The Pharmaceutical Journal
Vol 276 No 7383 p50-51
14 January 2006

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American Society of Health-System Pharmacists

Bird flu and pandemic preparedness — control measures and treatment

Avian influenza pandemics differ from natural disasters such as earthquakes or hurricanes in that the latter are usually short and geographically limited. In contrast, pandemics occur in waves and are, by definition, geographically widespread. Most critically, there are often volunteers to help with natural disasters, but people may be reluctant to volunteer to help in a pandemic.

Should the current avian influenza virus (H5N1) mutate into a form that can transfer between humans, then it is predicted that 25 per cent of the population could be infected. The treatment options include both antiviral agents and vaccines. A vaccine would be the more effective option but a vaccine cannot be made until the epidemic strain of the virus emerges. Currently in the US there are only three vaccine manufacturers and the technology that is used for vaccine preparation is suboptimal. Moreover, vaccine production relies on eggs, which may become in short supply if there is large scale slaughtering of chickens as a disease control measure.

The virus

Influenza viruses carry two surface antigens: a neuraminidase that enables easier penetration into the respiratory tract and a haemagglutinin, explained Kristi Kuper, director of infectious disease outcomes, Cardinal Health. There are nine subtypes of the neuraminidase and 16 subtypes of the haemagglutinin and it is the combinations of these that are used to characterise the viruses (eg, in this case H5N1). In addition, influenza A viruses carry an M2 ion channel.

The M2 ion channel blockers rimantidine and amantidine can be used to treat influenza A infections whereas neuraminidase blockers such as oseltamivir and zanamivir are active against both influenza A and B. Oseltamivir has been used in both prophylaxis and treatment of human avian influenza infection but experience with zanamivir is limited to in vitro and animal studies. A recent World Health Organization review of cases of bird flu in humans had concluded that early use of neuraminidase inhibitors was likely to be beneficial. However, there is uncertainty about whether a higher dose or longer duration of treatment is needed (than for seasonal flu). Concerns about resistance to antiviral agents have also been raised and oseltamivir-resistant organisms have already been isolated from some patients.

Control measures

Ryan Forrey, assistant director of pharmacy, Ohio State Medical Centre, had been in Singapore during the severe acute respiratory syndrome outbreak and experienced many of the control measures at first hand.

Thermal screening of individuals to identify those with pyrexia was introduced at airports and at hospital entrances. Those who were cleared were given a dated sticker to wear. In addition, thermometers were issued to all hospital staff and they were required to log into a website three times daily, on work days and leave days, to record their temperatures. In the emergency department, triage tents were erected and an electronic tracking system was implemented for all staff and visitors. Surgical masks were also worn.

Most hospitals in Singapore have large outpatient pharmacies and during the outbreak off-site pick-up of medicines and home delivery arrangements were introduced to avoid unnecessary visits to the hospital.

Because there were no effective medicines or vaccines for SARS, management relied on effective isolation and supportive care. All patients were sent to a single hospital and visiting was restricted. Inpatient and outpatient staff were kept apart and the pharmacists who served the SARS wards were allowed no contact with the other inpatient pharmacists. A pneumatic tube system was used to deliver medicines and satellite pharmacies were used to provide ward supplies. Staff restaurants were closed. In the wider community, changes in social behaviour were apparent, for example, Roman Catholics bowed instead of shaking hands during mass, taxi drivers refused to use some routes and many people wore surgical masks in public.

Turning to preparations for pandemic influenza, Dr Forrey said that it was best to assume that there would be no help from elsewhere and, in making pharmacy staffing plans, the possibility that staff may have to be donated to work elsewhere in the hospital should be considered. Off-site access to the hospital intranet was needed to enable remote checking of prescriptions. It has been assumed that the supply of oseltamivir would be limited and would therefore be reserved for confirmed cases of pandemic influenza. A key measure will be keeping health care workers healthy and so they should all be vaccinated for seasonal influenza. Those who are infected with pandemic influenza should receive treatment and post-exposure prophylaxis will also be provided.

It will be important to communicate the restrictions on antiviral use to the greater hospital community and to reassure staff about safety concerns, he said. All international students should be vaccinated for seasonal influenza so that if they develop signs of infection, it will be clear that it is the H5N1 strain. Signage to encourage hand washing and the use of sanitisers should be increased.

Keeping the media informed will be important and this should be handled through the hospital’s media representative. “Be honest, but limit the scope of what you say,” recommended Dr Forrey. For example, it would be unwise to say how much or how little oseltamivir was in stock because either could lead to a prejudicial headline.

Treatment

Working closely with public health authorities is essential in effective preparation for an influenza pandemic, advised John Zarek, director of clinical pharmacy services for the Swedish Medical Centre in Seattle, Washington. Preparations for avian influenza are particularly important in Seattle bacause it is a major portal for traffic from South East Asia, he said.

In early discussions with the public heath authority it has been agreed that oseltamivir will be reserved for treatment rather than prophylaxis. Priority groups will be hospital inpatients, health care and emergency services workers and pandemic responders, including public safety workers and key government decision-makers. Prophylactic treatment would only be offered if there were adequate supplies and then priority groups would include those eligible for post-exposure prophylaxis, health care and emergency services workers, intensive care staff and those at highest risk. Practical aspects of medicines supply and distribution are an important part of the plan.

The Department of Health and Human Services (HHS) has published a plan that calls for stockpiling of antivirals in preparation for the pandemic. Dr Zarek pointed out that this needs to be planned in the light of what the manufacturer can supply, the shelf-life of the products, the cost and the likelihood of having to treat episodes of seasonal flu in the meantime.

Another issue was the question of personal stockpiling. Neither the Centres for Disease Control nor the HHS has advised against personal stockpiling and, given that the national stockpile is inadequate, it would be a logical step for many people. Moreover, oseltamivir is widely available in the private sector for treatment of seasonal flu. The arguments against personal stockpiling include that it could cause shortages and give rise to difficulties in treating seasonal flu, the optimal dose and effectiveness are unknown, it may be used inappropriately because people may not know when to start therapy and distribution would be inequitable. Plans have also been drawn up for initial management of suspected cases.

During the discussion Dr Kuper was asked whether there was a rapid screening test for H5N1 influenza. A test was under investigation but at present only a six-hour screening procedure was available. In response to a question about stockpiling Dr Zarek said that his hospital had small stocks but in the event of an outbreak supplies would be shared with the local public health agency. The manufacturer, Roche Products, has a website that shows where there are outbreaks of seasonal flu and it plans to channel supplies to these areas. Dr Kuper commented that generic oseltamivir might also be available.