the diagnosis of ART-associated tuberculosis. Pre-ART IFN-gamma responses enabled stratification of participants into groups with risks of subsequent tuberculosis of 0.7%, 9.3%, and 30.0%. CONCLUSIONS: Type 1 effector T cell responses are prominent in ART-associated tuberculosis, but additional immune defects may be more important in paradoxical TB-IRIS. IFN-gamma release assays may contribute to the prediction and diagnosis of tuberculosis during early ART.

National burden of influenza-associated hospitalizations in Cambodia, 2015 and 2016.

INTRODUCTION: The burden of influenza in Cambodia is not well known, but it would be useful for understanding the impact of seasonal epidemics and pandemics and to design appropriate policies for influenza prevention and control. The severe acute respiratory infection (SARI) surveillance system in Cambodia was used to estimate the national burden of SARI hospitalizations in Cambodia. METHODS: We estimated age-specific influenza-associated SARI hospitalization rates in three sentinel sites in Svay Rieng, Siem Reap and Kampong Cham provinces. We used influenza-associated SARI surveillance data for one year to estimate the numerator and hospital admission surveys to estimate the population denominator for each site. A national influenza-associated SARI hospitalization rate was calculated using the pooled influenza-associated SARI hospitalizations for all sites as a numerator and the pooled catchment population of all sites as denominator. National influenza-associated SARI case counts were estimated by applying hospitalization rates to the national population. RESULTS: The national annual rates of influenza-associated hospitalizations per 100 000 population was highest for the two youngest age groups at 323 for < 1 year and 196 for 1-4 years. We estimated 7547 influenza-associated hospitalizations for Cambodia with almost half of these represented by children younger than 5 years. DISCUSSION: We present national estimates of influenza-associated SARI hospitalization rates for Cambodia based on sentinel surveillance data from three sites. The results of this study indicate that the highest burden of severe influenza infection is borne by the younger age groups. These findings can be used to guide future strategies to reduce influenza morbidity.