Influenza vaccine efficacy in young children attending childcare: A randomised controlled trial.

AIM: Influenza causes a substantial burden in young children. Vaccine efficacy (VE) data are limited in this age group. We examined trivalent influenza vaccine (TIV) efficacy and safety in young children attending childcare. METHODS: A double-blind, randomised controlled trial in children aged 6 to <48 months was conducted with recruitment from Sydney childcare centres in 2011. Children were randomised to receive two doses of TIV or control hepatitis A vaccine. Efficacy was evaluated against polymerase chain reaction-confirmed influenza using parent-collected nose/throat swabs during influenza-like-illness. Safety outcomes were assessed during 6 months of follow-up. RESULTS: Fifty-seven children were allocated to influenza vaccine and 67 to control; all completed the study. The influenza attack rate was 1.8 vs 13.4% in the TIV and control groups, respectively; VE 87% (95%CI: 0-98%). For children aged 24 to <48 months, 0 vs 8 (18.6%) influenza infections occurred in the TIV and control groups respectively, giving a VE of 100% (16-100%). Efficacy was not shown in children 6 to <24 months, probably due to insufficient power. Injection site and systemic adverse events were mostly mild to moderate with no significant differences, apart from more mild diarrhoea following dose 2 in TIV recipients (11.8 vs 0%). CONCLUSIONS: Influenza vaccine appeared efficacious in the subgroup of children aged 24 to <48 months, although caution is required due to the small number of participants. There were no serious adverse events and most parents would vaccinate again. Influenza vaccination in a childcare setting could be valuable and a larger confirmatory study would be helpful.

Australian vaccine preventable disease epidemiological review series: Influenza 2006 to 2015.

INTRODUCTION: Influenza is a major contributor to the preventable health burden of Australians each year. The National Immunisation Program provides influenza vaccine for those at highest risk of severe disease. This review of influenza epidemiology examines current data on influenza disease burden in Australia, in the context of several comparable countries having programs with much broader eligibility for influenza vaccine in children. METHODS: Influenza notifications (2006-2015), hospitalisations, and deaths (2006-2013) were sourced and age-specific rates calculated. Comparisons were made across age groups in the pre-pandemic, pandemic, and post-pandemic periods and by Indigenous and non-Indigenous status. RESULTS: The 2009 pandemic year and the 2012 non-pandemic season resulted in the highest rates of notification, hospitalisation and death. Influenza notification rates were 4.0 times higher and hospitalisation rates 2.1 times higher during 2011-2013 compared with 2006-2008. Death rates varied widely, but peaks corresponded to high-activity seasons. Influenza hospitalisation rates were highest among those aged <5 and ≥65 years, but influenza-attributable deaths were identified primarily in those aged ≥75 years. Significantly higher notification and hospitalisation rates were seen for all Indigenous people, but higher death rates were largely restricted to the 2009 pandemic year. CONCLUSIONS: Based on notifications, hospitalisations and deaths, burden of disease from influenza is highest at the extremes of life and is significantly higher among Indigenous people of all ages. This pattern of disease burden warrants consideration of widened eligibility for influenza vaccine under the National Immunisation Program to all Indigenous people and all children less than 5 years of age.

Quality of life for parents of children with influenza-like illness: development and validation of Care-ILI-QoL.

