Developed with joint collaboration of Ministry of Health-Government of Pakistan, World Health Organization and the National Institute of Health, Islamabad

Contents
1 Introduction
2 Collection and transportation of specimen
3 Epidemiology
4 Risk factors for increased transmission
5 Prevention and control measures
6 Hospital infection control guidance
7 Safety measures for Poultry bird workers, cullers and poultry transporter

1. Introduction
Avian influenza is a contagious infectious disease of birds caused by type A strains of the influenza virus. The disease, which was first identified in Italy in 1878, occurs worldwide among poultry populations. Birds are an especially important species because all known subtypes of influenza A viruses circulate among wild birds, which are considered the natural hosts for this variety of viruses. However, avian influenza viruses usually do not make wild birds sick, but can make domesticated birds very sick and often kill them.

This form of influenza is not usually known to infect humans, however once transmitted the infection may lead to development of this disease with symptoms of avian influenza ranging from typical influenza-like symptoms (e.g., fever, cough, sore throat and muscle aches) to eye infections, pneumonia, acute respiratory distress, viral pneumonia, and other severe and life-threatening complications.

Confirmed instances of avian influenza viruses infecting humans have been reported since 1997 mainly among the South East Asian countries known as the Hong Kong outbreak. All genes are of avian origin, indicating that the virus has not acquired human genes. The acquisition of human genes is known to increase the likelihood that a virus of avian origin can be readily transmitted from one human to another.

The current epidemic was first reported in October 2003 in Vietnam and is now known to spread to South Korea, Thailand and Laos and in all these countries it has been reported to be caused by the H5N1 strain of Influenza Type A variety of viruses. The World Health Organization (WHO) has reported that the H5N1 strain implicated in the outbreak has been sequenced. According to the latest figures provided by the WHO, that there have been 15 reported laboratory-confirmed cases of H5N1 strain in Vietnam,11 of which have been fatal. 5 cases have been reported from Thailand with all of them dying from the condition.

Infectious agent • H5N1 strain of Type A Influenza virus

Occurrence

Vietnam
Fifteen people have died among the 22 laboratory confirmed human cases. Median age among the human cases is 16.5 years and half of the cases were females. Since the beginning of the outbreak, nearly 3 million chickens have died/culled in the country.

South Korea
First time reported in the country on 12th December 2003, and nearly 1.1 million chickens and ducks have died/culled. No human cases have been reported

Thailand
• The 1st case was a 7-year-old boy from Suphanburi province who developed fever and cough on 3 Jan 2004 and progressed to Acute Respiratory Distress Syndrome (ARDS) on 13 Jan 2004. The 2nd case was a 6-year-old boy from Kanchanaburi province who developed fever on 6 Jan 2004 followed by severe pneumonia with ARDS a week later. Nearly 6 million chickens have died/culled in this country. To date a total of 9 cases have been reported with 7 of them dying from the disease. The median age of the human cases is 6 years and 20% of them are females.

Japan
More than 10,000 chickens have died/culled. First reported during the outbreak on the 12th of Jan 2004, there have been no reports of any human case of avian influenza.

Taiwan
Nearly 50,000 chickens have died with no reports of any human cases to date

Cambodia
Thousands of chicken have died (the exact number is yet to be disclosed ) however there have been no human cases reported officially to date

Indonesia
Millions of chickens are reported to have died over the recent months and is now confirmed to be caused by H5N1 strain of the Type A influenza virus.

China
Reports of avian influenza among bird populations (poultry chickens and ducks) have been reported (suspected or confirmed) from 14 of the countries 31 provinces and regions. The exact numbers of affected population are increasing and the outbreak is now confirmed to be cause by H5N1 strain. No human cases have been reported to date by the Chinese authorities.

Reservoir
Till now the reservoir seems to be wild and domestic chickens and turkeys, with humans being reported to only have symptomatic cases.

Mode of transmission
Route and mode of spread according to current evidences includes;

• Bird to bird
• Bird to person contact
• There is no scientific consensus on human to human spread of the H5N1 strain.

Incubation Period and characteristics of H5N1 virus
Incubation period is known to be of one week on an average. The virus is can be killed by heat (56 0 C for 6 hours or 60 0 C for 30 minutes). The virus is known to survive at cool temperatures, in contaminated manure of poultry birds for at least three months. In water the virus is known to survive upto 4 days at 22 degrees Celsius and more than 30 days at zero degrees C.

