Novel H1N1 (Swine) Epidemiology & Control Ahmed Mandil Prof of Epidemiology

1. Novel H1N1 (Swine) Epidemiology & Control Ahmed Mandil Prof of Epidemiology Dept of Family & Community Medicine College of Medicine, King Saud University

2. Influenza Virus Definitions Introduction Spread/Transmission Timeline/Facts Response Case-Definitions Treatment Other Protective Measures Conclusion & Recommendations HEADLINES

3. 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) Virus Credit: L. Stammard, 1995

4. 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 Definitions General

5. Timeline of Emergence Influenza A Viruses in Humans Reassorted Influenza virus (Swine Flu) H1 1976 Swine Flu Outbreak, Ft. Dix Avian Influenza H7 H9 H5 H5 H1 H3 H2 H1 2009 1918 1957 1968 1977 1997 2003 Asian Influenza H2N2 Hong Kong Influenza H3N2 Russian Influenza Spanish Influenza H1N1 1998/9

6. Lessons Learned formPast Pandemics First outbreaks March 1918 in Europe, USA Highly contagious, but not deadly Virus traveled between Europe/USA on troop ships Land, sea travel to Africa, Asia Warning signal was missed August, 1918 simultaneous explosive outbreaks in in France, Sierra Leone, USA 10-fold increase in death rate Highest death rate ages 15-35 years Cytokine Storm? Deaths from primary viral pneumonia, secondary bacterial pneumonia Deaths within 48 hours of illness Coincident severe disease in pigs 20-40 million killed in less than 1 year World War I –8.3 million military deaths over 4 years 25-35% of the world infected

7. Pandemics are unpredictable Mortality, severity of illness, pattern of spread A sudden, sharp increase in the need for medical care will always occur Capacity to cause severe disease in nontraditional groups is a major determinant of pandemic impact Epidemiology reveals waves of infection Ages/areas not initially infected likely vulnerable in future waves Subsequent waves may be more severe 1918- virus mutated into more virulent form 1957 schoolchildren spread initial wave, elderly died in second wave Public health interventions delay, but do not stop pandemic spread Quarantine, travel restriction show little effect Does not change population susceptibility Delay spread in Australia— later milder strain causes infection there Temporary banning of public gatherings, closing schools potentially effective in case of severe disease and high mortality Delaying spread is desirable Fewer people ill at one time improve capacity to cope with sharp increase in need for medical care Lessons Learned formPast Pandemics

8. Swine Influenza A(H1N1)Introduction • Swine Influenza (swine flu) is a respiratory disease of pigs caused by type A influenza that regularly cause outbreaks of influenza among pigs • Most commonly, human cases of swine flu happen in people who are around pigs • Swine flu viruses do not normally infect humans, however, human infections with swine flu do occur, and cases of human-to-human spread of swine flu viruses have been documented

9. Swine Influenza A(H1N1) 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

10. Swine Influenza A(H1N1) Transmission Through Species Human Virus Avian Virus Avian/Human Reassorted Virus Swine Virus Reassortment in Pigs

11. Swine Influenza A(H1N1) Facts • Virus described as a new subtype of A/H1N1 not previously detected in swine or humans • CDC determines 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

12. Swine Influenza A(H1N1) Global Response • The WHO raises the alert level to Phase 6 • WHO’s alert system was revised after Avian influenza began to spread in 2004 – Alert Level raised to Phase 3 • In Late April 2009 WHO announced the emergence of a novel influenza A virus • April 27, 2009: Alert Level raised to Phase 4 • April 29, 2009: Alert Level raised to Phase 5 • June 11, 2008: Alert Level raised to Phase 6 Source: WHO

13. GLOBALLY: March 1-December 23 At least 11,516 Deaths Africa Region (AFRO): 109 Americas Region (AMRO): 6,670 Eastern Mediterranean Region (EMRO): 663 Europe Region (EURO) : 2,045 South-East Asia Region (SEARO): 990 Western Pacific Region (WPRO) : 1,039 Swine Influenza A(H1N1)Status Update ECDC reported a total of 12,776 deaths – December 28, 2009 Source: WHO

14. Swine Influenza A(H1N1) CDC Estimates from April-November 14, 2009, By Age Group Source: CDC. http://www.cdc.gov/h1niflu/surveillanceqa.htm

15. Pandemic (H1N1) 2009 in the EMR as of 6 November, 2009 • 22/22 countries affected • Regular reports from 17 countries: 26,400 confirmed cases and 150 deaths. • Localized to moderate geographical distribution. • Increasing trend in most of the countries • Low to moderate intensity • Low to moderate impact on the health system

16. Pandemic H1N1 2009 in the EMR as of 6 November, 2009

17. The Epidemic Curve Initiation Acceleration Peak Decline aths 20% 15% Proportion of total cases, consultations, hospitalisations or de 10% 5% 0% 1 2 3 4 5 6 7 8 9 10 11 12 Week Single-wave profile showing proportion of new clinical cases, consultations, hospitalisations or deaths by week. Based on London, second wave 1918.

