Influenza (Flu) Research

2009 influenza A (H1N1) is a new and very different flu virus that is spreading worldwide among people.

For information about 2009 H1N1 flu, visit http://www.cdc.gov/h1n1flu/.

CDC carries out and supports flu research in an effort to reduce the health burden flu places on society and to promote improvements in human health. CDC supports collaborative research projects with the World Health Organization (WHO), state, local, and federal government partners, academic institutions, and other international partners. In addition, CDC also conducts its own public health research. Recent or ongoing areas of flu research by CDC include the reconstruction and analysis of the 1918 pandemic flu virus, laboratory testing to better understand human infection with avian influenza A viruses, epidemiology studies, research into new vaccine development methods and vaccine effectiveness studies. Additional information on CDC’s flu research can be found below.

1918 Pandemic Influenza Virus Research

What was the 1918 virus?

The so called “1918 virus” is the flu virus strain responsible for the 1918 pandemic that caused the deaths of an estimated 50 million people worldwide. An unusual feature of the 1918 pandemic was a high death rate among healthy adults 15-34 years of age. In fact, the 1918 pandemic virus was so virulent and deadly among healthy adults that it lowered the average life expectancy in the United States by more than 10 years. In contrast, most seasonal flu viruses—and the other two recorded pandemics of the 20th century—have caused higher death rates among the very young and the elderly.

Why is CDC studying the 1918 virus?

CDC is studying the 1918 virus to better understand pandemic flu viruses and to improve capacity to protect against future pandemic flu viruses. For more information regarding a CDC study on the 1918 virus, see Questions & Answers: Reconstruction of the 1918 Influenza Pandemic Virus.

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Avian Influenza (Bird Flu) Research

Why does CDC conduct research on bird flu viruses?

Birds are the natural hosts to all known subtypes of influenza A viruses, and while bird flu viruses mainly infect birds, they can—and have—crossed the species barrier to infect humans. Rarely, bird flu viruses may develop the capacity to infect and spread among humans. Those viruses that can spread efficiently among humans may lead to a pandemic. Because bird flu viruses are an important source of potential new human flu viruses, CDC seeks to learn more about these viruses and their properties, and how different bird flu subtypes and strains might affect humans.

Highly pathogenic avian influenza A (H5N1) viruses (Asian lineage) or so called “H5N1,” which began spreading in birds throughout Asia in 2003 and continue to spread to other regions, now meet two of the three conditions necessary for a pandemic to occur:

1. These are new influenza viruses in people to which there is little or no human immunity, and
2. These viruses have infected humans and caused illness.

However, highly pathogenic H5N1 viruses have not met the third condition for a pandemic: the viruses are not capable of easy and ongoing spread among humans.

Previous flu pandemics, particularly the 1918 pandemic, resulted in significant illness and death in humans. Again, because flu viruses change constantly, experts are concerned that highly pathogenic H5N1 viruses could develop the ability to spread easily among people, causing a pandemic.

Of the few bird flu viruses that have crossed the species barrier to infect humans, highly pathogenic H5N1 viruses have caused the largest number of detected cases of severe illness and death in humans. For this reason, CDC has focused considerable resources and time on monitoring H5N1 virus spread and monitoring changes in the virus, including the ability of influenza antiviral medications to work against H5N1 viruses.

What research has CDC conducted to better understand how H5N1 viruses are transmitted?

CDC’s Influenza Division is working to better understand bird flu viruses and their ability to infect and cause illness in mammals, including humans. Animal models have been developed in mice and ferrets to study how bird flu viruses infect and cause illness and to model how flu viruses may spread. In particular, the ferret model has been used to evaluate how H5N1 viruses might infect and cause illness in humans and other animals. Ferrets are useful in flu studies because their respiratory tract cells are similar to those of humans and are susceptible to similar types of viruses.

How has CDC research helped to improve testing for H5N1?

Research to improve testing for H5N1 viruses has strengthened the ability of the United States and foreign countries to quickly detect H5N1 viruses. In February 2006, the U.S. Food and Drug Administration (FDA) approved a lab test researched and developed by CDC to diagnose the avian influenza H5 virus (Asian strain). The real-time RT-PCR (reverse transcription polymerase chain reaction) primer and probe set is currently the only laboratory method cleared by FDA for avian influenza A/H5 testing and use in laboratory settings in the United States. The test has been made available to state public health laboratories, and also has been shared globally with the collaborating centers of the World Health Organization.

