Vitaly A. Stepensky, M3 Student Internal Medicine Teaching Rounds October 27, 2009

Vitaly A. Stepensky, M3 Student

Internal Medicine Teaching Rounds

October 27, 2009

Vitaly A. Stepensky 2

Overview For Today’s TalkOverview For Today’s Talk

I. Influenza Biology

• Family, Structure and Life Cycle

II. H1N1 Epidemiology

• Domestic and Global Emergence / Outbreaks

III. Clinical Presentation

• Signs, Symptoms, Treatment

IV. Questions Your Patients May Ask


Influenza Virus FamilyInfluenza Virus Family• Influenza A virus which causes influenza in birds and some mammals.

– Strains of all subtypes of influenza A virus have been isolated from wild birds, although disease is uncommon. Occasionally viruses are transmitted from wild aquatic birds to domestic poultry and this may cause an outbreak or give rise to human influenza pandemics.

• Influenza B virus is almost exclusively a human pathogen, and is less common than influenza A.

– The only other animal known to be susceptible to influenza B infection is the seal.

– Mutates at a rate 2-3 times lower than type A and consequently is less genetically diverse, with only one influenza B serotype.

– As a result of this lack of antigenic diversity, a degree of immunity to influenza B is usually acquired at an early age.

– Reduced rate of antigenic change, combined with its limited host range (inhibiting cross species antigenic shift), ensures that pandemics of influenza B do not occur.

• Influenza C virus infects humans and pigs, and can cause severe illness and local epidemics. However, influenza C is less common than the other types and usually seems to cause mild disease in children.

• Influenza virus tend to be labile, but can survive several hours (8+) in mucus covered surfaces.


Influenza Virus StructureInfluenza Virus Structure• Member of Orthomyxovirus family.

• Contain 7 to 8 segments of linear negative-sense

single stranded RNA.

• Virion can be spherical or filamentous in shape.

• Approximately 500 surface of envelope proteins.

• Hemagglutinin (H) is interposed irregularly by

clusters of Neuraminidase (N), with a ratio of HA

to NA of about 5 to 1.

– Hemagglutinin is a lectin that mediates binding

of the virus to target cells and entry of the viral

genome into the target cell.

– Neuraminidase is an enzyme involved in the

release of progeny virus from infected cells, by

cleaving sugars that bind the mature viral

particles.


Influenza Life CycleInfluenza Life Cycle

Neumann G, Noda T, Kawaoka Y. Emergence and pandemic potential of swine-origin H1N1 influenza virus. Nature. 2009 Jun 18;459(7249):931-9.

Uncoating Inhibitors

siRNA

Neuraminidase Inhibitors


Swine Flu EpidemiologySwine Flu Epidemiology


Old H1N1 EpidemiologyOld H1N1 Epidemiology

• The last H1N1 pandemic was the “Spanish Flu”, which lasted occurred from 1918 to 1919.

• Estimates show that 40 – 100 million people worldwide were killed.

– has been described as "the greatest medical holocaust in history" and may have killed as many people as the Black Death.

• The huge death toll was caused by an extremely high infection rate of up to 50% and the extreme severity of the symptoms.

– majority of deaths were from bacterial pneumonia (secondary infection), but the virus also killed people directly, causing massive hemorrhages and edema in the lung.

• The unusually severe disease killed between 2 and 20% of those infected, as opposed to the more usual flu epidemic mortality rate of 0.1%.


Pandemics of Human InfluenzaPandemics of Human Influenza

Palese P. Influenza: old and new threats Nat Med. 2004 Dec;10(12 Suppl):S82-7.

Old Hong Kong Flu1900

Spanish Flu1918

Asian Flu1957

Hong Kong Flu1968

H5N1

Avian Flu2006-08

Swine Flu2009


Old H1N1 EpidemiologyOld H1N1 Epidemiology

• Another unusual feature of this pandemic was that it mostly killed young

adults, with 99% of pandemic influenza deaths occurring in people under

65, and more than half in young adults 20 to 40 years old.

