H1N1/SWINE FLU Navpreet Sahsi

INFLUENZA Globally 250,000 to 500,000 deaths per year In the US (per year) 35,000 deaths > 200,000 hospitalizations $10 billion in lost productivity

HISTORICALLY Illness with influenza from pigs was first recongnized during influenza pandemic of 1918 (40 – 50 million deaths) 1976 – Swine flu outbreak occurred in Fort Dix New Jersey that caused more than 200 cases with serious illness in several people and one death More than 40 million people vaccinated Program was stopped short after 500 cases of GBS and 30 reported deaths as direct result of vaccine Between 1958 – 2005, 37 additional cases of swine influenza were reported Six cases of death

ZIMMER SM. NEJM :279

2009 PANDEMIC March/April 2009, outbreak of respiratory illnesses first noted in Mexico, eventually identified as related to H1N1 influenza April 17, 2009 – 2 cases in California of children in neighbouring counties June 24 – WHO raised pandemic alert level to phase 6 – widespread community transmission on two continents July 6 – 10,200 confirmed cases in Mexico with 119 deaths July 24 – 43,000 cases confirmed in US

CHOWELL G. ET AL. NEJM 2009; 361: 274.

AT HOME - June 10, 2009 – 47 cases in the Calgary area, and 2978 nationwide with 4 deaths - August 9, 2009 – no longer keeping track of cases – 64 deaths nationwide, 6 in Alberta.

TRANSMISSION Person – to –person Virus in present in respiratory secretions sneezing and coughing via large particle droplets or by aerosolized small-particle droplets Contact with surfaces contaminated with droplets Possibility of transmission from other bodily fluids (eg. Diarrheal stool)

PATIENT MYTHS “You can get the swine flu from eating pork.” “I got my flu shot this winter, so I’m protected from the swine flu.” “You can only get swine flu from direct contact with a pig.” “Taking vitamins can protect against influenza.”

YOU THINK YOU KNOW SWINE FLU? Incubation period? A) 0 – 1 days B) days C) 7 days D) 14 days

Answer: Well, precise incubation period has not been established but presumed to be….. B) 1 – 4 days

INFECTIVITY? A) One day prior to symptoms and one day post symptoms B) One week prior to symptoms and one day post symptoms C) One day prior to symptoms and one week post symptoms D) One week prior to symptoms and one week post symptoms

C ) One day prior to symptoms and one week post symptoms

CLINICAL MANIFESTATIONS Similar to those of seasonal influenza GI findings have been more common than with seasonal influenza Commonly Fever Cough Sore throat Malaise Headache Vomiting Diarrhea Arthralgias Remember - Atypical presentations in infants, elderly, immunocompromised

HIGH RISK GROUPS Who?

HIGH RISK Children younger than 5 years Age > 65 Less than 19 receiving long-term ASA therapy (Risk of Reye’s syndrome after infx) Pregnant Women Chronic Diseases COPD CVD (except isolated HTN) CRF Chronic Liver disease DM Immunosuppression – eg. HIV, transplant patients Poor handling of resp. secretions – eg. CF, cerebral palsy, spinal cord injuries, seizure disorders, NM disease

What about obesity? Not officially recognized as a risk factor but a disproportionate # of cases of severe H1N1 have been reported without underlying conditions

COMPLICATIONS About 2 to 5% of confirmed cases in the US and Canada have required hospitalization 6% in Mexico Of hospitalized patients, large majority fall into high risk category (75 – 85% in one study) Many reported cases of rapidly progressive pneumonia, respiratory failure, ARDS Most complications similar to seasonal flu URTIs (sinusitis, otitis media, croup) LRTIs (pneumonia, brochiolitis, status asthmaticus) Cardiac (myocarditis, pericardits) Neuro (encephalopathy/encephalitis, febrile seizures, status epilepticus) Toxic Shock syndrome Secondary bacterial pneumonia

