Avian Influenza: A Review

Jennifer K. Thomas; Jennifer Noppenberger

Am J Health Syst Pharm. 2007;64(2):149-165.

Abstract and Introduction

Abstract

Purpose: A review of the avian influenza A/H5N1 virus, including human cases, viral transmission, clinical features, vaccines and antivirals, surveillance plans, infection control, and emergency response plans, is presented.
Summary: The World Health Organization (WHO) considers the avian influenza A/H5N1 virus a public health risk with pandemic potential. The next human influenza pandemic, if caused by the avian influenza A/H5N1 virus, is estimated to have a potential mortality rate of more than a hundred million. Outbreaks in poultry have been associated with human transmission. WHO has documented 258 confirmed human infections with a mortality rate greater than 50%. Bird-to-human transmission of the avian influenza virus is likely by the oral-fecal route. The most effective defense against an influenza pandemic would be a directed vaccine to elicit a specific immune response toward the strain or strains of the influenza virus. However, until there is an influenza pandemic, there is no evidence that vaccines or antivirals used in the treatment or prevention of such an outbreak would decrease morbidity or mortality. Surveillance of the bird and human populations for the highly pathogenic H5N1 is being conducted. Infection-control measures and an emergency response plan are discussed.
Conclusion: Avian influenza virus A/H5N1 is a public health threat that has the potential to cause serious illness and death in humans. Understanding its pathology, transmission, clinical features, and pharmacologic treatments and preparing for the prevention and management of its outbreak will help avoid its potentially devastating consequences.

Introduction

The avian influenza A/H5N1 virus has the potential to cause devastating effects to agricultural poultry flocks and humans. Initially confined to Southeast Asia, the virus has now migrated to the Middle East, Europe, and former Soviet Union satellites. Outbreaks in poultry, primarily chickens and ducks, have been associated with human transmission. The World Health Organization (WHO) has documented 258 confirmed human infections with a mortality rate greater than 50%.^[1] WHO considers the avian influenza A/H5N1 virus a public health risk with pandemic potential and recommends that all nations develop a national influenza preparedness plan.^[2] The U.S. government has proposed a federal response, the Pandemic Influenza Plan.^[3,4]

The next human influenza pandemic, if caused by the avian influenza A/H5N1 virus, is estimated to have a potential mortality rate greater than a hundred million.^[5,6] The mathematical model estimates are based on the facts that humans have little or no immunity to the antigens of the influenza A/H5N1 virus and that the mortality rate so far has been approximately 57% for the cases that have been admitted to hospitals and reported to WHO.^[1] The number of human cases that may present to health care facilities is expected to far exceed bed capacity and resources for treatment.

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Cite this: Avian Influenza: A Review - Medscape - Jan 15, 2007.

Abstract and Introduction
Background
Human Cases
Viral Transmission
Clinical Features
Pharmaceutical Strategies: Vaccines and Antivirals
Surveillance and Prevention
Infection Control
Emergency Response Plan
Conclusion
AppendixSources for Pandemic Influenza Planning
References

Table 1. Preventive Vaccination Strategies Against Influenza Pandemic ^[44]
Vaccine Strategies	Realities and Limitations
Mass vaccinations	Vaccine production cannot begin until a pandemic occurs and viral strain is identified; a vaccine will not be available for the initial wave of pandemic6-mo lag time to availability Production capacity constraints secondary to limited available manufacturers and method of production Distribution, availability in areas of need, and administration require effective national plans
Targeted populations	As strain-specific vaccine is available, target high-priority groups (500 million out of a world population of 6.5 billion); should include essential personnel, health care workers, military, and government^[64] Others should include care givers, those at high risk of death in the population on the basis of age groups, those with chronic diseases, and the healthy^[64]
Targeted populations use current vaccines	Immunize more of the population in interpandemic years with current influenza vaccine for potential cross-protection against pandemic strain Develop H5N1 candidate vaccines and stockpile for use when conditions suggest there is a risk of a pandemic Before a pandemic, vaccinate the population where outbreaks are identified with an initial dose of H5N1 vaccine followed by a booster
Vaccine development and dosage	Developing vaccine using new and alternative technologies may require licensing and approval from the government drug agencies and intellectual property rights Low-dose monovalent vaccine should include the use of adjuvants to maximize yield of available vaccines Use the intradermal route of administration, which requires smaller dosages than the intramuscular route
Animal and bird vaccination	Culling of poultry is insufficient for containment United Nations Food and Agricultural Organization recommends vaccination of targeted poultry flocks Difficult to implement in countries with free-range poultry Cost : 2.5-5 cents per vaccination, but billions of vaccines required^[84]

