AVIAN INFLUENZA INTRODUCTION & HISTORY: Avian influenza (also known as bird flu or avian flu) is a type of influenza

virus that is hosted by birds but may infect several species of mammals. It was first identified in Italy in the early 1900s and is now spread world wide. Its first pandemic was in the year 1889, worst pandemic began in 1918. About 20 to 40 million people died of this disease. Subsequent pandemics occurred in 1957, 1968 and 1977. A strain of the H5N1- type of avian influenza that emerged in 1997 has been identified as the most likely source of a future pandemic. Virus was first defined and known as fowl plague in 1878. PUBLIC HEALTH IMPORTANCE: In UK, 1918 pandemic (23%), in 1957 to 1958 Pandemic (17%), 1969 to 1970 (8%) human populations developed influenza. Human influenza epidemics may also affect public health due to socio-economic impact and monopolization of health care resources during an epidemic. INFLUENZA IN BIRDS: There are two forms of disease. Very virulent viruses produce 100% mortality (Fowl plague or avian influenza). These belong to subtypes H5 and H7. Influenza A (H5N1) virus is an influenza A virus subtype that occurs mainly in birds. It was first isolated from birds (terns) in 1961 in South Africa. Like all bird flu viruses, H5N1 virus circulates among birds world wide. ETIOLOGY & NOMENCLATURE: Influenza viruses are members of family Orthomyxoviridiae. They are RNA viruses, are divided into three types (A, B and C) based on the antigenic differences between their nucleoprotein (NP) and matrix (M) proteins. Type A Influenza viruses naturally occur in humans, horses, swine and birds, Type B and C infect humans and type C also infects pigs. There are many subtypes of Influenza A virus, classified on the basis of Hemagglutinin (HA) and Neuraminidase (NA) proteins. Only Influenza A has been isolated from birds.

Viruses are grouped on the basis of antigenic nature of internal nucleocapsid or matrix protein. NOMEN CLATURE: The Nomenclature system includes the host of origin, geographic origin, strain number and year of isolation. A description of the two major surface antigens, the hemagglutinin and the neuraminidase is given in parenthesis, for example, (a) A (Swine/New Jersey/8/76 (H1N1) (b) A/duck/Alberta/35/76 (H1N1). MORPHOLOGY: Influenza virus particles are irregularly shaped roughly spherical particles or filamentous with the diameter of 80-120 nm (Fig-page 362, Carter). There are two distinct types of surface spikes (peplomers). One is rod shaped and corresponds to the hemagglutinin (HA), and the other is mushroomshaped and possesses neuraminidase (NA) activity. Both HA and NA are glycoproteins. Viruses are grouped on the basis of antigenic nature of internal nucleocapsid or matrix protein. Influenza A type is further sub typed on the basis of HA and NA antigens, fifteen HA (H1 to H15) and nine NA (N1 to N9). MOLECULAR BIOLOGY: Genome of influenza A and B viruses consist of 8 unique segments of ss RNA and influenza C possesses 7 segments of RNA. HA protein is responsible for binding of virions to host cell receptors and for fusion with host cell. HA is subject to high rate of mutation and is the major target of host immune response. NA functions to free virus particles from host cell receptors to enable progeny virions to escape from the cell and facilitate virus spread. Avian influenza viruses are of two types: (a) Low pathogenic avian influenza (LPAI) (b) High pathogenic avian influenza (HPAI) INFLUENZA VIRUSES IN WILD AND PET BIRDS: It was first isolated from feral birds in 1961 and from cage birds in 1975. Virus was isolated from 10.9% wild birds (Anseriform (family of bird) yielded

