Azithromycin and doxycycline are equally efficacious in achieving microbial cure and have similar tolerability. Further head-to-head trials comparing these antibiotics are unnecessary.
Many candidate HIV vaccines are designed to primarily elicit T-cell responses. Although repeated immunization with the same vaccine boosts antibody responses, the benefit for T-cell responses is ill-defined. We compared two immunization regimens that include the same recombinant adenoviral serotype 5 (rAd5) boost. Repeated homologous rAd5 immunization fails to increase T-cell responses, but increases gp140 antibody responses ten-fold. DNA prime, as compared with rAd5 prime, directs long-term memory CD8+ T cells toward a terminally differentiated effector memory phenotype with cytotoxic potential. Based on the kinetics of activated cells measured directly ex vivo, the DNA vaccination primes for both CD4+ and CD8+ T cells, despite the lack of detection of the latter until after the boost. These results suggest that heterologous prime-boost combinations have distinct immunological advantages over homologous prime-boosts, and suggest that the effect of DNA on subsequent boosting may not be easily detectable directly after the DNA vaccination.
BackgroundSepsis is a global threat but insufficiently studied in Southeast Asia. The objective was to evaluate management, outcomes, adherence to sepsis bundles, and mortality prediction of maximum Sequential Organ Failure Assessment (SOFA) scores in patients with community-acquired sepsis in Southeast Asia.MethodsWe prospectively recruited hospitalized adults within 24 h of admission with community-acquired infection at nine public hospitals in Indonesia (n = 3), Thailand (n = 3), and Vietnam (n = 3). In patients with organ dysfunction (total SOFA score ≥ 2), we analyzed sepsis management and outcomes and evaluated mortality prediction of the SOFA scores. Organ failure was defined as the maximum SOFA score ≥ 3 for an individual organ system.ResultsFrom December 2013 to December 2015, 454 adult patients presenting with community-acquired sepsis due to diverse etiologies were enrolled. Compliance with sepsis bundles within 24 h of admission was low: broad-spectrum antibiotics in 76% (344/454), ≥ 1500 mL fluid in 50% of patients with hypotension or lactate ≥ 4 mmol/L (115/231), and adrenergic agents in 71% of patients with hypotension (135/191). Three hundred and fifty-five patients (78%) were managed outside of ICUs. Ninety-nine patients (22%) died. Total SOFA score on admission of those who subsequently died was significantly higher than that of those who survived (6.7 vs. 4.6, p < 0.001). The number of organ failures showed a significant correlation with 28-day mortality, which ranged from 7% in patients without any organ failure to 47% in those with failure of at least four organs (p < 0.001). The area under the receiver operating characteristic curve of the total SOFA score for discrimination of mortality was 0.68 (95% CI 0.62–0.74).ConclusionsCommunity-acquired sepsis in Southeast Asia due to a variety of pathogens is usually managed outside the ICU and with poor compliance to sepsis bundles. In this population, calculation of SOFA scores is feasible and SOFA scores are associated with mortality.Trial registrationClinicalTrials.gov, NCT02157259. Registered 5 June 2014, retrospectively registered.Electronic supplementary materialThe online version of this article (10.1186/s40560-018-0279-7) contains supplementary material, which is available to authorized users.
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