Leon Heron

Immunogenicity of a Monovalent 2009 Influenza A(H1N1) Vaccine in Infants and Children: A Randomized Trial

CONTEXT In the ongoing influenza pandemic, a safe and effective vaccine against 2009 influenza A(H1N1) is needed for infants and children. OBJECTIVE To assess the immunogenicity and safety of a 2009 influenza A(H1N1) vaccine in children. DESIGN, SETTING, AND PARTICIPANTS Randomized, observer-blind, age-stratified, parallel group study assessing 2 doses of an inactivated, split-virus 2009 influenza A(H1N1) vaccine in 370 healthy infants and children aged 6 months to less than 9 years living in Australia. INTERVENTION Intramuscular injection of 15 microg or 30 microg of hemagglutinin antigen dose of monovalent, unadjuvanted 2009 influenza A(H1N1) vaccine in a 2-dose regimen, administered 21 days apart. MAIN OUTCOME MEASURES Hemagglutination inhibition assay to estimate the proportion of participants with antibody titers of 1:40 or greater, seroconversion, or a significant antibody titer increase, and factor increase in geometric mean titer. Assessments of solicited adverse events during 7 days and unsolicited adverse events for 21 days after each vaccination. RESULTS Following the first dose of vaccine, antibody titers of 1:40 or greater were observed in 161 of 174 infants and children in the 15-microg group (92.5%; 95% confidence interval [CI], 87.6%-95.6%) and in 168 of 172 infants and children in the 30-microg group (97.7%; 95% CI, 94.2%-99.1%). Corresponding seroconversion rates were 86.8% (95% CI, 80.9%-91.0%) and 94.2% (95% CI, 89.6%-96.8%), and factor increases in geometric mean titer were 13.6 (95% CI, 11.8-15.6) and 18.3 (95% CI, 15.7-21.4). All participants demonstrated antibody titers of 1:40 or greater after the second vaccine dose. Immune responses were robust regardless of age, baseline serostatus, or seasonal influenza vaccination status. The majority of adverse events were mild to moderate in severity. CONCLUSION One 15-microg dose of vaccine was immunogenic in infants and children starting at 6 months of age and vaccine-associated reactions were mild to moderate in severity. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00940108.

Norovirus Excretion in an Aged-Care Setting

ABSTRACT Norovirus genogroup II excretion during an outbreak of gastroenteritis was investigated in an aged-care facility. Viral shedding peaked in the acute stage of illness and continued for an average of 28.7 days. The viral decay rate was 0.76 per day, which corresponds to a viral half-life of 2.5 days.

Systematic review of clinical and epidemiological features of the pandemic influenza A (H1N1) 2009.

Please cite this paper as: Khandaker et al. (2011) Systematic review of clinical and epidemiological features of the pandemic influenza A (H1N1) 2009. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2011.00199.x.

Immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccine: systematic review and meta-analysis

Please cite this paper as: Yin et al. (2011) Immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccine: systematic review and meta‐analysis. Influenza and Other Respiratory Viruses 5(5), 299–305.

Impacts on influenza A(H1N1)pdm09 infection from cross-protection of seasonal trivalent influenza vaccines and A(H1N1)pdm09 vaccines: systematic review and meta-analyses.

