The following is a very informative article published in the June 2019 edition of the Clinical Communique by Professor Allen Cheng MB BS, FRACP, MPH, MBiostat, PhD Director, Infection Prevention and Healthcare Epidemiology Unit, Alfred Health Professor of Infectious Diseases Epidemiology, School of Public Health and Preventive Medicine, Monash University
“Ten years after the swine flu pandemic, it is timely to reflect on these two tragic cases of severe influenza in young adults. While the common perception of the pandemic was that it was a relatively mild season, it is important to note that critical care services came under considerable stress in 2009. Influenza continues to cause many thousands of hospital admissions each year in Australia, with a particularly high number of cases in 2017.
Although most infections are relatively mild, influenza can cause rare but serious complications. In children, influenza is a well described cause of severe neurological complications including encephalitis and status epilepticus, which can occur in children with no previous medical history (1). The incidence of severe influenza is highest at the extremes of age (2).
The NSW Coroner found that influenza caused more deaths in children than any other vaccine preventable disease, including meningococcal disease. The association between cardiac events and influenza is more complex; apart from infective myocarditis, studies have found an excess of other cardiac admissions, such as acute myocardial infarction at the time of increased influenza activity (3), and this is supported by case control studies showing an association between myocardial infarction and influenza (4).
Influenza diagnostics are useful to help confirm the diagnosis of influenza to target treatment and infection control interventions, but empiric treatment may be required, particularly in severely unwell patients. Many other respiratory infections can cause an influenza-like illness. Even in the peak of the influenza season, the proportion of influenza tests that are positive for influenza is usually less than 50% (5).
Balanced against the need to confirm a diagnosis is the need to start influenza antivirals quickly for the patient to receive the maximal benefit. Over the last 10 years, rapid and sensitive influenza diagnostic assays have become more widely available in hospitals, and to a lesser degree in primary care settings.
Despite good test performance, it is important to note that the sensitivity of the test also relies on the adequacy of specimen collection. In a small proportion of patients with lower respiratory tract infection, upper tract sampling may be negative (6).
Influenza antivirals may be considered in outpatients presenting within 48 hours of the onset of symptoms to reduce the duration of illness. The use of influenza antivirals is a controversial topic. A number of neuraminidase inhibitors antivirals are available in Australia, including oseltamivir, zanamivir and more recently peramivir.
Clinical trials have demonstrated that antivirals reduce the duration of illness in patients with uncomplicated influenza by around 17 hours, and are also effective in preventing influenza (7, 8). However, there is much less data on whether antivirals prevent clinically relevant complications of influenza, such as pneumonia, hospitalisation and death. Additionally, almost all studies were performed in outpatients, and evidence is scant on the use of antivirals in hospital inpatients with severe influenza.
Systematic reviews of the available studies suggest that antivirals reduce lower respiratory tract infections, but are less conclusive on whether they reduce the risk of hospitalisation (7, 8). Antivirals are not subsidised by the Pharmaceutical Benefits Scheme, but are widely available in community pharmacies and hospitals. Influenza antivirals should be given in hospitalised patients with severe influenza. There are few studies of antivirals in patients with severe influenza. In the absence of better evidence, it is reasonable to examine observational studies, while being conscious of potential confounders.
Confounders, or factors that are related to both antiviral use and outcomes (such as death) are likely to underestimate any potential protective effect of antivirals, as antivirals are likely to be given those who are more severely unwell. These studies suggest a substantial mortality benefit in patients given antivirals (9). The timely management of patients with severe infection, including pneumonia, should be evaluated and improved where necessary.
Secondary bacterial pneumonia is a known complication of influenza; previous studies have suggested that Streptococcus pneumoniae and Staphylococcus aureus are common causes (10). Recent interest has focused on early recognition, resuscitation and referral to improve outcomes from severe infections, including pneumonia (11).
Targeted actions include administration of supplemental oxygen, blood cultures and serum lactate, administration of antibiotics and intravenous fluids, and close clinical monitoring and referral as appropriate. Persisting hypotension despite adequate fluid challenge, respiratory failure and other organ dysfunction and an elevated lactate should trigger an escalation of care. Quality improvement projects have been associated with improved processes of care, and have also suggested a reduction in the risk of mortality (12, 13).
Ideally, these should be integrated into other procedures to facilitate timely treatment for deteriorating patients. Processes should exist at all levels of the health system to facilitate immunisation to all patients who want an influenza vaccination, particularly those at higher risk of severe infection. Influenza vaccination is an effective measure to reduce influenza and its complications, and is provided under the National Immunisation Program to elderly Australians, those with medical comorbidities, Indigenous Australians and pregnant women.
