Zhanhai Gao

Immunological responses to pneumococcal vaccine in frail older people.

UNLABELLED Advanced age has been associated with a wide range of defects in both the innate and adaptive immune systems including diminished specific antibody responses that increase the risk of invasive pneumococcal disease (IPD) and limit the effectiveness of vaccines. However, the elderly are a heterogeneous group and measures of overall frailty may be a better indicator of disease susceptibility (or vaccine response) than chronological age alone. AIM To evaluate the immunogenicity of the 7-valent conjugated pneumococcal vaccine (PCV7) versus 23-valent polysaccharide vaccine (23vPPV) and compare the immune response to four serotypes (4, 6B, 18C and 19F), with respect to age or frailty in an elderly population of previously unvaccinated hospitalized patients. METHOD 241 patients aged 60 years and over, recruited between 16 May 2005 and 20 February 2006, were randomised to 23PPV or PCV7 vaccine. We measured Frailty Index (FI), Barthel index and the MiniMental State. Serotype-specific IgG was measured by ELISA at base line and 6 months after vaccination. Antibody responses were defined by the ratio of post-vaccination to pre-vaccination IgG antibody concentration (poor < 2-fold increase, acceptable > or = 2.0 to 3.99-fold and strong > or = 4.0-fold increase). RESULTS Pre-immunization IgG was generally low and did not differ significantly by age or frailty. Post-immunization, IgG increased to all four serotypes; acceptable or strong response ranged between 29% for (6B) and 57% for (18C). There was no significant difference between the two vaccine types (23PPV versus PCV7). At 6 months post-vaccination, the highest geometric mean IgG concentrations (GMCs) were seen for serotype 19F and the lowest for serotype 4. Although there was some variation by serotype, responses after vaccination were lowest in the most frail or aged subjects. CONCLUSIONS Pneumococcal vaccines are perceived to offer low protection in the frail elderly, but our study showed that the proportion of this vulnerable population with acceptable responses is encouraging. Frailty, as measured by the Frailty Index, appears to be a better predictor of immune response to pneumococcal vaccines than age alone.

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

Please cite this paper as: MacIntyre et al. (2011) 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. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2010.00198.x.

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).

Differences in attitudes, beliefs and knowledge of hospital health care workers and community doctors to vaccination of older people

UNLABELLED Pneumococcal disease and influenza are major causes of morbidity and mortality particularly among the elderly. Influenza and pneumococcal vaccination are recommended for people aged 65 years and older or persons with chronic illness. However, despite the burden of disease related to pneumococcus and influenza and the availability safe, efficacious and cost-effective vaccines, health care providers continue to have doubts about these vaccines. Little is known about barriers for pneumococcal vaccination in the health care providers particularly in the primary health care setting. Since 2005 a publicly funded program offering free pneumococcal vaccine for elderly people over 65 years has been implemented in Australia. AIM To investigate knowledge, attitudes and practices around vaccination of elderly patients among hospital health care workers and community general practitioners and to explore the difference between hospital doctors and GP. METHODS A self-reported questionnaire survey distrubuted March and June 2007 to General physicians (GPs) whose practices are located in Western Sydney and health care staff consisting of Hospital Doctors (HD), hospital nurses (HN) and allied health care workers at a tertiary referral hospital in Western Sydney. Descriptive analyses were conducted; bivariate analyses were performed to investigate associations between variables. RESULTS Completed surveys were obtained for 56.3% (335/595) GPs and 42.1% (346/822) for HHCWs. The HHCWs comprised 37.5% (130/346) HD, 57.8% (200/346) HN and 4.6% (16/346) allied health care workers. GPs are more likely to support elderly vaccination than hospital doctors (98.8% compared to 93%, P=0.0007). GPs reported that the reason for not vaccinating patients in 88% (295/335) of the cases was due to patient refusal. GPs and HHCW both agreed that pneumococcal disease is a serious illness and that vaccination is an important preventive measure for the elderly. However, the majority 68.2% (88/129) of hospital doctors report that vaccinations are difficult to address due to multiple competing priorities compared to only 34.6% (116/335) of GPs, P<0.0001. Hospital doctors are more likely than GPS (24% vs. 17%) to report that patients often complain of adverse effects from pneumococcal vaccine. Hospital doctors 20% (104/130) are significantly less likely than GPs<1% (3/335) to have access to guidelines and other information regarding vaccination in the elderly. CONCLUSIONS GPs and hospital health care workers in our study were aware of, agreed with, immunization recommendation for the pneumococcal vaccine. Physician barriers to vaccination were patients refusals and competing priorities, particularly for hospital health care workers, who were less likely to see vaccination as a priority. Hospitalisation is an opportunity for vaccination, but utilisation of this opportunity is reduced by lack of access to information about immunization for hospital health care workers and competing priorities. These could be areas to target for improved uptake of the elderly immunization.

Modelling the impact of one-dose vs. two-dose vaccination regimens on the epidemiology of varicella zoster virus in Australia

We examined the impact of one-dose vs. two-dose vaccination strategies on the epidemiology of varicella zoster virus (VZV) in Australia, using a mathematical model. Strategies were assessed in terms of varicella (natural and breakthrough) and zoster incidence, morbidity, average age of infection and vaccine effectiveness (VE). Our modelling results suggest that compared to a one-dose vaccination strategy (Australias current vaccination schedule), a two-dose strategy is expected to not only produce less natural varicella cases (5% vs. 13% of pre-vaccination state, respectively) but also considerably fewer breakthrough varicella cases (only 11.4% of one-dose strategy). Therefore a two-dose infant vaccination programme would be a better long-term strategy for Australia.

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.

Abstract 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.

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.

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.

Changes in seroprevalence to hepatitis A in Victoria, Australia: A comparison of three time points

Serological data provide an important measure of past exposure and immunity to hepatitis A virus (HAV) infection in a population. National serosurveys from developed countries have typically indicated a decline in HAV seroprevalence over time as sanitation levels improve. We examined trends in the seroepidemiology of HAV antibodies in Victoria, Australia, drawing on cross-sectional samples taken at three time points over a 20-year period. Stored sera from 1988 (n=753), 1998 (n=1091), and 2008 (n=791) from persons aged 1-69 years were obtained from the state of Victoria, Australia. The within-year population adjusted results show a significant trend of increasing population HAV seroprevalence over time from 34.3% (95% CI 31.7-36.9) in 1988, to 40.0% (95% CI 37.1-42.8) in 1998 and 55.1% (95% CI 52.1-58.1) in 2008, P<0.0001. A particularly noticeable rise in population seroprevalence was observed between 1998 and 2008 for those aged 5-39 years. The increase in HAV seropositivity over time is in contrast to the declining rates of disease notification in Australia. Based on comparisons with other Australian data, it appears the increase in population seroprevalence over the last two decades is unlikely to be due to endemic transmission of infection. Instead, other factors, including increases in travel to HAV endemic regions, migration to Australia from HAV endemic regions and vaccine uptake are more likely causes. Ongoing monitoring of serological HAV profiles in the population is required to determine future policy direction to prevent increased burden.