18. With interventions Aims of community reduction of influenza transmission — mitigation • Delay and flatten epidemic peak. • Reduce peak burden on healthcare system and threat. • Somewhat reduce total number of cases. • Buy a little time. No intervention Daily cases Days since first case

19. Swine Influenza A(H1N1) Mediterranean & Middle East Confirmed Deaths As of December 28, 2009 n=1,246 Source: ECDC

20. Global Distribution of Reported Laboratory Confirmed Cases & Deaths of Swine Influenza A(H1N1), December 23, 2009 Source: WHO

21. Geographic Spread of Influenza ActivityBased Upon Country Reporting, Week 50, 2009 (07-23 December) Source: WHO

22. Impact on Healthcare Services Based Upon Degree of Disruption, As a Result of Acute Respiratory DiseasesWeek 50, 2009 (07-13 December) Source: WHO

23. Number of Specimens Positive for Influenza Sub-Type Source: CDC

24. Laboratory-Confirmed Cases & Deaths of New Influenza A(H1N1) by WHO Regions, September 20, 2009 At least 318,925 Cases & Over 3917 Deaths Overall Case-Fatality Rate (CFR) in Confirmed ~ 1.2% CFR = 2.5% CFR = 0.4% CFR = 0.3% CFR = 1.1% CFR = 0.5% CFR = 0.6% *Given that countries are no longer required to test and report individual cases, the number of cases reported actually understates the real number of cases. Source: WHO

25. Swine Influenza A(H1N1) 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

26. Comparison of Available Influenza Diagnostic Tests1 Source: CDC

27. Swine Influenza A(H1N1)Antiviral Protection • There are two flu antiviral drugs recommended • Oseltamivir or Zanamivir • 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 medicationsare recommended such as acetaminophen or non steroidal anti-inflammatory drugs. • Treatment is recommended for: • All hospitalized patients with confirmed, probable or suspected novel influenza (H1N1). • Patients who are at higher risk for seasonal influenza complications • If patient is not in a high-risk group or is not hospitalized, healthcare providers should use clinical judgment to guide treatment decisions Source: CDC

28. Swine Influenza A(H1N1)Antiviral Protection • Antiviral Chemoprophylaxis for Treatment: • Post-exposure: Duration chemoprophylaxis is 10 days after the last known exposure to novel (H1N1) influenza and may be considered in the following: • Close contacts of cases (confirmed, probable, or suspected) • Health care personnel, public health workers, or first responders who have had a recognized, unprotected close contact exposure to a person (confirmed, probable, or suspected) during that person’s infectious period. • Pre-exposure: Antivirals should only be used in limited circumstances, and in consultation with local medical or public health authorities. • Antiviral Use for Control of Novel H1N1 Influenza Outbreaks • A cornerstone for the control of seasonal influenza outbreaks in nursing homes and other long term care facilities. • If outbreaks were to occur, it is recommended that ill patients be treated with oseltamivir or zanamivir and that chemoprophylaxis with either oseltamivir or zanamivir be started as early as possible to reduce the spread of the virus as is recommended for seasonal influenza outbreaks in such settings. • Children Under 1 Year of Age • Oseltamivir is not licensed for use in children less than 1 year of age. Because infants experience high rates of morbidity and mortality from influenza, infants with novel (H1N1) influenza virus infections may benefit from treatment using oseltamivir. Source: CDC

29. Swine Influenza A(H1N1)Antiviral Protection 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 Source: CDC

30. Swine Influenza A(H1N1)Vaccine Protection • Novel H1N1 vaccine available for since Mid-September • Seventh Harvard Pandemic Survey • 38% of Children in the US immunized • 50% Adults do not intend to be immunized • 35% of parents do not intend to get their children immunized • Novel H1N1 vaccine is not intended to replace the seasonal flu vaccine – it is intended to be used along-side seasonal flu vaccine • Vaccines: • Inactivated influenza virus vaccines • CSL Ltd. of Australia • Novartis Vaccines of Switzerland • Sanofi Pasteur of France • 800,000 pre-filled syringes were recalled are for young children, ages 6 months to 3 years in the US • GlaxoSmithKline (GSK) of UK • Sinovac Biotech of China • Live-attenuated virus vaccine • MedImmune LLC of US (nasal-spray) • 4.5 million doses recalled due to decreased potency in the US

31. Swine Influenza A(H1N1)Vaccine Protection • CDC’s Advisory Committee on Immunization Practices (ACIP) recommends the following groups to receive the novel H1N1 influenza vaccine: • Pregnant women because they are at higher risk of complications and can potentially provide protection to infants who cannot be vaccinated; • Household contacts and caregivers for children younger than 6 months of age because younger infants are at higher risk of influenza-related complications and cannot be vaccinated. Vaccination of those in close contact with infants less than 6 months old might help protect infants by “cocooning” them from the virus; • Healthcare and emergency medical services personnel because infections among healthcare workers have been reported and this can be a potential source of infection for vulnerable patients. Also, increased absenteeism in this population could reduce healthcare system capacity; • All people from 6 months through 24 years of age • Children from 6 months through 18 years of age because we have seen many cases of novel H1N1 influenza in children and they are in close contact with each other in school and day care settings, which increases the likelihood of disease spread, and • Young adults 19 through 24 years of age because we have seen many cases of novel H1N1 influenza in these healthy young adults and they often live, work, and study in close proximity, and they are a frequently mobile population; and, • Persons aged 25 through 64 years who have health conditions associated with higher risk of medical complications from influenza. Source: CDC