– unusual since influenza is normally most deadly to the very young

(under age 2) and the very old (over age 70).

• The total mortality of the 1918–1919 pandemic is not known, but it is

estimated that up to 1% of the world's population was killed.

– as many as 25 million may have been killed in the first 25 weeks.

– HIV/AIDS is estimated to have killed 25 million in its first 25 years.


Impact of Old H1N1 on Life ExpectancyImpact of Old H1N1 on Life Expectancy

Palese P. Influenza: old and new threats Nat Med. 2004 Dec;10(12 Suppl):S82-7.


Old H1N1 and Genetic ShiftOld H1N1 and Genetic Shift

“When he compared the 1918

virus with today's human flu

viruses, Dr. Taubenberger

noticed that it had alterations in

just 25 to 30 of the virus's 4,400

amino acids. Those few changes

turned a bird virus into a killer

than could spread from person to

person.”

Hazard in Hunt for New Flu: Looking for Bugs in All the Wrong Places

The New York Times, Published: November 8, 2005


The New H1N1 of 2009The New H1N1 of 2009


General Statistics of New H1N1General Statistics of New H1N1

• H1N1 is a new influenza A virus that has never before circulated among humans. This virus is not related to previous or current human seasonal influenza viruses and is the result of novel reassortmant between human, avian and porcine influenza.

• In April 2009 the first confirmed cases of H1N1 influenza were detected in San Diego and Imperial County, California and in Guadalupe County, Texas.

• Since then 200,000+ confirmed cases and 2000+ deaths have been reported all over the world.

• There has been 6000+ hospitalizations and 500+ confirmed cases of death in US alone.

• Pandemic Phase 6 declared by World Health Organization (WHO) in June 2009.


Where Did Swine Flu Come From?Where Did Swine Flu Come From?


Neumann G, Noda T, Kawaoka Y. Emergence and pandemic potential of swine-origin H1N1 influenza virus. Nature. 2009 Jun 18;459(7249):931-9.

Reassortment of the H1N1 StrainsReassortment of the H1N1 Strains


Global Incidence and MortalityGlobal Incidence and Mortality

http://www.who.int/csr/disease/swineflu/history_map/InfluenzaAH1N1_maps.html

Vitaly A. Stepensky 18http://www.cdc.gov/h1n1flu/updates/international/map.htm

Global Incidence of Flu Subtypes Global Incidence of Flu Subtypes


H1N1 Activity in the USH1N1 Activity in the US

http://www.cdc.gov/h1n1flu/updates/us/#iligraph


H1N1 Until Proven OtherwiseH1N1 Until Proven Otherwise

http://www.cdc.gov/flu/weekly/index.htm#MS

Vitaly A. Stepensky 22http://www.cdc.gov/h1n1flu/qa.htm

Influenza Hospitalizations By AgeInfluenza Hospitalizations By Age


Influenza Deaths By AgeInfluenza Deaths By Age

http://www.cdc.gov/h1n1flu/qa.htm


Pandemic of New H1N1Pandemic of New H1N1

• On June 11th, the World Health Organization raised its pandemic alert level to the phase 6, indicating widespread community transmission on at least two continents.

• On October 23th, President Barack Obama declared a national emergency to deal with the rapid increase in illness from the H1N1 influenza virus.


Weekly Visits for Influenza Like IllnessWeekly Visits for Influenza Like Illness

http://www.cdc.gov/flu/weekly/index.htm#MS


Pneumonia and Influenza MortalityPneumonia and Influenza Mortality


Signs and Symptoms of New H1N1Signs and Symptoms of New H1N1


Signs and Symptoms of New H1N1Signs and Symptoms of New H1N1• Analysis of 642 cases identified in 41 states.

• Median age of patients was 20 years, with a range of 3 months to 81 years

– 40% of patients were between the ages of 10 to 18 years

• Patients presented with

– fever (94%)

– cough (92%)

– sore throat (66%)

– diarrhea (25%) and vomiting (25%)

• Hospitalization status was known for 399 patients, of whom 9% were

hospitalized, with an age range of 19 months to 51 years. Many of the

hospitalized patients had chronic medical conditions.