highest isolation rates, i.e. 15.2%) virus remains viable for long periods in lake water. Among caged birds passerine species yielded highest isolation of influenza Avirus INFLUENZA VIRUSES IN DOMESTIC POULTRY: At the end of the 19th century and in the early 20th century, fowl plague was probably enzootic in several countries. Since 1951, twelve outbreaks have occurred with significant spread of infection. Outbreaks of H5 N1 occurred in Hong Kong during 1997 with 70-100% mortality and have subsequently spread to live bird market. Since 1997, serious problem was associated with H9 N2 virus, which was reported from Iran, Saudi Arabia, Pakistan, China and other Asian countries. EPIDEMIOLOGY: Flu virus occurs naturally among birds. Wild birds carry the viruses world wide in their intestines, but usually do not get sick from them. However, bird flu is very contagious among birds and can make some domesticated birds (including chicken, ducks and turkeys) very sick and kill them. Bird flu viruses do not usually infect humans but several cases of human infection with bird flu viruses have occurred since 1997. All known subtypes of flu A viruses can be found in birds. How ever, when we talk about bird flu viruses we are referring to that influenza A subtypes chiefly found in birds. They do not usually infect humans. When we talk about human flu viruses, we are referring to those subtypes that occur, widely in humans. There are only three know A subtypes of human flu viruses (H1N1, H1N2 and H3N3). It is likely that some genetic parts of current human influenza A viruses came from birds originally. Influenza A viruses are constantly changing and they might adapt over time to infect and spread among humans. A pathogenic, or active, strain of bird flu will kill birds quickly and spread rapidly through a population. If a wild, migratory bird catches the flu, it can carry it many miles to other wild or domesticated groups. Avian influenza viruses do not normally infect species other than birds and pigs. Bird flu mixes with human kind of flu, and thus spreads in human through direct contact with birds. Extensive investigation has revealed that the close contact of the human beings with infected poultry spreads flu in them. Hong Kongs entire poultry population estimated at around 1.5 million birds was destroyed. This helped in checking the transmission of

flu to human beings otherwise it would have been averted to a pandemic. During the 1983-1984 epidemic in the United States of America, the H5N2 virus initially caused low mortality, but within six months became highly pathogenic, with a mortality approaching 90%. Control of the out break required destruction of more than 17 million birds at a cost of nearly US $65million. During a 1999-2001 epidemic in Italy, H7N1 virus, initially of low pathogenically, mutated within 9 months to a highly pathogenic form. More than 13 million birds died or were destroyed. gun in 1992 was highly fatal and continued up to 1995. SPREAD OF FLU (AVIAN INFLUENZA): Infected birds shed flu virus in their saliva, nasal secretions and faeces. Susceptible birds become infected when they come in contact with excretions or surfaces that are contaminated with excretions of infected birds. Most cases of bird flu infection in human beings are from contact with infected poultry or contaminated surfaces. Spread of avian influenza viruses from one ill person to another has rarely been reported and transmission has not been observed to continue beyond one person. BIRD FLU IN ASIA AND EUROPE (H5 N1): Eight countries in Asia (Cambodia, China, Indonesia, Japan, Laos, South Korea, Thailand and Vietnam) had outbreak of bird flu during late 2003 and as early as 2004. At that time more than100 million birds in the affected countries either died from the disease or were killed in order to control the outbreak. By March 2004, out breaks of bird flu were reported in Asian countries like Cambodia, China (Tibet), Indonesia, Kazakhstan, Malaysia , Mongolia, Russia, Siberia, Thailand and Vietnam. Most recently, influenza H5 N1 has been reported among poultry in Turkey and Romania. Human infections of influenza A (H5 N1) have been reported in Cambodia, Indonesia, Thailand and Vietnam. RISK TO HUMANS: The risk from bird flu is generally low to most of the people because the viruses occur mainly among birds and do not usually infect humans. However, during on outbreak of bird flu among poultry (domesticated chickens, ducks, and turkeys) An

there is a possible risk to people who come in contact with infected birds or surfaces that have been contaminated with excretions from infected birds. SYMPTOMS IN BIRDS: Avian influenza affects the respiratory, enteric, or nervous systems of many species of birds. Viruses of relatively low virulence may cause few signs whereas others cause high mortality. Most out breaks produce respiratory signs such as sneezing, coughing, sinusitis and lubrication. Other signs include depression, diarrhoeas and decline in egg production or fertility. Disease caused by high pathogenic virus is called fowl plague.