PURPOSE: Influenza-like illnesses (ILI) cause paediatric morbidity and affect the quality of life (QoL) of children and their parents. We have developed a disease-specific questionnaire (Care-ILI-QoL) to measure the QoL of caregivers of children with ILI. METHODS: The drafting of the Care-ILI-QoL questionnaire was based on a systematic review, a quantitative survey, qualitative interviews with parents, and meetings with paediatricians. Children aged 6-48 months recruited from childcare centres in Sydney, Australia, were followed up during the 2011 influenza season. Care-ILI-QoL and SF-12v2 Acute Form were administered to the parent of a sick child 2 weeks after the onset of ILI, and again 2 weeks after the child had recovered. Exploratory factor analysis was conducted. Internal consistency, concurrent validity, discriminant validity, homogeneity of items, and responsiveness were tested. RESULTS: Out of the 125 children enrolled from 48 childcare centres, 55 children had ILI (total 75 ILI episodes). Care-ILI-QoL was reduced from 25 to 16 items covering four factors: Daily Activities, Perceived Support, Social Life, and Emotions (Cronbach's alphas 0.90, 0.92, 0.78, and 0.72, respectively). Care-ILI-QoL has satisfactory concurrent and discriminant validity, good internal consistency, and excellent responsiveness. Total QoL and factor scores correlated well with SF-12v2 scores. Total QoL scores were significantly lower in parents who perceived their child as very/extremely sick, sacrificed 10 hours or more in work or recreation in caring for the child, or whose child had two or more general practitioner visits. Total QoL and factor scores were significantly higher after the child had recovered than when the child had ILI. CONCLUSIONS: Care-ILI-QoL is the first ILI-specific QoL instrument for parents and is demonstrated to be valid and reliable in a developed country setting where the child is affected by ILI. It has the potential to be applied in clinical and research settings to assist measurement of disease burden, as a needs assessment tool for resources or to inform policy changes.

The impact of influenza-like illness in young children on their parents: a quality of life survey.

BACKGROUND: Influenza-like illness can cause excess paediatric morbidity and burden on parents. OBJECTIVES: We determined the quality of life (QoL) impact of children's influenza-like illness (ILI) on their parents. METHODS: We conducted a prospective cohort study in childcare centres and a general practice in Sydney, Australia. Using PAR-ENT-QoL, we measured QoL of parents of children aged 6 months-3 years before the 2010 influenza season, then again for parents of children with ILI (ILI group) using SF-12v2 Acute Form and PAR-ENT-QoL, and contemporaneously for parents of aged-matched children without ILI (non-ILI group). RESULTS: Of 381 children enrolled from 90 childcare centres, 105 developed ILI. PAR-ENT-QoL scores of the ILI group were significantly lower in the post-ILI follow-up interviews than at baseline (60.99 vs. 79.77, p < 0.001), and those of non-ILI group at follow-up interviews (60.99 vs. 84.05, p < 0.001). SF-12v2 scores of the ILI group were also significantly lower than those of non-ILI group: physical component summary (50.66 vs. 53.16, p = 0.011) and mental component summary (45.67 vs. 53.66, p < 0.001). Two factors were significantly associated with parental QoL: total time spent caring child during ILI and whether the child had severe ILI or not. Correlations between PAR-ENT-QoL and SF-12v2 scores were satisfactory. CONCLUSIONS: Parents had significantly lower QoL while their child had ILI, compared with before ILI and with parents of children without ILI. The public health impact of ILI in children on the QoL in families is far from negligible. QoL measurement can complement economic evaluation of ILI disease burden and provide a more complete picture of impact.

New insights into microbial and metabolite signatures of coral bleaching.

Coral bleaching and coral reef degradation have been severely increased due to anthropogenic impacts, especially global warming. Studies have indicated the key role of host-microbiome symbiotic relationships for the coral holobiont health and development, although not all of the mechanisms of interaction have been fully explored. Here, we explore bacterial and metabolic shifts within coral holobionts under thermal stress, and its correlation with bleaching. Our results showed obvious signs of coral bleaching after 13 days of heating treatment, and a more-complex co-occurrence network was observed in the coral-associated bacterial community of the heating group. The bacterial community and metabolites changed significantly under thermal stress, and genera Flavobacterium, Shewanella and Psychrobacter increased from <0.1 % to 43.58 %, 6.95 % and 6.35 %, respectively. Bacteria potentially associated with stress tolerance, biofilm formation and mobile elements decreased from 80.93 %, 62.15 % and 49.27 % to 56.28 %, 28.41 % and 18.76 %, respectively. The differentially expressed metabolites of corals after heating treatment, such as Cer(d18:0/17:0), 1-Methyladenosine, Trp-P-1 and Marasmal, were associated with cell cycle regulation and antioxidant properties. Our results can contribute to our current understanding on the correlations between coral-symbiotic bacteria, metabolites and the coral physiological response to thermal stress. These new insights into the metabolomics of heat-stressed coral holobionts may expand our knowledge on the mechanisms underlying bleaching.

