OK Blackburn - your introduction was OK, and Dr. Martin s presentation was great, but. what s going to kill us all????

OK Blackburn - your introduction was OK, and Dr. Martin s presentation was great, but. what s going to kill us all????

Most experts believe - and worry about - a novel viral respiratory infection that is both highly contagious w/ high mortality

Nov., 2002: quietly and out of nowhere, an outbreak of severe respiratory illness with high mortality emerges in Guangdong Province, a rural area of southern China. Chinese government initially silent on this. 3-4 months later, (Feb., 2003): After attending a wedding from that same area, a physician becomes ill while staying overnight at a hotel in Hong Kong. 12 other hotel guests subsequently are infected (route of spread??) before returning home to multiple different regions of the world

February, 2003 An American businessman traveling from China to Singapore becomes ill and is hospitalized in Hanoi, Vietnam, where he dies of a respiratory illness Medical staff caring for this patient, utilizing usual precautions, also become ill. Ultimately, 7 HCWs die Dr. Carlo Urbani, an Italian physician who investigated and reported this outbreak to W.H.O. becomes ill. He, too, dies

March 12, 2003: W.H.O. issues Global Alert about cases of a newly recognized cause of severe, and often lethal pneumonia (but this began in November, 2002!) Severe Acute Respiratory Syndrome

SARS Acute febrile respiratory illness; otherwise, non-specific symptoms No effective treatment No vaccine Many cases in HCWs caring for SARS patients Most cases in China, but also rapid spread to 37 countries, INCLUDING Canada (Toronto, Ottawa; 251 cases / 44 deaths) and U.S. Ultimately, worldwide, >8000 cases / >800 deaths Significant human - human transmission w/ 10% mortality Ro = 3 Ultimately found to be due to a novel coronavirus (SARS-CoV)

Almost the Next Big One -highly contagious/deadly- Incredibly heroic (and very expensive) efforts by Chinese and Canadian health authorities, care providers, WHO, CDC, and numerous others in multiple countries contained this outbreak and prevented further spread No additional cases since 2003

MERS (Middle Eastern Respiratory Syndrome) First isolated from the lungs of a 60 y.o. male who died of respiratory failure in June, 2012, in Jeddah, Saudi Arabia by Dr. A. Zaki, an Egyptian virologist In September, a 49 y.o. Qatari man developed respiratory and renal failure and was transferred to the U.K. for ECMO Never before seen strain of coronavirus - MERS - CoV

MERS (as of July, 2017): 2080 laboratory confirmed cases; 722 deaths - 35% case mortality Majority of deaths from respiratory and renal failure Majority of cases from the Middle East, but has now been seen in 27 countries

Non-specific respiratory and/or GI symptoms. Most all had fever (98%), cough (83%), SOB (72%) Almost none had rhinorrhea (4%). MERS thrombocytopenia common Shock, AKI, Source (?): bats -> camels -> humans; unknown if human -> human transmission is occurring in asymptomatic individuals Most all had some comorbidity. Particularly high risk: diabetes, CRF Treatment: supportive only Vaccine: none available

MERS Human - human transmission? YES, though (currently) not easily; HOWEVER, intrahospital transmission to other patients and health care providers has been observed w/ high mortality. Intrafamial transmission also described Ro = 0.69 (est. worst case scenario as of summer, 2013)

Influenza - the Basics Of the 3 different genera, both A and B are major human pathogens; both can be deadly A is subtyped on basis of 17 different surface hemagglutinins(h) and 10 distinct neuramidase (N) antigens H - viral binding to cell receptors N - viral release from infected cells minor changes in antigens -> antigenic drift - usually no big deal major change -> antigenic shift - more severe disease, pandemics in less immune population (So far), only H1, H2, H3, N1, N2 associated w/ extensive outbreaks in humans

Seasonal Influenza - the Basics usually first seen in Asia, attributed to gene reassortment between human and animal (birds/poultry/swine) influenza viruses usually late fall, winter months (northern temperate climates) infects ~ 20-30% of U.S. population each year up to ~ 200,000 hospitalizations (U.S.) mortality rate: 0.1-0.6 % 3,500-49,000/yr (U.S.); 250,000-500,000 worldwide timing of pandemics completely unpredictable

Seasonal Influenza - the Traditional Basics - But Some Aspects Wrong No big deal - in healthy children and adults, abrupt onset fever, muscle aches, headache, fatigue, dry cough, sore throat, lasting 3-5 days - NOT ALWAYS TRUE! Complications/death, averaging ~36,000 deaths/yr, confined to infants, the elderly, others with significant co-morbidities - NOT TRUE! Most serious: pneumonia, including secondary bacterial (S. aureus, pneumococcus, Grp A streptococcus) Immunization recommended only for high risk ; not recommended in pregnancy - NOT