DIAGNOSIS Who to test? Basics - Those who will require hospitalization - Those who are at high risk for severe complications (High risk group)

Important definitions (from CDC) Influenza-like illness (ILI) – fever (T > 37.8) with cough or sore throat in absence of known cause other than influenza Severe Respiratory Illness (SRI) – respiratory symptoms including history of fever > 38, new onset of cough or breathing difficulty, with severe illness progression within first 72 hours Pneumonia, ARDS, encephalitis, or other severe and life threatening complications

From Alberta Health Services If mild ILI symptoms – NO LAB TESTING Mild ILI and high risk – NP swab considered Severe symptoms (admission to hospital) or SRI – NP swab plus additional testing as appropriate Note turn around time for NP swab – 3 days

TREATMENT Currently vast majority of strains appear sensitive to neuraminidase inhibitors – oseltamivir (Tamiflu) and zanamivir (Relenza) How soon to treat? A) ASAP B) Within 24 hours C) Within 48 hours D) Within 96 hours E) Within 7 days

Obviously A) therapy should begin as soon as possible However, evidence of benefit in seasonal influenza is strongest for treatment within 48 hours CDC still recommends therapy even after 48 hours of illness since some studies of hospitalized patients have demonstrated benefit

WHO GETS TAMIFLU? Basics All hospitalized patients with confirmed or suspected H1N1 infection Patients at increased risk for complications If you’re thinking about swabbing them, you should at least be thinking about treating them.

DOSING Treatment - Tamiflu 75 mg PO BID x 5 days Prophylaxis – 75 mg PO OD x ? Relenza – 10 mg (2 puffs) BID x 5 days Prophylaxis – 10 mg OD

WHAT ABOUT KIDS? Tamiflu approved in US/Canada in individuals > 1 year of age, Relenza > 7 years old Limited safety data on kids < 1 year From Health Canada: “ Health Canada’s Interim Order permits the expanded use of oseltamivir as a treatment or prophylaxis for children under 1 year of age, for infection caused by the pandemic (H1N1) 2009 virus due to recent clinical data suggesting its comparable safety profile identified in children over 1.” Dosing in children – 2 mg/kg PO BID If no weight measures then by age: 0 – 3 months – 12 mg BID 3 – 5 months – 20 mg BID 6 – 11 months – 25 mg BID

PREGGERS? True or False: Tamiflu and Relenza are safe in pregnant women

True!!! Pregnancy category C – meaning that clinical studies not done. But no adverse events noted. Health Canada states that current benefits outweigh risks.

PREGGERS? When are pregnant women most susceptible to H1N1 virus? A)First Trimester B) Second Trimester C) Third Trimester D) Immediately post - partum

Answer C) Third Trimester However, women are at increased susceptibility during second trimester until about 4 weeks post- partum.

BREASTFEEDING? You decide to treat a woman who is two weeks post-partum that presents with worrysome respiratory symptoms. She asks you if it is safe to breast feed her newborn baby while on antiviral therapy. What do you tell her?

Safe!! “ Due the anti-infective benefits of human milk for infants and the low dosages of antiviral passed to the baby through breastmilk, it is recommended that women continue to breastfeed their baby when taking antiviral medications.” – Health Canada Dosing – same as in other adults – 75 mg PO BID or 10 mg inhaled BID. “Preferred agent is Zanamivir (Relenza) in pregnant/breastfeeding women although both safe.” – Alberta Health Services

REFERENCES Zimmer, SM. Historical Perspective – Emergence of Influenza A (H1N1) Viruses. NEJM 2009; 361: 279 – 285. Chowell, G. et al. Severe Respiratory Disease Concurrent with the Circulation of H1N1 Influenza. NEJM 2009; 361: Public Health Agency of Canada World Health Organization Influenza A (H1N1) Alberta Health Services Epidemiology, clinical manifestations, and diagnosis of pandemic H1N1 influena (“swine influenza”) Treatment of pandemic H1N1 influenza (“swine influenza”)