Influenza Vaccine
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IMPORTANCE:
Clinical studies have been inconclusive about the effectiveness of N95 respirators and medical masks in preventing health care personnel (HCP) from acquiring workplace viral respiratory infections.
OBJECTIVE:
To compare the effect of N95 respirators vs medical masks for prevention of influenza and other viral respiratory infections among HCP.
DESIGN, SETTING, AND PARTICIPANTS:
A cluster randomized pragmatic effectiveness study conducted at 137 outpatient study sites at 7 US medical centers between September 2011 and May 2015, with final follow-up in June 2016. Each year for 4 years, during the 12-week period of peak viral respiratory illness, pairs of outpatient sites (clusters) within each center were matched and randomly assigned to the N95 respirator or medical mask groups.
INTERVENTIONS:
Overall, 1993 participants in 189 clusters were randomly assigned to wear N95 respirators (2512 HCP-seasons of observation) and 2058 in 191 clusters were randomly assigned to wear medical masks (2668 HCP-seasons) when near patients with respiratory illness.
MAIN OUTCOMES AND MEASURES:
The primary outcome was the incidence of laboratory-confirmed influenza. Secondary outcomes included incidence of acute respiratory illness, laboratory-detected respiratory infections, laboratory-confirmed respiratory illness, and influenzalike illness. Adherence to interventions was assessed.
RESULTS:
Among 2862 randomized participants (mean [SD] age, 43 [11.5] years; 2369 [82.8%]) women), 2371 completed the study and accounted for 5180 HCP-seasons. There were 207 laboratory-confirmed influenza infection events (8.2% of HCP-seasons) in the N95 respirator group and 193 (7.2% of HCP-seasons) in the medical mask group (difference, 1.0%, [95% CI, -0.5% to 2.5%]; P = .18) (adjusted odds ratio [OR], 1.18 [95% CI, 0.95-1.45]). There were 1556 acute respiratory illness events in the respirator group vs 1711 in the mask group (difference, -21.9 per 1000 HCP-seasons [95% CI, -48.2 to 4.4]; P = .10); 679 laboratory-detected respiratory infections in the respirator group vs 745 in the mask group (difference, -8.9 per 1000 HCP-seasons, [95% CI, -33.3 to 15.4]; P = .47); 371 laboratory-confirmed respiratory illness events in the respirator group vs 417 in the mask group (difference, -8.6 per 1000 HCP-seasons [95% CI, -28.2 to 10.9]; P = .39); and 128 influenzalike illness events in the respirator group vs 166 in the mask group (difference, -11.3 per 1000 HCP-seasons [95% CI, -23.8 to 1.3]; P = .08). In the respirator group, 89.4% of participants reported "always" or "sometimes" wearing their assigned devices vs 90.2% in the mask group.
CONCLUSIONS AND RELEVANCE:
Among outpatient health care personnel, N95 respirators vs medical masks as worn by participants in this trial resulted in no significant difference in the incidence of laboratory-confirmed influenza.
TRIAL REGISTRATION:
ClinicalTrials.gov Identifier: NCT01249625.
In vaccinating adults, clinicians face 2 types of challenges: (1) staying current on recommendations for influenza, pneumococcal, hepatitis A and B, zoster, and other vaccines and (2) addressing systemic barriers to implementing practices that increase vaccination rates. Although adult immunization rates remain suboptimal, there has been much good news in adult vaccination recently. New high-dose and adjuvanted influenza vaccines help improve immune response and may reduce influenza complications in older adults. The new recombinant zoster vaccine offers significantly more efficacy against zoster outbreaks and postherpetic neuralgia than zoster vaccine live. Pertussis vaccine given during the third trimester of pregnancy may prevent between 50% and 90% of pertussis infections in infants. Shorter time for completion (1 vs 6 months) of new, adjuvanted hepatitis B vaccine may increase adherence. Clinicians can address systemic barriers to increasing vaccination rates in their clinics and health care systems by following the Centers for Disease Control and Prevention's Standards for Adult Immunization Practice. Clinicians can help increase vaccination rates by writing standing orders and by advocating for nurses or medical assistants to receive training and protected time for assessing and documenting vaccination histories and administration. Strong recommendations that presume acceptance of vaccination are effective with most patients. Communication techniques similar to motivational interviewing can help with vaccine-hesitant patients. Clinicians, as experts on providing preventive services, can educate community leaders about the benefits of immunization and can inform vaccine experts about challenges of implementing vaccination recommendations in clinical practice and strategies that can work to raise vaccination rates.
The US Advisory Committee on Immunization Practices recommends that infants beginning at birth receive several vaccines directed against a variety of infectious diseases that currently pose threats of morbidity and mortality to infants and those around them, including the 3-dose hepatitis B (HepB) series. The first dose is due at birth. This series protects against maternal-infant transmission of the HepB virus and against exposure the rest of the infant's life. At age 2 months infants are to receive not only their second dose of HepB vaccine but also a series of vaccines directed against diphtheria, tetanus, pertussis, pneumococcus, rotavirus, poliovirus, and Haemophilus influenzae type b. At 4 months, infants are to repeat those vaccines except for the HepB vaccine. At age 6 months infants are to finish the HepB series and receive the third doses of the other vaccines received at 2 and 4 months except for the rotavirus vaccine, depending on the brand used. Also, starting at 6 months, depending on the time of year, infants are to begin a 2-dose series against influenza separated by 28 days. Each of these vaccines is due at a time when the vaccine works to protect against an immediate risk and to provide long-term protection. These vaccine-preventable diseases vary in terms of the nature of exposure, the form of the morbidity, the risk of mortality, and the ability of routine vaccination to prevent or ameliorate harm.
BACKGROUND:
Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents.
METHODS:
We conducted two randomized, double-blind, controlled trials involving otherwise healthy outpatients with acute uncomplicated influenza. After a dose-ranging (10 to 40 mg) placebo-controlled trial, we undertook a placebo- and oseltamivir-controlled trial of single, weight-based doses of baloxavir (40 or 80 mg) in patients 12 to 64 years of age during the 2016-2017 season. The dose of oseltamivir was 75 mg twice daily for 5 days. The primary efficacy end point was the time to alleviation of influenza symptoms in the intention-to-treat infected population.
RESULTS:
In the phase 2 trial, the median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter in the baloxavir groups than in the placebo group (P<0.05). In the phase 3 trial, the intention-to-treat infected population included 1064 patients; 84.8 to 88.1% of patients in each group had influenza A(H3N2) infection. The median time to alleviation of symptoms was 53.7 hours (95% confidence interval [CI], 49.5 to 58.5) with baloxavir, as compared with 80.2 hours (95% CI, 72.6 to 87.1) with placebo (P<0.001). The time to alleviation of symptoms was similar with baloxavir and oseltamivir. Baloxavir was associated with greater reductions in viral load 1 day after initiation of the regimen than placebo or oseltamivir. Adverse events were reported in 20.7% of baloxavir recipients, 24.6% of placebo recipients, and 24.8% of oseltamivir recipients. The emergence of polymerase acidic protein variants with I38T/M/F substitutions conferring reduced susceptibility to baloxavir occurred in 2.2% and 9.7% of baloxavir recipients in the phase 2 trial and phase 3 trial, respectively.
CONCLUSIONS:
Single-dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza. Evidence for the development of decreased susceptibility to baloxavir after treatment was also observed. (Funded by Shionogi; JapicCTI number, 153090, and CAPSTONE-1 ClinicalTrials.gov number, NCT02954354 .).