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PREGNANCY & H1N1 (NOVEL
INFLUENZA)
Salah Roshdy Ahmed ,MD
Professor of OB/GYN,
Sohag University . 2014
OBJECTIVES:
To discuss Influenza A H1N1
Epidemiology
Signs & symptoms
Risk factors
Diagnosis
Treatment and Prevention
INFLUENZA
Acute respiratory illness caused by infection with influenza
viruses.
Affects the upper and/or lower respiratory tract and is often
accompanied by systemic signs and symptoms:
fever
headache
myalgia
weakness
Credit: L. Stammard, 1995
• RNA, enveloped
• Viral family: Orthomyxoviridae
• Size:
80-200nm or .08 – 0.12 μm (micron) in diameter
• Three types • A, B, C
• Surface antigens • H (haemaglutinin)
• N (neuraminidase)
INFLUENZA VIRUS
o Influenza A viruses categorized by subtype according to two surface proteins…..
Hemagglutinin (H) – 16 known - Site of attachment to host cells - Antibody to HA is protective
Neuraminidase (N) – 9 known - Helps release virions from cells - Antibody to NA can help modify disease
severity
N
H
H1 N1
H2 N2
H3 N3
H4 N4
H5 N5
H6 N6
H7 N7
H8 N8
H9 N9
H10
H11
H12
H13
H14
H15
H16
Haemagglutinin subtype Neuraminidase subtype
INFLUENZA A
The Influenza A virus subtypes that have been
confirmed in humans, ordered by the number of
known human pandemic deaths, are:
H1N1 caused "Spanish Flu" and 2009 H1N1
outbreak
H2N2 caused "Asian Flu"
H3N2 caused "Hong Kong Flu"
H5N1 is "bird flu", endemic in avian
H7N7 has unusual zoonotic potential
H1N2 is currently endemic in humans and pigs
H9N2, H7N2, H7N3, H10N7 (avian)
INFLUENZA B
Influenza B viruses are only known to infect
humans and seals giving them influenza.
This limited host range is apparently
responsible for the lack of Influenza virus B
caused influenza pandemics in contrast with
those caused by the morphologically similar
Influenza virus A as both mutate by both
genetic drift and reassortment.
INFLUENZA C
Influenza C viruses are known to infect
humans and pigs giving them influenza.
Flu due to the type C species is rare
compared to types A or B, but can be severe
and can cause local epidemics.
WHAT IS THE NOVEL
INFLUENZA A (H1N1)?
Quadruple Reassortment
2 swine strains,
1 human strain,
1 avian strain of influenza
Reassortment is the mixing of the genetic material
of a species into new combinations in different
individuals
1. Emergence of a Novel Swine-Origin Influenza A (H1N1) Virus in Humans. N Engl J Med 2009;361 2. Epidemiology, clinical manifestations, and diagnosis of swine H1N1 influenza A. Uptodate, May 15, 2009
PIG THE CREATOR
MUTATION PROPERTIES
Antigenic drift Changes in proteins by genetic point mutation &
selection
Ongoing and basis for change in vaccine each year
Antigenic shift Changes in proteins through genetic reassortment
Produces different viruses not covered by annual
vaccine
Definitions
SWINE INFLUENZA A(H1N1)
A confirmed case of H1N1 infection is defined as a person with an acute febrile respiratory
illness with laboratory confirmed H1N1 virus infection by one or more of the following tests: real-time RT-PCR
viral culture
A probable case of H1N1 infection
is defined as a person with an acute febrile respiratory illness who is: positive for influenza A, but negative for H1 and H3 by
influenza RT-PCR, or
positive for influenza A by an influenza rapid test or an influenza immunofluorescence assay (IFA) plus meets criteria for a suspected case
Source: CDC
SWINE INFLUENZA A(H1N1)
A suspected case of H1N1 infection
is defined as a person with acute febrile respiratory illness with onset
within 7 days of close contact with a person who is a confirmed case of H1N1 virus infection, or
within 7 days of travel to community where there are one or more confirmed H1N1 cases, or
resides in a community where there are one or more confirmed swine influenza cases
Source: CDC
HOSTS AND RESERVOIRS
Type A: Exists in humans and animals
Type B & C: Exclusively in humans
Reservoir in animals:
Pigs, aquatic birds
Located in the digestive tube: fecal transmission
Reservoirs in humans :
3 sub-types circulate H1N1, H1N2 et H3N2.