Table 2. Guidelines on Pharmacologic Management of Humans Infected with Avian Influenza A ^[68,69]
Management Type and Patient Population	Drug
Management Type and Patient Population	Oseltamivir^a	Zanamivir	Amantadine	Rimantadine
Treatment
Adults and teenagers	Age ≥ 13 yr: 75 mg twice daily for 5 days (renal dosage adjustment)	10 mg twice daily for 5 days^b	Age 10-65 yr: 100 mg twice daily for 5 days Age >65 yr: 100 mg daily for 5 days^c Hemodialysis pts.: 200 mg every 7 days	Age ≥ 12 yr: 100 mg twice daily for 5 days^d
Children	Age ≥ 1 yr: twice daily for 5 days^e Weight ≤ 15 kg: 30 mg Weight >15-23 kg: 45 mg Weight >23-40 kg: 60 mg Weight >40 kg: 75 mg	Age ≥ 7 yr^f: 10 mg twice daily for 5 days	Age 1-9 yr: 5 mg/kg/day in 2 divided doses max. 150 mg for 5 days^g Age 10-12 yr: 100 mg twice daily for 5 days	Age ≥ 12 yr: use adult treatment protocol^h
Prevention
Adults and teenagers	Age ≥ 13 yr: 75 mg once daily for 7-10 days after last known exposureⁱ	10 mg once daily for 7-10 days after last known exposure^j	Same as for treatment, except duration is 7-10 days after last known exposure	Age ≥ 10 yr: 100 mg twice daily for 7 days after last known exposure^d,k
Children	Age 1-13 yr: once daily for 7-10 days after last known exposure^d Weight ≤ 15 kg: 30 mg Weight >15-23 kg: 45 mg Weight >23-40 kg: 60 mg Weight >40 kg: 75 mg	Age ≥ 5 yr: 10 mg once daily for 7-10 days after last known exposure^a	Same as for treatment, except duration is 7-10 days after last known exposure	Age <10 yr: 5 mg/kg/day in 2 divided doses max. 150 mg Age ≥ 10 yr: see adult prevention

^aA new warning concerning adverse effects of oseltamivir is found at www.fda.gov/Medwatch/safety/2006/safety06.htm#tamiflu.
^bOral inhalationtwo inhalations by Diskhaler.
^cRenal dose adjustment if creatinine clearance (CL_cr) <50 mL/min/1.73 m².
^dDose adjustment in elderly, renal failure (CL_cr <10 mL/min), or hepatic dysfunction: 100 mg daily.
^eSuspension available.
^fNot approved for use in children <7 years of age.
^gSyrup available.
^hNot approved for use in children <12 years of age.
ⁱProphylaxis up to eight weeks may be considered safe.
^jOral inhalationtwo inhalations by Diskhaler; prophylaxis duration up to 28 days reported.
^kProphylaxis duration up to seven weeks reported.

