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Some more pieces in the swine flu puzzle, but the overall picture is still lacking

Some more pieces in the swine flu puzzle appear in today’s edition of the Medical Journal of Australia (some of the articles were previously rapid online publications).

When you put them together, the impression is that there are many more pieces still missing. The overall pandemic picture is incomplete, highlighting many gaps in knowledge – and the need for a thorough review of our response.

There are plenty of suggestions for policy revision, for eg around border control measures, testing and the need to better incorporate multidisciplinary prespectives in planning.

Here is a summary of the papers:

1. A pandemic response to a disease of predominantly seasonal intensity

Heath Kelly, Head of the Epidemiology Unit at the Victorian Infectious Diseases Reference Laboratory, (who has previously written about some of these issues in Crikey) examined the proportion of requested laboratory tests that were positive for influenza between 2004 and 2009, and compared influenza-like illness rates with the proportion of positive tests.

• The results confirm that the rate of circulation of influenza virus was relatively high in 2003 and 2007, as the proportion of positive tests was also highest in those 2 years. The proportion of tests positive in 2009, when swine flu was the dominant circulating strain, was about the same as the proportions in 2004 and 2006, years known to be characterised by relatively low influenza activity.

• The manifestation of swine flu infection, acknowledged to be most often mild, ranges from undiagnosed asymptomatic infection to serious illness and death. For seasonal influenza, the proportion of asymptomatic infection is between 25% and 33%, and 63% of people volunteering to be infected with seasonal H1N1 influenza experimentally do not have a fever.

• The pandemic paradox is that, while disease in the community appears to be mild, and the risk of hospitalisation low (reported as 0.3% for the first 10 weeks of the pandemic in Victoria), 20% of hospitalised patients required intensive care.

• Up to 7 August 2009, 74 of the 2052 Australian patients hospitalised with confirmed pandemic (H1N1) 2009 influenza infection (4%) were pregnant. The estimated admission rate for pregnant women with confirmed swine flu infection in Australia was 31.2 per 100 000, compared with the estimated admission rate for the remainder of the population of 9.7 per 100 000. Pregnant women were just over three times as likely to be admitted to hospital with confirmed swine flu infection as the rest of the population (relative risk, 3.2; 95% CI, 2.6–4.1).

• Although case numbers are high, and there are problems in intensive care units, the number of deaths from swine flu may not be as high as the numbers modelled to die from seasonal influenza. In Victoria, as the pandemic appears to have waned, 24 deaths from pandemic (H1N1) 2009 influenza were recorded by 23 September 2009. We don’t know the numbers who die from seasonal influenza each year because we don’t test for seasonal influenza with the same enthusiasm that we have tested for swine flu. However, a comparison based on modelling estimates that about 3000 people aged at least 50 years will die from seasonal influenza each year in Australia. In Victoria, this might equate to 750 people — considerably higher than the number of swine flu deaths to date.

• Modelling suggests that 85%–90% of deaths from seasonal influenza occur in people aged at least 65 years, while the median age of people who died from swine flu to 21 August 2009 in Australia is 54 years.

• Billions of dollars are spent globally on the surveillance, control, treatment and prevention of influenza but we have a poor understanding of the behaviour of the virus at the population level. In no country where influenza treatment and prevention is provided, at least in part, from the public purse do we really understand the annual burden of disease proven — not modelled — to be due to influenza. Because we do not understand this burden for seasonal influenza, we cannot base our response to the pandemic on an informed comparison.

***

2. Hospitalised adult patients with pandemic (H1N1) 2009 influenza in Melbourne

Doctors conducted a prospective case analysis of 112 patients admitted to seven hospitals in Melbourne with laboratory-confirmed pandemic (H1N1) 2009 influenza between 1 May and 17 July 2009. They say it is the largest series of hospitalised pandemic patients reported to date. The findings may not be representative as the study didn’t include all Melbourne hospitals and might have included more severe cases than if the patients from smaller hospitals had also been included.

Interestingly, an eighth large hospital was asked to join the study but declined. I wonder which one, and why? (any tips from Croakey readers appreciated).

