Emerging Diseases

Avian Influenza

The disease, which is a source of widespread, panic these days and origin of multiple apprehensions is none other than Bird Flu. Being a clinician, I am always bombarded with question from all circles regarding the nature of this disease, the mode of its spread and, of course, how big a disaster it can be? So here are few answers. Flu is a viral disease caused by a family of viruses known as Orthomyxovirus. There are three members of this group: Influenza virus A, B & C. Type A influenza virus infects both birds as well as animals. “Avian Influenza viruses” infect wild birds as well as domestic birds (primarily found in wild birds only). “Mammalian Influenza virus”, on the other hand, infects human beings as well as their close neighbours like pigs and horses. (Some strains are also found to infect seals and whales.) It is emphasised that Avian Influenza viruses do not usually directly infect humans or circulate among humans. Avian Influenza virus usually does not make wild birds sick but can make domestic birds very sick and kill them. This virus does not usually infect humans; however, several instances of human infections and outbreaks have been reported since 1997.When such infections occur, public health authorities monitor the situation closely because of concerns about the potential for more widespread infection in the human population. Influenza virus is segmented in nature. So it has ability to change its formulation. Once inside the host cell, eight segmented RNA genome of Influenza A virus undergoes high frequency recombination termed as reassortment leading to change in antigenic properties of virus. This change in antigenicity of virus is labelled as antigenic shift. Epidemics and Pandemics occur when antigenicity of the virus has changed sufficiently that pre-existing immunity of many people is no longer effective. Human Influenza virus has the property of contiguity. It very rapidly spreads from one person to another by micro-droplets emitted from nose and mouth of infected person while speaking, coughing or sneezing. While Avian Influenza virus has the property of causing deadly infection in human beings. If an Avian and Human Influenza A virus infect the same cell (e.g.: in a farmer’s respiratory tract), reassortment could occur between them and a new variant of Human A virus could appear, which will be both, contagious as well as deadly and so it will cause the most devastating, quickly spreading pandemic which can erase the human race from the face of this earth. Spread of Influenza virus takes place via micro-droplets from one person to another. Similarly Avian Influenza virus can also spread from birds to human beings only by micro-droplets and essentially not by eggs and meat. To explain it further, if a bird (say chicken) was infected with Avian Influenza A virus in its lifetime, its meat or eggs will not transmit the virus to human beings. But a live infected bird can transmit virus to the person in close contact, that is, a bird fancier or a farmer. This forms the basis of extermination of whole farms or flocks of birds whenever flu is identified in domestic or farming birds. The incubation period of Influenza A virus is 1-4 days. Person infected can transmit virus one day before to seven days after the appearance of symptoms. This duration is known as period of infectivity. Symptoms, if not complicated by super-added bacterial infection or pneumonia, can spontaneously resolve within 4-7 days. Symptoms are fever, headache, malaise, myalgia, prostration, nausea, vomiting, conjunctivitis, eye pain(photophobia) and also depression. Complications can be as deadly as pneumonia caused by Pneumococcus, H.Influenzae or Staph aureus. Other complications can be Bronchitis, Sinusitis, Otitis needia, Encephalitis, Pericarditis, or Coma with deranged liver function tests. Diagnosis of influenza is based on clinical features and investigations. Laboratory test earliest to become positive is PCR (polymerase chain reaction), becomes positive within 36 hours. Other investigations, more of epidemiological interest, are: assay of antibody titre against Influenza virus by Haemagglutination inhibition test or by Complete fixation test and cell culture from throat washing and fluorescent antibody staining of infected cells for identification of virus in them. Even if a definitive diagnosis is established, there are not many treatment options available. Two Antiviral drugs, that is, Amantadine and Rimantadine are approved for both treatment as well as prevention of Influenza A. Main indication of these drugs is in prevention of Influenza in a confined, elderly unimmunised population such as a retirement home, where Influenza can be life-threatening. If treatment is started within first 24-48 hours of exposure, it can reduce the duration and severity of symptoms. As in the famous verse “Prevention is better than cure”, main mode of prevention in this case is vaccine. Unfortunately no vaccine of Avain Influenza A virus is available for human beings but human influenza vaccine is available, which consists of killed Influenza A and B virus. Human vaccine is usually reformulated each year to contain current antigenic strains of viruses. It is given to people belonging to high-risk categories in the months of September/October and is meant for one particular season only. As for Avian virus, best we can do is to avoid bird company. So, the conclusion that we can draw from this discussion is that Influenza (human flu as well as bird flu) spreads essentially by micro-droplets. There is absolutely no harm in eating eggs and meat. Therefore, it is advised not to raise unnecessary alarm among population.

