Amy Ray, MD
Health Policy On-line Chapter
Influenza is an acute viral illness which causes significant human morbidity and mortality. It is known to have caused disease for several hundred years, and in 2006, it remains at the forefront of the daily news. As threats of H5N1 or avian influenza as well as drug-resistant influenza loom large, many questions face public health practitioner, including who is at risk for disease, what medications are available to treat influenza, how can spread be thwarted. This chapter will provide the latest influenza information for the public health practitioner and clinician alike.
Influenza epidemics have been recognized as early as the 12th century (1). Characterized by fever, cough, malaise, and body aches, influenza cyclically causes disease every one to three years. The high attack rate and periodicity made influenza outbreaks describable by astute observers prior to the advent of virologic techniques which later identified the virus as the causative agent. Combined with the high attack rate, the virus’ ability to change itself keeps a human population susceptible to epidemic outbreaks. In 1580, the first pandemic, or disease worldwide, was described, and since, thirty-one pandemics have been recorded. The most devastating occurred in 1918-1919, when estimates place death counts at 21 million worldwide or greater (2).
Influenza virus is classified in the viral family Orthomyxoviridae. Disease is caused most commonly by influenza A, B, or C. The types of influenza differ in their host(s), epidemiology, and clinical features. For example, influenza A affects human, birds, swine, equine, and marine animals. It also possesses the ability to change its surface proteins, resulting in decreased immunity in a newly exposed population. Influenza B infects humans only, where influenza C infects both humans and swine.
Influenza viruses have proteins on their surface called neuraminidase and hemagglutinin by which strains are identified. Influenza A viruses have at least fifteen distinct hemagglutinins described and nine distinct neuraminidase proteins. The avian influenza which is sporadically causing disease in humans currently is commonly referred to as “H5N1”, indicating that the virus has the 5th hemagglutin described and the first neuraminidase.
Influenza causes an acute, usually self-limited illness which is characterized by fever, malaise, body aches, and dry cough. It affects the respiratory system primarily, including the lungs, sinuses, and nasal passages. The incubation period, or time from exposure to the virus to infection, is 1 to 2 days. It can be distinguished from other respiratory viral illnesses by the systemic manifestations of high fever for 3 days on average with accompanying headache, chills, and lack of appetite with diffuse muscles aches. A contagious illness, influenza is spread via respiratory secretions and contaminated surfaces. Humans at the extremes of age, those who are immunocompromised secondary to chronic disease or required medications, and those with underlying cardiac or pulmonary disease can suffer complications of influenza, including bacterial pneumonia, myositis or inflammation of the muscles, myocarditis or inflammation of the heart muscle, and neurological complications such as encephalitis.
epidemiology of influenza-associated morbidity and mortality is
staggering. The burden of disease is
usually expressed in rates of pneumonia which exceed the expected rate and in
influenza-related hospitalizations and deaths during epidemics (3, 4). In temperate climates, the disease incidence
follows a typical pattern of peaking in the winter months at the height of influenza
season and troughs in the summer months.
Influenza has an attack rate of 10-40 percent; therefore, when a susceptible population is exposed to influenza, up to 40 per cent will acquire the disease. Those most at risk for infection are the very young and the elderly, and mortality is highest for the elderly. Other categories of persons at high risk for acquiring influenza include the immunocompromised such as persons with HIV/AIDS or transplant recipients and pregnant women.
An influenza epidemic is characterized by a sharp increase in disease within one location, such as city, state, or country. For influenza A, the disease peaks in 2 to 3 weeks and lasts 5 to 6 weeks. Typically, the first sign of an influenza A outbreak is an increase in the number of children with respiratory illness associated with fever, although occasionally the first sign of an outbreak will occur within a nursing home in a community. The numbers of admissions to hospitals for pneumonia, exacerbations of asthma and chronic obstructive pulmonary disease, and heart failure rise, as well as school and work absenteeism. The outbreak usually stops prior to infection of all susceptible hosts within a community for unknown reason(s), but increased awareness and infection control measures contribute to cessation of the epidemic.
influenza virus can be isolated from an infected individual’s nasal or upper
airways secretions. Viral culture, or
growth of the virus from a clinical specimen on special media, takes three to
seven days. The most common method of
diagnosis is a rapid influenza test, which tests the patient’s secretions for
the presence of a viral antigen. These
tests are easy to perform and results can be obtained as quickly as thirty
minutes. For these reasons, the rapid
influenza test(s) are widely available in the
In addition to viral culture or antigen detection methods, the diagnosis is often suspected on epidemiological and clinical grounds. If influenza is known to be present in a community, when a patient presents with signs and symptoms consistent with influenza, the clinical diagnosis alone is often correct (6, 7).
