Iman Ridda

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.

Difficulties in recruiting older people in clinical trials: An examination of barriers and solutions

Limited information exists regarding optimal methods for the recruitment and retention of older people in clinical trials. The aim of this review is to identify common barriers to the recruitment of older people in clinical trials and to propose solutions to overcome these barriers. A review of literature was performed to identify common difficulties in recruiting older people. This in combination with our experience during recruitment for a randomized control trial, have highlighted numerous barriers. Population-specific recruitment strategies, simple informed-consent processes, and effective communication between the researcher and subject are effective strategies to overcome these barriers.

Research: The challenges of clinical trials in the exclusion zone: The case of the frail elderly

Frail older people have been systematically excluded from randomised controlled trials (RCT). We aim to recruit older, frail hospitalised patients in an RCT and evaluate the frailty index (FI) as a measure to describe the types of people included in the study. We recruited 315 hospitalised patients aged 65 years; age ranged from 60 to 102 years. Baseline assessment scores ranged as follow: Mini‐Mental Status Examination from 7 to 30, Barthel index from 5 to 100 and FI from 2 to 24. Total deaths were 20 (6%). We demonstrated that it is feasible to recruit frail older people into RCTs. The FI does not show any ‘floor’ or ‘ceiling’ effects. We can measure frailty in an RCT cohort, and we believe that clinical trials should include more frail older people and that the use of an FI can facilitate such trials and generate reliable data to guide future medical practice in a rapidly ageing society.

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.

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.

Lack of pneumococcal carriage in the hospitalised elderly.

UNLABELLED There have been few surveys of Streptococcus pneumoniae and Neisseria meningitidis carriage in sick or frail elderly people who, with the very young, comprise the group who are at highest risk for pneumococcal disease. We studied pneumococcal carriage among participants in a pneumococcal immunisation study in the frail elderly. METHODS Subjects aged >or=60 years were recruited from a large tertiary referral hospital in Sydney, Australia. Nose and throat swabs were collected at the time of enrolment and 12 months after immunisation. RESULTS Before immunisation, only 1 of 315 participants was identified as a nasal carrier of S. pneumoniae; another was identified as throat carrier of N. meningitidis. None of the participants examined after immunisation was carrying either S. pneumoniae or N. meningitidis. CONCLUSION The low rate of pneumococcal carriage in this population of hospitalised elderly patients was unexpected. The most likely reason is that long-term carriage is rare in this population and suggests that pneumococcal disease primarily follows recent acquisition of S. pneumoniae types not associated with carriage.

The Aetiological Role of Human Papillomavirus in Oesophageal Squamous Cell Carcinoma: A Meta-Analysis

Background The aetiological role of human papillomavirus (HPV) in oesophageal squamous cell carcinoma (OSCC) has been widely researched for more than three decades, with conflicting findings. In the absence of a large, adequately powered single case-control study, a meta-analysis of all available case-control studies is the most rigorous way of identifying any potential association between HPV and OSCC. We present the first global meta-analysis of case-control studies investigating the role of HPV in OSCC. Methods Case-control studies investigating OSCC tissue for presence of HPV DNA were identified. 21 case-control studies analyzing a total of 1223 cases and 1415 controls, met our inclusion criteria. HPV detection rates were tabulated for each study and all studies were assessed for quality. The random effects method was used to pool the odds ratios (OR). Results From all OSCC specimens included in this meta-analysis, 35% (426/1223) were positive for HPV DNA. The pooled OR for an HPV-OSCC association was 3.04 (95% CI 2.20 to 4.20). Meta-regression analysis did not find a significant association between OR and any of the quality domains. Influence analysis was non-significant for the effect of individual studies on the pooled estimate. Studies conducted in countries with low to medium OSCC incidence showed a stronger relationship (OR 4.65, 95% CI 2.47 to 8.76) than regions of high OSCC incidence (OR 2.65, 95% CI 1.80 to 3.91). Conclusions Uncertainty around the aetiological role of HPV in OSCC is due largely to the small number and scale of appropriately designed studies. Our meta-analysis of these studies suggests that HPV increases the risk of OSCC three-fold. This study provides the strongest evidence to date of an HPV-OSCC association. The importance of these findings is that prophylactic vaccination could be of public health benefit in prevention of OSCC in countries with high OSCC incidence.

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.

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.