Period of Communicability
There is no evidence of transmission during the incubation period or convalescence periods. Communicability increases with the severity of disease and degree of direct exposure. The virus is known to survive in cold temperatures and in contaminated manure of birds for upto three months. In water it may survive upto 4 days at 22 degrees C and more than 30 days at zero degrees C

Portal of entry
Faeco-oral route (amongst human or birds)
Upper respiratory tract among humans

Portal of exit
• Faeces, saliva and nasal secretions of infected birds
• Main upper respiratory tract among humans

Source of infection
• Faeces among birds
• Respiratory discharge among humans

Susceptibility and resistance
• All age and sex groups are susceptible. Most of the cases have occurred among the poultry bird handlers, which could be explained by length and degree to the source of infection. Growing concern has been raised in the scientific community since the onset of outbreak is that there may be a possibility of reassortment of the H5N1 strain with an existing human influenza strain among such persons who get exposed to the H5N1 strain while concurrently suffering from a exposure/episode of human influenza. In such cases a combination (reassortment) of the two strains may lead to a new/mutated version of the influenza virus for which currently no medication and vaccine have been developed and which may carry high transmission properties and may lead to higher case fatality rates than the H5N1 form. Initial analysis of viruses isolated from the recently fatal cases in Vietnam indicates that the viruses are invariably resistant to the anti-retroviral drugs like M2 inhibitors (rimantidine and amantadine). Studies to confirm the effectiveness of neuraminidase inhibitors against the current H5N1 strains are currently underway.

Clinical picture
• Initially flu-like symptoms
• Rapid onset of high grade fever (> 38oC) followed by muscle aches,
headache, sore throat.
• In some cases there may be unilateral or bilateral pneumonia, progressing to acute respiratory distress requiring assisted breathing on respirator.

Case Fatality Rate (CFR)
• In the current outbreak, the case fatality rate is ranging from 70 - 75 % among the reported human cases of Vietnam and Thailand
Diagnosis Hemagglutinin inhibition (HAI), ELISA, IFA with HF5 monoclonal antibodies and RT-PCR have been developed. Virus isolation is the key factor in identifying the sub-type of the influenza virus

Specimens for laboratory tests
• Throat and/or nasopharyngeal swab
• Nasopharyngeal aspirate
Blood for complete examination and serology
• Blood for molecular biological studies

Collection and transportation of clinical specimens
Procedure for specimen collection among humans
Nasopharyngeal swab
• Insert a sterile swab beneath the inferior turbinate of either nostrils and leave in place for a few seconds.
• Slowly withdraw with a vigorous rotating motion against the mucosal surface of the nostril.
• Repeat the same procedure in the other nostril using a new sterile swab.
• Collect the tip of each swab in a vial containing 2-3 ml of viral transport media (VTM) with the applicator stick broken off.
Throat swabs
• Take a swab after vigorous rubbing from the posterior pharynx.
• Collect the swab into vial with the applicator stick broken off containing VTM in it.
Nasopharyngeal aspirates
• Nasopharyngeal secretions are aspirated through a catheter connected to a mucous trap and fitted to a vacuum source.
• The catheter is connected into a nostril parallel to the palate, vacuum is applied and the catheter is slowly withdrawn with a rotation motion.
• Mucous from the other nostril is collected with the same catheter in similar manner.
• After collecting mucous from both the nostrils, the catheter is flushed with 3 ml of VTM.
Sera collection
Collect 3-5 ml of human blood soon after the onset of clinical symptoms. Two samples need to be taken from each patient, one sample during the first week of illness and the second 2-4 weeks later.
Postmortem specimens
• Collect tissue and heart blood in fatal cases.
• Divide lungs tissue into two, place half portion in 10% formalin or formal-saline and the remaining half as fresh.
Procedure for specimen collection among poultry birds
In liaison with designated laboratories, full blood and post mortem specimens (intestinal contents, anal and oro-nasal swabs, trachea, lung, intestine, spleen, kidney, brain, liver and heart) may be collected for identification of virus through similar diagnostic techniques as for humans.

Draft case definition

Possible Case
Person with acute respiratory illness, characterized by fever
(temperature >38 degrees C) and cough and/or sore throat and either
contact with a confirmed case of influenza A (H5N1) during the infectious
period OR recent (less than 1 week) visit to a poultry farm in an area
known to have outbreaks of Pathogenic avian influenza (HPAI) OR worked in a laboratory that is processing samples from persons or animals that are suspected for highly HPAI virus infection.

Probable Case
Possible case AND limited laboratory evidence for Influenza A (H5N1) (such as IFA + using HF5 monoclonal antibodies) OR no evidence for another cause of disease.

Confirmed Case
Positive viral culture for avian influenza A (H5N1) virus OR positive PCR
for influenza (H5) virus OR a 4-fold rise in H5-specific Ab titer.
Exclusion criteria • A case should be excluded if an alternative diagnosis can fully explain the illness

3. Epidemiology
Incidence and Geographical Distribution • The avian influenza began with reports in poultry birds in Vietnam since October 2003. Since then poultry birds have been affected in South Korea, Thailand, Taiwan, Japan, Cambodia and Indonesia
• From the available information and retrospective surveillance, it is apparent that the human form of the disease may have started in Vietnam in October 2003, however on January 26, 2004 the Vietnam government reported its first confirmed cases in the south of the country, with two cases in Ho Chi Minh City. Since then human cases have been reported from Thailand.

Seasonality Cases among bird populations can occur year round. However cases and outbreaks in poultry chicken are known to occur more commonly during winter months.

Human outbreaks have been reported since 1997 (5 outbreaks in all before the present one). Seasonal patterns may converge with the bird outbreak seasonality, which is known to be more common in winters.

Alert threshold Even a single case must lead to an alert and adequate response.

