Cross-Species Cross-Species Transmission of Transmission of Avian Influenza Avian Influenza

(H5N1) to (H5N1) to HumansHumans

Thomas Thacker, Thomas Thacker, B.S., PA-SB.S., PA-S

Frank Romanelli, Pharm. D., MPH, BCPS

Why did the Why did the chicken cross chicken cross

the road?the road?

HOWHOW did the did the chicken cross chicken cross

the road?the road?

Why should we Why should we care?care? 1918 “Spanish” 1918 “Spanish” Flu PandemicFlu Pandemic

1957 “Asian” 1957 “Asian” Flu PandemicFlu Pandemic 1958 “Hong Kong” 1958 “Hong Kong” Flu Flu

PandemicPandemic 1997 Avian Influenza (H5N1) in 1997 Avian Influenza (H5N1) in

HumansHumans ““Bird” Bird” Flu PandemicFlu Pandemic ?? > 50% Mortality> 50% Mortality

Why should we Why should we care?care?

Avian influenza (H5N1) has caused Avian influenza (H5N1) has caused more severe human infections than more severe human infections than any other AIVany other AIV

Avian Influenza (H5N1) Mutation?Avian Influenza (H5N1) Mutation? Person-to-Person Transmission?Person-to-Person Transmission? NO Human Immunity/NO VaccineNO Human Immunity/NO Vaccine High Rates of Dz & Mortality?High Rates of Dz & Mortality? Resistance to AntiviralsResistance to Antivirals

EpidemiologyEpidemiology Transmission: direct, close, or Transmission: direct, close, or

indirect contact with infected indirect contact with infected birds or their biological productsbirds or their biological products

Numerous Instances of Avian Numerous Instances of Avian Influenza (H5N1) Infections in Influenza (H5N1) Infections in

HumansHumansTIME LINE OF AVIAN INFLUENZA (H5N1) INFECTIONS IN HUMANS.

1997 Emergence of human infections with avian influenza (H5N1) directly linked to bird species

2003 Two cases of avian influenza (H5N1) in China and Hong Kong; among members of a Hong Kong family that had traveled to China; source of infection not determined; one person recovered, the other died, another family member died of an unknown respiratory illness in China but no definitive testing was performed In January the WHO reports cases of avian influenza (H5N1) in Asia, Africa, the Pacific, Europe, and the Near East Infections with avian influenza (H5N1) in Thailand and Vietnam; mostly resulting from contact with infected poultry; one probable human-to-human transmission in Thailand Probable human-to-human transmission of avian influenza (H5N1) from an ill child to mother in Thailand Atypical fatal case of avian influenza (H5N1) causing encephalitis in a Vietnamese child

2004

Confirmed infections with avian influenza (H5N1) in Vietnam, Thailand, and Cambodia

2005 Infections with avian influenza (H5N1) in Cambodia, China, Indonesia, Thailand, and Vietnam; in association with ongoing poultry infection; transmission to at least two Vietnamese individuals who ingested uncooked duck Infections with avian influenza (H5N1) in Azerbaijan, Cambodia, China, Djibouti, Egypt, Indonesia, Iraq, Thailand, and Turkey; in association with ongoing and expanding poultry infection; most cases a result of contact with infected poultry; transmission from dead wild swans to several children in Azerbaijan

2006

In June, the WHO reported human-to-human transmission of avian influenza (H5N1) within an Indonesian family

Human Cases of Human Cases of Avian Influenza Avian Influenza

(H5N1)(H5N1)WHO Laboratory-confirmed Human Cases of

Avian Influenza (H5N1)

46

97

116

4

32

42

80

0

10

20

30

40

50

60

70

80

90

100

110

120

2003 2004 2005 2006

Year

Num

ber o

f Cas

es/D

eath

s

Cases

Deaths

*The number of cases includes deaths.

PathophysioPathophysiologylogy

Modalities of Cross-Species Modalities of Cross-Species Transmission of Avian Influenza Transmission of Avian Influenza

(H5N1):(H5N1):Amino Acid Mutations

Adaptive Mutations

Indirect AIV Transmissions

Direct AIV Transmissions

Genetic Reassortments

Antigenic Shift Mechanisms RBS Modification Mechanisms

Antigenic ShiftAntigenic Shift

Antigenic ShiftAntigenic Shift

Dx Findings Associated Dx Findings Associated with Dz Caused by Avian with Dz Caused by Avian

Influenza (H5N1)Influenza (H5N1) LeukopeniaLeukopenia LymphopeniaLymphopenia ThrombocytopeThrombocytope

niania Elevated Elevated

aminotransferasaminotransferaseses

DICDIC

PancytopeniaPancytopenia HyperglycemiaHyperglycemia Elevated Elevated

creatininecreatinine Infiltrates & Infiltrates &

consolidation consolidation on CXRon CXR

Sxs of Dz Caused by Sxs of Dz Caused by Avian Influenza Avian Influenza

(H5N1): (H5N1): FLU-LIKEFLU-LIKECOMMON SYMPTOMS LESS COMMON SYMPTOMS

Fever Vomiting

Cough Abdominal pain

Sore throat Pleuritic pain

Hoarseness Bleeding from the nose and gums

Myalgia Acute encephalitis

Dyspnea Conjunctivitis (rarely)

Acute respiratory distress Watery diarrhea

Tachypnea Cardiac dilatation

Crackle breath sounds Supraventricular tachyarrhythmias

Intermittent sputum production Pulmonary hemorrhage

Pneumonia Pneumothorax

Respiratory failure Reye’s syndrome

Multisystem organ failure (MSOF) Sepsis

Renal dysfunction

Management & Tx of Dz Management & Tx of Dz Caused by Avian Caused by Avian Influenza (H5N1)Influenza (H5N1)

Mechanical Mechanical ventilationventilation

Intensive careIntensive care CorticosteroidsCorticosteroids Empirical broad-spectrum Empirical broad-spectrum

antibioticsantibiotics

Management & Tx of Dz Management & Tx of Dz Caused by Avian Caused by Avian Influenza (H5N1)Influenza (H5N1)

Tamiflu™ Tamiflu™ (oseltamivir)(oseltamivir)

Relenza™ Relenza™ (zanamivir)(zanamivir)

Prevention of Dz Caused by Prevention of Dz Caused by Avian Influenza (H5N1): Avian Influenza (H5N1):

GOOD HYGIENEGOOD HYGIENE

Recipe for an Avian Recipe for an Avian Influenza (H5N1) Influenza (H5N1)

Pandemic in HumansPandemic in Humans1.1. Infect humans and cause DzInfect humans and cause Dz2.2. Evoke an ineffective immune Evoke an ineffective immune

responseresponse3.3. Spread from human to humanSpread from human to human??I had a little bird,I had a little bird,

Its name was Enza,Its name was Enza,I opened the I opened the

window,window,And in-flu-enza.And in-flu-enza.

-Children’s Rhyme, -Children’s Rhyme, 1918 “Spanish” Flu 1918 “Spanish” Flu

PandemicPandemic

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National Institute of Allergy and Infectious Diseases National Institutes of Health [homepage on

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Smith DJ. Predictability and preparedness in influenza control. Science. 2006; 312: 392-4.

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