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Mask ventilation and coughing during oro-tracheal suctioning produce aerosols that enhance nosocomial transmission of respiratory infections. We examined the extent of exhaled air dispersion from a human-patient-simulator during mask ventilation by different groups of healthcare workers and coughing bouts. The simulator was programmed to mimic varying severity of lung injury. Exhaled airflow was marked with tiny smoke particles, and highlighted by laser light-sheet. We determined the normalized exhaled air concentration in the leakage jet plume from the light scattered by smoke particles. Smoke concentration ≥20% was considered as significant exposure. Exhaled air leaked from mask-face interface in the transverse plane was most severe (267 ± 44 mm) with Ambu silicone resuscitator performed by nurses. Dispersion was however similar among anesthesiologists/intensivists, respiratory physicians and medical students using Ambu or Laerdal silicone resuscitator, p = 0.974. The largest dispersion was 860 ± 93 mm during normal coughing effort without tracheal intubation and decreased with worsening coughing efforts. Oro-tracheal suctioning reduced dispersion significantly, p < 0.001, and was more effective when applied continuously. Skills to ensure good fit during mask ventilation are important in preventing air leakage through the mask-face interface. Continuous oro-tracheal suctioning minimized exhaled air dispersion during coughing bouts when performing aerosol-generating procedures.

Mask ventilation and coughing during oro-tracheal suctioning produce aerosols that enhance nosocomial transmission of respiratory infections. We examined the extent of exhaled air dispersion from a human-patient-simulator during mask ventilation by different groups of healthcare workers and coughing bouts. The simulator was programmed to mimic varying severity of lung injury. Exhaled airflow was marked with tiny smoke particles, and highlighted by laser light-sheet. We determined the normalized exhaled air concentration in the leakage jet plume from the light scattered by smoke particles. Smoke concentration ≥20% was considered as significant exposure. Exhaled air leaked from mask-face interface in the transverse plane was most severe (267 ± 44 mm) with Ambu silicone resuscitator performed by nurses. Dispersion was however similar among anesthesiologists/intensivists, respiratory physicians and medical students using Ambu or Laerdal silicone resuscitator, p = 0.974. The largest dispersion was 860 ± 93 mm during normal coughing effort without tracheal intubation and decreased with worsening coughing efforts. Oro-tracheal suctioning reduced dispersion significantly, p < 0.001, and was more effective when applied continuously. Skills to ensure good fit during mask ventilation are important in preventing air leakage through the mask-face interface. Continuous oro-tracheal suctioning minimized exhaled air dispersion during coughing bouts when performing aerosol-generating procedures.

A successful vaccine development strategy for areas with clustered H5N1 events requires conduct of vaccine trials in potentially non-naïve subjects and evaluation of post-vaccination responsiveness. An open-label, randomized, phase I/II study therefore assessed the immunogenicity and safety of two different dose levels of an inactivated, non-adjuvanted, whole virus clade 2.1 (A/Indonesia/05/2005) H5N1 Vero cell-derived influenza vaccine in healthy adults (21-45 years) from a region where the virus has been circulating (Hong Kong) as well as Singapore. Subjects (N=110) were randomized 1:1 to receive two vaccinations with either 3.75 μg or 7.5 μg H5N1 haemagglutinin antigen 21 days apart. Safety, immunogenicity (microneutralization [MN] and single radial haemolysis [SRH] at baseline and post-vaccination) and cross-reactivity against a heterologous clade 1 strain (A/Vietnam/1203/2004) of the vaccine were assessed. Pre-existing immunity to the vaccine strain was 14% which is higher than previously reported for these regions. Two vaccinations with either vaccine formulation induced high seroprotection rates (MN titre ≥ 1:20) against the vaccine strain A/Indonesia/05/2005: 82.7% and 86.5% in the 3.75 μg and 7.5 μg dose groups. Seroconversion rates and fold increase exceeded the CPMP criterion of >40% and >2.5 for MN and SRH in both dose groups after the second vaccination, while the seroprotection rate in the 7.5 μg dose group determined by SRH was only marginally lower (69.2%) than the CPMP criterion of >70%. Thus, 11 of 12 CHMP criteria were fulfilled. A cross-reactive antibody response against the heterologous A/Vietnam/1203/2004 strain was demonstrated after the second vaccination (>21% by MN and ≥ 25% by SRH). Persistence of antibodies against the vaccine strain was also demonstrated 6 months after the first vaccination, indicating that a booster vaccination would be effective in those who have received two priming doses. No serious adverse events were re

