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Just-in-Time Lecture Swine “North American” Influenza A (H1N1) Outbreak : Potential for a Pandemic (Version 5, first JIT lecture issued April 26; Lecture Updated Daily) Thursday, April 30, 2009 Rashid A. Chotani, MD, MPH, DTM Adjunct Assistant Professor Uniformed Services University of the Health Sciences (USUHS) 240-367-5370 [email protected] CHOTANI © 2009. Acknowledgement The Author acknowledges the efforts, hard work and diligence for hosting this lecture, web-management & translations and thanks the entire Supercourse Team, specially the following. Dr. Ronald E. LaPorte, University of Pittsburgh, USA Dr. Faina Linkov, University of Pittsburgh, USA Dr. Eugene Shubnikov, Institute of Internal Medicine, Russia Dr. Nicolás Padilla Raygoza, Universidad de Guanajuato, México Dr. Ali Ardalan, Tehran University of Medical Sciences, Iran Dr. Mehrdad Mohajeri, Tehran University of Medical Sciences, Iran Dr. Seyed Amir Ebrahimzadeh, Tehran University of Medical Sciences, Iran Dr. Nasrin Rahimian. Tehran University of Medical Sciences, Iran •It is truly a global effort •http://www.pitt.edu/~super1/ CHOTANI © 2009. OUTLINE 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Influenza Virus Definitions Introduction History in the US Current Situation in the US Current Situation in Mexico Current Situation Globally Spread/Transmission Case-Definitions Guidelines • • • 11. 12. 13. 14. CHOTANI © 2009. Clinicians Laboratory Workers General Population Treatment Other Protective Measures Summary Conclusion & Recommendations Virus • 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) CHOTANI © 2009. Credit: L. Stammard, 1995 Haemagglutinin subtype H1 H2 H3 H4 H5 H6 H7 H8 H9 H10 H11 H12 H13 H14 H15 H16 Neuraminidase subtype N1 N2 N3 N4 N5 N6 N7 N8 N9 Definitions: General • Epidemic – a located cluster of cases • Pandemic – worldwide epidemic • 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 CHOTANI © 2009. Survival of Influenza Virus on Surfaces and Affect of Humidity & Temperature* • Hard non-porous surfaces 24-48 hours • Plastic, stainless steel • Recoverable for > 24 hours • Transferable to hands up to 24 hours • Cloth, paper & tissue • Recoverable for 8-12 hours • Transferable to hands 15 minutes • Viable on hands <5 minutes only at high viral titers • Potential for indirect contact transmission *Humidity 35-40%, Temperature 28C (82F) CHOTANI © 2009. Source: Bean B, et al. JID 1982;146:47-51 Swine Flu: Introduction • Swine Influenza (swine flu) is a respiratory disease of pigs caused by type A influenza that regularly cause outbreaks of influenza among pigs • Swine flu viruses do not normally infect humans, however, human infections with swine flu do occur, and cases of human-tohuman spread of swine flu viruses has been documented • Most commonly, human cases of swine flu happen in people who are around pigs but it’s possible for swine flu viruses to spread from person to person also CHOTANI © 2009. Swine Flu: History in US • A swine flu outbreak in Fort Dix, New Jersey, USA occurred in 1976 that caused more than 200 cases with serious illness in several people and one death • • More than 40 million people were vaccinated However, the program was stopped short after over 500 cases of Guillain-Barre syndrome, a severe paralyzing nerve disease, were reported • 30 people died as a direct result of the vaccination • In September 1988, a previously healthy 32year-old pregnant woman in Wisconsin was hospitalized for pneumonia after being infected with swine flu and died 8 days later. • From December 2005 through February 2009, a total of 12 human infections with swine influenza were reported from 10 states in the United States CHOTANI © 2009. Swine Flu: Current Situation in the US • Since March 2009, 91 of confirmed human cases with one death from 10 States have been reported. • 1st death reported in a child (22 months) that had came from Mexico who died in a hospital in the Houston area • 5 cases (3 in CA & 2 in TX) hospitalized • All have the same genetic pattern based on preliminary testing • Virus is being described as a new subtype of A/H1N1 not previously detected in swine or humans • Samples from the Mexico outbreak match swine influenza isolates from patients in the United States CHOTANI © 2009. Source: CDC Swine Flu: Current Situation in the US • CDC has determined that this virus is contagious and is spreading from human to human • The virus contains gene segments from 4 different influenza types: • • • • • North American swine, North American avian, North American human, and Eurasian swine The Strategic National Stockpile (SNS) is releasing one-quarter of its • • • Anti-viral drugs Personal protective equipment and Reparatory protection devices • President Obama today asked Congress for an additional $1.5 billion to fight the swine flu • On April 27, 2009, the CDC issued a travel advisory that recommends against all nonessential travel to Mexico CHOTANI © 2009. Source: CDC Swine Flu: US Human Cases As of April 28, 2009 • MMWR, April 28, 2009 / 58(Dispatch);1-3 • 47 patients reported to CDC with known ages (out of 64), the median age was 16 years (range: 3-81 years), • 38 (81%) were aged <18 years; • 51% of cases were in males. • Of the 25 cases with known dates of illness onset, onset ranged from March 28 to April 25 • five patients hospitalized. • Of 14 patients with known travel histories, • 3 had traveled to Mexico; • 40 of 47 patients (85%) had not been linked to travel or to another confirmed case. CHOTANI © 2009. Source: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm58d0428a2.htm Swine Flu: US Human Cases As of April 29, 2009 Total Number of Confirmed Cases = 91; 1 Death No. of Confirmed Cases 60 40 20 0 Arizona California Indiana Kansas 1 14 1 2 Massachu Michigan setts Navada New York Ohio Texas 1 51 1 15 1 Deaths No. of laboratory confirm ed cases 2 2 US States CHOTANI © 2009. Source: CDC Swine Flu: Current Situation in Mexico • A total of approximately 2,498 suspected cases, 159 deaths and 1311 hospitalizations (for pneumonia) have been reported in 31 of 32 States in Mexico (April 28, Ministry of Health) • 26 Laboratory confirmed • First case in Oaxaca, April 13, 2009 • Woman died of pneumonia • Mexico City: Over 854 cases of pneumonia, 59 of them fatal • San Luis Potosi: 24 cases with 3 deaths • Mexicali (near the US border): 4 cases with no deaths • The illness outbreak in Mexico City prompted the country's health minister to cancel classes in Mexico City and advised students and adults to avoid crowded public places and large events CHOTANI © 2009. Source: WHO, CDC, PAHO & ProMED Swine Flu: Current Situation in Mexico • The virus in Mexico has primarily struck otherwise healthy young adults, (20-50 years) which is a departure from seasonal influenza, which typically affects the very young and very old • CDC's laboratory analyzed 14 samples from severely ill Mexican patients and found that 7 of them had the same swine flu mix as the virus that infected the US patients (preliminary report) • Canada's national laboratory has confirmed swine flu A/H1N1 in 18 isolates from Mexican patients, 12 of which were genetically identical to the swine flu viruses from California CHOTANI © 2009. Source: WHO, CDC & ProMED Country Lab Confirmed Death in Lab Confirmed Suspected Suspected Dead Australia 0 0 91 Austria 1 0 5 Argentina 0 0 Bolivia 0 Brazil 0 Belgium TOTAL TOTAL Dead 0 91 0 0 6 0 10 0 10 0 0 2 0 2 0 0 22 0 22 0 0 0 7 0 7 0 Canada1 13 0 19 0 32 0 Chile 0 0 24 0 24 0 Columbia 0 0 42 0 42 0 Costa Rica 1 0 21 0 22 0 France 0 0 32 0 32 0 Germany 3 0 5 0 8 0 Guatemala 0 0 1 0 1 0 Greece 0 0 1 0 1 0 Honduras 0 0 1 0 1 0 Hong Kong 0 0 5 0 5 0 Israel 2 0 1 0 3 0 Italy 0 0 1 0 1 0 Ireland 0 0 4 0 4 0 Mexico 33 7 2498 152 1311 2531 159 New Zealand 11 0 57 0 0 68 0 Norway 0 0 1 0 1 0 Peru 0 0 2 0 2 0 Poland 0 0 3 0 3 0 Russia 0 0 1 0 1 0 Slovakia 0 0 1 0 1 0 South Korea 0 0 6 0 6 0 Spain 4 0 35 0 39 0 Sweden 0 0 24 0 24 0 Switzerland 0 0 5 0 5 0 Uruguay 0 0 2 0 USA 91 1 0 0 UK 5 0 20 Venezuela 0 0 3 164 8 2952 152 TOTAL CHOTANI © 2009. Hospitalized 2 2 0 91 1 0 25 0 0 3 0 3116 160 5 1318 5:00 AM April 30 Swine Flu: Current Situation Globally • The WHO raised the alert level to Phase 5, meaning there are large clusters (e.g., 25-50 cases lasting 2 to 4 weeks), but human-tohuman spread is still localized. • • 164 confirmed cases worldwide with 8 deaths (Mexico & US) • • WHO’s alert system was revised after Avian influenza began to spread in 2004, and April 27 was the first time it was raised above Phase 3 and on