Table 3. Evidence Supporting the Use of Antiviral Agents ^a[68,69]
Condition	Antiviral Agent	Strength of Evidence
Neuraminidase inhibitors available	Oseltamivir	Strong
	Zanamivir as an alternative	Weak
	Amantadine or rimantadine should not be used as first- line monotherapy	Strong
	Combination neuraminidase inhibitors and adamantanes^b	Weak
Neuraminidase inhibitors not available	Amantadine or rimantadine as first-line monotherapy if local surveillance data indicate susceptible H5N1	Weak
High-risk exposure groups where neuraminidase inhibitors available	Prophylaxis with oseltamivir or alternative zanamivir	Strong
High-risk exposure groups where neuraminidase inhibitors not available	Possible prophylaxis with amantadine or rimantadine if H5N1 susceptible	Weak
	Do not administer during pregnancy	Strong
Moderate-risk exposure groups where neuraminidase inhibitors available	Possible prophylaxis with oseltamivir or alternative zanamivir	Weak
	Do not administer during pregnancy	Strong
Moderate-risk exposure groups where neuraminidase inhibitors not available	Possible prophylaxis with amantadine or rimantadine if H5N1 susceptible	Weak
Low-risk exposure groups	Prophylaxis with oseltamivir or alternative zanamivir should probably not be administered	Weak
	Amantadine or rimantadine should not be administered	Weak
	Do not administer during pregnancy	Strong
	Elderly and renally impaired persons should not receive amantadine or rimantadine	Strong

^aOverall quality of evidence on which to base a summary assessment was very low for all antivirals.
^bConsider only when susceptibility data are available and in the context of prospective data collection.

Table 4. Barrier Precaution Recommendations for Persons Providing Care for Patients with Respiratory Illness or Suspected or Confirmed Avian Influenza Infection ^[94]
Barrier Precaution	Point of Exposure
Barrier Precaution	Close Contact (<1 m) with Pts. with Acute Febrile Respiratory Illness Who Have No Known AI Risk Factors^a	Entry to AI Isolation Room or Area, No Anticipated Pt. Contact	Close Contact (<1 m) with AI Infected Pts. in or out of Isolation Room or Area	Performance of Aerosol-Generating Procedure on AI Pts.^b,c
Hand hygiene^d	Yes	Yes	Yes	Yes
Gloves	Not routinely	Risk assessment	Yes^e	Yes
Apron	Not routinely	Risk assessment^f	Not routinely^g	Not routinely^g
Gown	Not routinely	Risk assessment^f	Yes^g	Yes^g
Hair cover	Not routinely	Not routinely	Not routinely	Yes
Surgical mask on health care worker	Yes	Not routinely^h	Not routinely^h	Not routinelyⁱ
Particulate respirator	Not routinely	Yes	Yes	Yes
Eye protection	Risk assessment	Risk assessment^j	Yes	Yes
Surgical mask on patient	Yes	No	Not routinely^k	No

^aBird exposure in regions with avian influenza (AI) infections in animals or exposure to AI-infected patients.
^bAerosol-generating procedures create aerosols of different sizes (large-particle and small-particle aerosols). Examples of aerosol-generating procedures include endotracheal intubation, aerosolized or nebulized medication administration, diagnostic sputum induction, bronchoscopy, airway suctioning, tracheostomy care, chest physiotherapy, nasopharyngeal aspiration, positive pressure ventilation via face mask, high-frequency oscillatory ventilation, and postmortem excision of lung tissue.
^cWhenever possible, aerosol-generating procedures should be performed in negative pressure rooms, side rooms, or other closed single-patient areas with minimal staff present. Personal protective equipment should cover the torso, arms, hands, eyes, nose, and mouth.
^dStandard precautions are the minimum level of precautions indicated for all patients at all times.
^eGloves should be worn in accordance with standard precautions. If glove demand is likely to exceed supply, glove use should always be prioritized for contact with blood and body fluids (ambidextrous nonsterile gloves) and contact with sterile sites (sterile gloves).
^fGloves and gowns or aprons should be worn during cleaning procedures.
^gIf splashing with blood or body fluids is anticipated and gowns that are not fluid-resistant are used, a waterproof apron should be worn over the gown.
^hIf particulate respirator is not available, use tightly fitting surgical mask.
ⁱIf particulate respirator is not available, use tightly fitting surgical mask and face shield.
^jUse eye protection if close contact (<1 m) with patient is possible.
^kProvide surgical mask for patient (if tolerated) when patient is outside of isolation room or area.

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Avian Influenza: A Review

Abstract and Introduction

Abstract

Introduction

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References

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