A randomized clinical trial of the immunogenicity of 7-valent pneumococcal conjugate vaccine compared to 23-valent polysaccharide vaccine in frail, hospitalized elderly.

BACKGROUND: Elderly people do not mount strong immune responses to vaccines. We compared 23-valent capsular polysaccharide (23vPPV) alone versus 7-valent conjugate (PCV7) vaccine followed by 23vPPV 6 months later in hospitalized elderly. METHODS: Participants were randomized to receive 23vPPV or PCV7-23vPPV. Antibodies against serotypes 3, 4, 6A, 6B, 9V, 14, 18C, 19A, 19F, 23F were measured by enzyme-linked immunosorbent (ELISA) and opsonophagocytic (OPA) assays at baseline, 6 months and 12 months. RESULTS: Of 312 recruited, between 40% and 72% of subjects had undetectable OPA titres at baseline. After one dose, PCV7 recipients had significantly higher responses to serotypes 9V (both assays) and 23F (OPA only), and 23vPPV recipients had significantly higher responses to serotype 3 (ELISA), 19F and 19A (OPA only). In subjects with undetectable OPA titres at baseline, a proportionately greater rise in OPA titre (P<0.01) was seen for all serotypes after both vaccines. The GMT ratio of OPA was significantly higher at 12 months in the PCV7-23vPPV group for serotypes 6A, 9V, 18C and 23F. OPA titre levels for these serotypes increased moderately after 6 months, whereas immunity waned in the 23vPPV only arm. CONCLUSION: We did not show overwhelming benefit of one vaccine over the other. Low baseline immunity does not preclude a robust immune response, reiterating the importance of vaccinating the frail elderly. A schedule of PCV7-23vPPV prevents waning of antibody, suggesting that both vaccines could be useful in the elderly. Follow up studies are needed to determine persistence of immunity. TRIAL REGISTRATION: The Australian Clinical Trials Registry ACTRN12607000387426.

Efficacy of face masks and respirators in preventing upper respiratory tract bacterial colonization and co-infection in hospital healthcare workers.

OBJECTIVE: We compared the efficacy of medical masks (MM) and N95 respirators (N95) in preventing bacterial colonization/infection in healthcare workers (HCWs). METHODS: A cluster randomized clinical trial (RCT) of 1441 hospital HCWs randomized to medical masks or N95 respirators, and compared to 481 control HCWs, was performed in Beijing, China, during the winter season of 2008-2009. Participants were followed for development of clinical respiratory illness (CRI). Symptomatic subjects were tested for Streptococcus pneumoniae, Bordetella pertussis, Chlamydia pneumoniae, Mycoplasma pneumoniae or Haemophilus influenza type B by multiplex polymerase chain reaction (PCR). RESULTS: The rate of bacterial colonization was 2.8% in the N95 group (p=0.02), 5.3% among medical mask users (p<0.01) and 7.5% among the controls (p=0.16). N95 respirators were significantly protective (adjusted RR 0.34, 95% CI: 0.21-0.56) against bacterial colonization. Co-infections of two bacteria or a virus and bacteria occurred in up to 3.7% of HCWs, and were significantly lower in the N95 arm. CONCLUSIONS: N95 respirators were significantly protective against bacterial colonization, co-colonization and viral-bacterial co-infection. We showed that dual respiratory virus or bacterial-viral co-infections can be reduced by the use of N95 respirators. This study has occupational health and safety implications for health workers.

Attitudes, knowledge and perceptions towards whooping cough and pertussis vaccine in hospitalized adults.

