Medical Device Daily

As the number of infections and deaths continue to rise – and for the first time in four decades – the World Health Organization (Geneva, Switzerland) has declared a pandemic influenza outbreak of an entirely new virus: swine (H1N1) influenza.

"The world is now at the start of the 2009 pandemic," said Margaret Chan, WHO director general, during a press conference on Thursday. "We are in the earlier phase of the pandemic. The virus is spreading. No previous pandemic has been detected so early or watched so closely in real time."

As of June 11, 2009, 74 countries have reported 28,774 cases of lab-confirmed swine flu infections and 144 people have died.

Chan told a global audience of news reporters via teleconference that even though the virus has not been comparatively deadly since it emerged in April, "We do not know how this virus will behave under conditions typically found in the developing world. To date, the vast majority of cases have been detected and investigated in comparatively well-off countries. Let me underscore two of many reasons for this concern. First, more than 99% of maternal deaths, which are a marker of poor quality care during pregnancy and childbirth, occurs in the developing world. Second, around 85% of the burden of chronic diseases is concentrated in low- and middle-income countries.

"Although the pandemic appears to have moderate severity in comparatively well-off countries, it is prudent to anticipate a bleaker picture as the virus spreads to areas with limited resources, poor healthcare and a high prevalence of underlying medical problems," she said.

Chan and other WHO authorities earlier in the day met in an emergency meeting. Before raising the alert from 5 to the highest level, 6, she said they consulted with leading influenza experts, virologists and public health officials. The decision was made in line with procedures set out in International Health Regulations.

H1N1 was first isolated from a pig in 1930 and the current human outbreak was first noted in early spring of 2009. It causes a respiratory disease that isn't particularly harsh in terms of symptoms for most people. What is notable about this version of the flu is that it attacks a very different population of people. Typically the old, very young and those with underlying health conditions suffer the most from the flu. But most of the people who have gotten sick from H1N1 are between the ages of five and 24, and 40% of those hospitalized were between the ages of 19 and 49, a twist that has alarmed public health officials.

"This pattern is significantly different from that seen during epidemics of seasonal influenza, when most deaths occur in frail elderly people," she said.

Many of those who have developed severe cases have underlying conditions. The WHO reported that the most frequent conditions are respiratory diseases (notably asthma), cardiovascular disease, diabetes, autoimmune disorders and obesity.

"We know, too, that this early, patchy picture can change very quickly," Chan said. "The virus writes the rules and this one, like all influenza viruses, can change the rules, without rhyme or reason, at any time. Globally, we have good reason to believe that this pandemic, at least in its early days, will be of moderate severity. As we know from experience, severity can vary, depending on many factors, from one country to another."

However, up to half of the severe and/or fatal infections occurred in previously healthy young and middle-aged people.

Chan also discussed the fact that previous pandemics typically took six to nine months to travel the globe – but that was via ship or rail. With today's air travel, the spread is expected to come much faster, including a second wave.

"Countries should prepare to see cases, or the further spread of cases, in the near future," she said. "Countries where outbreaks appear to have peaked should prepare for a second wave of infection."

All of this in light of the fact that no vaccine for H1N1 is yet available. She predicted that the first batches will be ready in mid-September. Those will likely be rationed to people at greatest risk.

"Without question, pregnant women are at increased risk of complications," she said. "This heightened risk takes on added importance for a virus like this one that preferentially infects younger age groups."

She added that vaccine makers are shifting into high gear so that vaccines will be available "soon" to ensure the largest possible supply of pandemic protection in the months to come. But a more specific timetable or plan of action for widespread vaccination has not yet been determined.

"Pending the availability of vaccines, several non-pharmaceutical interventions can confer some protection," she said. "Normally it takes four to six months to make a vaccine. For the next few months, no country will have vaccine. The challenge of the world is to look at who should get the vaccine, which groups get the vaccines."

Specific guidance on vaccine distribution will be coming in the next few weeks.

When asked if health authorities have noted any sort of mutation in the H1N1 virus, Chan said no. But interestingly, an analysis of the genomic data for H1N1 reveals that there is an increasing lethality related to the infection.

Replikins (Boston), a biotech firm that has conducted analyses, this week published a new sequence showing an increase in the Replikin count of H1N1 using the company's FluForecast software. Replikins are a new group of peptides related to the rapid replication function in viral and other diseases.

"Last month the H1N1 genomic data indicated some bad and some good news. While it indicated an increase in the infectivity of the H1N1 virus, its lethality appeared to remain relatively low," Sam Bogoch, MD, chairman of Replikins, said in a statement. "However, the FluForecast analysis of new data of the past few weeks on 144 new specimens published on PubMed, indicate an increase in the current H1N1 outbreak's capacity for lethality. Since the software also permitted the automated analysis of all sequence data available on PubMed for all previous years, it was noted that this is the first such significant increase in the Replikin Count of the H1N1 Lethality Gene in 76 years. This is cause for concern and an accelerated vaccine effort."

Despite many unknowns, the WHO did not enact any sort of travel restrictions or closures.

"We have a head start and this places us in a strong position," Chan said. "But it also creates a demand for advice and reassurance in the midst of limited data and considerable scientific uncertainty. Guidance on specific protective and precautionary measures has been sent to ministries of health in all countries."

She advised countries with few cases, or none at all, to be vigilant. Those with widespread transmission should stay focused on patient managements.

She also said WHO is suggesting a limit to testing and investigation of patients, because "such measures are resource intensive and can very quickly strain capacities."

Properly diagnosing swine flu may start with a rapid flu test, but confirmation of this novel infection is made only by reverse-transcription polymerase chain reaction (RT-PCR) or viral culture.

"Rapid influenza diagnostic tests can help in the diagnosis and management of patients who present with signs and symptoms compatible with influenza," reported the Centers for Disease Control and Prevention (CDC; Atlanta). "Data are not yet available to inform recommendations on the use of rapid influenza diagnostic tests in patients with novel H1N1 virus infection. It is reasonable to assume that rapid diagnostic tests that detect influenza A viral nucleoprotein antigen can detect novel H1N1 flu infection in respiratory specimens as these nucleoprotein antigens are highly conserved across influenza A viruses. However, the sensitivity and specificity of the different rapid tests is not yet known for this novel virus."

The CDC reported several incidents of false positive and false negative results and has advised physicians to use those tests with caution.

The CDC developed and distributed its own RT-PCR detection panel and viral culture via Emergency Use Authorization (EUA) from the FDA, but various government agencies still tapped medical technology companies to step forward with their advanced diagnostics to help with surveillance. A slew of other diagnostics firms, producing both the rapid and PCR-type tests, geared up as well when government health agencies confirmed the potential of a pandemic months ago.

Now that a pandemic is official, what's next? How will health authorities know when to lower the threat level? Chan said the Level 6 could go on for months. As the virus spreads, people will begin to develop immunity, but building immunity across populations could take a couple of years.

"Influenza pandemics, whether moderate or severe, are remarkable events because of the almost universal susceptibility of the world's population to infection," she said. "We are all in this together, and we will all get through this, together."