This information has been prepared as a service by the American Veterinary Medical Association. Redistribution is acceptable, but the document’s original content and format must be maintained, and its source must be prominently identified. Please contact Dr. Gail Golab (800.248.2862, ext. 6618) with questions or comments.

BSE Backgrounder
(updated 4 February 2005)
v 2.4

Causative agent

Bovine spongiform encephalopathy (BSE), commonly referred to as “mad cow disease,” belongs to the family of diseases known as transmissible spongiform encephalopathies (TSE). The causative agent of BSE has not been fully characterized, but three possibilities have been proposed: an unconventional virus, a prion (a self-replicating protein), or a virino (incomplete virus) comprising naked nucleic acid protected by host proteins. The theory accepted by most scientists is that BSE is caused by a prion. The agent does not invoke a detectable immune response or inflammatory reaction in its host and is extremely resistant to sterilization processes.

Natural distribution

A chronic, degenerative neurologic disease of cattle, BSE has been diagnosed in native-born cattle in Austria, Belgium, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Ireland, Israel, Italy, Japan, Liechtenstein, Luxembourg, the Netherlands, Poland, Portugal, Slovakia, Slovenia, Spain, Switzerland, and the United Kingdom. More than 95% of cases identified have developed in the United Kingdom. A single case of BSE was confirmed in the United States in December 2003, but the cow was from Canada. Other countries with a single case are Austria, Finland, Greece, and Israel. In early 2005, BSE was confirmed as developing in a single goat that was slaughtered in 2002 in France.

Transmission

Researchers believe that BSE is spread to cattle through feeding of contaminated meat and bone meal from scrapie-infected sheep or cattle with previously unidentified BSE. Offal tissues of particular risk include the brain, spinal cord, eyes, spleen, distal ileum, and certain other nervous tissues. Bovine spongiform encephalopathy does not appear to be spread horizontally (contact between cattle or contact between cattle and other TSE-affected species).

Clinical signs of BSE in cattle

In cattle, BSE causes progressive degeneration of the central nervous system. Clinical signs may include changes in temperament (e.g., apprehension, nervousness, unwillingness to move through doorways, belligerence), hyperesthesia, ptyalism, pruritis of the head, fine muscular fasciculations, moaning, tachypnea and bradycardia, incoordination, proprioceptive deficits, abnormal postures, abnormal gait, decreased milk production, loss of body condition despite a normal appetite, recumbency, and death. The incubation period ranges from 2 to 8 years and the health of affected animals typically deteriorates over a period of 2 weeks to 6 months. The disease is uniformly fatal. Most cattle affected are between 3 and 6 years old, although BSE has been diagnosed in younger and older cattle.

Diagnosis

Unfortunately, no laboratory test to confirm BSE in a live animal currently exists. Bovine spongiform encephalopathy is most often diagnosed by postmortem microscopic examination of brain and spinal cord tissue or by detection of the abnormal form of the prion protein. Examination will reveal bilaterally symmetrical neuronal vacuolation and spongiform degeneration, often with hypertrophy of astrocytes. Vacuolation is greatest in the medulla oblongata; the central gray matter of the midbrain; and the paraventricular area of the hypothalamus, thalamus, and septal area.

Immunoblotting (Western) and ELISA are used to detect the presence of the abnormal prion protein in brain and spinal cord tissue. Immunohistochemistry is used to confirm the presence of the abnormal prion protein.