April 29 to Phase 5. Case-fatality ~ 5% 2,952 suspected cases worldwide with 160 deaths (Mexico & US) • Case-fatality ~ 5% • 1,318 hospitalized • European Union (EU) Health Commissioner Androulla Vassiliou issued a travel advisory to the 27 EU member countries recommending that “non-essential” travel to affected parts of the U.S. and Mexico be suspended CHOTANI © 2009. Inter-Pandemic Phase New Virus in Animals, NO Human Cases Pandemic ALERT New Virus Causes Human Cases PANDEMIC Low Risk of Human Cases 1 High Risk of Human Cases 2 No or Very Limited Human-toHuman Transmission 3 Evidence of Increased Human-toHuman Transmission 4 Evidence of Significant Humanto-Human Transmission 5 Efficient & Sustained Human-toHuman Transmission 6 Swine Flu: Transmission Through Species Reassortment in Pigs Human Virus Avian Virus Avian/Human Reassorted Virus Swine Virus CHOTANI © 2009. Swine Flu: Transmission to Humans • Through contact with infected pigs or environments contaminated with swine flu viruses • Through contact with a person with swine flu • Human-to-human spread of swine flu has been documented also and is thought to occur in the same way as seasonal flu, through coughing or sneezing of infected people CHOTANI © 2009. Swine Flu: US Case Definitions (Updated) • A confirmed case of swine influenza A (H1N1) virus infection is defined as a person with an acute febrile respiratory illness with laboratory confirmed swine influenza A (H1N1) virus infection at CDC by one or more of the following tests: • • • A probable case of swine influenza A (H1N1) virus infection is defined as a person with an acute febrile respiratory illness who is: • • • real-time RT-PCR viral culture 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 A suspected case of swine influenza A (H1N1) virus infection is defined as a person with acute febrile respiratory illness with onset • • • CHOTANI © 2009. within 7 days of close contact with a person who is a confirmed case of swine influenza A (H1N1) virus infection, or within 7 days of travel to community either within the United States or internationally where there are one or more confirmed swine influenza A(H1N1) cases, or resides in a community where there are one or more confirmed swine influenza cases. Source: CDC Swine Flu: US Case Definitions • Infectious period for a confirmed case of swine influenza A (H1N1) virus infection is defined as 1 day prior to the case’s illness onset to 7 days after onset • Close contact is defined as: within about 6 feet of an ill person who is a confirmed or suspected case of swine influenza A (H1N1) virus infection during the case’s infectious period • Acute respiratory illness is defined as recent onset of at least two of the following: rhinorrhea or nasal congestion, sore throat, cough (with or without fever or feverishness) • High-risk groups: A person who is at high-risk for complications of swine influenza A (H1N1) virus infection is defined as the same for seasonal influenza (see Reference) CHOTANI © 2009. Source: CDC Swine Flu: Guidelines for Clinicians • Clinicians should consider the possibility of swine influenza virus infections in patients presenting with febrile respiratory illness who • live in areas where human cases of swine influenza A (H1N1) have been identified or • have traveled to an area where human cases of swine influenza A (H1N1) has been identified or • have been in contact with ill persons from these areas in the 7 days prior to their illness onset • If swine flu is suspected, clinicians should obtain a respiratory swab for swine influenza testing and place it in a refrigerator (not a freezer) • once collected, the clinician should contact their state or local health department to facilitate transport and timely diagnosis at a state public health laboratory CHOTANI © 2009. Source: CDC Swine Flu: Guidelines for Clinicians • Signs and Symptoms • Influenza-like-illness (ILI) • Fever, cough, sore throat, runny nose, headache, muscle aches. In some cases vomiting and diarrhea. (These cases had illness onset during late March to mid-April 2009) • Cases of severe respiratory disease, requiring hospitalization including fatal outcomes, have been reported in Mexico • The potential for exacerbation of underlying chronic medical conditions or invasive bacterial infection