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 .