H5N1

Dr Rahmini Shabariah SpA
 family
Orthomyxoviridae
 large, single-stranded
RNA virus
 2 major surface
glikoprotein  serotype
 1/. hemagglutinin (H) &
2/. neuromidase (N)
 project as spikes
through the envelope
 H1-15 and N1-9
type type type
A B C
• human & animal • human • human
• primary pathogen • primary pathogen • sporadic cases
• mild – severe • mild - moderate • mild
• AURI & ALRI AURI, • AURI,
• epidemic, poten’ly • epidemic • no epidemic
pandemic
Avian Influenza
Nelson 17th ed, 2004
 animal host, mainly aves  reservoir for
diverse strain
 potential for infecting human
 any of 15H & 9H in animal may be
introduced into humans
 many serotypes, potential changes
◦ antigenic drift: minor changes within a serotype
◦ antigenic shift: major changes within a serotype
 migratory avian host  spread of disease
Nelson 17th ed, 2004

 live in the water: 4 days in 220C, and
>30 days in 00C
 live in avian feces up to 32 days
 very labile, mutate easily: LPAI  HPAI
 in chicken carcasses, die in 800C for 1’ and

600C for 30’
 in chicken egg, die in 640C for 5’
 die in: alcohol 70%, formalin 2-5%,
chlorine, iodine, fenol, Na/K hypochloride

 Avian influenza H5N1 in poultry confirmed
in Asia
 South Korea, Vietnam, Japan, Thailand,
Cambodia, Taiwan, Laos, China, Indonesia,

Pakistan, Malaysia
 possible virus sources:
◦ birds migration
◦ transportation of infected poultry
 1997: Hong Kong (H5N1) 18 cases, 6 died
 1999: China & Hong Kong (H9N2) 2 cases
 2002: Virginia (H7N2);1 seropositive case
 2003: Fujian, Hong Kong (H5N1) 2 cases, 1
died
 2003: Netherlands (H7N7); 89 cases, 1 died
 2003: Hong Kong (H9N2); 1 case
 2004-2005: Canada (H7N3); Vietnam
(H5N1) 87 cases; Thailand (H5N1) 17
cases; Cambodia (H5N1) 4 cases;
Indonesia (H5N1) 1 case
Spanish flu Asian flu Hong Kong
1918 1957 flu 1968
• virus H1N1 • virus H2N2 • virus H3N2

• 40-50 million • China, Feb • Hongkong,
death 1957 early 1968
• 50% victim • spread to USA • spread quickly
young healthy in 4 months to USA
people • 1 million death • still circulate
• die in a few today
days
Age Onset Clinical Lab Duration
8y 24.06.05 fever,cough, positive 20 days

diarrhea,RDS serology
1y 29.06.05 fever,cough, - 10 days
diarrhea,RDS
38 y 02.07.05 fever,cough, positive 10 days
cold,diarrhea, PCR
RDS
 limited cases, only 109 confirmed cases up to
July 2005
 vary clinical features, usually with respiratory
symptoms, but one cases without respiratory
symptoms at all
 progressive clinical process leading to death
despite aggressive treatment  retrospective
analysis
 incubation period for human influenza: 2-
3 days (range 1-7 days )
 incubation period for avian influenza: 3
days (2-4)
 clinical features: vary, from asymptomatic,
mild ILI (Influenza like illness) to severe
ARDS (Acute respiratory distress
syndrome)
 similar with the usual influenza  ILI
 Acute respiratory febrile illness
◦ fever >380C
◦ cough
◦ coryza / runny nose
◦ sore throat
◦ myalgia
◦ headache
◦ malaise
 can progress rapidly, to pneumonia and
ARDS
ARDS
fever Pneumoniae
Severe ILI
Mild-Modr ILI
diarrhea
asymptomatic
seizure
all patient with ILI ???
all patient with
pneumonia ???
 fever >380C
 cough, coryza, sore throat
AND, 1 of the following:

 in the last week, visiting a farm with an AI
outbreak in the poultry OR

 history of contact with a confirmed AI case
OR
 working in the lab which processing AI
virus specimen
suspect case AND
 progressive clinical features, leading to
pneumonia / respiratory failure / death OR