Although a vaccine for H1N1pdm influenza did not become available until September 2009, available data suggest that seasonal vaccine coverage is incomplete – in older Australians, around 70-80% are vaccinated, but in children and younger adults, coverage is much lower (14). Clinical trials have demonstrated a reduction in the risk of confirmed influenza (15), and some Influenza antivirals should be given in hospitalised patients with severe influenza. Clinical Communiqué – Issue NO: 02 / June 2019 CONNECTING WITH CLINICIANS Page 9 studies have also demonstrated a reduction in respiratory hospitalisations (16). As the effectiveness of the influenza vaccine is expected to vary from year to year due to differences in “match” between vaccine and circulating strains, surveillance systems are required to monitor effectiveness. These studies have consistently demonstrated that influenza vaccination reduces the risk of medical presentation and hospitalisation.Studies have also demonstrated a reduction in respiratory hospitalisations (16).
As the effectiveness of the influenza vaccine is expected to vary from year to year due to differences in “match” between vaccine and circulating strains, surveillance systems are required to monitor effectiveness. These studies have consistently demonstrated that influenza vaccination reduces the risk of medical presentation and hospitalisation with confirmed influenza (17).”
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1. Britton PN, Blyth CC, MacartneyK, Dale RC, Li-Kim-Moy J,Khandaker G, et al. The Spectrum and Burden of Influenza-Associated Neurological Disease in Children: Combined Encephalitis and Influenza Sentinel Site Surveillance From Australia 2013-2015. Clin Infect Dis. 2017;65(4):653-60.
2. Li-Kim-Moy J, Yin JK, Patel C, Beard FH, Chiu C, Macartney KK, et al. Australian vaccine preventable disease epidemiological review series: Influenza 2006 to 2015.Commun Dis Intell Q Rep.2016;40(4):E482-E95.
3. Newall AT, Viboud C, Wood JG.Influenza-attributable mortality in Australians aged more than 50 years: a comparison of different modelling approaches. Epidemiol Infect. 2010;138(6):836-42.
4. Macintyre CR, Heywood AE, Kovoor P, Ridda I, Seale H, Tan T, et al. Ischaemic heart disease, influenza and influenza
vaccination: a prospective case control study. Heart. 2013;99(24):1843-8.
5. Thursky K, Cordova SP, Smith D, Kelly H. Working towards a simple case definition for influenza surveillance. J Clin Virol. 2003;27(2):170-9.
6. Bogoch, II, Andrews JR, Zachary KC, Hohmann EL. Diagnosis of influenza from lower respiratory tract sampling after negative upper respiratory tract sampling. Virulence. 2013;4(1):82-4.
7. Jefferson T, Jones M, Doshi P, Spencer EA, Onakpoya I, Heneghan CJ. Oseltamivir for influenza in adults and children:
systematic review of clinical study reports and summary of regulatory comments. BMJ. 2014;348:g2545.
8. Dobson J, Whitley RJ, Pocock S, Monto AS. Oseltamivir treatment for influenza in adults: a meta-analysis of randomised
controlled trials. Lancet.2015;385(9979):1729-37.
9. Muthuri SG, Venkatesan S,Myles PR, Leonardi-Bee J, Al Khuwaitir TS, Al Mamun A, et al.Effectiveness of neuraminidase
inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of
individual participant data. LancetRespir Me.d 2014;2(5):395-404.
10. Chertow DS, Memoli MJ. Bacterial coinfection in influenza: a grand rounds review. JAMA. 2013;309(3):275-82.
11. Dellinger RP, Levy MM,Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165-228.
12. Burrell AR, McLaws ML, FullickM, Sullivan RB, Sindhusake D. SEPSIS KILLS: early intervention saves lives. Med J Aust.
13. Seymour CW, Gesten F, Prescott HC, Friedrich ME,Iwashyna TJ, Phillips GS, et al. Time to Treatment and Mortality
during Mandated Emergency Care for Sepsis. N Engl J Med. 2017;376(23):2235-44.
14. Blyth CC, Macartney KK,Hewagama S, Senenayake S,Friedman ND, Simpson G, et al. Influenza epidemiology,
vaccine coverage and vaccineeffectiveness in children admitted to sentinel Australian hospitals in 2014: the Influenza Complications Alert Network (FluCAN). Euro Surveill. 2016;21(30).
15. Osterholm MT, Kelley NS,Sommer A, Belongia EA. Efficacy and effectiveness of influenzavaccines: a systematic review andmeta-analysis. Lancet Infect Dis. 2012;12(1):36-44.
16. DiazGranados CA, Dunning AJ, Kimmel M, Kirby D, Treanor J, Collins A, et al. Efficacy ofhigh-dose versus standard-dose
influenza vaccine in older adults. N Engl J Med. 2014;371(7):635-45.
17. Rondy M, El Omeiri N, Thompson MG, Leveque A, Moren A, Sullivan SG. Effectiveness of influenza vaccines in preventing
severe influenza illness among adults: A systematic review and meta-analysis of test-negative design case-control studies. J
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