SYMPTOMS IN HUMANS: Symptoms of bird flu in humans range from typical flu like symptoms (fever, cough, sore throat and muscle aches) to eye infections, pneumonia, severe respiratory disease and other life threatening complications. PATHOGENESIS: Highly virulent viruses cause hemorrhagic, necrotic and congestive changes. Hemorrhagic changes are frequently severe in oviduct and intestine. Some times no lesion is found in lung despite of high titer of virus. In broilers encephalitis may develop. Virus replication is restricted to respiratory and intestinal tracts (as host proteases or trypsin like enzymes are found in these sites) PIGS AS AN INTERMEDIATE HOST: Pigs are the major reservoir of H1N1 and H3N2 influenza viruses. They are involved in interspecies transmission of influenza viruses. Pigs are susceptible to avian and human influenza virus due to presence of receptors for avian (a 2-3galactose sialic acid) and human (alpha 2-6- galactose sialic acid). Thus pigs provide a potential link from birds to humans. IMMUNOPROPHYLAXIS: Currently there is no commercially available vaccine to protect humans against the H5 N1 virus that is being seen in Asia and Europe. However, vaccine

development efforts are taking place. Research studies to test a vaccine to protect humans against H5 N1 virus began in April 2005 and a series of clinical trial is underway. Vaccination, however, currently is the most effective measure for prevention. Vaccine efficacy varies between 60-90% and depends on closeness of antigenic match. At present Vaccines prepared with inactivated or killed virus particles are licensed for use. Self replicative RNA vaccines elicit protection against influenza A viruses. Annual vaccination using the current vaccine is necessary because of potential changes in viruses and the immunity is short lived. LABORATORY DIAGNOSIS: A definite diagnosis requires virus isolation and identification or the demonstration of rising antibody title by HI, Viral Neutralization Test, FAT, Agar gel precipitation test and ELISA. Avian influenza virus can be cultivated in duckling, calf and monkey kidney cell cultures from samples of trachea, lung, our sac, sinus exudates or cloacal swabs. TREATMENT AND CONTROL: Recovered birds remain immune to subsequent challenge by a homologous strain for at least several months. Birds immunized parenterally with inactivated vaccines are completely protected against challenge by heterologus strain with the same HA and are partially protected against heterologus strains possessing the same neuraminidase. Following immunization, chickens remain immune for at least 84 days, approximately twice as long as turkeys remain immune. In practice, however, appropriate vaccines are rarely available to the poultry industry owing to great genetic and antigenic diversity among avian viruses. There is hope that a polyvalent vaccine with a broader protective range may be developed in due course of time. For the most part, control of avian influenza is through the prevention of exposure. Careful husbandry to prevent the introduction of the virus into the flock is important. New birds should not be introduced into a started flock, and careful precautions should be taken to prevent either direct or indirect contact with wild, migratory or exotic birds. Since turkeys have also been found to be susceptible to a

strain of influenza typically associated with pigs, it is a good management practice not to have pigs on the same farm as turkeys. TREATMENT: The H5 N1 virus currently infecting birds in Asia that has caused human illness and death is resistant to Amantadine and Rimantadine, two antiviral medications commonly used for influenza. Two other antiviral medications oseltamavir and zanamavir would probably work to treat flu caused by H5 N1 virus, but additional studies still need to be done to prove their effectiveness. PREPAREDNESS STATUS OF INDIA: Government issued notice to all concerned for continual watch. Corporate sectors of poultry already geared to avert any outbreak. Awareness campaigns. Strengthening of Poultry disease diagnostic Labs. Strict quarantine on foreign imports. Monitoring of migratory birds.