• The virus was sensitive to both oseltamivir and zanamivir.Dawood FS, Jain S, et al. Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team, Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009;360(25):2605-2615.


Complications Following InfluenzaComplications Following Influenza

• Upper respiratory tract disease (sinusitis, otitis media, croup)

• Lower respiratory tract disease (pneumonia, bronchiolitis, ARDS)

• Cardiac (myocarditis, pericarditis)

• Neurological (encephalopathy, encephalitis, seizures, status epilepticus)

• Toxic shock syndrome

• Secondary bacterial pneumonia with or without sepsis


Caution In High Risk Groups Caution In High Risk Groups

• Individuals with the following conditions should contact their healthcare

providers immediately if they experience flu-like symptoms (fever of at

least 100 F, cough, sore throat, body aches, diarrhea, vomiting):

– Pregnancy

– Asthma

– Heart Disease

– Immuno-compromised

– Diabetes

http://www.carle.org/pdf/Carle_H1N1_Flu_Testing.pdf


Protecting Yourself and Reducing Spread Protecting Yourself and Reducing Spread


Protecting Yourself and Reducing SpreadProtecting Yourself and Reducing Spread

• Wash your hands often with soap and warm water, especially after a cough or sneeze. Wash for at least 20 seconds.

– Chorus of “Sweet Caroline” (Neil Diamond)

– Rap in the middle of the “Bohemian Rhapsody”

– Lady MacBeth’s “Out Damned Spot” soliloquy

• Alcohol-based hand wipes or gel sanitizers are also effective.

• Get a goodnights sleep; 6-8 hours every night to keep your immune system healthy.

• Keep hydrated each day to “flush toxins” maintain healthy mucous membranes.

• Keep your body strong, nourished, and ready to fight infection. Eat well, including whole grains, vegetables, and vitamin-rich fruits (or a multi-vitamin).


Benefits (Collaterally) of H1N1Benefits (Collaterally) of H1N1

• Diarrheal diseases are the biggest killer of

children under age 5 worldwide; in Bolivia,

30,000 children die each year from such

illnesses.

• Starting in April, sudsy cartoon hands were

everywhere, promoting hand-washing on

billboards, at soccer games, in classrooms

and on TV.

• “We see a steady 10% to 15% drop in the

rate of incidence of acute diarrheal diseases

in all age groups, compared with last year's

numbers at this time.” says Dr. René Lenis,

Bolivia's director of epidemiology.


Students/Residents…If You Feel SickStudents/Residents…If You Feel Sick

• Stay home if you’re sick for 7 days after your symptoms begin or until you’ve been symptom-free for 24 hours, whichever is longer.

– Non-healthcare personnel may return to work/school 24 hours after their body temp returns to normal (98.6) without anti-pyretic medications.

Faking Out Attendings

• Limit contact with other people as much as possible.

• Rest, drink fluids and maintain nutrition.

• Take anti-pyretic medications (Tylenol, Ibuprofen).

No rounds today.



When To Seek Medical HelpWhen To Seek Medical Help

• Emergency warning signs in adults:

– Difficulty breathing or shortness of breath

– Pain or pressure in the chest or abdomen

– Sudden dizziness

– Confusion

– Severe or persistent vomiting

– Flu-like symptoms improve but then return with fever and worse cough

• Emergency warning signs in children:

– Fast breathing or trouble breathing

– Bluish or gray skin color

– Not drinking enough fluids

– Severe or persistent vomiting

– Not waking up or not interacting

– Irritable, the child does not want to be held

– Flu-like symptoms improve but then return with fever and worse cough



Influenza Treatment OptionsInfluenza Treatment Options

• There are four different antiviral drugs that are licensed for use in

the US for the treatment of influenza:

– M2 Inhibitors (viral un-coating)

• Amantadine (Symmetrel)

• Rimantadine (Flumadine)

– Neuraminidase Inhibitors

• Oseltamivir (Tamiflu) – Oral

• Zanamivir (Relenza) – Inhalant

• Samples of 2009 H1N1 flu viruses have shown resistance to

Amantidine and Rimantadine; thus Oseltamivir and Zanamivir are

the recommended treatments.