• The cases ranged in age from 15 to 79. The median age was 42.

• 31 per cent had asthma, 18 per cent had diabetes, 13 per cent were pregnant; 21 per cent had no risk factors for severe disease.

• 3 per cent of the patients were thought to have been infected in a hospital.

• 27 per cent of patients were admitted to an intensive care unit, staying there for between three and 14 days.

• Three patients died during study, all during or following an ICU admission.

• 81 per cent met the clinical case definition of fever with either cough or sore throat.

***

3. The rational clinician in a pandemic setting

David Bradt and Joseph Epstein reflected on their experience as clinical advisers in the Victorian Department of Human Services Emergency Operations Centre.

• They highlighted concerns with case management: “Unfortunately, laboratory results for the novel virus were not available to influence early clinical decision making for any given patient. Lacking patient-specific laboratory data, some practising infectious disease physicians managed their patients “not in quarantine and … generally not receiving antiviral therapy” This approach ignores important aspects of community-based influenza management.”

• Practitioner calls to the DHS Emergency Operations Centre swine flu hotline revealed commonly shared concerns over using antiviral therapy (the category B1 drugs oseltamivir and zanamivir) in some high-risk populations, especially pregnant women. We believe the Victorian public health guidance on category B1 drugs does not sufficiently recognise the evidence for the adverse consequences of influenza infection during pregnancy. Health authorities internationally have made unequivocal calls for the use of oseltamivir in pregnant patients with confirmed, probable or suspected pandemic (H1N1) 2009 infection.

• Medical logistics underlie many of the problems reported in the swine flu pandemic. For the disaster medicine community, problems in communication, transportation and commodity distribution are predictable consequences of inadequately tested disaster plans. We embrace the calls of our infectious disease and general practitioner colleagues for enhanced multidisciplinary pandemic planning.

• Health authorities internationally have dismissed such border control measures as thermal imaging, mandatory questionnaires, and interviews – although these are recommended in national pandemic planning. “We believe border control measures undertaken for the swine flu pandemic in Australia have little scientific justification. Given the domestic response to both international travellers and Victorians travelling interstate, exemplified by calls to restrict both domestic and international travel, we believe the political imperative to take action exacerbates public health mythology. It also heightened interstate and international tensions. The modern traveller has unwittingly become cast as the enemy of the people.”

• Overall, the dimensions of the current pandemic oblige substantial further changes to national and state pandemic plans. Central to these changes is detail about scalability (escalation and de-escalation) in response to new pandemic circumstances. The lessons to date from case definitions, laboratory diagnosis, case management, medical logistics and travel restrictions should be promptly integrated into present plans.

***

4. Comparison of adult patients hospitalised with pandemic (H1N1) 2009 influenza and seasonal influenza during the “PROTECT” phase of the pandemic response

This study was a retrospective medical record review of all patients admitted to Liverpool Hospital in Sydney, with laboratory-confirmed influenza from the initiation of the “PROTECT” phase of the pandemic response on 17 June until 31 July 2009.

• Sixty-four adults were admitted to Liverpool Hospital with influenza, 48 with pandemic (H1N1) 2009 influenza and 16 with seasonal influenza. Thirteen patients were admitted to the ICU. Seven required invasive ventilation, with 2 patients requiring ongoing extracorporeal membrane oxygenation (ECMO). Five patients died (mortality rate, 8%) with two deaths occurring after the study period.

•  The clinical course and outcomes of pandemic (H1N1) 2009 influenza virus are comparable to those of the current circulating seasonal influenza in Sydney. The high number of hospital admissions reflects a high incidence of disease in the community rather than an enhanced virulence of the novel pandemic influenza virus.

• Five of the 64 cases of influenza (all pandemic [H1N1] 2009) were health-care associated.

• Other reports have suggested pregnant women are at increased risk of severe complications from pandemic flu, but this study did not show that pregnant women with pandemic flu were worse off than pregnant women with seasonal flu. This may have been because of the small numbers in the study “and a definitive answer to this question requires a multicentre study”.