Whooping cough or pertussis is a major cause of morbidity and mortality for adults and children around the world. There has been a rise in pertussis-related deaths in the elderly; pertussis vaccination is not currently routinely recommended in adults, excepting new parents and other adults household members including grandparents and care-givers of young children. Currently, there is lack of clear vaccine recommendations after the age of 50 years. Given the increase in adult pertussis, adult vaccine recommendations are a policy consideration. The study surveyed a convenience sample of patients previously recruited in a case control study designed to examine the burden of influenza with and without AMI in adults aged ≥ 40 years. Our findings showed that only 9.6% had received the pertussis vaccination within the past five years and 79.4% of participants had no knowledge of the pertussis adult booster vaccine, and 30.7% of participants who had regular contact with children under the age of two years in the past 12 months. The results showed that even though there is general acceptance of prevention by vaccines, there is low awareness about pertussis vaccination. This lack of knowledge presents a barrier against pertussis vaccination thus it is imperative that any future adult immunisation policy recommendations around pertussis vaccine include awareness programs in the target population.

Evidence for the aetiology of human papillomavirus in oesophageal squamous cell carcinoma in the Chinese population: a meta-analysis.

OBJECTIVES: We aimed to conduct a meta-analysis of human papillomavirus (HPV) as a risk factor for oesophageal squamous cell carcinoma (OSCC) in China, using all eligible studies published in the English and Chinese language literature. DESIGN: The random effect model was used to analyse the pooled OR. The I(2) and Q tests were included in the subgroup analyses. SETTING: Literature searches of databases including MEDLINE, PUBMED, EMBASE and Chinese National Knowledge Infrastructure (CNKI) and other available resources were performed to retrieve studies investigating OSCC tissue from Chinese participants for the presence of HPV DNA. PRIMARY OUTCOME MEASURE: A collective analysis of OSCC cases and control specimens was carried out from 15 case-control studies (6 in the English language and 9 in the Chinese language) for HPV prevalence. RESULTS: Of a total of 1177 OSCC and 1648 oesophageal control samples, 55% (642/1177) of cancer specimens and 27% (445/1648) of control samples were positive for HPV DNA. A positive strong association between HPV DNA and OSCC was observed among the included studies, with a pooled OR of 3.69 (95% CI 2.74 to 4.96). Heterogeneity and publication bias were not observed in the analysis. Subgroup analyses of the included studies also supported the measure of association of causal links between HPV and OSCC. CONCLUSIONS: This meta-analysis provides the strongest evidence until now of an association between HPV and OSCC in the Chinese population. China has a high burden of OSCC, making this an important research finding. A strength and new contribution of this study is combining data from the English and Chinese language literature to analyse all studies conducted in China. These findings may inform the population level use of prophylactic HPV vaccination to reduce the burden of OSCC in China.

Ischaemic heart disease, influenza and influenza vaccination: a prospective case control study.

BACKGROUND: Abundant, indirect epidemiological evidence indicates that influenza contributes to all-cause mortality and cardiovascular hospitalisations with studies showing increases in acute myocardial infarction (AMI) and death during the influenza season. OBJECTIVE: To investigate whether influenza is a significant and unrecognised underlying precipitant of AMI. DESIGN: Case-control study. SETTING: Tertiary referral hospital in Sydney, Australia, during 2008 to 2010. PATIENTS: Cases were inpatients with AMI and controls were outpatients without AMI at a hospital in Sydney, Australia. MAIN OUTCOME MEASURES: Primary outcome was laboratory evidence of influenza. Secondary outcome was baseline self-reported acute respiratory tract infection. RESULTS: Of 559 participants, 34/275 (12.4%) cases and 19/284 (6.7%) controls had influenza (OR 1.97, 95% CI 1.09 to 3.54); half were vaccinated. None were recognised as having influenza during their clinical encounter. After adjustment, influenza infection was no longer a significant predictor of recent AMI. However, influenza vaccination was significantly protective (OR 0.55, 95% CI 0.35 to 0.85), with a vaccine effectiveness of 45% (95% CI 15% to 65%). CONCLUSIONS: Recent influenza infection was an unrecognised comorbidity in almost 10% of hospital patients. Influenza did not predict AMI, but vaccination was significantly protective but underused. The potential population health impact of influenza vaccination, particularly in the age group 50-64 years, who are at risk for AMI but not targeted for vaccination, should be further explored. Our data should inform vaccination policy and cardiologists should be aware of missed opportunities to vaccinate individuals with ischaemic heart disease against influenza.

