ATS 2009: Second Wave of H1N1 Flu Feared in the Fall

Kristina Rebelo

May 20, 2009

May 20, 2009 (San Diego, California) — In a special panel session here at ATS 2009: the American Thoracic Society International Conference, experts and public-health officials discussed the current situation and ways hospitals can prepare for a potential second wave of infections in the fall.

The novel influenza A (H1N1) virus "sneaked in the door while health authorities who should have known better were busy closing windows," said Carol J. Cardona, DVM, PhD, ACPV, from the Department of Population Health and Reproduction, and professor in the School of Veterinary Medicine, University of California, Davis, to an overflow crowd of thoracic and critical-care physicians.

"This virus has followed the pattern of all historic pandemics, and we've missed some precursors out there and we've missed some signals," Dr. Cardona said. She is a virologist and an expert in determining how disease-causing agents damage their hosts. Dr. Cardona's segment of the presentation was entitled "Swine Flu: Molecular Clues to the Origin, Transmission, and Pathogenesis of the Virus."

Failure to Detect Precursors

Dr. Cardona said she anticipates mutations in the virus. "Expect to see stepwise changes over time and incremental changes over time in influenza A viruses." She pointed out that there is opportunity for reassortment between and among viruses that will result in the generation of new antigenically novel strains filtered through poultry and pigs to humans. "You have several segments from one, then another, and then a third, for a triple reassortment; this results in big leaps in the genome," she said, referring to the origins of H1N1.

"We're providing ample opportunity with animals being raised quickly in large groups, where you have many, many generations. It's an efficient way to raise food and an effective way to spread viruses," Dr. Cardona said. "It is the replicative properties of influenza virus hemagglutinin [HA] subtype diversity mutants with altered receptor-binding properties that underlie virulence and spread. The viruses come together and reassert into pathogens that can infect humans. The disease outcomes are influenced by host immunity; viruses with novel HAs can evade host immunity and cause these diseases."

Dr. Cardona explained that there are no antibodies to H1N1 influenza, which is why it has spread so rapidly. "And that's the unusual thing about this virus: we failed to detect precursors and we failed to find it in swine." She said that the H1N1 influenza has the ability to spread quickly. "It could happen within a few days, the mutation in animals, and infect other species," she said, pointing out the recent swine herd in Canada where, earlier this month, a traveler carried the new H1N1 virus from Mexico to Canada, infecting his family along with a herd of swine, according to Canadian health officials.

Also on the panel was Rear Admiral Kenneth G. Castro, MD, acting chief/science officer of the Centers for Disease Control and Prevention Emergency Operation Center, who told attendees that because this H1N1 influenza is spread from person to person, it's beginning to prepare for a pandemic. "This is what we are preparing for and worrying about," he said. The title of his presentation was "Human Cases in the United States of Swine Influenza."

He predicted that we have not seen the last of this H1N1 influenza: "Clearly, this virus has readily spread across the [United States] at a time we're no longer experiencing influenza. The criteria for this virus have nothing to do with the severity problem in pandemic planning. This is very likely to be circulating and you can expect to see it again when our virus season occurs."

Dr. Castro pegged the number of confirmed or probable cases in the United States at 5469, with 6 deaths (as of May 20, 7 deaths; a 44 year-old man in St. Louis who had visited Mexico died) in 48 states and the District of Columbia. Only Wyoming and West Virginia have had no confirmed cases. The median age is 17 years (range, 1 month - 87 years); 63% of those afflicted had an underlying medical condition at the time of illness onset. The average stay in a hospital is 4 days, with a median stay of 5 days (range, 2 - 31 days); 24% were admitted to the hospital's intensive care unit (ICU).

He described the clinical presenting characteristics as fever, cough, shortness of breath, and sore throat, with 52% of presentations having abnormal findings of bilateral infiltrates consistent with pneumonia; 31% also had asthma or diabetes. Of the population presenting to hospitals, 66% were treated with antivirals and 85% were treated with 1 to 7 antibiotics (overlapping), with a median of 3. "Everything has been thrown into the equation to try to treat these hospitalized patients," Dr. Castro said.

He recommended that patients with any early signs of influenza stay home, and he pointed out that closing schools was no guarantee that students wouldn't assemble at local malls.

Second Wave Likely

Also on the panel was Christian E. Sandrock, MD, MPH, deputy health officer of Yolo County in Sacramento, California, and assistant clinical professor, Division of Pulmonary and Critical Care Medicine, University of California, Davis, School of Medicine. He told the audience: "With regard to what may happen in the Southern Hemisphere in the next few months, I get to be intensely prophetic or the village fool." His presentation was entitled "H1N1 2009: Should We Be Concerned About a Second 'Wave'?"