H1 has better affinity than H3 for cell receptors.
WHAT IS A PANDEMIC?
• There is a new strain of influenza
A virus and humans have little or
no immunity to it.
• The virus spreads from person-
to-person.
• There is a global outbreak with
sustained person- to-person
transmission.
20TH CENTURY FLU PANDEMICS
Pandemic Year
Influenza A
virus
subtype
People
infected
(approx)
Deaths
(est.)
Case
fatality rate
1918 flu
pandemic 1918–19 H1N1
0.5 to 1
billion
(near 50%)
20 to 50
million[ >2.5%
Asian flu 1956–58 H2N2 2 million <0.1% ?
Hong Kong
flu 1968–69 H3N2 1 million <0.1%
19
PANDEMIC H1N1/09 VIRUS
Novel strain of influenza A
The strain contained genes from four different
flu viruses:
1. North American swine influenza,
2. North American avian influenza,
3. Human influenza,
4. Two swine influenza viruses typically found
in Asia and Europe.
20
22
EPIDEMIOLOGY
Incubation period- 1-7 days
Transmission PRIMARY CASE –direct contact with
pigs
SECONDARY CASES
sneezing, coughing , resp droplets,
body fluids(diahrroeal stool) contact
surfaces
RISK FROM DRINKING WATER OR
SWIMMING POOLS.
Free chlorine levels typically used in drinking water or
swimming pools treatment are adequate to inactivate
highly pathogenic H5N1 avian influenza.
Free chlorine levels recommended by CDC (1–3 parts
per million [ppm} for pools and 2–5 ppm for spas).
It is likely that other influenza viruses such as novel
H1N1 would also be similarly inactivated by
chlorination.
There has never been a documented case of
influenza virus infection associated with water
exposure.
HOW LONG CAN INFLUENZA VIRUS REMAIN
VIABLE ON OBJECTS ?
Studies have shown that influenza virus can survive on environmental surfaces and can infect a person for 2 to 8 hours after being deposited on the surface.
HOW H1N1 VIRUS SPREADS
Spreads through
coughing or sneezing of
infected people
Some people may
become infected by
touching something
with flu viruses on it and
then touching their
mouth, nose or eyes.
PREGNANCY -MATERNAL
Physiologic adaptations to pregnancy may increase virulence of viral infections Alterations in maternal
immunity
Increased oxygen consumption, decreased functional residual capacity
Increased physiologic dead space due to upward displacement by uterus
Hormonally mediated hyperventilation
PREGNANCY- FETUS
Susceptible to external influences on development Direct effect of an infectious
agent
Indirect effect due to hyperthermia, release of inflammatory cytokines
Teratogenic concerns from medications used to treat infection
Prematurity related medical and developmental complications
PREGNANT WOMEN ARE A HIGH-RISK
POPULATION FOR H1N1
6x more likely to get infected with H1N1
4x more likely to be hospitalized
6x more likely to die than other adults
Deaths related to pneumonia with
subsequent ARDS requiring mechanical
ventilation
• In seasonal influenza, viremia is believed to occur infrequently and placental transmission appears to be rare – may differ with novel influenza strains
• Hyperthermia is a risk factor for some types of birth defects and other adverse outcomes
• Influenza virus itself is not known to be teratogenic.
Fetal Concerns Regarding Influenza
During Pregnancy
• Clinical outcomes data has NOT shown teratogenic effects of the most commonly recommended influenza medications oseltamivir, zanamivir.
• Influenza vaccine has no adverse fetal effects and has been recommended for pregnant patients since 2005.