A randomized clinical trial of three options for N95 respirators and medical masks in health workers.

RATIONALE: We compared three policy options for the use of medical masks and N95 respirators in healthcare workers (HCWs). OBJECTIVES: A cluster randomized clinical trial of 1,669 hospital-based HCWs in Beijing, China in the winter of 2009-2010. METHODS: Participants were randomized to medical masks, N95 respirators, or targeted use of N95 respirators while doing high-risk procedures or barrier nursing. Outcomes included clinical respiratory illness (CRI) and laboratory-confirmed respiratory pathogens in symptomatic subjects. MEASUREMENTS AND MAIN RESULTS: The rate of CRI was highest in the medical mask arm (98 of 572; 17%), followed by the targeted N95 arm (61 of 516; 11.8%), and the N95 arm (42 of 581; 7.2%) (P < 0.05). Bacterial respiratory tract colonization in subjects with CRI was highest in the medical mask arm (14.7%; 84 of 572), followed by the targeted N95 arm (10.1%; 52 of 516), and lowest in the N95 arm (6.2%; 36 of 581) (P = 0.02). After adjusting for confounders, only continuous use of N95 remained significant against CRI and bacterial colonization, and for just CRI compared with targeted N95 use. Targeted N95 use was not superior to medical masks. CONCLUSIONS: Continuous use of N95 respirators was more efficacious against CRI than intermittent use of N95 or medical masks. Most policies for HCWs recommend use of medical masks alone or targeted N95 respirator use. Continuous use of N95s resulted in significantly lower rates of bacterial colonization, a novel finding that points to more research on the clinical significance of bacterial infection in symptomatic HCWs. This study provides further data to inform occupational policy options for HCWs. Clinical trial registered with Australian New Zealand Clinical Trials Registry http://www.anzctr.org.au (ACTRN 12609000778280).

Models of strategies for control of rubella and congenital rubella syndrome-a 40 year experience from Australia.

We investigated the impact of vaccination on rubella epidemiology in Australia, using a mathematical model fitted to Australian serosurvey data and incorporating pre-vaccination European estimates of rubella transmissibility. Mass infant measles-mumps-rubella (MMR) vaccination produced a 99% reduction in both rubella and congenital rubella syndrome (CRS) incidence by 2010 compared to the pre-vaccination era (1960-70). The model is consistent with reductions in CRS based on surveillance of congenital hearing impairment. Model simulations suggest that selective schoolgirl vaccination (1971-88) was associated with a 90% reduction in CRS incidence, but only a 1-4% reduction in rubella incidence. Our model predicted that these reductions in rubella were much less vulnerable to reductions in MMR vaccine coverage than for measles. In the future, a less than 15% decrease in MMR vaccine coverage is estimated to have minimal impact before 2060, but a 20% reduction may result in a 7-fold increase in rubella incidence, with the effective reproductive number R rising from 0.28 to 0.78 by 2060. The 99% reduction in both rubella and CRS incidence and low effective reproductive number (R≤0.28) we documented after 2010 are consistent with Australia having achieved rubella elimination.

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.

Current epidemiology of rubella and congenital rubella syndrome in Australia: progress towards elimination.

This study evaluates the evidence for elimination of rubella and congenital rubella syndrome (CRS) in Australia, drawing on three national serosurveys conducted between 1996 and 2007 and supported by statutory notification and vaccine coverage data. Anti-rubella IgG seropositivity was defined as ≥ 10 IU/ml by EIA. Between 1998 and 2007, rubella notifications fell >100-fold, to an average of 2 cases per million and there were five confirmed cases of CRS, two of which were locally acquired in 2003. Weighted overall seropositivity remained constant among 1-49 year-olds (89.6% in 1999; 88.1% in 2007). Between 2002 and 2009, 95% of children received at least one dose of the measles-mumps-rubella (MMR) vaccine. All three serosurveys provided estimates for R less than 0.5, well below the epidemic threshold of 1. All available data are supportive of Australia being considered for elimination status. Further reductions in incidence of CRS will require continued attention to vaccine coverage in overseas-born women, as well as the maintenance of current high coverage level of two-dose MMR vaccination.