Camp Funston, Kansas 1918

The 1918-1919 Influenza Pandemic ( Spanish flu) 2 different strains of influenza A, subtype H1N1 of avian ancestry est. mortality rate ~ 2.5 % (much higher than seasonal/non-pandemic influenza) ~675,000 U.S. deaths ~50-100 million deaths worldwide!! similar mortality rates today would predict over 1 million U.S. fatalities

If it were today: Worldwide Pop n = 6.5 billion U.S. Pop n = 300 million Farmington Hills Pop n = 80 K Non-pandemic (Mortality =.03-.06%) 4-800,000 36,000 7-15 severe pandemic (mortality = 2.5%) 30-55 million (some est. as high as 360 million) 1.5-2 million 400-650 (assumes an attack rate of ~ 1/3rd of the population)

The 1918-1919 Influenza Pandemic High mortality in young, healthy adults due to: acute onset of ARDS-like syndrome - cytokine storm necrotizing bronchopneumonia, often w/ secondary bacterial infection

Spring, 2009 ~ March 9, 2009: 4 y.o.edgar Hernandez of La Gloria, Veracruz, Mexico became the first known person to be infected w/ a novel strain of H1N1 influenza 6 weeks later - Tuesday, April 21: MMWR Dispatch - Swine Influenza A (H1N1) in Two Children [adjacent counties in southern California] Thursday, April 23: HAN Alerts describing 5 infected children and 2 adults in California and Texas. Friday night 11 o clock local news: One sentence mentioning Swine flu Saturday, April 25: widespread news coverage, including link between the first case and the cases in California

What was so worrisome? Why March/April? Why Mexico? A novel strain; NO VACCINE Susceptibility to available anti-virals? High mortality rate in Mexico - 4%: 19 of 473 confirmed cases Of 19 reported deaths (source: msnbc news) A 9, 12, and 13 y.o. 9 deaths of persons between ages of 21-39

Worldwide Pop n = 6.5 billion U.S. Pop n = 300 million Farmington Hills, MI Pop n = 80 K Non-pandemic (Mortality =.03-.06%) 4-800,000 36,000 7-15 severe pandemic (mortality = 2.5%) 30-55 million 1.5-2 million 400-650 H1N1 if 4% mortality** 80 million!! 4 million!! 960!! *assumes an attack rate of ~ 1/3 the population ** based on reported mortality rates from Mexico 5/03/09 (reliability unknown)

~ two weeks later (mid-may 2009) Hey Dr. Blackburn - I just found out about this and I have tickets to Cancun!! Should I go?

37, 246 confirmed or probable cases 211 deaths Mortality: 0.57 %

0.45 % mortality

A/H1N1/pdm (by the end of the 2009-10 flu season) In spite of low mortality rate and susceptibility to oseltamivir: 12,000 deaths in U.S. 151,000-575,000 deaths worldwide 80% of these less than 65 years of age young obese pregnant

This is an official CDC HEALTH ADVISORY (Dec 24,2013) Notice to Clinicians: Early Reports of ph1n1-associated Illnesses for the 2013-14 Influenza Season Summary From November through December 2013, CDC has received a number of reports of severe respiratory illness among young and middle-aged adults, many of whom were infected with influenza A (H1N1) pdm09 (ph1n1) virus. Multiple ph1n1-associated hospitalizations, including many requiring intensive care unit (ICU) admission, and some fatalities have been reported. The ph1n1 virus that emerged in 2009 caused more illness in children and young adults, compared to older adults, although severe illness was seen in all age groups... For the 2013-14 season, if ph1n1 virus continues to circulate widely, illness that disproportionately affects young and middleaged adults may occur.

Post-influenza bacterial pneumonia Staphylococcal aureus pneumococcus Group A streptococcus Any of these can be life-threatening

Baltimore, winter of 2003-2004 Characteristics of pts w/ severe CA-MRSA (post-influenza bacterial) pneumonia* Pt Age (yrs) Hemoptysis Shock Cavitary lesions Duration Hosp. + Influ. A titers 1 31 + + + 41 days yes 2 52 + + + 2 days? 3 20 - + + 108 days yes 4 33 + + + 102 days? *Francis et al. CID 2005; 40:100-7 Note: Current pneumonia guidelines [www.idsociety.org: (1/31/07)] now consider the possibility of post-influenza MRSA pneumonia

