Preparing for flu pandemics: A look back can provide clues to the future

December 2006

Preparing for the next pandemic means learning from the past.

History suggests that influenza pandemics have probably happened during at least the last four centuries. During the 20th century, three pandemics and several pandemic scares have occurred.

Reviewing the past pandemics, along with seasonal influenza, is necessary because much can be learned, according to Arnold Monto, MD, professor of epidemiology, University of Michigan School of Public Health in Ann Arbor.

The greatest unknown is the concern about surge capacity and how we can manage all these events taking place during a short period of time throughout the country and the world, according to Monto.

The last pandemic occurred in 1968, but the most recent pandemic scares occurred in 1997 and 1999.

In 1997, at least a few hundred people became infected with the avian A/H5N1 flu virus in Hong Kong and 18 people were hospitalized; six people died. This virus was different because it moved directly from chickens to people, rather than having been altered by infecting pigs as an intermediate host. In addition, many of the most severe illnesses occurred in young adults similar to illnesses caused by the 1918 Spanish flu virus. To prevent the spread of this virus, all chickens (approximately 1.5 million) in Hong Kong were slaughtered. The avian flu did not easily spread from one person to another, and after the poultry slaughter, no new human infections were found.

“If we have a pandemic caused by H5N1, attack rates will be different in different age groups. We cannot predict what it will look like. We know that H5N1 involves younger individuals, not just 20- to 40- year olds, but younger individuals with a higher case mortality. We have no way of estimating what the impact would be if this virus mutates or reassorts to be able to transmit person-to-person. We also have problems estimating from past experience on the use of antivirals, on the availability and need for antibiotics, given the kind of complications that may or may not be seen,” said Monto.

In 1999, another novel avian flu virus – A/H9N2 – was found that caused illnesses in two children in Hong Kong. Although both of these viruses have not gone on to start pandemics, their continued presence in birds, their ability to infect humans, and the ability of influenza viruses to change and become more transmissible among people is an ongoing concern.

Pandemics

The Spanish Influenza pandemic is the catastrophe against which all modern pandemics are measured. It is estimated that approximately 20%-40% of the worldwide population became ill and that more than 20 million people died. Between September 1918 and April 1919, approximately 500,000 U.S. deaths from the flu occurred. Many people died from this illness very quickly. Some people who felt well in the morning became sick by noon, and were dead by nightfall. Those who did not succumb to the disease within the first few days often died of bacterial complications from the flu, such as pneumonia.

Reports of the pandemic began with symptoms like headache, cough, muscle aches, back ache but then nose bleeds and diarrhea were also noted with this vaccine strain.

“Pneumonia was a frequent cause of death, leading to the assumption that a bacterial component existed also,” said Monto. “Therefore, stockpiling of antibiotics may also be advisable in pandemic preparedness.”

One of the most unusual aspects of the Spanish flu was its ability to kill young adults, according to Monto. The reasons for this remain uncertain. With the Spanish flu, mortality rates were high among healthy adults as well as the usual high-risk groups. The attack rate and mortality was highest among adults 20 to 50 years old. The severity of that virus has not been seen again.

In February 1957, the Asian influenza pandemic was first identified in the Far East. Immunity to this strain was rare in people younger than 65 years of age, and a pandemic was predicted. In preparation, vaccine production began in late May 1957, and health officials increased surveillance for flu outbreaks.

Unlike the virus that caused the 1918 pandemic, the 1957 pandemic virus was quickly identified, due to advances in scientific technology. Vaccine was available in limited supply by August 1957. The virus came to the United States quietly, with a series of small outbreaks over the summer of 1957. When U.S. children went back to school in the fall, they spread the disease in classrooms and brought it home to their families. Infection rates were highest among school children, young adults, and pregnant women in October 1957. Most influenza-and pneumonia-related deaths occurred between September 1957 and March 1958. The elderly had the highest rates of death, according to Monto.

By December 1957, the worst seemed to be over. However, during January and February 1958, there was another wave of illness among the elderly. This is an example of the potential “second wave” of infections that can develop during a pandemic. The disease infects one group of people first, infections appear to decrease and then infections increase in a different part of the population. Although the Asian flu pandemic was not as devastating as the Spanish flu, about 69,800 U.S. deaths occurred.