Respiratory viruses transmission from children to adults within a household.

BACKGROUND: The aim of this study was to examine the rate of transmission of influenza and other respiratory viruses from children attending an Emergency Department to their family members in the household using active surveillance. METHODS: A prospective hospital-based study was conducted over three consecutive winters (2006-2008) in children aged <1-15 years presenting with influenza-like illness (ILI). 168 children with ILI and their healthy families were recruited over three winter seasons. RESULTS: Respiratory viruses were detected in 101 (60.8%) children with ILI; in 91/166 (54.8%) a single pathogen was detected, and in the remaining 10 children more than one virus was detected concurrently. Influenza was the most common virus detected (34/101), followed by rhinoviruses (22/101) and adenoviruses (14/101). Of influenza viruses, 21/34 were influenza A and 13/34 influenza B. Meeting the clinical definition of ILI did not differentiate between influenza and other viruses. Clinical ILI developed within one week of follow up in 12% (26/205) of the family members who were swabbed. Viral pathogens were detected in 42.3% (11/26) of the symptomatic family members. In 6/11 cases the same virus was detected in the adult and child. The lower estimate of the household risk of transmission of respiratory viruses, based on concordant proven infection in both child and adult, from a single sick child to adult household contacts is therefore 3% per week. CONCLUSION: This study provides quantitative, prospective data on rates of household transmission of infection from children to adults.

Equity and access: understanding emergency health service use by newly arrived refugees.

OBJECTIVES: To determine issues that affect newly resettled refugees in accessing an emergency department (ED). DESIGN, SETTING AND PARTICIPANTS: We conducted a descriptive community survey using a semistructured questionnaire. Newly resettled refugees from the Middle East and Africa were interviewed, statistical analysis was performed, and standard content analysis methods were applied to free-text responses. MAIN OUTCOME MEASURES: Emergency health-seeking behaviour, sociocultural barriers and beliefs about Australia's emergency health services. RESULTS: Half the African refugees (53/106) (50%), compared with only 15/49 (31%) of the Middle Eastern refugees, preferred an ED service over other forms of care for an urgent medical condition (P = 0.024). Qualitative data revealed that most newly resettled refugees understand how to use the emergency health services. However, while most indicated that they were able to make a call for emergency medical help, a substantial number of our respondents revealed that they were afraid to make such a call for fear of security implications, on the basis of experiences from their home countries. CONCLUSION: Reasons for differences in preferences of health care access, and determining how best to educate the community on the use of ED services, warrant further investigation. From a policy perspective, the increasing health care needs of refugees need re-examination when planning health care provision to refugees.

A cluster randomized clinical trial comparing fit-tested and non-fit-tested N95 respirators to medical masks to prevent respiratory virus infection in health care workers.

