We've study, published today in Communicable Diseases Intelligence (CDI) - a peer-reviewed journal published by the Australian Department of Health - which, in light of Australia's current `summer flu' outbreak (see Australia: An Early Surge In Flu Cases), is of particular interest.
We know influenza and other respiratory viruses can circulate year round - and with increased international travel, the risk of importing out-of-season flu viruses rises - but testing and surveillance are often scaled back during non-winter months.As a result, it isn't known how much of this year's `summer flu' in Australia can be attributed to increased flu activity, and how much is due to increased awareness and testing.
Admittedly, both seem likely factors.Today's study wasn't looking for influenza, but found it - along with RSV, and an unexpected number of Picornavirus infections (which include rhinoviruses) - among 72 adults hospitalized with Community Acquired Pneumonia (CAP) during non-winter months in Melbourne Australia.
Specifically, 1/3rd (n=24) of the 72 cases tested were positive for respiratory viruses in this study. Furthermore, 80% of the PCR positive cases - including all 8 RSV & Influenza cases - had not been diagnosed as a viral infection prior to testing.As we've discussed previously, CAP is the #1 cause of hospitalization of adults with an infectious disease in the United States, and yet, in more than half of the cases the type of infection (viral, fungal, bacterial) is never actually identified.
A 2015 study published in the NEJM (see The CDC’s EPIC CA-Pneumonia Study) followed 2500 cases over 5 years and found that in the majority (62%) of cases no definitive pathogenic agent was identified.
Specifically, they found:Even without a definitive diagnosis, patients can be treated empirically. But it is very much worth knowing if a patient hospitalized with the disease is infectious.
The most commonly detected pathogens were:
- one or more viruses in 530 (23%) cases
- bacteria in 247 (11%) cases
- bacterial and viral pathogens in 59 (3%) cases
- and a fungal or mycobacterial pathogen in 17 (1%) of cases
- Human rhinovirus (in 9% of patients)
- Influenza virus (in 6%)
- and Streptococcus pneumoniae (in 5%).
Some excerpts from today's study, after which I'll return with a postscript.
Respiratory viruses in adults hospitalised with Community-Acquired Pneumonia during the non-winter months in Melbourne: Routine diagnostic practice may miss large numbers of influenza and respiratory syncytial virus infections.
Lucy A Desmond, Melanie A Lloyd, Shelley A Ryan, Edward D Janus and Harin A Karunajeewa
Community-Acquired Pneumonia (CAP) is one of the highest health burden conditions in Australia. Disease notifications and other data from routine diagnosis suffers from selection bias that may misrepresent the true contribution of various aetiological agents.
However existing Australian prospective studies of CAP aetiology have either under-represented elderly patients, not utilised Polymerase Chain Reaction (PCR) diagnostics or been limited to winter months.
We therefore sought to re-evaluate CAP aetiology by systematically applying multiplex PCR in a representative cohort of mostly elderly patients hospitalised in Melbourne during non-winter months and compare diagnostic results with those obtained under usual conditions of care.
Seventy two CAP inpatients were prospectively enrolled over 2 ten-week blocks during non-winter months in Melbourne in 2016-17. Nasopharyngeal and oropharyngeal swabs were obtained at admission and analysed by multiplex-PCR for 7 respiratory viruses and 5 atypical bacteria .
Median age was 74 (interquartile range 67-80) years, with 38 (52.8%) males and 34 (47.2%) females. PCR was positive in 24 (33.3%), including 12 Picornavirus (50.5% of those with a virus), 4 RSV (16.7%) and 4 influenza A (16.7%). CAP-Sym questionnaire responses were similar in those with and without viral infections. Most (80%) pathogens detected by the study, including all 8 cases of influenza and RSV, were not otherwise detected by treating clinicians during hospital admission.
One third of patients admitted with CAP during non-winter months had PCR-detectable respiratory viral infections, including many cases of influenza and RSV that were missed by existing routine clinical diagnostic processes.