Cross-reacting antibodies against the pandemic (H1N1) 2009 influenza virus in older Australians.

OBJECTIVE: To assess background pre-pandemic cross-reacting antibodies to the pandemic (H1N1) 2009 virus in older populations in Australia. DESIGN, SETTING AND PARTICIPANTS: Data were opportunistically generated from three cross-sectional pre-pandemic studies involving people aged 60 years or older: a 3-year (2006-2008) study of influenza outbreaks in aged care facilities (ACFs) in Sydney; an investigation of a respiratory virus outbreak in an ACF in rural New South Wales in June 2009; and a non-influenza serosurvey undertaken in NSW in 2007 and 2008. MAIN OUTCOME MEASURE: Prevalence of pandemic (H1N1) 2009 haemagglutination inhibition (HAI) antibody titres ≥ 1:40 (putative protective level) in pre-pandemic sera. RESULTS: In total, 259 serum samples from individuals aged 60 years or older (range, 60-101 years) were tested. More than half of the individuals tested were women (151/259; 58.3%). About a third of individuals (37.5%) had cross-reacting HAI antibody titres ≥ 1:40. The prevalence of cross-reacting antibodies was highest in the oldest age groups (≥ 85 years), with more than 60% of these people having HAI antibody titres ≥ 1:40. The proportion of subjects with HAI antibody titres ≥ 1:40 decreased significantly and successively in younger groups to only 12% of those aged 60-64 years. CONCLUSIONS: Our study suggests a pre-existing influenza A antibody reserve in most of the oldest group of people that was cross-reactive to the new pandemic (H1N1) 2009 virus; this is likely to be lifelong and to have provided them with clinical protection against the first wave of the pandemic. Pandemic influenza control measures need to focus more on younger adults naive to the pandemic virus and at increased risk of severe disease.

Complete mitochondrial genome of the jellyfish, Chrysaora pacifica (Goette, 1886) (Cnidaria, Scyphozoa) and the phylogenetic relationship in the related species.

The complete mitochondrial genome sequences of giant jellyfish Chrysaora pacifica, a scyphozoan species inhabiting the Bohai Sea water in China, is firstly described and analyzed in this research. The mitogenome is a circular molecule 16,964 bp in length, including 13 protein-coding genes (Cox 1, Cox2, Atp 8, Atp 6, Cox 3, ND2, ND5, ND 6, ND3, ND4L,ND1,ND4, Cob), 2 tRNAs (trnW, trnM), 2 rRNA genes (small subunit RNA and large subunit RNA). The neighbor-joining (NJ) phylogenetic tree in the related species showed that C. pacifica is close to Chrysaora quinquecirrha.

Morphology and phylogeny of two Phialina species (Ciliophora, Haptoria) from northern China.

The morphology and infraciliature of two haptorian ciliates, Phialina clampi nov. spec. and P. caudata (Kahl, 1933) nov. comb. (original combination: Lacrymaria caudataKahl, 1933), isolated from sandy sediments of an estuary in Yantai, northern China, were investigated using live observations and protargol preparations. Phialina clampi nov. spec. is distinguished from its congeners by the following traits: extended cells about 80-300 × 18-50 µm in vivo; a single oval-shaped macronucleus; caudally located contractile vacuole; two types of extrusomes: type I about 20-35 × 1-4 µm in size, type II 1.5-3.0 × 0.7-1.0 µm in size and attached to somatic cortex; 27-31 somatic kineties. Phialina caudata is characterized as follows: extended cells about 80-170 × 20-45 µm in vivo; body radish-shaped, with a sharp posterior end; a single globular to oval macronucleus and micronucleus; subterminal contractile vacuole; 20-24 somatic kineties. Phylogenetic analyses based on SSU rRNA gene sequences indicate that P. caudata clusters with an unidentified Phialina before grouping with Phialina clampi, which form a basal clade of the family Lacrymariidae.

Assessing Interventions To Improve Influenza Vaccine Uptake Among Health Care Workers.