with swine influenza virus infection should be considered • Non-hospitalized ill persons who are a confirmed or suspected case of swine influenza A (H1N1) virus infection are recommended to stay at home (voluntary isolation) for at least the first 7 days after illness onset except to seek medical care CHOTANI © 2009. Source: CDC Swine Flu: Guidelines for Clinicians FDA Issues Authorizations for Emergency Use (EUAs) of Antivirals • On April 27, 2009, the U.S. Food and Drug Administration (FDA) issued EUAs in response to requests by the Centers for Disease Control and Prevention (CDC) for the swine flu outbreak • One of the reasons the EUAs could be issued was because the U.S. Department of Health and Human Services (HHS) declared a public health emergency on April 26, 2009 • The swine influenza EUAs aid in the current response: CHOTANI © 2009. • Tamiflu: Allow for Tamiflu to be used to treat and prevent influenza in children under 1 year of age, and to provide alternate dosing recommendations for children older than 1 year. Tamiflu is currently approved by the FDA for the treatment and prevention of influenza in patients 1 year and older. • Tamiflu and Relenza: Allow for both antivirals to be distributed to large segments of the population without complying with federal label requirements that would otherwise apply to dispensed drugs and to be accompanied by written information about the emergency use of the medicines. Swine Flu: Biosafety Guidelines for Laboratory Workers • Diagnostic work on clinical samples from patients who are suspected cases of swine influenza A (H1N1) virus infection should be conducted in a BSL-2 laboratory • All sample manipulations should be done inside a biosafety cabinet (BSC) • Viral isolation on clinical specimens from patients who are suspected cases of swine influenza A (H1N1) virus infection should be performed in a BSL-2 laboratory with BSL-3 practices (enhanced BSL-2 conditions) • Additional precautions include: • • • • • • • recommended personal protective equipment (based on site specific risk assessment) respiratory protection - fit-tested N95 respirator or higher level of protection shoe covers closed-front gown double gloves eye protection (goggles or face shields) Waste • CHOTANI © 2009. all waste disposal procedures should be followed as outlined in your facility standard laboratory operating procedures Source: CDC Swine Flu: Biosafety Guidelines for Laboratory Workers • Appropriate disinfectants • 70 per cent ethanol • 5 per cent Lysol • 10 per cent bleach • All personnel should self monitor for fever and any symptoms. Symptoms of swine influenza infection include diarrhea, headache, runny nose, and muscle aches • Any illness should be reported to your supervisor immediately • For personnel who had unprotected exposure or a known breach in personal protective equipment to clinical material or live virus from a confirmed case of swine influenza A (H1N1), antiviral chemoprophylaxis with zanamivir or oseltamivir for 7 days after exposure can be considered CHOTANI © 2009. Source: CDC Swine Flu: Guidelines for Laboratory Workers FDA Issues Authorizations for Emergency Use (EUAs) of Diagnostic Tests • On April 27, 2009, the U.S. Food and Drug Administration (FDA) issued EUAs in response to requests by the Centers for Disease Control and Prevention (CDC) for the swine flu outbreak • One of the reasons the EUAs could be issued was because the U.S. Department of Health and Human Services (HHS) declared a public health emergency on April 26, 2009 • The swine influenza EUAs aid in the current response: • CHOTANI © 2009. Diagnostic Test: Allow CDC to distribute the rRT-PCR Swine Flu Panel diagnostic test to public health and other qualified laboratories that have the equipment and personnel to perform and interpret the results. Swine Flu: Guidelines for General Population • Covering nose and mouth with a tissue when coughing or sneezing • Dispose the tissue in the trash after use. • Handwashing with soap and water • Especially after coughing or sneezing. • Cleaning hands with alcohol-based hand cleaners • Avoiding close contact with sick people • Avoiding touching eyes, nose or mouth with unwashed hands • If sick with influenza, staying home from work or school and limit contact with others to keep from