The complications of influenza infection include both viral and bacterial pneumonia and are associated with a high rate of morbidity and mortality in vulnerable groups, often overwhelming hospital services during the winter months. The most common cause of bacterial pneumonia is the pneumococcus, which causes the majority of community acquired pneumonia. Pneumococcal bacteraemia is a serious invasive disease with a high mortality that is frequently associated with pneumococcal pneumonia. Therefore, both Streptococcus pneumoniae and the influenza A and B viruses are important pathogens commonly affecting the 65 years and over age group and others with high risk conditions.

9.1 Influenza vaccination

Influenza vaccine is prepared each year using viruses similar to those considered most likely to be circulating in the forthcoming winter. The UK Departments of Health¹¹⁵ recommend that the influenza vaccine is given to all people aged 65 years or older and to people of any age

• with chronic respiratory disease including asthma
• with chronic heart disease
• with chronic renal disease
• with immunosuppression due to disease or treatment
• with diabetes mellitus
• in long stay residential care
• health and social care workers of all ages who have regular direct contact with high risk
  patients or clients.
  Evidence level 4

One RCT revealed that hospital employees show no significant reduction in influenza-like illness, severity of illness or sickness absenteeism.¹²⁹ A more recent study, showed 25% fewer episodes of upper respiratory illness, 43% fewer days of sick leave and 44% fewer visits to physicians' offices for upper respiratory tract illness in those receiving active vaccine.¹³⁰ Another RCT has shown that influenza vaccination of healthy working adults reduces the rates of influenza-like illness, lost workdays and physician visits during the year when the vaccine and circulating viruses are similar. However, during a season when the vaccine is poorly matched, vaccination does not reduce influenza-like illness, physician visits or lost workdays. During both seasons, no overall economic benefits can be demonstrated.¹³¹ Evidence level 1+

Influenza vaccination is recommended for those aged >=65 years and for people of any age with underlying chronic disease or living in long-stay residential care, and for health and social care workers.

Influenza vaccine is contraindicated for those with hypersensitivity to hen's eggs.

9.2 Pneumococcal vaccination

The current 23-valent pneumococcal polysaccharide vaccine (PPV) covers more than 95% of invasive disease serotypes in Scotland.¹³²

Four large early RCTs confirmed the high efficacy of PPV against both pneumococcal pneumonia and invasive pneumococcal disease in immunocompetent adults who are at risk because of their occupational or social circumstances.^{133,134,135,136} As a result the vaccine was licensed in 1977, before large RCTs could be conducted amongst higher risk groups including the elderly, those with underlying medical conditions and those specifically immunocompromised by HIV, haematological disorders/malignancies and splenic dysfunction. The high efficacy in immunocompetent younger adults was used to under-estimate required sample sizes for the trials in higher risk groups where efficacy was bound to be lower and the actual sample sizes required even higher. As a result, the published RCTs in the elderly and those with underlying medical conditions have not consistently shown a benefit in terms of reduced pneumococcal pneumonia ^137,138 although at least three have demonstrated a non-statistically significant reduced risk of pneumococcal bacteraemia.^132,139,140 Other RCTs for specific high risk groups, including the severely immunocompromised and those with advanced malignancy, were inadequate in sample size and were primarily designed to assess immunogenicity and safety.^141,142,143 One exception is the large study of black Ugandans with HIV which showed no benefit in this high risk group.¹⁴⁴ Evidence level 1+,1-

Systematic reviews or meta-analyses of these small and flawed RCTs have been published.^145,146,147 The verdict regarding the efficacy amongst elderly and other higher risk patients differ amongst the three publications with only one ¹⁴⁶ concluding that the vaccine was equally efficacious for the elderly, institutionalised people or those with chronic disease. Evidence level 1-

However, there is now an extensive literature calling into question the validity of meta-analyses that group together inadequately sized and otherwise flawed studies using different outcome measures ^{148,149,150,151,152} and the advantages of observational studies in this situation.^153,154 As a result, the most valid conclusion of the review of RCTs is that they fail to provide estimates of efficacy against pneumococcal pneumonia in the elderly, those with underlying medical conditions and the severely immunocompromised, which therefore remain unknown. It can reasonably be assumed that the efficacy of PPV in these higher risk groups is less than that estimated in the original studies, decreasing with increasing degree of immunocompromised state.

The more numerous observational studies have consistently shown a benefit. Four out of five case control studies,^{155,156,157,158,159} a prospective cohort study,¹⁶⁰ and an indirect cohort study^161,162,163 have all demonstrated clear protective effects with the use of the vaccine against invasive pneumococcal infection, a clear and unambiguous endpoint. In addition, the vaccine was associated with fewer hospitalisations for pneumonia, fewer deaths and direct medical care cost savings in patients with chronic lung disease.^164,165 As a result, the current international consensus is that the vaccine can be considered to be 50-80% effective against invasive pneumococcal disease.^166,167,168 Evidence level 2++,4

Two recent studies of cost-effectiveness, one based in America ¹⁶⁹ and the other in five European countries ¹⁷⁰ suggest that, based on the reduction of pneumococcal bacteraemia, the vaccine is cost-effective. Compared with preventing bacteraemic pneumococcal pneumonia alone (the bulk of invasive pneumococcal disease), the cost-effectiveness of pneumococcal vaccination increases substantially when only a small proportion of additional cases of non-bacteraemic pneumococcal pneumonia are prevented.¹⁷¹

Although some of the evidence is conflicting, it seems reasonable to conclude that at least in immunocompetent patients, the current vaccine is clinically highly effective for preventing pneumococcal pneumonia and associated bacteraemia. The evidence of benefit in terms of preventing invasive pneumococcal disease in the elderly and those with underlying medical conditions remains persuasive. Efficacy against pneumococcal pneumonia in these higher risk groups is unknown because it has yet to be properly studied. Nevertheless, the possibility that PPV prevents some pneumococcal pneumonia in the elderly and those with underlying medical conditions remains likely even though the efficacy is expected to be lower in these groups and even lower in immunocompromised patients.

Given the need to prevent this infection in the increasing numbers of elderly and in the face of increasing antimicrobial resistance to S. pneumoniae, it seems reasonable to specifically advocate its use in the 65+ age group, particularly given the recent reduction in the age-related indication for influenza vaccine and the evidence that the protective effects of simultaneous pneumococcal and influenza vaccination (at different sites) are additive and that their concurrent administration is safe.¹⁷² Evidence level 1++

Pneumococcal polysaccharide vaccine (PPV) should be given to all those aged two years or older in whom pneumococcal infection is likely to be more common or more serious in terms of increased morbidity and mortality (those with chronic lung disease, underlying medical conditions or severely immunocompromised).

PPV should be given to all people over the age of 65 years, on a one-off basis, to be administered when patients receive their routine annual influenza vaccine.

Pneumococcal and influenza vaccines can safely be given concurrently at different sites.

Current UK Department of Health Joint Committee on Vaccination and Immunisation
guidelines¹⁷³ recommend that PPV should not be given during acute infection and is not recommended during pregnancy. Revaccination with PPV within three years is contraindicated but revaccination after five years should be considered in those at increased risk including asplenic, hyposplenic and nephrotic patients.