BACKGROUND: We compared the efficacy of medical masks, N95 respirators (fit tested and non fit tested), in health care workers (HCWs). METHODS: A cluster randomized clinical trial (RCT) of 1441 HCWs in 15 Beijing hospitals was performed during the 2008/2009 winter. Participants wore masks or respirators during the entire work shift for 4 weeks. Outcomes included clinical respiratory illness (CRI), influenza-like illness (ILI), laboratory-confirmed respiratory virus infection and influenza. A convenience no-mask/respirator group of 481 health workers from nine hospitals was compared. FINDINGS: The rates of CRI (3·9% versus 6·7%), ILI (0·3% versus 0·6%), laboratory-confirmed respiratory virus (1·4% versus 2·6%) and influenza (0·3% versus 1%) infection were consistently lower for the N95 group compared to medical masks. By intention-to-treat analysis, when P values were adjusted for clustering, non-fit-tested N95 respirators were significantly more protective than medical masks against CRI, but no other outcomes were significant. The rates of all outcomes were higher in the convenience no-mask group compared to the intervention arms. There was no significant difference in outcomes between the N95 arms with and without fit testing. Rates of fit test failure were low. In a post hoc analysis adjusted for potential confounders, N95 masks and hospital level were significant, but medical masks, vaccination, handwashing and high-risk procedures were not. INTERPRETATION: Rates of infection in the medical mask group were double that in the N95 group. A benefit of respirators is suggested but would need to be confirmed by a larger trial, as this study may have been underpowered. The finding on fit testing is specific to the type of respirator used in the study and cannot be generalized to other respirators. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN: ACTRN12609000257268 (http://www.anzctr.org.au).

Face mask use and control of respiratory virus transmission in households.

Many countries are stockpiling face masks for use as a nonpharmaceutical intervention to control virus transmission during an influenza pandemic. We conducted a prospective cluster-randomized trial comparing surgical masks, non-fit-tested P2 masks, and no masks in prevention of influenza-like illness (ILI) in households. Mask use adherence was self-reported. During the 2006 and 2007 winter seasons, 286 exposed adults from 143 households who had been exposed to a child with clinical respiratory illness were recruited. We found that adherence to mask use significantly reduced the risk for ILI-associated infection, but <50% of participants wore masks most of the time. We concluded that household use of face masks is associated with low adherence and is ineffective for controlling seasonal respiratory disease. However, during a severe pandemic when use of face masks might be greater, pandemic transmission in households could be reduced.

Infection outcomes in splenectomized patients with hemoglobinopathies in Australia.

OBJECTIVE: To assess the infection risk of splenectomized persons with hemoglobinopathies in Australia. METHODS: This was an Australia cohort study of infections and vaccinations in 63 patients with hemoglobinopathies followed longitudinally from 1967 to 2006, and an investigation into the risk factors for poor outcome. RESULTS: There were 28 cases of bacterial infection that necessitated hospitalization in the cohort, resulting in an incidence of 1.4 bacterial infections per 100 patient-years. There was one death (1.6%) as a direct result of bacterial infection. Hepatitis C was diagnosed in 28 patients (44%). The spectrum of infection included pneumonia (6/28), cellulitis (6/28), bacteremia (4/28), and skin abscess (3/28). Notably, Klebsiella species organisms were isolated in 9/28 cultures. CONCLUSIONS: Infectious complications in this group of patients cause serious morbidity and mortality. This cohort may be a target for novel preventive strategies such as more immunogenic vaccines, patient registries, and/or education programs.

The impact of behavioural changes on the prevalence of human immunodeficiency virus and hepatitis C among injecting drug users.

BACKGROUND: Prevalence of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) in the injecting drug user (IDU) community can differ considerably. In Australia in 1997, HIV prevalence among attendees at Needle Exchange Programs was 1% while HCV prevalence was 50%. The impact that different needle-sharing behaviour and drug injecting use may have on the future levels of these viruses is uncertain. METHOD: We develop a mathematical model of the number of people who inject drugs with each of these infections to determine their changes under different scenarios. The impact of transmission probabilities and needle sharing on the incidence and prevalence of HIV and HCV infections are assessed. RESULTS: Critical levels of needle sharing, below which total infections would fall to minimal levels, were estimated to be 17 IDU partners per year for HIV compared with 3 IDU partners per year for HCV. Current average levels of needle sharing in Australia are estimated to be six IDU partners per year. CONCLUSIONS: This analysis suggests that under current drug injecting behaviour, HIV prevalence in IDU in Australia should remain below 1% but that HCV prevalence will stay elevated.