Treatment of influenza is available; however, no study has shown benefit of treatment if given 48 hours after the clinical onset of disease. In healthy human hosts, influenza viral replication is rapidly limited, especially in humans who have been exposed to influenza in the past.
The antiviral drugs active against influenza include amantadine and rimantadine, which are M2 inhibitors, and zanamivir and oseltamivir, which are neuraminidase inhibitors. The M2 inhibitors are active against influenza A only. The neuraminidase inhibitors are active against both influenza A and B. All four drugs can be used for prophylaxis after exposure to influenza. Drug resistance has occurred to both classes of medications, though rarely to the neuraminidase inhibitors (8, 9).
effective means of preventing influenza is vaccination. First available in 1943 in the
influenza vaccination is direly important to public health, meeting production
goals and population demands is often challenging. During the fall of 2004, the citizens of the
shortage of influenza vaccine highlights the current problems with vaccine
supply and demand. The entire
In September 2005, the United States Government Accountability Office (GAO) submitted a report to the United States Congress entitled, “Influenza Vaccine: Shortages in 2004-2005 Season Underscore the Need for Better Preparation” (13). Within the report, the authors review the actions taken by various governmental agencies at the local, state, and federal level to deal with the shortages of influenza vaccine as well as underscore the lessons learned from the shortage. The primary action taken within all sectors of government was the redistribution of vaccine supply to those most at risk, including new CDC recommendations on recipients during the shortage. During mid-December through January, health officials then broadened recommendations to more widely serve the population.
report highlights three interrelated lessons from the influenza vaccine
shortage during the 2004-2005 season. Prior
to the announcement of the thwarted supply of vaccine from Chiron, the CDC had
no contingency plan in order to contend with a severe shortage. A number of states utilized emergency
responsiveness plans and health directives in lieu of a specific federal plan
from the CDC. Although federal agencies
purchased more vaccine from other suppliers not licensed in the
The influenza season of 2004-2005 proved to be mild to moderate, and the CDC’s postseason data indicate the levels of vaccination in high-risk groups approached historical rates (14). Clearly, had the season been more severe, the lack of planning and delayed purchase of vaccine could have been disastrous. The Department of Health and Human Services agreed with the GAO in terms of the importance of contingency planning, and approval for additional suppliers of influenza vaccine is ongoing.
What distinguishes H5N1 from other influenza viruses is its habitat and virulence among fowl. Given that it is spread by migratory birds, it is unlikely to be contained. It can be spread from birds to mammals, and like all influenza viruses, H5N1 will continue to evolve. Most, if not all, human cases have been a result of direct contact with infected poultry. No sustained human-to-human transmission has occurred, and this mode of transmission is needed in order for H5N1 influenza to result in a pandemic.
Symptoms of avian influenza in humans are not unlike those caused by more typical human influenza, including fever, headache, body aches, and cough. More severe manifestations such as pneumonia and acute respiratory distress syndrome have occurred. The number of cases in humans may be an underestimate, as only the more severe cases are currently being reported.
Currently, there is no H5N1 vaccine for humans, although the United States National Institute of Allergy and Infectious Diseases (NIAID) is working on vaccine development based upon currently circulating H5N1. NIAID is collaborating with industry to increase the vaccine production capability and researching new types of influence vaccines (16). The neuraminidase inhibitors are active against H5N1; however, drug resistance is a concern, and additional studies are needed to confirm efficacy of these medications against H5N1 influenza.
A severe influenza pandemic whether caused by H5N1 or another influenza strain will undoubtedly take a large toll on society, including high rates of death, illness, social disruption, and economic loss. Deaths caused by pandemic influenza will depend upon the virulence of the virus, the number of infections, and the degree of preparedness. In order to prepare for a pandemic of influenza, the World Health Organization (WHO) is leading the global efforts. Keys to success are early detection of outbreaks and containment, vaccine supply, medication supply, adequate food and water stores, and clear delineation of roles and responsibilities of governments. The WHO has planned a draft protocol to the facilitate the early detection of an outbreak in order to thwart a pandemic at its start (17) The plan is extremely time-dependent and involves early detection and confirmation of the disease, rapid containment via isolation or social distancing, and mass administration of antiviral drugs within the outbreak zone in order to prevent future infections. An international stockpile of oseltamivir has been established which amounts to 3 million treatment courses which will be used in the event of sustained, person-to-person transmission. In addition to international planning, the WHO has outlined emergency preparedness goals for individual nations (18), many of whom are also stockpiling antiviral agents and coordinating governmental and private sector plans.
Influenza is a viral illness which causes significant morbidity and mortality. Its consequences are most harsh for those persons at the extremes of age. Successful management of future epidemics and prevention of a pandemic include early detection of disease, efficient containment, adequate and accurate vaccine supplies, medication supplies, and management of health care resources. Adequate planning for contingencies and communication among international and local agencies are fundamental, as is personal preparedness.
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