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Abkhazia: Influenza Prevention and Treatment plan

Influenza A virus is a member of the family Orthomyxoviridae. Influenza viruses are enveloped, with a segmented, single-stranded RNA genome. This family also contains influenza B and C viruses. Point mutations in the envelope protein hemagglutinin (H), referred to as antigenic drift, result in the emergence of new strains of influenza A and B viruses and the resultant annual outbreaks and epidemics. Subtyping of influenza A virus is based on antigenic characteristics of two envelope proteins, H and neuraminidase (N). New influenza A virus subtypes emerge as the result of reassortment of H and N sequences from two different subtypes, referred to as antigenic shift. These new subtypes are responsible for influenza pandemics. There are currently 16 recognized H subtypes and 9 recognized N subtypes.

While virtually all combinations of influenza A subtypes naturally infect waterfowl and shorebirds, certain subtypes infect poultry and mammalian species. Subtypes H1N1, H3N2, H2N2 and H1N2 have circulated, or are currently circulating widely, among humans. Subtype H5N1, causing highly pathogenic avian influenza, was identified in 1996 in southern China. Influenza A H5N1 is significant, though not unique, in its ability to cross normal species barriers and directly infect humans. Avian subtypes H9N2 and H7N7 are also known to cause infection in humans, so public health influenza surveillance programs monitor for emergence of any novel strains in humans. However, the wide geographical distribution of H5N1 in avian species, and the number and severity of human infections are unprecedented. If, or when, the virus reassorts to a strain transmitted readily among humans, and unless there is a dramatic decrease in the pathogenicity of the resulting virus, the result will likely be an influenza pandemic with mortality rates not seen since the 1918 pandemic.
1.2.1.    Epidemiology
The classical epidemiologic cycle of influenza A virus includes wild waterfowl and shorebirds, which are naturally infected; domestic waterfowl and poultry, which acquire virus from wild birds; pigs, which serve as “mixing vessels” for both avian and mammalian adapted strains; and humans, who are susceptible to the reassorted viruses. Reassortment can also occur during human-to-human transmission. Influenza A virus also infects maritime mammals, including seals and whales, dogs, and horses. The H5N1 virus has bypassed this epidemiologic cycle, crossed normal species barriers, and is capable of being transmitted directly from poultry to humans. First identified as a cause of highly pathogenic avian influenza in southern China in 1996, the virus has since spread to Southeast Asia, Middle East, Eastern and Western Europe, and Africa. H5N1 has been found in domestic fowl and a variety of migratory and resident wild bird species. Avian influenza strains infect the intestinal tract and are shed at high titers in feces. Transmission rates are high among birds congregating at bodies of water. The presence of H5N1 in a number of migratory bird species has resulted in its rapid spread among continents. In addition to birds, the virus has also been found in several mammalian species. Felines have become infected as a result of consumption of infected dead birds. Human infections caused by H5N1 were first identified in 1997. Human H5N1 infections are the result of exposure to high viral titers in infected birds or feces. There is evidence of human-to-human transmission, yet secondary cases are very limited due to avian host specificity of H5N1. Hundreds of confirmed human cases of avian influenza H5N1 have been reported to the World Health Organization, and the mortality rate has been approximately 50%. Human cases have been reported from Azerbaijan, Cambodia, China, Djibouti, Egypt, Indonesia, Iraq, Thailand, Turkey, and Viet Nam.
Influenza pandemics result from the emergence of antigenically distinct subtypes of influenza A virus. During the twentieth century, influenza pandemics occurred in 1918, 1957 and 1968. The subtypes causing these pandemics all had avian origins, and adapted to high transmissibility among humans. Pathogenicity among the pandemic virus strains varied.
Influenza virus is considered a Category C biothreat agent. Agents in this category are emerging, readily available, and easily disseminated. In addition, they are capable of causing high morbidity and mortality rates.
1.2.2.    Clinical Features
Influenza caused by H5N1 shares features with those caused by the Spanish influenza pandemic of 1918. Morbidity and mortality are severe in previously healthy, young and middle-aged persons. The innate immune response is in part responsible for pathogenesis, causing fluid accumulation in the lungs. While influenza caused by H5N1 is notable for its aggressive course and high mortality rates, evidence indicates that mild disease and asymptomatic infections occur. Symptomatic cases are characterized by high fever, cough, and lower respiratory tract symptoms (shortness of breath, pulmonary infiltrates) in virtually 100% of patients. Diarrhea occurs more frequently than with influenza caused by human-adapted subtypes. The frequency of pneumonia and diarrhea distinguish avian from seasonal influenza. Over 50% of reported H5N1 influenza cases were fatal. Death is primarily due to respiratory or multi-organ failure. Unlike human-adapted subytpes, H5N1 is found in relatively high titers in lower respiratory tract specimens, throat swabs and stool. Although it is not known if infections with a pandemic strain will have frequently demonstrable viremia, the current H5N1 virus has been isolated from serum.
1.2.3.    Treatment and Prevention
Recent isolates of influenza A H5N1 show varying resistance to the adamantanes (amantadine and rimantadine): clade 1 viruses are resistant, while the majority of clade 2 viruses are sensitive. The neuraminidase inhibitors, oseltamivir and zanamivir, are active against influenza A H5N1. However, the emergence of high-level resistance to oseltamivir during oseltamivir treatment has been demonstrated in some patients with influenza A H5N1 infections. These two patients had detectable virus at the end of a full course of treatment. An important component of avian influenza A H5N1 pandemic preparedness programs is the stockpiling of adequate supplies of neuraminidase inhibitors. Clinical trials and development efforts are currently ongoing for both inactivated and attenuated influenza A H5N1 vaccines.
2.    Purpose
The purpose of this plan is to provide a guide for the Center for Disease Control and Prevention in Abkhazia for detecting and responding to an influenza pandemic. This plan must be periodically reviewed and updated to ensure that its assumptions, resources, priorities, and plans are consistent with current knowledge and changing infrastructure. In addition, in the event of a pandemic, the judgments of the public health leadership, based on the epidemiology of the outbreak and the extent of population infection, may alter or override anticipated strategies and plans.

Ramaz Mitaishvili, MD

Glendale, CA 

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