Fetal Concerns Regarding Influenza
During Pregnancy
CLINICAL FEATURES
Vomiting or diarrhea (not typical for influenza but reported by recent cases of swine influenza infection)
CLINICAL FEATURES
Influenza‐like illness symptoms:
Fever
Cough
Sore throat
Rhinorrhea
Headache
Muscle pain
Malaise
No dyspnoea
33
Pregnant
Non-
pregnant
Risk ratio
(95% CI)*
Fever 33 (97%) 131 (92%) 1·1 (1·0–1·1)
Cough 32 (94%) 133 (94%) 1·0 (0·9–1·1)
Rhinorrhea 20 (59%) 71 (50%) 1·2 (0·8–1·6)
Sore throat 17 (50%) 97 (68%) 0·7 (0·5–1·0)
Headache 16 (47%) 90 (63%) 0·7 (0·5–1·1)
Shortness of breath¶ 14 (41%) 35 (25%) 1·7 (1·0–2·7)
Myalgia 12 (35%) .. ..
Vomiting 6 (18%) 22 (15%) 1·1 (0·5–2·6)
Diarrhea 4 (12%) 28 (20%) 0·6 (0·2–1·6)
Conjunctivitis 3 (9%) 12 (8%) 1·0 (0·3–3·5)
MANIFESTATIONS OF H1N1 FLU IN PREGNANCY
Jamieson DJ et al., Lancet 374:451-8, 2009
DANGER SIGNS IN ALL PATIENTS
Tachypnea
Dyspnea
Cyanosis
Bloody or coloured sputum
Chest pain
Altered mental status
High fever that persists beyond 3 days
Hypotension
Hypoxia
CLINICAL FEATURES –COMPLICATED OR
SEVERE INFLUENZA
Presenting secondary complications:
1. renal failure
2. multi‐organ failure
3. septic shock.
Other complications
1. musculoskeletal (rhabdomyolysis)
2. cardiac (myocarditis).
36
CLINICAL FEATURES – SUGGESTIVE CNS
COMPLICATION
1. Unconscious
2. Drowsiness
3. Recurring or persistent convulsions
4. Confusion
5. Severe weakness or paralysis.
37
COMPLICATIONS
Progressive Pneumonia
Respiratory Failure – cause of most deaths
Acute Respiratory Distress Syndrome
Anna R Thorner, MD. Treatment and prevention of swine H1N1
influenza. Uptodate, May 14, 2009.
PNEUMONIA -
Virus can cause pneumonia leading to death
Rapid onset, often within one day after infection
Attributed to "cytokine storm“
Deaths among healthy young people during the first
weeks of the 2009 flu pandemic were attributed to
this cause
39
LABORATORY DIAGNOSIS
(WHO guidelines 21 August 2009)
40
DIAGNOSTIC TESTS
RT PCR
QUIDEL
CULTURE
DFA/IFA
DIAGNOSTIC TEST
Real-Time Reverse Transcription-
Polymerase Chain Reaction (rRT-PCR)
Detection
Qualitative for Influenza A, B, H1, and H3
Positive for influenza A and negative for H1
and H3
If reactivity of real-time RT-PCR for influenza
A is strong , it is more suggestive of a novel
influenza A virus.
Novel H1N1 Influenza (Swine Flu)
http://www.cidrap.umn.edu/cidrap/content/infl
uenza/swineflu/biofacts/swinefluoverview.html
TESTS
Culture
Isolation of H1N1 influenza A virus - diagnostic
too slow
negative viral culture does not exclude H1N1 influenza A infection
LABORATORY FINDINGS
CBC- leucocytosis/ lymphopenia
Elevated CPK, LDH
Elevated UREA,CREATININE
Elevated AST,ALT
CHEST RADIOGRAPH-bilateral patchy
pneumonia.
PREVENTION- HYGIENE
LIMIT CONTACT
PROPHYLAXIS
VACCINATION
TREATMENT- ANTI VIRAL MEDICATIONS
ANTIPYRETIC
SUPPORTIVE HOME CARE
HOSPITALIZATION
TREATMENT
Treatment is recommended for pregnant
women with suspected or confirmed influenza,
regardless of trimester of pregnancy
Do not delay treatment because of a negative
rapid influenza diagnostic test or inability to
test or while awaiting test results
OSELTAMIVIR (TAMIFLU)
Adult dose
Rx for acute illness: 75 mg
PO bid for 5 d
Prophylaxis: 75 mg PO qd
available as 30-mg, 45-mg,
and 75-mg oral capsules
and as a powder for
suspension that contains
12 mg/mL after
reconstitution.