Post-influenza CA-MRSA Pneumonia 17 pts from 9 states All w/ influenza-like illness, abnormal CXR 71% laboratory confirmed influenza Median age: 21 Respiratory symptoms 4 days prior to + culture 81% admitted to ICU 62% intubated, 46% required chest tubes 5 deaths (30%); only 1 with underlying disease Hageman et al. Emerg Infect Dis 2006;12(6):894-899

Prevention of Influenza: Vaccine - based on best guess of what s to come Cons: it may not be effective I always get sick after getting the vaccine I m young, I m healthy and I never get sick I m afraid of getting Guillian-Barre syndrome I m allergic to eggs This is all a government conspiracy

Vaccine Historically, estimated effectiveness ~ 60-70%, although can be lower in some instances and in some years (48% overall for 2016-2017 flu season) decreases incidence of influenza decreases hospitalization for influenza improves outcome for those hospitalized decreases cardiovascular events may decrease incidence of post-influenza bacterial infections - a big deal! may protect those around you, including your family may decrease likelihood of Guillian-Barre

Vaccine: Most everyone over the age of 6 months, including pregnancy quadrivalent vaccine up until age 65 high dose tetravalent if over 65 or perhaps younger if immunocompromised; (in the future: high dose quadrivalent?) NEW: No contraindication if egg allergy NEW: No live vaccine

Treatment Options for Influenza: ( Assuming current susceptibility patterns) Standard options - preferrably started w/in 48 hrs of illness: oseltamivir* 75mg po bid x 5 days (may still be beneficial even up to day 8**) renally adjusted zanamivir 10mg via inhalation bid x 5 days adamantanes (amantadine/rimantadine) usually not effective *expensive!! **based on H5N1 data

Treatment Options for Influenza: For the sicker patient: higher doses (?), longer tx w/ oseltamivir; Rx even if after 48-72 hrs of symptoms no inhaled zanamivir don t forget secondary bacterial infection Failing tx or simply desperate: IV peramivir* (if unlikely resistance to oseltamivir) *investigational IV zanamivir** (if likely resistance to oseltamivir) **Also investigational other meds w/ anti-inflammatory properties not generally considered for use in these situations e.g. statins and others

Controversial: Masking for those HCWs who refuse mandatory influenza vaccine

Tamiflu may be effective beyond the traditional window of 48-72 hrs post symptoms The Take Homes Influenza, including type B, can be deadly across all demographic groups Influenza vaccine can prevent some of these deaths and mitigate many other complications of this infection Vaccine can be given to almost all individuals with a history of egg allergy Post- influenza bacterial pneumonia can be a very serious complication of influenza Pneumococcal vaccine may prevent some of these episodes Early recognition followed by prompt and appropriate antibiotics can be life saving The incidence of Guillain-Barre syndrome is far lower following vaccination than from influenza itself

When the Next Big One arrives...it will be signaled first by quiet, puzzling reports from faraway places - reports to which disease scientists and public health officials, but few of the rest of us, pay close attention. 5/9/13 - D. Quammen. NYT

Uyeki SM. In the Clinic Influenza. Ann Intern Med. 2017;167:ICT34-47 http://www.cdc.gov/ References: Assiri A et al. Hospital Outbreak of Middle East Respiratory Syndrome Coronavirus. N Engl J Med 2013;369:407-416 Baxter R et al. Lack of Association of Guillian-Barre Syndrome with Vaccinations. CID 2013;57:197-204 Berry, John. The Great Influenza: the Story of the Deadliest Pandemic in History. Penguin Books 2005 Bischoff W. Exposure to Influenza Virus Aerosols During Routine Patient Care. JID 2013;207:1037-1046 Castilla J et al. Influenza Vaccine Effectiveness in Preventing Outpatient, Inpatient, and Severe Cases of Laboratory-Confirmed Influenza. CID 2013;57:167-175 Falsey A et al. Bacterial Complications of Respiratory Tract Viral Illness: A Comprehensive Evaluation. JID 2013;208:432-441 Fleming-Dutra K. Effect of the 2009 Influenza A(H1N1) Pandemic on Invasive Pneumococcal Pneumonia. JID 2013;202:1135-1143 Hyle EP et al. Missed Opportunities for MMR Vaccination Among departing U.S. Adult Travelers Receiving Pretravel Health Consultations. Ann Intern Med. 2017:167:77-84 Morens D et al. The 1918 Influenza Pandemic: Insights for the 21st Century. JID 2007;195:1018-1028 Perlman S et al. Person-to-Person Spread of the MERS Coronavirus - An Evolving Picture. N Engl J Med 2013;369:466-467 Tomljenovic L and Shoenfeld Y. Association between vaccination and Guillain-Barre syndrome. Lancet Infectious Diseases 2013;13:730-731

Thank you