Cross-protection by seasonal trivalent influenza vaccines (TIVs) against pandemic influenza A H1N1 2009 (now known as A[H1N1]pdm09) infection is controversial; and the vaccine effectiveness (VE) of A(H1N1)pdm09 vaccines has important health-policy implications. Systematic reviews and meta-analyses are needed to assess the impacts of both seasonal TIVs and A(H1N1)pdm09 vaccines against A(H1N1)pdm09.We did a systematic literature search to identify observational and/or interventional studies reporting cross-protection of TIV and A(H1N1)pdm09 VE from when the pandemic started (2009) until July 2011. The studies fulfilling inclusion criteria were meta-analysed. For cross-protection and VE, respectively, we stratified by vaccine type, study design and endpoint. Seventeen studies (104,781 subjects) and 10 studies (2,906,860 subjects), respectively, reported cross-protection of seasonal TIV and VE of A(H1N1)pdm09 vaccines; six studies (17,229 subjects) reported on both. Thirteen studies (95,903 subjects) of cross-protection, eight studies (859,461 subjects) of VE, and five studies (9,643 subjects) of both were meta-analysed and revealed: (1) cross-protection for confirmed illness was 19% (95% confident interval=13-42%) based on 13 case-control studies with notable heterogeneity. A higher cross-protection of 34% (9-52%) was found in sensitivity analysis (excluding five studies with moderate/high risk of bias). Further exclusion of studies that recruited early in the pandemic (when non-recipients of TIV were more likely to have had non-pandemic influenza infection that may have been cross-protective) dramatically reduced heterogeneity. One RCT reported cross-protection of 38% (19-53%) for confirmed illness. One case-control study reported cross-protection of 50% (40-59%) against hospitalisation. (2) VE of A(H1N1)pdm09 for confirmed illness was 86% (73-93%) based on 11 case-control studies and 79% (22-94%) based on two cohort studies; VE against medically-attended ILI was 32% (8-50%) in one cohort study. TIVs provided moderate cross-protection against both laboratory-confirmed A(H1N1)pdm09 illness (based on eight case-control studies with low risk of bias and one RCT) and also hospitalisation. A finding of increased risk from seasonal vaccine was limited to cases recruited early in the pandemic. A(H1N1)pdm09 vaccines were highly effective against confirmed A(H1N1)pdm09 illness. Although cross-protection was less than the direct effect of strain-specific vaccination against A(H1N1)pdm09, TIV was generally beneficial before A(H1N1)pdm09 vaccine was available.

Neurologic complications of influenza A(H1N1)pdm09 Surveillance in 6 pediatric hospitals

Objective: We sought to determine the range and extent of neurologic complications due to pandemic influenza A (H1N1) 2009 infection (pH1N1′09) in children hospitalized with influenza. Methods: Active hospital-based surveillance in 6 Australian tertiary pediatric referral centers between June 1 and September 30, 2009, for children aged <15 years with laboratory-confirmed pH1N1′09. Results: A total of 506 children with pH1N1′09 were hospitalized, of whom 49 (9.7%) had neurologic complications; median age 4.8 years (range 0.5–12.6 years) compared with 3.7 years (0.01–14.9 years) in those without complications. Approximately one-half (55.1%) of the children with neurologic complications had preexisting medical conditions, and 42.8% had preexisting neurologic conditions. On presentation, only 36.7% had the triad of cough, fever, and coryza/runny nose, whereas 38.7% had only 1 or no respiratory symptoms. Seizure was the most common neurologic complication (7.5%). Others included encephalitis/encephalopathy (1.4%), confusion/disorientation (1.0%), loss of consciousness (1.0%), and paralysis/Guillain-Barré syndrome (0.4%). A total of 30.6% needed intensive care unit (ICU) admission, 24.5% required mechanical ventilation, and 2 (4.1%) died. The mean length of stay in hospital was 6.5 days (median 3 days) and mean ICU stay was 4.4 days (median 1.5 days). Conclusions: Neurologic complications are relatively common among children admitted with influenza, and can be life-threatening. The lack of specific treatment for influenza-related neurologic complications underlines the importance of early diagnosis, use of antivirals, and universal influenza vaccination in children. Clinicians should consider influenza in children with neurologic symptoms even with a paucity of respiratory symptoms.

Viral respiratory infections among Hajj pilgrims in 2013

Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged in the Arabian Gulf region, with its epicentre in Saudi Arabia, the host of the ‘Hajj’ which is the world’s the largest mass gathering. Transmission of MERS-CoV at such an event could lead to its rapid worldwide dissemination. Therefore, we studied the frequency of viruses causing influenza-like illnesses (ILI) among participants in a randomised controlled trial at the Hajj 2013. We recruited 1038 pilgrims from Saudi Arabia, Australia and Qatar during the first day of Hajj and followed them closely for four days. A nasal swab was collected from each pilgrim who developed ILI. Respiratory viruses were detected using multiplex RT-PCR. ILI occurred in 112/1038 (11%) pilgrims. Their mean age was 35 years, 49 (44%) were male and 35 (31%) had received the influenza vaccine pre-Hajj. Forty two (38%) pilgrims had laboratory-confirmed viral infections; 28 (25%) rhinovirus, 5 (4%) influenza A, 2 (2%) adenovirus, 2 (2%) human coronavirus OC43/229E, 2 (2%) parainfluenza virus 3, 1 (1%) parainfluenza virus 1, and 2 (2%) dual infections. No MERS-CoV was detected in any sample. Rhinovirus was the commonest cause of ILI among Hajj pilgrims in 2013. Infection control and appropriate vaccination are necessary to prevent transmission of respiratory viruses at Hajj and other mass gatherings.