ZANAMIVIR (RELENZA)
Adult dose
Rx for acute illness: 10 mg
inhaled orally bid for 5 d
Prophylaxis of household
contact: 10 mg inhaled orally
qd for 10 d
(initiate within 36 h)
Prophylaxis for community
outbreak: 10 mg inhaled orally
qd for 28 d (initiate within 5 d of
outbreak)
powder form for inhalation via
the Diskhaler oral inhalation
device
SWINE INFLUENZA A(H1N1)
Source: CDC
Oseltamivir (Tamiflu) Zanamivir (Relenza)
Treatment Prophylaxis Treatment Prophylaxis
Adults 75 mg capsule
twice per day for 5
days
75 mg capsule
once per day
Two 5 mg
inhalations (10 mg
total) twice per day
Two 5 mg
inhalations (10 mg
total) once per day
Children 15 kg or less: 60
mg per day divided
into 2 doses
30 mg once per
day
Two 5 mg
inhalations (10 mg
total) twice per day
(age, 7 years or
older)
Two 5 mg
inhalations (10 mg
total) once per day
(age, 5 years or
older) 15–23 kg: 90 mg
per day divided
into 2 doses
45 mg once per
day
24–40 kg: 120 mg
per day divided
into 2 doses
60 mg once per
day
>40 kg: 150 mg
per day divided
into 2 doses
75 mg once per
day
Dosing recommendations for antiviral treatment of children younger than 1 year using oseltamivir. Recommended treatment
dose for 5 days. <3 months: 12 mg twice daily; 3-5 months: 20 mg twice daily; 6-11 months: 25 mg twice daily
Dosing recommendations for antiviral chemoprophylaxis of children younger than 1 year using oseltamivir. Recommended
prophylaxis dose for 10 days. <3 months: Not recommended unless situation judged critical due to limited data on use in this
age group; 3-5 months: 20 mg once daily; 6-11 months: 25 mg once daily
WHEN IS HOSPITALIZATION NEEDED?
Respiratory symptoms- shortness of breath
Intractable nausea, vomiting
Fever unresponsive to acetaminophen
Contractions, abdominal pain, preterm labor
Decreased fetal movement
POST-EXPOSURE CHEMOPROPHYLAXIS
Consider if close contact with suspected or
confirmed case
Zanamivir (Relenza®) Two 5mg inhalations qd
Oseltamivir (Tamiflu®) 75 mg qd
10 day duration
Zanamivir is recommended in pregnancy due to
less systemic absorption
CDC RECOMMENDATIONS FOR LABOR WITH
H1N1 (AUGUST 2009)
Place surgical mask on ill mother during labor & delivery, if tolerable
Mother should consider avoiding close contact with infant until:
antiviral medication for 48 hours
fever has fully resolved
she can control coughs and secretions
When in contact with the infant, mother should do following until 7 days after symptom onset and symptom-free for 24 hours:
wear a facemask
change to clean gown or clothing
adhere to strict hand hygiene and cough etiquette
CDC RECOMMENDATIONS FOR
POSTPARTUM WITH H1N1 (AUGUST 2009)
Newborns should be considered potentially
infectious or infected if delivery occurs 2 days
before through 7 days after onset of maternal
illness.
Encourage breast feeding- use pump if in
isolation until mother can breast feed.
SAFETY OF INFLUENZA VACCINATION
DURING PREGNANCY
11 studies published between 1964 and
2008 about safety of influenza
vaccination during pregnancy
None identified maternal or fetal
problems with influenza vaccination
One prospective randomized trial
showed significant benefits to mothers
and newborns
VACCINE TYPES
Live attenuated vaccine (not licensed for
use in pregnant women)
Multidose inactivated vaccine
Prefilled single dose inactivated vaccine
(preservative-free)
H1N1 VACCINE
Strongly recommended for
Pregnant women.
Parents of children under 6 months.
Health care providers with direct patient
contact.