In early 1968, the Hong Kong influenza pandemic was first detected. The first U.S. cases were detected as early as September of that year, but illness did not become widespread until December. Deaths from this virus peaked in December 1968 and January 1969. Those older than 65 were most likely to die. The same virus returned in 1970 and 1972. The number of deaths between September 1968 and March 1969 for this pandemic was 33,800, making it the mildest pandemic in the 20th century.

There could be several reasons why fewer people in the United States died from this virus. First, the Hong Kong flu virus was similar in some ways to the Asian flu virus that circulated between 1957 and 1968. Earlier infections by the Asian flu virus might have provided some immunity against the Hong Kong flu virus that may have helped to reduce the severity of illness during the Hong Kong pandemic. Second, instead of peaking in September or October, like pandemic influenza had in the previous two pandemics, this pandemic did not gain momentum until near the school holidays in December. Since children were at home and did not infect one another at school, the rate of influenza illness among schoolchildren and their families declined. Third, improved medical care and antibiotics that are more effective for secondary bacterial infections were available for those who became ill.

Monto said paying attention to these influenza pandemics hold important lessons for today.

Defining how these viruses reassort could be the key to stopping the illness in its tracks.

Monto’s talk was particularly timely, in light of a recent letter published in Nature, in which Yoshihiro Kawaoka and his colleagues noted identifying two key changes that allow the virus to reassort.

Kawaoka, a professor of virology at both the University of Wisconsin-Madison and the University of Tokyo and colleagues noted that identifying these mutations could help those trying to fight the illness slow transmission.

This information is particularly needed now, as more cases are reported throughout Europe and Asia.

Just last month, the Ministry of Health in Indonesia confirmed an additional two cases of human infection with the H5N1 avian influenza virus. Of the 74 cases confirmed to date in Indonesia, 56 have been fatal.

As reports continue on the global spread of avian flu, government officials here are taking steps to prepare for the flu.

Earlier this year, the federal government released a pandemic influenza preparedness plan.

In October, officials with the World Health Organization announced their plan for boosting vaccines, in the brochure, Global pandemic influenza action plan to increase vaccine supply.

“We are presently several billion doses short of the amount of pandemic influenza vaccine we would need to protect the global population. This situation could lead to a public health crisis,” Marie-Paule Kieny, Director, WHO Initiative for Vaccine Research said in a press release.

“The Global Action Plan sets the course for what needs to be done, starting now, to increase vaccine production capacity and close the gap. In just three to five years we could begin to see results that could save many lives in case of a pandemic.”

The Global Action Plan identifies and prioritizes practical solutions for reducing the potential pandemic influenza vaccine supply gap; these are contained in eight strategies with activities for the short (tangible results in less than five years), medium (five to ten years) and long (more than ten years) terms. Activities need to be undertaken simultaneously.

The three main approaches to closing the vaccine supply gap are identified in the Global Action Plan as:

• an increase in seasonal influenza vaccine use to provide protection against seasonal influenza and at the same time use the increased demand to stimulate industry to produce more;
• an increase in production capacity through measures such as improving vaccine production yields and building new plants; and
• and further research and development to design more potent and effective vaccines that would induce protection after one dose and/or broad spectrum and long-lasting immunity, and produce vaccines more efficiently and quickly.

Last month, the United States and Mexico signed an agreement to boost cooperation on pandemic influenza preparedness among the six Mexican states and four U.S. states that share the international boundary.

Meeting in Hermosillo, Sonora, México, Health and Human Services Assistant Secretary for Public Health Emergency Preparedness Craig Vanderwagen and the Mexican Director-General of Epidemiology of the Mexican Federal Secretariat of Health Pablo Kuri signed a joint declaration to strengthen the commitment of the two nations to coordinate preparedness efforts, domestic and international disease surveillance activities, and response planning in the event of an outbreak of pandemic influenza.

The agreement was finalized during the 14th meeting of the US- México Border Health Commission, established in July 2000 to provide international leadership to enhance health and the quality of life among residents along both sides of the United States- México border.

The commission’s purpose is to raise awareness about public health issues in the region and the health and medical challenges faced by border populations.

For more information:

• Monto A, Hayden F, Bell D, Keitel W. Confronting pandemic influenza: Evidence-based interventions. Session 144. Presented at the 46th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy. Sep. 27-30, 2006. San Francisco.
• National Vaccine Program Office. Pandemics and pandemic scares in the 20th century. http://www.dhhs.gov/nvpo/pandemics/flu3.htm#8.