What research is CDC doing to assess the ability of H5N1 viruses to cause a flu pandemic?

CDC continues to research H5N1 viruses in order to asses their likelihood of changing into a pandemic flu virus. In an effort to better understand how H5N1 viruses are transmitted, and whether they could mix (reassort) with existing human flu viruses to become more transmissible, CDC conducted an experiment involving ferrets in 2006. In a secure laboratory setting, researchers mixed genetic material from H5N1 viruses and human flu viruses in an attempt to determine if a pandemic-capable virus would emerge. Although CDC researchers were able to successfully create viruses sharing genes from both H5N1 and human flu viruses, the resulting viruses appeared to lack the molecular and biologic properties needed for efficient spread among ferrets. The results suggested that H5N1 viruses require further genetic change to gain the properties needed to cause a human pandemic. View the article.

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Other Research

Disease Detection

What funding does CDC provide for flu diagnosis research?

In 2006, CDC awarded $11.4 million in contracts to four companies working to develop low-cost, rapid diagnostic tests that can distinguish between seasonal flu and bird flu within 30 minutes. Once developed, health care workers will be able to use these tests to quickly and accurately test patients for H5N1 and other emerging flu viruses.

How does improving testing for seasonal flu and H5N1 benefit people?

Tests used at doctor’s offices and hospitals to confirm cases of flu, also known as point-of-care (POC) tests, play an important role in identifying and tracking the spread of flu. By funding research and development of rapid response POC tests, CDC is working to create a public health network capable of quickly identifying the start of a pandemic. In addition, CDC also is funding research to improve flu tests used by public health laboratories, which can classify flu viruses by type and subtype. In preparation for a possible pandemic, public health laboratories must be able to test a large number of flu samples within a short period of time. CDC funding will aid research and development of these “high-throughput” laboratory tests, which when used in combination with POC tests, will improve the nation's ability to quickly detect an emerging pandemic.

Children

What recent research has CDC done to protect children from seasonal flu?

CDC conducts research to address the impact of flu on children. Recent work in this area includes:

• A study on laboratory-confirmed flu virus infections resulting in deaths in children in 2003-04 was used to better understand potential risk factors for severe and fatal flu cases in children (people aged 18 and younger) and to make recommendations to reduce flu-related deaths in children. This study suggested that chronic neurological or neuromuscular disorders could place children at greater risk from flu, and this information resulted in expanded flu vaccination recommendations for children with these conditions.
• A study on the number of doctor’s visits and trips to the emergency room among children as a result of flu virus infection improved understanding of the health impact of flu on children, and it also influenced the Advisory Committee on Immunization Practices’ (ACIP) decision to expand vaccination recommendations.

Can you give more information on the study involving children’s visits to emergency rooms and doctor’s offices?

This CDC study counted the number of reported flu-associated visits by children aged 5 years and younger to doctor’s offices or emergency rooms during the 2002-04 flu seasons. The study concluded that outpatient visits associated with flu were common among children younger than 5 years old and highlighted the burden that flu places on the health of children in the United States. The study’s findings played a critical role in the ACIP decision to expand annual flu vaccination recommendations from children 6-23 months of age to children 6-59 months of age in 2006. The results of this study appeared in the New England Journal of Medicine on July 6, 2006, in an article entitled “The Underrecognized Burden of Influenza in Young Children.”

What has CDC research taught us about the impact of flu in children younger than 6 months?

CDC researchers discovered that flu-associated deaths were highest in children younger than 6 months of age, underscoring the importance of protecting children younger than 6 months (who are too young to receive the vaccine) by vaccinating those around them, including household contacts and caregivers. The results of this analysis appeared on December 15, 2005, in the New England Journal of Medicine in an article entitled “Influenza-Associated Deaths Among Children in the United States, 2003-2004.”

How has CDC research impacted vaccination recommendations for children with disabilities?