infecting them CHOTANI © 2009. Source: CDC Swine Flu: Treatment • No vaccine available • Antivirals for the treatment and/or prevention of infection: • • Oseltamivir (Tamiflu) or Zanamivir (Relenza) • Use of anti-virals can make illness milder and recovery faster • They may also prevent serious flu complications • For treatment, antiviral drugs work best if started soon after getting sick (within 2 days of symptoms) • Warning! Do NOT give aspirin (acetylsalicylic acid) or aspirin-containing products (e.g. bismuth subsalicylate – Pepto Bismol) to children or teenagers (up to 18 years old) who are confirmed or suspected ill case of swine influenza A (H1N1) virus infection; this can cause a rare but serious illness called Reye’s syndrome. For relief of fever, other anti-pyretic medications are recommended such as acetaminophen or non steroidal anti-inflammatory drugs. CHOTANI © 2009. Source: CDC Swine Flu: Other Protective Measures Defining Quarantine vs. Isolation vs. Social-Distancing • Isolation: Refers only to the sequestration of symptomatic patents either in the home or hospital so that they will not infect others • Quarantine: Defined as the separation from circulation in the community of asymptomatic persons that may have been exposed to infection • Social-Distancing: Has been used to refer to a range of nonquarantine measures that might serve to reduce contact between persons, such as, closing of schools or prohibiting large gatherings CHOTANI © 2009. Source: CDC Swine Flu: Other Protective Measures Personnel Engaged in Aerosol Generating Activities • CDC Interim recommendations: • Personnel engaged in aerosol generating activities (e.g., collection of clinical specimens, endotracheal intubation, nebulizer treatment, bronchoscopy, and resuscitation involving emergency intubation or cardiac pulmonary resuscitation) for suspected or confirmed swine influenza A (H1N1) cases should wear a fit-tested disposable N95 respirator • Pending clarification of transmission patterns for this virus, personnel providing direct patient care for suspected or confirmed swine influenza A (H1N1) cases should wear a fit-tested disposable N95 respirator when entering the patient room • Respirator use should be in the context of a complete respiratory protection program in accordance with Occupational Safety and Health Administration (OSHA) regulations. CHOTANI © 2009. Source: CDC Swine Flu: Other Protective Measures Infection Control of Ill Persons in a Healthcare Setting • Patients with suspected or confirmed case-status should be placed in a single-patient room with the door kept closed. If available, an airborne infection isolation room (AIIR) with negative pressure air handling with 6 to 12 air changes per hour can be used. Air can be exhausted directly outside or be recirculated after filtration by a high efficiency particulate air (HEPA) filter. For suctioning, bronchoscopy, or intubation, use a procedure room with negative pressure air handling. • The ill person should wear a surgical mask when outside of the patient room, and should be encouraged to wash hands frequently and follow respiratory hygiene practices. Cups and other utensils used by the ill person should be washed with soap and water before use by other persons. Routine cleaning and disinfection strategies used during influenza seasons can be applied to the environmental management of swine influenza. CHOTANI © 2009. Source: CDC Swine Flu: Other Protective Measures Infection Control of Ill Persons in a Healthcare Setting • Standard, Droplet and Contact precautions should be used for all patient care activities, and maintained for 7 days after illness onset or until symptoms have resolved. Maintain adherence to hand hygiene by washing with soap and water or using hand sanitizer immediately after removing gloves and other equipment and after any contact with respiratory secretions. • Personnel providing care to or collecting clinical specimens from suspected or confirmed cases should wear disposable non-sterile gloves, gowns, and eye protection (e.g., goggles) to prevent conjunctival exposure. CHOTANI © 2009. Source: CDC Types of protective masks • Surgical masks • • High-filtration respiratory mask • • • • CHOTANI © 2009. Easily available and commonly used for routine surgical and