Prevention

Because the primary source of transmission of BSE has been shown to be abnormal proteins derived from BSE-infected ruminants in feed, the Food and Drug Administration (FDA) has established regulations that prohibit the feeding of most mammalian proteins to ruminants in the United States. The United States Department of Agriculture’s Animal and Plant Health Inspection Service (USDA-APHIS) has restricted importation of live ruminants and ruminant products (e.g., fetal bovine serum, meat-and-bone meal, bonemeal, bloodmeal, offal, fats, glands) from countries where BSE has been diagnosed. The USDA has determined that importation of live ruminants and ruminant products from Canada presents a minimal risk of introducing BSE. Importation under specified conditions will be allowed from Canada after March 7, 2005. Because of concerns about cross-contamination of rendered products of nonruminant origin with the BSE agent, since 2000 the USDA has also prohibited all imports of rendered animal protein products, regardless of species.

Treatment

No treatment currently exists for cattle affected with BSE. The disease is uniformly fatal.

Infection control

Veterinarians are trained to recognize the clinical signs and pathologic manifestations of BSE in cattle. The USDA-APHIS has distributed videotapes, fact sheets, literature reviews, and risk assessments on BSE to state and federal veterinarians, colleges of veterinary medicine, extension veterinarians, private practitioners, and producers. Veterinary diagnostic laboratories have been provided with microscope slides showing typical lesions of BSE to assist in pathologic confirmation of suspect cases.

An active interagency surveillance program, coordinated by the USDA-APHIS, collects samples from cattle exhibiting signs of neurologic disease, cattle condemned at slaughter for suspected neurologic disease, cattle for which results of rabies testing conducted at veterinary diagnostic laboratories is negative, and aged nonambulatory cattle and examines these for the presence of abnormal prions.

Cattle destined for slaughter in the United States are evaluated by the Food Safety and Inspection Service (USDA-FSIS) for signs of disease, including central nervous system impairment. Animals showing signs of systemic disease, including those exhibiting signs of neurologic impairment, are condemned and not used for human food. The USDA also prohibits tissues from nonambulatory (disabled) cattle from entering the human food supply. This information has been prepared as a service by the American Veterinary Medical Association. Redistribution is acceptable, but the document’s original content and format must be maintained, and its source must be prominently identified. Please contact Dr. Gail Golab (800.248.2862, ext. 6618) with questions or comments.

Transmissible Spongiform Encephalopathies in Other Animals

The family of transmissible spongiform encephalopathies (TSE) in animals includes scrapie, affecting sheep and goats; transmissible mink encephalopathy; chronic wasting disease, affecting deer and elk; and, in humans, kuru, classic and variant Creutzfeldt-Jakob disease, Gerstmann-Straussler syndrome, and fatal familial insomnia. A neurologic disease in exotic ruminants and exotic and household cats in the United Kingdom has been linked to BSE, and is suspected to be caused by eating feed contaminated with the BSE agent.

Implications of BSE for Humans

Variant Creutzfeldt-Jakob disease (vCJD) is a transmissible spongiform encephalopathy having epidemiologic and pathologic evidence of a causal link with BSE. It primarily affects young adults (median age at death is 28 years). Symptoms include early psychiatric and sensory abnormalities, eventually followed by ataxia, dementia, and myoclonus. Median duration of illness is 14 months. Current thinking is that vCJD may be caused by ingestion of products contaminated with the BSE agent.

Tissues considered to be of greater risk (e.g., skull, brain, trigeminal ganglia, eyes, vertebral column, spinal cord, and dorsal root ganglia of cattle more than 30 months old, and the distal ileum of cattle of all ages) have been banned from entering the human food supply in the United States, Canada, and European Union. In the United States, tissues from nonambulatory (disabled) cattle also may not be used for human food. Milk and milk products are not believed to pose a transmission risk, and tallow and gelatin are considered safe if they have been prepared by a manufacturing process that inactivates or removes the BSE agent.

Variant CJD must be differentiated from classic CJD, which is the TSE most often identified in humans. Classic CJD occurs worldwide at a rate of about 1 to 2 cases/1 million people. Mean age of onset is 65 years and median duration of illness is 4.5 months. Hereditary predisposition accounts for approximately 5 to 10% of cases, a sporadic form accounts for approximately 85 to 90% of cases, and a small number of cases are iatrogenic (transmitted via contaminated surgical equipment, transplants [e.g., cornea, dura mater], or administration of natural human growth hormone).