A CDC study showed that chronic neurological or neuromuscular disorders could place children at greater risk of death from flu. This information was instrumental in the decision to expand the annual flu vaccination recommendations in 2005 to include all people with certain neurological conditions that could compromise their breathing. The results of this analysis appeared on December 15, 2005, in the New England Journal of Medicine in an article entitled “Influenza-Associated Deaths Among Children in the United States, 2003-2004.”

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New Vaccine Development

What vaccines are in development that do not require a shot?

CDC is collaborating with private sector partners to test a new skin patch delivery technology that could be used in place of a traditional shot during a pandemic. A skin patch can be easily applied. During a pandemic, the skin patch could be distributed to individuals seeking vaccination, and it could provide an effective means of vaccinating large numbers of people quickly. Testing in mice has been promising so far.

What new, faster methods of producing flu vaccine are in development?

Since the 1970s, pharmaceutical companies have produced flu vaccine by injecting flu virus into fertilized chicken eggs—a process that requires at least six months and hundreds of millions of eggs to produce the amount of seasonal flu vaccine needed for the U.S. population. The process to manufacture a pandemic flu vaccine would be similar. Because of these production constraints, if a pandemic were to emerge, vaccine manufacturers would not be able to quickly produce vaccine. Therefore, CDC and collaborators from academia are researching alternative methods of producing flu vaccine. CDC is currently testing new vaccine strategies that do not rely on growth of virus in eggs. If successful, these new methods of vaccine production could boost vaccine production speed and supply, which would greatly benefit pandemic preparedness efforts.

Seasonal Vaccine Effectiveness

What is CDC doing to assess the effectiveness of the flu vaccine?

CDC is conducting several assessments of the effectiveness of seasonal influenza vaccines. While a number of research studies have demonstrated that flu vaccination works, the effectiveness of the flu vaccine can vary from year to year and among different groups of people. The ability of a flu vaccine to protect a person depends on at least two things:

1. The age and health status of the person getting the vaccine and
2. The similarity or “match” between the virus strains in the vaccine and those in circulation.

Because flu viruses and the seasonal flu vaccine change constantly, it is helpful to conduct periodic vaccine effectiveness studies. See Flu Vaccine Effectiveness: Questions and Answers for Health Professionals for more information.

What age groups is CDC studying to determine the effectiveness of the flu vaccine?

CDC, in collaboration with outside partners, conducts flu vaccine effectiveness studies that focus on laboratory-confirmed flu in both children and adults to determine how well the flu vaccine protects people from flu each year. The findings from these studies are then used to update vaccine recommendations or even support the need for new methods of vaccine production.

What vaccine effectiveness studies are being conducted among children?

CDC is conducting several vaccine effectiveness studies among children. Two studies are being conducted during the 2006-07 influenza season among children 6-59 months of age through CDC's Emerging Infections Program (EIP) and the New Vaccine Surveillance Network (NVSN). These studies will assess effectiveness of the vaccine in preventing laboratory-confirmed flu hospitalizations among children in this age group.

The New Vaccine Surveillance Network is another tool being used to assess flu vaccine effectiveness among children. Researchers participating in this collaborative effort collect flu specimens from children aged 5 and younger who are admitted to a hospital, emergency department or outpatient practice with respiratory illness or fever. All children who meet the study entry criteria are tested for flu, and researchers note whether or not study participants have received seasonal flu vaccine. Data collected from this study will help researchers determine the effectiveness of the flu vaccine for children.

What is CDC doing to improve the effectiveness of the seasonal flu vaccine among the elderly?

CDC is researching why people’s immune systems do not function as well when they grow older. This research is helping CDC develop strategies to overcome this by enhancing the bodies’ defense mechanisms to prevent infection and increasing the effectiveness of vaccines in the elderly. In a pioneering study, researchers in CDC’s Influenza Division demonstrated that human immune defenses become weaker with age. Currently, CDC is investigating new ways to boost immune function at the time of vaccination to improve immune response. In addition, CDC is working on pre-clinical studies on bird flu vaccines for the elderly. The outcomes of these studies will help to design improved vaccines to better protect the elderly.

For more information about flu vaccine effectiveness, visit Questions & Answers: Vaccine Effectiveness.

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