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Objective The contribution of bacterial co-infection to critical illness associated with 2009 influenza A (H1N1) [pH1N1] virus infection remains uncertain. The objective of this study was to determine if bacterial co-infection increased the morbidity and mortality of pH1N1. Design Retrospective and Prospective cohort study Setting 35 adult U.S. intensive care units over the course of one year Patients 683 critically ill adults with confirmed or probable pH1N1 Interventions None Measurements and Main Results A confirmed or probable case was defined as a positive pH1N1 test result or positive test for influenza A that was otherwise not subtyped. Bacterial co-infection was defined as documented bacteremia or any presumed bacterial pneumonia with or without positive respiratory tract culture within 72 hours of ICU admission. The mean age was 45±16 years, mean BMI 32.5±11.1 kg/m2, and mean APACHE II score 21±9, with 76% having at least one co-morbidity. Of 207 (30.3%) patients with bacterial co-infection on ICU admission, 154 had positive cultures with Staphylococcus aureus (n=57) and Streptococcus pneumoniae (n=19) the most commonly identified pathogens. Bacterial co-infected patients were more likely to present with shock (21 vs. 10%; P=0.0001), require mechanical ventilation at the time of ICU admission (63 vs. 52%; P=0.005) and have longer duration of ICU care (median 7 vs. 6 days; P=0.05). Hospital mortality was 23%; 31% in bacterial co-infected patients and 21% in patients without co-infection (P=0.002). Immunosuppression (RR 1.57; 95% CI 1.20–2.06; P=0.0009) and Staphylococcus aureus at admission (RR 2.82; 95% CI: 1.76–4.51; P<0.0001) were independently associated with increased mortality. Conclusions Among ICU patients with pH1N1, bacterial co-infection diagnosed within 72 hours of admission, especially with Staphylococcus aureus, was associated with significantly higher morbidity and mortality.

BACKGROUND The safety and efficacy of vaccines to prevent Ebola virus disease (EVD) were unknown when the incidence of EVD was peaking in Liberia. METHODS We initiated a randomized, placebo-controlled, phase 3 trial of the chimpanzee adenovirus 3 vaccine (ChAd3-EBO-Z) and the recombinant vesicular stomatitis virus vaccine (rVSVΔG-ZEBOV-GP) in Liberia. A phase 2 subtrial was embedded to evaluate safety and immunogenicity. Because the incidence of EVD declined in Liberia, the phase 2 component was expanded and the phase 3 component was eliminated. RESULTS A total of 1500 adults underwent randomization and were followed for 12 months. The median age of the participants was 30 years; 36.6% of the participants were women. During the week after the administration of vaccine or placebo, adverse events occurred significantly more often with the active vaccines than with placebo; these events included injection-site reactions (in 28.5% of the patients in the ChAd3-EBO-Z group and 30.9% of those in the rVSVΔG-ZEBOV-GP group, as compared with 6.8% of those in the placebo group), headache (in 25.1% and 31.9%, vs. 16.9%), muscle pain (in 22.3% and 26.9%, vs. 13.3%), feverishness (in 23.9% and 30.5%, vs. 9.0%), and fatigue (in 14.0% and 15.4%, vs. 8.8%) (P<0.001 for all comparisons); these differences were not seen at 1 month. Serious adverse events within 12 months after injection were seen in 40 participants (8.0%) in the ChAd3-EBO-Z group, in 47 (9.4%) in the rVSVΔG-ZEBOV-GP group, and in 59 (11.8%) in the placebo group. By 1 month, an antibody response developed in 70.8% of the participants in the ChAd3-EBO-Z group and in 83.7% of those in the rVSVΔG-ZEBOV-GP group, as compared with 2.8% of those in the placebo group (P<0.001 for both comparisons). At 12 months, antibody responses in participants in the ChAd3-EBO-Z group (63.5%) and in those in the rVSVΔG-ZEBOV-GP group (79.5%) remained significantly greater than in those in the placebo group (6.8%, P<0.001 for both comparisons). CONCLUSIONS A randomized, placebo-controlled phase 2 trial of two vaccines that was rapidly initiated and completed in Liberia showed the capability of conducting rigorous research during an outbreak. By 1 month after vaccination, the vaccines had elicited immune responses that were largely maintained through 12 months. (Funded by the National Institutes of Allergy and Infectious Diseases and the Liberian Ministry of Health; PREVAIL I ClinicalTrials.gov number, NCT02344407.)

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