examination procedures Special microstructure filter disc to flush out particles bigger than 0.3 micron. These masks are further classified: • oil proof • oil resistant • not resistant to oil The more a mask is resistant to oil, the better it is The masks have numbers beside them that indicate their filtration efficiency. For example, a N95 mask has 95% efficiency in filtering out particles greater than 0.3 micron under normal rate of respiration. The next generation of masks use Nano-technologywhich are capable of blocking particles as small as 0.027 micron. Summary • There is evidence of circulation of a strain previously undetected in pigs and humans • WHO raised the alert level to Phase 5, meaning there are large clusters (e.g., 25-50 cases lasting 2 to 4 weeks), but human-to-human spread is still localized. • 164 confirmed cases worldwide (10 countries) with 8 deaths (Mexico & US); Case-fatality ~ 5% • 2,952 suspected cases worldwide (34 countries) with 160 deaths (Mexico & US); Case-fatality ~ 5% • 1,318 hospitalized • In the US epidemiological data on one study reported • • • 47 patients (out of 64), the median age was 16 years (range: 3-81 years), 38 (81%) were aged <18 years; 51% of cases were in males. • In Mexico, healthy young adults, (20-50 years) affected by the disease • Huge disparity of mortality seen between Mexico and other countries such as US • No vaccine is available • Anti-virals available: • • Oseltamivir (Tamiflu) or Zanamivir (Relenza) • EU issues a travel advisory to the 27 EU member countries recommending “non-essential” travel to affected parts of the U.S. and Mexico be suspended • US issued a travel advisory that recommends against all non-essential travel to Mexico CHOTANI © 2009. Conclusion/Recommendations 1. At present, there are cases in Canada and the United States who do not have a history of travel to Mexico, so there are now 3 countries reporting human to human spread of the virus – the virus should be renamed “North American” H1N1 influenza 2. Most people do not have immunity to this virus and, as it continues to spread, more cases, more hospitalizations and more deaths are expected in the coming days and weeks. • Each locality/jurisdiction needs to • have enhanced disease and virological surveillance capabilities • develop a plan to house large number of severely sick and provide care if needed & to deal with mildly sick at home (voluntary quarantine) • healthcare facilities/hospitals need to focus on stringent infection prevention and control 3. In the Northern Hemisphere influenza viral transmission traditionally stops by the beginning of May but in pandemic years (1957) sporadic outbreaks occurred during summer among young adults • Likelihood that • this wave will fade in North America within the next 3-5 weeks (influenza virus cannot survive high humidity or temperature) • will reappear in autumn in North America as a highly pathogenic second wave • will continue to circulate and cause disease in Australia & New Zealand CHOTANI © 2009. Conclusion/Recommendations 4. Border Closure and Travel Restrictions: • The disease has already crossed borders and continents, thus, border closure or travel restrictions will not change the course of the spread of disease • Most recently, the 2003 experience with SARS demonstrated the ineffectiveness of such measures • In China, 14 million people were screened for fever at the airport, train stations, and roadside checkpoints, but only 12 were found to have probable SARS • Singapore reported that after screening nearly 500,000 air passengers, none were found to have SARS • passive surveillance methods (in which symptomatic individuals report illness) can be important tools 5. School Closures: • Preemptive school closures will just delay the spread of disease, once they reopen (as they cannot be closed indefinitely), the disease will spread again. Furthermore, this would put unbearable pressure on single-working parents and would be devastating to the economy • Closure after identification of a large cluster would be appropriate as the absenteeism rate among students and teachers would be high enough to justify this action 6. High priority should be given to include the present “North American” (swine) influenza A/H1N1 virus in next years vaccine CHOTANI © 2009.