Despite official recommendations for health care workers to receive the influenza vaccine, uptake remains low. This systematic review of randomized controlled trials was conducted to understand the evidence about interventions to improve influenza vaccine uptake among health care workers. We identified twelve randomized controlled trials that, collectively, assessed six major categories of interventions involving 193,924 health care workers in high-income countries. The categories were educational materials and training sessions, improved access to the vaccine, rewards following vaccination, organized efforts to raise vaccine awareness, reminders to get vaccinated, and the use of lead advocates for vaccination. Only one of the four studies that evaluated the effect of a single intervention in isolation demonstrated a significantly higher vaccine uptake rate in the intervention group, compared to controls. However, five of the eight studies that evaluated a combination of strategies showed significantly higher vaccine uptake. Despite the low quality of the studies identified, the data suggest that combined interventions can moderately increase vaccine uptake among health care workers. Further methodologically appropriate trials of combined interventions tailored to individual health care settings and incorporating less-studied strategies would enhance the evidence about interventions to improve immunization uptake among health care workers.

Cost of management of severe pneumonia in young children: systematic analysis.

BACKGROUND: Childhood pneumonia is a major cause of childhood illness and the second leading cause of child death globally. Understanding the costs associated with the management of childhood pneumonia is essential for resource allocation and priority setting for child health. METHODS: We conducted a systematic review to identify studies reporting data on the cost of management of pneumonia in children younger than 5 years old. We collected unpublished cost data on non-severe, severe and very severe pneumonia through collaboration with an international working group. We extracted data on cost per episode, duration of hospital stay and unit cost of interventions for the management of pneumonia. The mean (95% confidence interval, CI) and median (interquartile range, IQR) treatment costs were estimated and reported where appropriate. RESULTS: We identified 24 published studies eligible for inclusion and supplemented these with data from 10 unpublished studies. The 34 studies included in the cost analysis contained data on more than 95 000 children with pneumonia from both low- and-middle income countries (LMIC) and high-income countries (HIC) covering all 6 WHO regions. The total cost (per episode) for management of severe pneumonia was US$ 4.3 (95% CI 1.5-8.7), US$ 51.7 (95% CI 17.4-91.0) and US$ 242.7 (95% CI 153.6-341.4)-559.4 (95% CI 268.9-886.3) in community, out-patient facilities and different levels of hospital in-patient settings in LMIC. Direct medical cost for severe pneumonia in hospital inpatient settings was estimated to be 26.6%-115.8% of patients' monthly household income in LMIC. The mean direct non-medical cost and indirect cost for severe pneumonia management accounted for 0.5-31% of weekly household income. The mean length of stay (LOS) in hospital for children with severe pneumonia was 5.8 (IQR 5.3-6.4) and 7.7 (IQR 5.5-9.9) days in LMIC and HIC respectively for these children. CONCLUSION: This is the most comprehensive review to date of cost data from studies on the management of childhood pneumonia and these data should be helpful for health services planning and priority setting by national programmes and international agencies.

The threat of human influenza: the viruses, disease impacts, and vaccine solutions.

Influenza is an acute respiratory illness that remains an important cause of excessive morbidity and mortality with substantial economic cost to the population. Influenza, being a virus that frequently mutates, is not amenable to elimination. Vaccination remains the most effective preventive measure. This review summarises the latest developments in the fields of biology and epidemiology relating to clinical and economic impacts of influenza disease, and vaccination. We suggest that future efforts should focus on developing safer, more effective, and cost-effective prophylactic vaccines for influenza.

Vaccination of Older Adults with Dementia Against Respiratory Infections.

People with dementia are at a greater risk of complications from respiratory infections therefore can benefit from vaccinations against influenza, pneumococcal disease and pertussis. This review aimed to evaluate the uptake and impact of vaccination in older adults with dementia against respiratory infections and identify knowledge gaps. Key databases were explored, search results were assessed, relevant studies identified, and data were synthesised and summarised. Most available data suggest that older adults with dementia are less likely to receive influenza or pneumococcal vaccine while a few studies indicate an increase in vaccination uptake but poor immunogenicity. Among dementia patients, community dwellers have a lower vaccination rate than home care residents. However, vaccinations against influenza and pneumococcal disease can benefit individuals with dementia by reducing both mortality and morbidity. Health professionals caring for patients with dementia could play a role in fostering vaccination of these individuals.