Community Acquired Pneumonia (CAP) is Australia’s sixth leading cause of death and the leading non-obstetric cause of hospital admission. 1,2 A number of factors may have compromised our understanding of CAP aetiology in Australia.
Firstly, information on the microbial aetiology of CAP derived from notification data and other routine diagnosis is compromised by selection and ascertainment biases, highly variable approaches to diagnostic testing and the limited scope of existing surveillance and mandatory reporting processes.
Secondly, most of Australia’s CAP healthcare burden manifests in patients over age 65 who now account for 73% of hospital bed stays for CAP. 2 However this group has, in many ways been understudied relative to younger, more diagnostically homogeneous populations. Research studies of CAP aetiology therefore risk under-representing the population in which the greatest burden occurs.
Thirdly, previous Australian studies examining CAP aetiology have been limited mainly to winter months 4-9 even though these months may only account for < 30% of the total annual burden of CAP in Australia.
Therefore, we designed a prospective study with the following objectives:
1. To describe respiratory viral and atypical bacterial pathogen prevalence by multiplex Polymerase Chain Reaction (PCR) in a representative group of adult patients with CAP during non-winter months.(SNIP)
2. To compare diagnostic yields from systematic application of multiplex PCR in all CAP patients with those achieved by routine clinician-initiated testing under usual conditions of clinical care.
This study adds to existing knowledge by detecting viral respiratory pathogens in one third of adult patients admitted with a diagnosis of CAP under a GIM service during the non-wintermonths. It reinforces how difficult, if not impossible, it is to predict the presence of viral infections at the time of admission based purely on symptomatology, existing routine diagnostic tests and “seasonality”.
It demonstrates how discretionary testing based on “clinical suspicion” can miss a large proportion of influenza and RSV infections. These are highly transmissible in healthcare settings where they are associated with significant morbidity and mortality, especially in vulnerable populations such as the frail elderly admitted to GIM wards. 6
Our study adds to existing data suggesting that, rather than the application of clinical algorithms or “discretionary” testing that have poor negative predictive value, the only way to reliably exclude these important potential agents of nosocomial infection in CAP patients is routine use of an appropriately high sensitivity diagnostic test. 21,33
However, at present complex issues of diagnostic costs, diagnostic delay and other resource utilisation implications (such as the availability and use of suitable isolation facilities) also need to be factored into the “risk-benefit equation” when considering alternative approaches.
At our study hospitals, like many others in Australia, the need to institute respiratory isolation procedures in anyone tested for influenza (pending results that may not be available for >24 hours) creates additional stresses on hospital resources, and can therefore represent a perverse disincentive that actually discourages testing.
This may have been a factor explaining the high numbers of “missed” influenza and RSV in our study. Newer testing platforms with more rapid turnaround times may help alleviate this problem but the clinical utility and cost effectiveness of these tools has not yet been reported.
Our study suggests that a more comprehensive testing strategy (applying high sensitivity diagnostics to all CAP patients) could unmask a currently hidden significant disease burden and therefore could help reduce risks of nosocomial infection. Our study also suggests it is important that review of current hospital policy approaches should be considered for both winter and non-winter months.
One of the realities of living in our highly mobile 21st century society is that seasons, and locales, don't matter as much as they once did.
Millions of people travel internationally every day, and a traveler can catch a virus in New York City, London, or Hong Kong - and travel to Melbourne, Tokyo, or Seoul - before the first symptom appears.
Over the past couple of years we've seen an uptick in the number, and intensity , of `summer flu' outbreaks (see Macao, Hong Kong & Guangdong Province All Reporting Heavy Flu Activity). While the reasons behind them aren't well understood, they do seem to be increasing.
Which - when added to the above study's conclusions - suggests that the need for out-of-season testing of hospitalized patients for respiratory viruses is only going to increase over time.