Safety
Use “Flu Shot” (fragments of
killed/inactivated virus) not “nasal spray”
(live-attenuated virus),
2009 H1N1 Influenza Vaccine and Pregnant Women. CDC September
3, 2009 http://www.cdc.gov/h1n1flu/vaccination/pregnant_qa.htm
WHEN TO ADMINISTER
Can be given at any time during
pregnancy
Can also be given postpartum, providing
indirect protection for infants <6 months
Recommended even for women who have
had influenza-like illness
MEDICATION SUMMARY
Treatment Chemoprophylaxis
Oseltamivir
(Tamiflu®)
75-mg capsule twice
per day for 5 days*
75-mg capsule once
per day for 10 days*
Zanamivir
(Relenza®)
Two 5-mg inhalations
(10 mg total) twice per
day for 5 days
Two 5-mg inhalations
(10 mg total) once per
day for 10 days*
Antiviral medication dosing recommendations for treatment or
chemoprophylaxis of novel influenza A (H1N1) infection
*Currently recommended first choice medications. CDC: Updated Interim Recommendations for the Use of Antiviral Medications in the
Treatment and Prevention of Influenza for the 2009-2010 Season. 10/16/2009
SWINE INFLUENZA A(H1N1) GUIDELINES FOR GENERAL POPULATION
Covering nose and mouth with a tissue when coughing or sneezing
Hand washing with soap and water
Cleaning hands with alcohol-based hand cleaners
Avoiding close contact with sick people
Avoiding touching eyes, nose or mouth with unwashed hands
AVOID CLOSE CONTACT
Avoid close contact
with people who are
sick. When you are
sick, keep your
distance from others
to protect them from
getting sick too.
Aerosols spread the
virus in any
environment
STAY HOME WHEN YOU ARE SICK.
If possible, stay home
from work, school,
and errands when you
are sick. You will help
prevent others from
catching your illness.
COVER YOUR MOUTH AND NOSE.
Cover your mouth and
nose with a tissue
when coughing or
sneezing. It may
prevent those around
you from getting sick
CLEAN YOUR HANDS.
Washing your hands
often will help protect
you from germs.
Hand washing proved
to be best procedure
in prevention of
Majority of
Communicable
diseases.
AVOID TOUCHING YOUR EYES, NOSE OR
MOUTH.
Germs are often
spread when a person
touches something
that is contaminated
with germs and then
touches his or her
eyes, nose, or mouth.
PRACTICE OTHER GOOD HEALTH HABITS.
Get plenty of sleep, be
physically active,
manage your stress,
drink plenty of fluids.
Unnecessary
Migration of people
from epidemic and
endemic areas to be
reduced.
HEALTHY HABITS REDUCES THE
ATTACKS
SIMPLE MEASURES CARRY GET GOOD
BENEFITS
Cover your mouth
and nose. Use a
tissue when you
cough or sneeze and
drop it in the trash. If
you don’t have a
tissue, cover your
mouth and nose as
best you can.
CLEAN HANDS SAVES YOU
Clean your hands
often. Clean your
hands every time you
cough or sneeze.
Hand washing stops
germs. Alcohol-based
gels and wipes also
work well.
WARNING Aspirin or aspirin-containing products should not be
administered to any confirmed or suspected ill case of
novel influenza A (H1N1) virus infection aged 18
years old and younger due to the risk of Reye’s
syndrome.
Children 5 years of age and older and teenagers with
the flu can take medicines without aspirin, such as
acetaminophen and ibuprofen .
ACOG / CDC
Released
Oct 15, 2009
Usable for
office, clinic
or OB Triage
ACOG
websitehttp://www
.acog.org/departments/re
sourceCenter/2009H1N1T
riageTreatment.pdf
CONCLUSIONS
Data available thus far suggest that pregnant women are more susceptible to H1N1 influenza & they are at increased risk for complications and death.
CONCLUSIONS
Pregnant women should be informed about the signs and symptoms of H1N1 influenza.
Pregnant women who present with signs and symptoms consistent with influenza should be treated empirically with oseltamivir.
CONCLUSIONS
Proof of diagnosis is not required for treatment.
Post-exposure prophylaxis with zanamivir or oseltamivir can be considered for pregnant women
CONCLUSIONS
Both seasonal and 2009 H1N1 influenza vaccines recommended for pregnant women
2009 H1N1 vaccine safety expected to be similar to seasonal influenza vaccine
Obstetrical care providers should take a very active part in promoting vaccination .
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