32. Swine Influenza A(H1N1): Face Mask and Respirator Protection Source: CDC

33. Swine Influenza A(H1N1) 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 non-quarantine measures that might serve to reduce contact between persons, such as, closing of schools or prohibiting large gatherings Source: CDC

34. Swine Influenza A(H1N1) 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. Source: CDC

35. 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. Swine Influenza A(H1N1) Other Protective Measures Source: CDC

36. 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. Swine Influenza A(H1N1) Other Protective Measures Source: CDC

37. Summary WHO raised the alert level to Phase 6 on June 11, 2009 As of December 28, 2009, worldwide more than 208 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including at least 13,000 deaths Northern Hemisphere: Overall disease activity has recently peaked. Central and Eastern Europe, and in parts of West, Central, and South Asia: Continued increases in influenza activity United States and Canada: Influenza activity continues to be geographically widespread but overall levels of influenza-like-illness has declined substantially Approximately 53% of hospitalized cases in Canada had an underlying medical condition Europe: Widespread and active transmission continued to be observed throughout the continent Overall pandemic influenza activity appears to have recently peaked across a majority of countries Western and Central Asia: Virus circulation remains active throughout the region, however disease trends remain variable East Asia: Influenza transmission remains active but appears to be declining overall Central and South America and the Caribbean: influenza transmission remains geographically widespread but overall disease activity has been declining or remains unchanged in most parts, except for in Barbados and Ecuador, were recent increases in respiratory diseases activity have been reported Southern Hemisphere: Sporadic cases of pandemic influenza continued to be reported without evidence of sustained community transmission.

38. Summary In the US Highest incidence of lab-confirmed cases reported among 5-24 years old Highest hospitalization rate among 0-4 years old Underlying health conditions confers high risk of complications and deaths In Mexico Majority of the cases reported in health young adults 70% of the deaths were reported in healthy young adults, 20-54 years Individuals 60+ seem to be protected as the number of cases and have a lower case-fatality compared to the rest of the population In EU Majority of the cases reported in health young adults (20-29 years) Globally Number of deaths being reported is rising Vaccine Total Adverse Events: 5.4% (0.3% fatal) Sanofi Pasteur & MedImmune vaccine recalled due to potency issues Anti-virals (oseltamivir and zanamivir) Oseltamivir resistance reported recently in immunocompromised patents

39. Conclusion/Recommendations Past experience with pandemics have taught us that the second wave is worse than the first causing more deaths due to: Primary viral pneumonia, Acute Respiratory Distress Syndrome (ARDS), & Secondary bacterial infections, particularly pneumonia Fortunately compared to the past now we have vaccines, anti-virals and antibiotics (to treat secondary bacterial infections) & rT-PCR based rapid diagnostic devices This pandemic is milder than previously predicted with a case-fatality less than 1% At present most of the deaths due to the novel H1N1 strain has been reported from the Americas. Disease seems to be affecting the healthy strata of the population based upon epidemiological data Anecdotal data suggests that the number of deaths among the pediatric population has risen recently due to infection with the novel H1N1 Most of these deaths however have been reported in cases with underlying medical conditions 60 years and above age group seems to show some protection against this strain suggesting past exposure and some immunity

40. Conclusion/Recommendations 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 increasing surge capacity and stringent infection prevention/control General population needs to follow basic precautions 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 This novel H1N1 strain has survived high humidity or temperature and continued to spread during the summer months and will continue to spread and cause infection

41. Conclusion/Recommendations School Closures: Preemptive school closures merely delay the spread of disease Once schools reopen the disease transmits and spreads Puts unbearable pressure on single-working parents and would be devastating to the economy Closure after identification of a large cluster would be appropriate as absenteeism rate among students and teachers would be high enough to justify this action Burden of Disease & Mortality Actual burden of the disease will be higher than the regular seasonal flu despite the availability of vaccine, antivirals and excellent public knowledge With the variation in reporting it is very difficult to appreciate the total number of deaths It is imperative to appreciate that “times-have-changed” Though this strain has spread very quickly across the globe and seems to be highly infectious, today we are much better prepared than 1918 There is better surveillance, communication, understanding of infection control, vaccines, anti-virals, antibiotics and advancement in science and resources to produce countermeasures quickly

42. References World Health Organization (WHO): http://www.who.int/csr/disease/avian_influenza/en/ World Organization for Animal Health (OIE): http://www.oie.int/wahid-prod/public.php? Centers for Disease Control & Prevention (CDC): http://www.cdc.gov/flu/avian/index.htm Chotani R. Just-in-time, H1N1 Influenza. Epidemiology Supercourse. December 2009. El-Bushra H. Global and Regional Update on Human Pandemic Influenza A H1N1 2009. Cairo: WHO/EMRO, 2009