Epidemiology of respiratory viral infections in children enrolled in a study of influenza vaccine effectiveness.

BACKGROUND: Influenza-like illness (ILI) confers a high annual morbidity in young children. We report the epidemiology of ILIs in children who participated in an influenza vaccine effectiveness study during the 2010 Southern Hemisphere influenza season in Sydney, Australia. METHODS: Children aged 0·5-3 years were prospectively recruited from child care centres (CCCs). We classified them as fully vaccinated, partially vaccinated and unvaccinated according to their receipt of unadjuvanted vaccines containing influenza A (H1N1)pdm09. For 13 weeks commencing 30 July 2010, parents reported when their children developed an ILI (fever ≥37·8°C/feverishness plus ≥1 respiratory symptom) and collected nose and/or throat swabs for multiplex respiratory virus polymerase chain reaction (PCR) testing. Health impacts were assessed by telephone interview at enrolment and two weeks after each ILI. RESULTS: There were 124 ILIs reported in 105 of 381 enrolled children. Swabs were taken in 117 ILIs: 175 viruses were identified from 103 swabs. Adeno- and rhinoviruses were most frequently identified; 44% of swabs yielded multiple viruses. No virus was associated with more severe symptoms, although rhinovirus-related ILIs lasted longer. Nose swabs had a higher virus detection rate than throat swabs. Influenza-vaccinated children were 1·6 times (P = 0·001) more likely than unvaccinated children to have a non-influenza ILI. CONCLUSION: Adeno- and rhinoviruses were the most common viruses causing ILI. Swabs taken by parents are an effective method for sample collection. Influenza-like illness was more common in children vaccinated against influenza in this observational study, but prior health-seeking behaviour may have contributed to this difference.

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

BACKGROUND: 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. METHODS: We conducted a prospective cohort study in 90 childcare centres and one general practitioner clinics in Sydney, Australia, during 2010. Healthy children aged ≥6 months to <3 years were enrolled. Economic impacts of ILI (temperature ≥37·8°C or parental report of fever, plus ≥1 respiratory symptoms) were collected at 2 and 4 weeks after ILI onset by telephone interview. Parent-collected respiratory specimens were tested for respiratory viruses using real-time PCR (RT-PCR). Costs associated with healthcare visits, medication usage, carer time lost (work or recreation) and home care and/or additional childcare were collected. Influenza-like illness costs were described and further analysed using a Tobit model. Zero-inflated Poisson regression was employed to compare the numbers of healthcare visits for each ILI. RESULTS: Of 381 children enrolled and analysed, 105 developed 124 ILIs. Specimens were available for 117 ILIs: five were positive by RT-PCR for A(H1N1)pdm09, 39 for adenovirus, 39 for rhinovirus, 15 for a coronavirus and 27 for a polyomavirus. The mean cost of all ILIs was AU$626 (95% confidence interval: AU$484-768) per ILI with no significant differences observed between viruses. Carers lost on average 13 hours of work and 3 hours of leisure time per ILI. Independent drivers of ILI costs were having both parents in employed work and longer duration of ILI. In multivariate analyses, four variables were significantly associated with an increased number of healthcare visits per ILI: non-Caucasian child, living in a detached house, both parents in employed work and having an ILI with one or more viruses identified. CONCLUSIONS: For families with a child attending childcare, ILIs cause a substantial economic burden. An ILI in a child with working parents and/or with longer duration appears to cost more in monetary terms. Healthcare visits were increased if the child was non-Caucasian, lived in a detached house, had working parents or had a virus-positive ILI. Our findings on the estimates and determinants of economic impacts from respiratory virus infection highlight the importance and feasibility of an interdisciplinary (epidemiology/health economics) approach to such research.

The importance of pertussis in older adults: a growing case for reviewing vaccination strategy in the elderly.

Pertussis or whooping cough is increasingly being shown to be a respiratory infection affecting the elderly and a significant percentage of older people infected with Bordetella pertussis experience considerable morbidity and even mortality. However, current knowledge of burden of disease is limited largely to passive surveillance data with little well-designed active surveillance to better ascertain the true burden of pertussis in the elderly, to inform vaccination strategies. The current review aims to identify gaps in knowledge to inform policy considerations relating to pertussis vaccination among the elderly.