4. Risk factors for increased transmission
Population movement • Travel to/from the countries from where cases of avian influenza have been reported.
Access to health services • Prompt identification of the cases is paramount to rapidly implement the control measures and for successful treatment.

5. Prevention and Control measures
Care and Management of the Cases

• Among Poultry birds
World Health Organization recommends culling of birds (burn or burial) with spraying of disinfectants at the site of the burial; as a measure to stay ahead of the battle to prevent the spill over of this form of influenza into human populations.
Among Human Population

• Good supportive care including intensive therapy has been shown to improve the prognosis.

• 2003-04 trivalent influenza vaccine (flu shots) OR intranasally administered live, attenuated influenza vaccine (LAIV, a nasal-spray flu vaccine) for chemoprophylaxis is available.

• Two classes of drugs are available. These are the M2 inhibitors (amantadine and rimantadine) and the neuraminidase inhibitors (oseltamivir and zanimivir). These drugs have been licensed for the prevention and treatment of human influenza in some countries, and are thought to be effective regardless of the causative strain.

Management of suspected human case
• Patients with suspected avian influenza symptoms should be isolated and cared for using barrier-nursing techniques by providing surgical mask to the patient.
• Detailed clinical, contact and travel history including occurrence of acute respiratory diseases in contact persons during the last 10 days.
• X-ray chest (CXR) and complete blood count:
If CXR is normal,
- discharge the patient with advice to seek medical care if respiratory
symptoms worsen
- improve personal hygiene and
- avoid public areas and transportation, confine at home until well.
• If CXR demonstrates unilateral or bilateral infiltrates with or without interstitial infiltrations, see management of probable case.

Management of probable case
Hospitalize under isolation or cohorted with other avian influenza patients
• Lab investigation to exclude known cause of atypical pneumonia:
- Complete blood picture
- Serology from blood samples
- Throat and/or nasopharyngeal swabs and cold agglutinin
- Bronchoalveolar lavage
• Specimens should be collected on alternate day and investigated in the
laboratories with proper containment facilities (BL3)
• CXR as clinically indicated
• Treat as clinically indicated (symptomatic treatment)
- Broad spectrum antibiotics have not proven effective in halting bird flu progression to date. Effectiveness of treatment by M2 inhibitors and neuroaminadase inhibitors is under investigation.

Management of contact of suspected and probable cases
• Reassurance
• Record name and contact in detail.
• Advice to seek medical assistance in the event of fever or respiratory symptoms worsen.
- Immediately report to the health authority.
- Do not report to work until advised by the physician.
Minimize contact with family members and friends and avoid public places.
Hospital Infection Control Guidance
• Strict adherence with barrier nursing of avian influenza patient
• Use precautions for airborne, droplet and contact transmissions
• Rapidly divert the patient reporting to health care facility with flu-like symptoms to a separate area to minimize transmission to others.
• Suspect case should wear surgical masks until avian influenza is excluded
• Isolate the patient and accommodate as follows;
- Negative pressure rooms with door closed
- Single room with their own bathroom facilities
- Cohort placement in an area with an independent air supply and exhaust system
- Turn off air condition in a facility and open windows for good ventilation
- Patient under investigation for avian influenza should be separated from those diagnosed with the syndrome
• Disposable equipments should be used. If devices are to be reused, they should be sterilized with broad-spectrum disinfectants (bactericidal, fungicidal or veridical) of proven efficacy.
• Restrict movement of patient as much as possible. If necessary, patient should wear surgical mask to minimize dispersal of droplets.
• Visitors, staff, students and volunteers should wear N95 masks on entering the room of the patient
• Hand washing before and after contact with any patient is the most important hygienic measure in preventing the spread of infection.
• Health Care Workers (HCWs) should wear gloves for all patients handling and gloves should be changed after any contact with the items likely to be contaminated with respiratory secretions.
• HCWs must wear protective eyewear or face shields or masks during procedures where there is potential splashing, splattering or spraying of blood or other body substances of the patients suspected, probable or confirmed avian influenza.
• Standard precautions should be applied when handling any clinical wastes. Gloves and protective clothing should be worn while handling clinical waste bags and containers. Manual handling should be avoided and clinical waste should be placed in leak-resistant biohazard bags or containers labeled and disposed of safely.

Safety measures for Poultry bird workers, cullers and poultry transporters

Ensure that the cullers use the following protective items:
• N95 respirator masks are preferred. Standard well-fitted surgical masks should be used if N95 respirators are not available
• Protective clothing, preferably coveralls plus an impermeable apron or surgical gowns with long cuffed sleeves that can be either disinfected or discarded.
• Heavy duty rubber work gloves that may be disinfected
• Goggles/protective glasses;
• Rubber or polyurethane boots that can be disinfected or protective foot covers that can be discarded
• Persons at high risk for severe complications of influenza (e.g. the immuno-compromised, the over 60 years old, or people with known chronic heart or lung disease) should avoid working with affected chickens.
• All persons who have been in close contact with the infected poultry should wash their hands frequently with soap and water. Cullers and transporters should disinfect their hands after the operation.