Estimates and determinants of economic impacts from influenza-like illnesses caused by respiratory viruses in Australian children attending childcare: a cohort study.

Influenza and other respiratory infections cause excess winter morbidity in children. This study assessed the economic impact of influenza‐like illness (ILI) on families with children attending childcare using a societal perspective.

Changes in the prevalence of influenza-like illness and influenza vaccine uptake among Hajj pilgrims: A 10-year retrospective analysis of data.

BACKGROUND Influenza is an important health hazard among Hajj pilgrims. For the last ten years, pilgrims are being recommended to take influenza vaccine before attending Hajj. Vaccination coverage has increased in recent years, but whether there has been any change in the prevalence of influenza-like illness (ILI) is not known. In this analysis, we examined the changes in the rate of ILI against seasonal influenza vaccine uptake among Hajj pilgrims over the last decade. METHOD Data for this analysis is a synthesis of raw and published data from eleven Hajj seasons between 2005 and 214. For seven Hajj seasons the data were obtained from studies involving pilgrims of UK, Saudi Arabia and Australia; and for the remaining four Hajj seasons data were abstracted from published studies involving pilgrims from multiple countries. The data from both sources were synthesised to estimate the relative risk (RR) of acquisition of ILI in vaccinated versus unvaccinated pilgrims. RESULTS The pooled sample size of the included studies was 33,213 with most pilgrims being in the age band of 40-60 years (range: 0.5 to 95 years) and a male to female ratio of 1.6. The pilgrims originated, in order of frequency, from Iran, Australia, France, UK, Saudi Arabia, Indonesia, India, Algeria, Ivory Coast, Nigeria, Somalia, Turkey, Syria, Sierra Leone and USA. Except for one year (2008), data from individual years did not demonstrate a noticeable change in the rate of ILI against influenza vaccine coverage, however the combined data from all studies suggest that the prevalence of ILI decreased among Hajj pilgrims as the vaccine coverage increased over the last decade (RR 0.2, P<0.01). CONCLUSION This analysis suggests that influenza vaccine might be beneficial for Hajj pilgrims. However, controlled trials aided by molecular diagnostic tools could confirm whether such an effect is real or ostensible.

Knowledge, attitude and practice (KAP) survey concerning antimicrobial use among Australian Hajj pilgrims

Resistance to antimicrobial agents has increased for reasons relating to the use and misuse of antimicrobials in human, agriculture and aquaculture. Antimicrobial use is quite high during mass gatherings such as the Hajj pilgrimage. To reduce non-prescription use and inappropriate prescribing of antimicrobials, a more thorough understanding of their use and the motives behind why patients request, even demand, antimicrobials, fail to adhere to the prescription is important. Therefore, we conducted a knowledge, attitude and practice (KAP) survey among Australian Hajj pilgrims in Mecca during Hajj 2013 using an anonymous, self-administered questionnaire concerning antimicrobial use. Our sample consisted of 229 adult Australian subjects. Mean age was 42.4 (SD±12.7) years, 178 (77.9%) were male and 80 (34.9%) used antimicrobials during their stay in Saudi Arabia. Twenty one (26.3%) obtained these in Saudi Arabia without prescription, and about half (38, 47.5%) brought them from Australia. Of the respondents, 55.8% believed that antibiotics are effective against viruses, 53.6% thought that antibiotics are effective against common cold and flu, 78.6 % that humans themselves can become resistant to antibiotics and 75.9% knew that overuse or unnecessary use of antibiotics can cause them to lose effectiveness. This study has revealed that Hajj pilgrims have inappropriate access to antimicrobials in Saudi Arabia as well as in Australia. A large scale education campaign and tighter control on prescribing and dispensing of antimicrobials could improve the appropriate antimicrobial use among Hajj pilgrims.