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.

Nasopharyngeal carriage of Streptococcus pneumoniae: prevalence and risk factors in HIV-positive children in Tanzania.

BACKGROUND: Pneumococcal colonization of the nasopharynx is especially common in young children and is a pre-requisite for pneumococcal disease. Those with immunosuppression, such as HIV, are at higher risk of colonization and disease, especially at older ages. Currently, vaccination schedules are only offered to children under 6 months of age, despite the large impact of pneumococcal disease in older unvaccinated children with HIV. We conducted a study to assess the prevalence of, and risk factors for, pneumococcal carriage in HIV-positive children aged <15 years. METHODS: We collected a single nasopharyngeal swab from 142 HIV-infected children aged 1-14 years over a 2-month period. To detect carriage of pneumococcus, these samples were cultured and serotyped; PCR was performed on negative samples. We also collected epidemiological data via survey and medical records. RESULTS: The overall carriage rate was 81% and was at least 76% in those aged 5-14 years. The 7-, 10-, and 13-valent pneumococcal vaccines would cover 37%, 37%, and 49% of children with carriage, respectively. In the multivariate analysis, we identified increase in weight since last visit (p=0.028) and the existence of care-givers who had respiratory symptoms in the past week (p=0.022) as risk factors for carriage. Weight gain was also significantly associated with antiretroviral use (p=0.002). CONCLUSIONS: These data illuminate the little known area of pneumococcal carriage in older HIV-infected children as well as finding novel risk factors for pneumococcal carriage, namely the association with household members who have respiratory symptoms and with an increase in the child's weight prior to swabbing. Weight gain may be due to an increase in health enabling more mobility and increasing the risk of acquiring carriage. The carriage rate observed (81%) is one of the highest recorded. Further research should address whether vaccination can prevent the acquisition of carriage and so protect against disease.

Treating and preventing influenza in aged care facilities: a cluster randomised controlled trial.

BACKGROUND: Influenza is an important cause of morbidity and mortality for frail older people. Whilst the antiviral drug oseltamivir (a neuraminidase inhibitor) is approved for treatment and prophylaxis of influenza during outbreaks, there have been no trials comparing treatment only (T) versus treatment and prophylaxis (T&P) in Aged Care Facilities (ACFs). Our objective was to compare a policy of T versus T&P for influenza outbreaks in ACFs. METHODS AND FINDINGS: We performed a cluster randomised controlled trial in 16 ACFs, that followed a policy of either "T"-oseltamivir treatment (75 mg twice a day for 5 days)-or "T&P"-treatment and prophylaxis (75 mg once a day for 10 days) for influenza outbreaks over three years, in addition to enhanced surveillance. The primary outcome measure was the attack rate of influenza. Secondary outcomes measures were deaths, hospitalisation, pneumonia and adverse events. Laboratory testing was performed to identify the viral cause of influenza-like illness (ILI) outbreaks. The study period 30 June 2006 to 23 December 2008 included three southern hemisphere winters. During that time, influenza was confirmed as the cause of nine of the 23 ILI outbreaks that occurred amongst the 16 ACFs. The policy of T&P resulted in a significant reduction in the influenza attack rate amongst residents: 93/255 (36%) in residents in T facilities versus 91/397 (23%) in T&P facilities (p=0.002). We observed a non-significant reduction in staff: 46/216 (21%) in T facilities versus 47/350 (13%) in T&P facilities (p=0.5). There was a significant reduction in mean duration of outbreaks (T=24 days, T&P=11 days, p=0.04). Deaths, hospitalisations and pneumonia were non-significantly reduced in the T&P allocated facilities. Drug adverse events were common but tolerated. CONCLUSION: Our trial lacked power but these results provide some support for a policy of "treatment and prophylaxis" with oseltamivir in controlling influenza outbreaks in ACFs. TRIAL REGISTRATION: [corrected] Australian Clinical Trials Registry ACTRN12606000278538.