He compared previous worldwide pandemic patterns that occurred in the twentieth century — the 1918, 1957, 1968/1969, and 1977 (in children) pandemics that represented 3 different antigenic subtypes of the influenza A virus (H1N1, H2N2, and H2N2) — to this current swine-origin influenza A (H1N1) virus first detected in April 2009.

"The 1 difference in pattern is that this current virus is widespread, around the world to multiple continents, and we're heading toward a second wave. We're moving in that direction," he said, "and the second wave is very likely."

Dr. Sandrock said there is no vaccine that will protect against the virus, but he said that if populations are old enough to have experienced the 1968 strain, for instance, they may have a host-adapted MHC I primed T-cell response with epitopes, [which] is appropriate for viral clearance [and] may confer some protection and result in a mild to moderate disease, where the host would just "feel crummy." Dr. Sandrock added that patients who present with asthma and a fever should not be written off but should be screened for influenza.

When asked how quickly he thought the current virus would mutate, he called that the "million-dollar question." Dr. Sandrock noted that "it takes a while for the virus to mutate and spread, but once it's up and going, we'll see a surge in the numbers and deaths."

Lewis Rubinson, MD, PhD, assistant professor of medicine, pulmonary and critical care medicine, Harborview Medical Center in Seattle, Washington, gave a segment entitled, "Swine Flu: What if the Critical Care Need Increases?" He said that the goals of the ICU in this era of phase 5 are to keep the hospital staff safe. "One of the hardest things for providers is how to integrate into the hospital but not take it over; there's nothing worse than having a leader working alone."

(The World Health Organization [WHO] raised the worldwide pandemic alert level to phase 5 on April 29; phase 5 is a "strong signal that a pandemic is imminent"; however, there is a current debate at the WHO World Health Assembly in Geneva, Switzerland, as to whether the WHO should raise the alert level to phase 6, which would indicate that a pandemic is under way. US Secretary of Health and Human Services Kathleen Sebelius said in Geneva that the United States is already taking phase 6 measures.)

Risk Stratification and Prophylaxis

Dr. Rubinson warned that triaging could get very confusing if coordination and integration within the rest of the institution are not on board. "When you have groups operating independently, you can lose control of the system," he said. "You don't have convalescent homes evacuating patients to emergency rooms." Dr. Rubinson said that hospitals needed to have standardized decision-making in place. "Maybe we should start thinking about risk stratification and prophylaxis at this point in time — the key interventions should take place in cases where patients might not survive if we do not provide them."

He suggested that hospitals start looking around at items most frequently used in their ICUs and get stocked up now. "Even if you're a behemoth, you will be competing with all the other behemoths for supplies, and if you run out of something like corticosteroids or ventilator circuits, you're in trouble." Dr. Rubinson noted that even if this virus "fizzles out," stockpiled supplies will eventually be used.

He said it might get to the point that entire hospitals will be converted to ICU care, because institutions cannot care for ill patients in tents that are not equipped with liquid oxygen systems. He suggested that acute respiratory distress syndrome and asthma would be the predominant conditions of presenting patients. "Despite excellent care, people are still dying and until recently there were no good data to predict just how sick people would be; these are sick people who will require a full-court press of what we can provide."

Rounding out the group was Guillermo Dominguez-Cherit, MD, who heads up the ICU in the Department of Critical Care Medicine, Instituto Nacional de Ciencias Medicas y Nutrición in Mexico City, Mexico, whose presentation was entitled "Caring for Critically Ill Patients in Mexico City Infected with Swine Flu." He informed attendees that as of May 4, 2009, there were a total of 3646 cases, with 70 deaths as of May 18, 2009. He described life in Mexico since April 17, when the Minister of Health closed schools and took other extreme measures. He showed slides of empty streets and business centers. "You can imagine the impact on the economy," he said.

Staffing in Mexico's hospitals had been an issue, with some employees refusing to come to work, final-year nursing students were being used to staff ICUs, and they were recruiting physicians from other departments, such as anesthesia and surgery, to help care for the influenza patients, Dr. Dominguez-Cherit said.

He added that at least half of all hospitalized patients had 2 or more comorbidities, and 78% had bilateral infiltrates on presentation. Other symptoms were respiratory distress, fever (100%), diarrhea, conjunctivitis, vomiting, coryza, weakness, and myalgias. The time from the first symptom to admittance to a medical facility was 6 days, and once in the hospital, the time to ICU admittance was 1.6 days, with an average hospital stay of 9.5 days. The locations of deaths within medical facilities were the ICU and the emergency department.

Dr. Dominguez-Cherit suggested that a global plan be in place so that action could be quickly taken to combat the anticipated influx of disease.

ATS 2009: American Thoracic Society International Conference: Special Session. Presented May 19, 2009.

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