• It remains unclear whether antiviral drugs alter the clinical course of severe influenza infection.

***

5. The changing phases of pandemic (H1N1) 2009 in Queensland: an overview of public health actions and epidemiology

Queensland Health staff provide an overview of the State’s initial public health response.

•  In Queensland, 593 laboratory-confirmed cases were notified with a date of onset between 26 April and 22 June 2009, when the Protect phase of the Australian Health Management Plan for Pandemic Influenza was implemented; 16 hospitalisations and no deaths were reported during this time.

•  The largest number of confirmed cases was reported in the 10–19-years age group (167, 28% of cases), followed by the 20–29-years age group (153, 26% of cases).

• A total of 48 schools (2.8% of all schools in Queensland) and five childcare centres were closed. Parents were also requested to keep their children away from school for 7 days if they had returned from an area of sustained community transmission.

• To reduce the demand on hospitals and general practices, “flu clinics” were set up, usually as a short-term response to clusters necessitating the assessment and management of large numbers of contacts. Nine flu clinics, mostly hospital-based, were set up and assessed 2551 patients.

• A key challenge for clinicians and public health officials alike was keeping up with the stream of changing information. Priorities for public health action, case definitions and testing criteria changed regularly as the pandemic evolved, because of emerging information about the behaviour of the virus and change in phases.

• Other challenges were delays in obtaining test results in remote areas because of the distance from laboratories, the volume of requests for tests stretching laboratories to capacity, and the logistical difficulties of distributing antiviral drugs in remote areas of Queensland.

• Border measures required the investment of significant clinical and public health resources and had only a low pick-up rate. The low sensitivity and usefulness of border measures were questioned after the 2003 outbreak of severe acute respiratory syndrome. We recommend that border screening should be formally evaluated in the context of the influenza pandemic and in reviews of pandemic plans.

• A comprehensive evaluation of the pandemic plan and response is required so that we are better prepared for dealing with the next, and possibly worse, pandemic.

**

6. Pandemic influenza testing at the coalface: time for reassessment?

Two pathologists employed by Symbion Health argue that greater use of the private pathology sector would create a more effecitve, timely response.

They say:

• Australian federal and state governments were advised several years ago that an influenza pandemic would overwhelm Australian public reference laboratories, and that these predictions were realised during the pandemic outbreak.

• In WA, for eg, PathWest was being used in an inefficient manner — spending a huge amount of precious time and expertise processing an enormous number of specimens that would subsequently be reported as negative (96% of the total) while the private pathology laboratories were referring a large number of specimens (requiring packaging and transport by courier) that they were technically equipped to process. After the first phase of the pandemic, reporting did not meet the benchmark turnaround time and was no longer clinically helpful in making management decisions.

• A more efficient approach for pandemic influenza diagnosis could be developed by implementing a “hub and spoke” system, whereby specimens are screened for influenza A nucleic acids by the receiving laboratories and only positive specimens are referred for further characterisation. This would free up a vast amount of resources at both laboratory sites for efficient processing.

• This could be achieved by: directing some pandemic funding to private laboratories for specific pandemic influenza screening tests (as in the Queensland model); or adjusting the Medicare Benefits Schedule PCR reimbursement item (number 69496) to make such testing economically viable in the private sector.

***

So there you go – it seems that it’s time we stopped patting ourselves on the back about how well we have coped with the pandemic (or perhaps that should read, “how lucky we’ve been”), and started drawing and applying some lessons...

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  1. chazzai says:

    Re the very first point. What were the numbers of tests each year? I would imagine we did far more tests last year than in previous years. Wouldn’t that mean a proportion of positive results similar to previous years implied higher influenza activity than in the years with similar results?

  2. Croakey says:

    If you follow the link to Heath Kelly’s paper, you will see that he acknowledges there have probably been increased rates of presentation and of testing, which is why he looked at the proportion of requested lab tests that were positive for influenza, “a metric that corrects for increased testing associated with higher numbers of diagnostic requests for possible influenza, not necessarily associated with higher levels of influenza circulation”. He also acknowledges that this comparison may be biased by increased rates of presentation and testing.

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