BackgroundThe effect of corticosteroid treatment on the viral load of Severe Acute Respiratory Syndrome (SARS) patients is unknown.ObjectiveTo compare the plasma SARS-CoV RNA concentrations in ribavirin-treated patients who received early hydrocortisone therapy with those who received placebo.Study designSerial plasma SARS-CoV RNA concentrations measured in the setting of a prospective, randomized double-blinded, placebo-controlled trial designed to assess the efficacy of "early" (<7 days of illness) hydrocortisone use in previously healthy SARS patients were analyzed. SARS-CoV RNA was quantified using a one-step real-time RT-PCR assay targeting the nucleocapsid gene.ResultsAmong 16 non-ICU cases, SARS-CoV RNA was detected in plasma since day 3-4 after fever onset; viral concentration peaked in the first week, which then rapidly declined in the second week of illness. On days 8, 12, 16, and 20, the cumulative proportion of patients with undetectable virus in plasma was 31%, 69%, 92%, and 100%, respectively. Plasma SARS-CoV RNA concentrations in the second and third week of illness were significantly higher in patients who received initial hydrocortisone treatment (n = 9), as compared to those who received placebo (n = 7)(AUC; Mann-Whitney, P = 0.023). The median time for SARS-CoV to become undetectable in plasma was 12 days (11-20 days) versus 8 days (8-15 days), respectively.ConclusionOur findings suggested "early" corticosteroid treatment was associated with a higher subsequent plasma viral load.

BackgroundThe effect of corticosteroid treatment on the viral load of Severe Acute Respiratory Syndrome (SARS) patients is unknown.ObjectiveTo compare the plasma SARS-CoV RNA concentrations in ribavirin-treated patients who received early hydrocortisone therapy with those who received placebo.Study designSerial plasma SARS-CoV RNA concentrations measured in the setting of a prospective, randomized double-blinded, placebo-controlled trial designed to assess the efficacy of "early" (<7 days of illness) hydrocortisone use in previously healthy SARS patients were analyzed. SARS-CoV RNA was quantified using a one-step real-time RT-PCR assay targeting the nucleocapsid gene.ResultsAmong 16 non-ICU cases, SARS-CoV RNA was detected in plasma since day 3-4 after fever onset; viral concentration peaked in the first week, which then rapidly declined in the second week of illness. On days 8, 12, 16, and 20, the cumulative proportion of patients with undetectable virus in plasma was 31%, 69%, 92%, and 100%, respectively. Plasma SARS-CoV RNA concentrations in the second and third week of illness were significantly higher in patients who received initial hydrocortisone treatment (n = 9), as compared to those who received placebo (n = 7)(AUC; Mann-Whitney, P = 0.023). The median time for SARS-CoV to become undetectable in plasma was 12 days (11-20 days) versus 8 days (8-15 days), respectively.ConclusionOur findings suggested "early" corticosteroid treatment was associated with a higher subsequent plasma viral load.

Nearly two years since the start of the SARS-CoV-2 pandemic, which has caused over 5 million deaths, the world continues to be on high COVID-19 alert. The World Health Organization (WHO), in collaboration with national authorities, public health institutions and scientists have been closely monitoring and assessing the evolution of SARS-CoV-2 since January 2020 (WHO 2021a; WHO 2021b). The emergence of specific SARS-CoV-2 variants were characterised as Variant of Interest (VOI) and Variant of Concern (VOC), to prioritise global monitoring and research, and to inform the ongoing global response to the COVID-19 pandemic. The WHO and its international sequencing networks continuously monitor SARS-CoV-2 mutations and inform countries about any changes that may be needed to respond to the variant, and prevent its spread where feasible. Multiple variants of the virus have emerged and become dominant in many countries since January 2021, with the Alpha, Beta, Gamma and Delta variants being the most prominent to date. (Table 1).

The emergence and spread of antimicrobial-resistant bacterial, viral, and fungal pathogens for which diminishing treatment options are available is of major global concern. New viral respiratory tract infections with epidemic potential, such as severe acute respiratory syndrome, swine-origin influenza A H1N1, and Middle East respiratory syndrome coronavirus infection, require development of new antiviral agents. The substantial rise in the global numbers of patients with respiratory tract infections caused by pan-antibiotic-resistant Gram-positive and Gram-negative bacteria, multidrug-resistant Mycobacterium tuberculosis, and multiazole-resistant fungi has focused attention on investments into development of new drugs and treatment regimens. Successful treatment outcomes for patients with respiratory tract infections across all health-care settings will necessitate rapid, precise diagnosis and more effective and pathogen-specific therapies. This Series paper describes the development and use of new antimicrobial agents and immune-based and host-directed therapies for a range of conventional and emerging viral, bacterial, and fungal causes of respiratory tract infections.