 laboratory test positive for H5N1 Ag OR
 no other proven etiology
a person with acute respiratory febrile illness,
with >1 of the following:
 positive viral culture for influenza A/H5
 positive PCR for influenza A/H5
 positive IFA (Immuno-fluorescent antibody)
test to H5 antigen using monoclonal
antibodies
 4-fold rise in H5 specific antibody titre in
paired serum sample
the disease will have bad prognosis if:
 late hospitalized
 older age
 pneumonia
 leucopenia
 lymphopenia
 bad general condition, severely ill
 fever >380C
 tachypnea, dyspnea
 ronchi, crackles
 respiratory failure
 marked leucopenia
 marked lymphopenia
marked and progressive abnormalities, but non
specific
 extensive bilateral infiltrates
 diffuse, multifocal, or patchy infiltrates
 lobar collapse
 focal consolidation
 air bronchogram
 early implementation of infection control
precautions to minimize nosocomial
spread of disease
 proper case management to prevent severe
illness and death
 early identification and follow up of
persons at risk of infection to facilitate
early intervention with antiviral therapy to
reduce morbidity an mortality an limit
further spread of the disease
WHO Guidelines Feb 2004

 use high efficiency mask
 a negative pressure room – if available –
is recommended
 isolate the patient to a single room, if not
available bed should be placed >1m
apart, preferably separated by a physical
barrier (curtain, partition)
 appropriate Personal Protective
Equipment (PPE)

 limit the number of Health Care Workers
(HCWs) who have direct contact with the
patient(s),
 restrict the number of visitors and
provide them with appropriate PPE
 dispose of waste properly
 linen and reusable materials should be
handled separately and disinfected

 if not requiring hospitalization, educate
patient and family on personal hygiene and
infection control
 if clinically indicated, hospitalize patients
 take respiratory & blood specimens for lab
testing for influenza and other infections
 treat with neuromidase inhibitor, such as
oseltamivir
 provide supportive care, monitor oxygen
saturation and treat desaturation with
supplemental oxygen as required
 take respiratory and blood specimens serially to
check for possible bacterial infection
 consider IV antibiotic therapy to control secondary
bacterial infections as required
 steroids should be used only in the context of
clinical trial
 avoid salicylates in children<18 years because the
risk of Reye syndrome, instead use paracetamol or
ibuprofen

 Isolation room
◦ beware of airborne transmission
◦ infectious period, the first 7 days of symptoms
 Moved to ward
◦ PCR or culture of nasopharyngeal swab is negative
for several times
◦ no fever for 7 days
 rest
 body defense mechanism improvement
 antiviral therapy
 antibiotic
 respiratory care
 anti-inflammation : steroid (prednisolone
2mg/kg/hari), if needed
 immuno-modulator
should be given in the first 48 hours
two kinds:
 M2 protein inhibitor:
◦ amantadine (Symmetrel, Symadine)

◦ rimantadine (Flumadine)
 Neuromidase inhibitor:
◦ oseltamivir (Tamiflu)
◦ zanamivir (Relenza)
 adult patients remain in hospital for 7 days
after resolution of fever
 children patients remain in hospital for 21
days after resolution of fever

 human to human transmission is very rare
 clinical features of AI are not specific, and
vary from asymptomatic to severe ARDS
 the severe form, progress rapidly and
usually fatal
 acute respiratory febrile illness with
progressive clinical features should be
suspected as an AI
 oseltamivir is an important drug for
treatment and prevention of AI
 AI has a potential to become a new
pandemic
 increase awareness of this potential threat

H5N1

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H5N1

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Dr Rahmini Shabariah SpA

Nelson 17th ed, 2004

 in chicken carcasses, die in 800C for 1’ and

chlorine, iodine, fenol, Na/K hypochloride

Cambodia, Taiwan, Laos, China, Indonesia,

• virus H1N1 • virus H2N2 • virus H3N2

8y 24.06.05 fever,cough, positive 20 days

AND, 1 of the following:

outbreak in the poultry OR

pneumonia / respiratory failure / death OR

WHO Guidelines Feb 2004

WHO Guidelines Feb 2004

WHO Guidelines Feb 2004

WHO Guidelines Feb 2004

◦ amantadine (Symmetrel, Symadine)

days after resolution of fever

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