• For pregnant patients:

– Oseltamivir and Zanamivir are “Pregnancy Category C” medications.

– Oseltamivir is preferred because of its systemic activity.

– The drug of choice for chemoprophylaxis is less clear. Zanamivir may be preferable because of its limited systemic absorption.

• For pre-exposure prophylaxis:

– Oseltamivir should be given during the potential exposure period and continued for 10 days after the last known exposure to a person with H1N1 influenza.

• For post-exposure prophylaxis:

– Oseltamivir should be given for 10 days after the last known exposure.

• Close contacts who are at high-risk for complications of influenza.

• Health care personnel, public health workers, or first responders.


Who Should Get H1N1 VaccineWho Should Get H1N1 Vaccine

• When vaccine is first available, the CDC Advisory Committee on Immunization Practices (ACIP) has recommended the 2009 H1N1 vaccine for the following 5 target groups (approximately 159 million persons nationally):

– Pregnant women.

– Household and caregiver contacts of children younger than 6 months of age (e.g. parents, siblings, and daycare providers).

– Health care and emergency medical services personnel.

– Persons from 6 months through 24 years of age.

– Persons aged 25 through 64 years who have medical conditions associated with a higher risk of influenza complications.

• Once providers meet the demand for vaccine among persons in these initial target groups, vaccination is recommended for all persons 25 through 64 years of age.

• Current studies indicate that the risk for infection among persons age 65 or older is less than the risk for younger age groups, thus once vaccine demand among younger age groups has been met, programs and providers should offer vaccination to people 65 or older.

http://www.cdc.gov/h1n1flu/vaccination/public/vaccination_qa_pub.htm


Questions From Your PatientsQuestions From Your Patients

• Will the seasonal flu vaccine also protect against the 2009 H1N1 flu?

– The seasonal flu vaccine is not expected to protect against the 2009 H1N1 flu.

• Will this vaccine be made differently than the seasonal influenza vaccine?

– No. This vaccine will be made using the same processes and facilities that are used to make the currently licensed seasonal influenza vaccines.

• Can the seasonal vaccine and the 2009 H1N1 vaccine be given at the same time?

– Inactivated 2009 H1N1 vaccine can be administered at the same visit as any other vaccine.

– Live 2009 H1N1 vaccine can be administered at the same visit as any other live or inactivated vaccine EXCEPT seasonal live attenuated influenza vaccine.

http://www.cdc.gov/h1n1flu/vaccination/public/vaccination_qa_pub.htm



• Why aren’t you testing me for H1N1?

– Most people with flu symptoms do not need at test for 2009 H1N1 because the results do not change how you are treated.

• But I need to know for certain if I have “the swine flu.”

– Accurate lab tests (RT-PCR) are only available at certain labs and the tests can take several weeks. The test results will not change the treatment you receive.

• Can I get sick from eating pork?

– H1N1 is not a a food borne illness…it is a respiratory disease. All foods are safe to eat if properly prepared (160 F for pork) .



• Can I get H1N1 from being around pigs / swine?

– Yes, the H1N1 flu can spread via contact with infected pigs or their contaminated environment.

• How long can an infected person spread H1N1 flu to others?

– Similar to the seasonal flu, it is thought that a person is contagious from one day prior to their symptoms and for seven days after their symptoms begin.

• How long can H1N1 live outside the body?

– Studies have shown that the virus will survive for around 8 hours, at room temperature, on contaminated surfaces.

Vitaly A. Stepensky, M3 Student Internal Medicine Teaching Rounds October 27, 2009

Documents

Transcript of Vitaly A. Stepensky, M3 Student Internal Medicine Teaching Rounds October 27, 2009