Novel H1N1 (Swine) Epidemiology & Control

Ahmed MandilProf of Epidemiology

Dept of Family & Community MedicineCollege of Medicine, King Saud University

1. Influenza Virus2. Definitions3. Introduction4. Spread/Transmission 5. Timeline/Facts6. Response 7. Case-Definitions8. Treatment9. Other Protective Measures10. Conclusion &

Recommendations

HEADLINES

Credit: L. Stammard, 1995

• 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

• 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

Timeline of EmergenceInfluenza A Viruses in Humans

1918 1957 1968 1977 1997

1998/9

2003

H1

H1

H3H2

H7

H5H5H9

SpanishInfluenza

H1N1

AsianInfluenza

H2N2

RussianInfluenza

AvianInfluenza

Hong Kong

InfluenzaH3N2

2009

H1

Reassorted Influenza virus (Swine Flu)

1976 Swine Flu Outbreak, Ft.

Dix

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

• 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

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

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

Swine Influenza A(H1N1) Transmission Through Species

Avian Virus

Human Virus

Swine Virus

Avian/HumanReassorted Virus

Reassortment in Pigs

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

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

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

Source: WHO

Swine Influenza A(H1N1)Status Update

ECDC reported a total of 12,776 deaths – December 28, 2009

Swine Influenza A(H1N1) CDC Estimates from April-November 14, 2009, By Age Group

Source: CDC. http://www.cdc.gov/h1niflu/surveillanceqa.htm

2009 H1N1 Mid-Level Range* Estimated Range*

Cases    

0-17 years ~16 million ~12 million to ~23 million18-64 years ~27 million ~19 million to ~38 million

65 years and older ~4 million ~3 million to ~6 millionCases Total ~47 million ~34 million to ~67 million

Hospitalizations    

0-17 years ~71,000 ~51,000 to ~101,00018-64 years ~121,000 ~87,000 to ~172,000

65 years and older ~21,000 ~15,000 to ~29,000Hospitalizations Total ~213,000 ~154,000 to ~303,000

Deaths    

0-17 years ~1,090 ~790 to ~1,55018-64 years ~7,450 ~5,360 to ~10,570

65 years and older ~1,280 ~920 to ~1,810Deaths Total ~9,820 ~7,070 to ~13,930

Pandemic (H1N1) 2009 in the EMR as of 6 November, 2009

22/22 countries affectedRegular reports from 17 countries: 26,400 confirmed cases and 150 deaths.Localized to moderate geographical distribution.Increasing trend in most of the countriesLow to moderate intensity Low to moderate impact on the health system

•

CountryCountry Cumulative number Cumulative number

of confirmed casesof confirmed cases

Cumulative Cumulative

number of number of

deathsdeaths

TrendTrend

KuwaitKuwait 66, , 640640 1717 IncreasingIncreasingUAEUAE 7979 00 NANABahrainBahrain 793793 66 NANA

LebanonLebanon 761761 22 NANAEgyptEgypt 11, 592, 592 55 IncreasingIncreasingSaudi ArabiaSaudi Arabia 4, 1194, 119 2828 NANAPalestine Palestine 777777 11 IncreasingIncreasingMoroccoMorocco 484484 00 IncreasingIncreasingJordanJordan 22, , 050050 33 Increasing Increasing QatarQatar 2323 11 NANA

YemenYemen 629629 1717 IncreasingIncreasingOmanOman 33, , 329329 2525 IncreasingIncreasing

IranIran 11, , 638638 2222 IncreasingIncreasingTunisiaTunisia 11, , 285285 00 IncreasingIncreasingIraqIraq 11, , 080080 77 IncreasingIncreasingLibyaLibya 2121 00 UnchangedUnchangedSyriaSyria 160160 66 IncreasingIncreasingAfghanistanAfghanistan 772772 1010 IncreasingIncreasingSudanSudan 77 00 Unchanged Unchanged PakistanPakistan 55 00 UnchangedUnchangedDjiboutiDjibouti 99 00 UnchangedUnchangedSomaliaSomalia 22 00 UnchangedUnchangedTotalTotal 26,40026,400 150150

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

The Epidemic Curve

Single-wave profile showing proportion of new clinical cases, consultations, hospitalisations or deaths by week. Based on London, second wave 1918.

0%

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1 2 3 4 5 6 7 8 9 10 11 12Week

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Initiation Acceleration Peak Decline

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.

Dailycases

Days since first case

No intervention

42

7

109

147

4071

16 275 1

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8

97110

15

415

627

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Swine Influenza A(H1N1) Mediterranean & Middle East Confirmed Deaths

n=1,246

Source: ECDC

As of December 28, 2009

Global Distribution of Reported Laboratory Confirmed Cases & Deaths of Swine Influenza A(H1N1), December 23, 2009

Source: WHO

Geographic Spread of Influenza ActivityBased Upon Country Reporting,

Week 50, 2009 (07-23 December)

Source: WHO

Impact on Healthcare Services Based Upon Degree of Disruption, As a Result of Acute Respiratory Diseases

Week 50, 2009 (07-13 December)

Source: WHO

Number of Specimens Positive for Influenza Sub-Type

Source: CDC

Laboratory-Confirmed Cases & Deaths of New Influenza A(H1N1) by WHO Regions, September 20, 2009

8264

130448

11621

53000

30293

85299

41 2948 72 154 340 3620

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120000

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*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.

At least 318,925 Cases & Over 3917 DeathsOverall Case-Fatality Rate (CFR) in Confirmed ~ 1.2%

Source: WHO

CFR = 0.5%

CFR = 2.5%

CFR = 0.6%

CFR = 1.1%

CFR = 0.3%

CFR = 0.4%

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

Comparison of Available Influenza Diagnostic Tests1

Influenza Diagnostic Tests

Method Availability TypicalProcessing Time2

Sensitivity3 for2009 H1N1influenza

Distinguishes 2009 H1N1 influenza from other influenza A

viruses?

Rapid influenza diagnostic tests (RIDT)4

Antigen detection

Wide 0.5 hour 10 – 70% No

Direct and indirectImmunofluorescence

assays (DFA and IFA)5

Antigen detection

Wide 2 – 4 hours 47–93% No

Viral isolation in tissue cellculture

Virus isolation

Limited 2 -10 days - Yes 6

Nucleic acid amplification tests

(including rRT-PCR) 7

RNA detection

Limited8  48 – 96 hours [6-8 hours toperform test]

86 – 100% Yes

Source: CDC

• 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 medications are 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

Swine Influenza A(H1N1) Antiviral Protection

Source: CDC

• 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.

Swine Influenza A(H1N1) Antiviral Protection

Source: CDC

Source: CDC

Oseltamivir (Tamiflu) Zanamivir (Relenza)

Treatment Prophylaxis Treatment Prophylaxis

Adults 75 mg capsule twice per day for 5 days

75 mg capsule once per day

Two 5 mg inhalations (10 mg total) twice per day

Two 5 mg inhalations (10 mg total) once per day

Children 15 kg or less: 60 mg per day divided into 2 doses

30 mg once per day Two 5 mg inhalations (10 mg total) twice per day (age, 7 years or older)

Two 5 mg inhalations (10 mg total) once per day (age, 5 years or older)

15–23 kg: 90 mg per day divided into 2 doses

45 mg once per day

24–40 kg: 120 mg per day divided into 2 doses

60 mg once per day

>40 kg: 150 mg per day divided into 2 doses

75 mg once per day

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

Swine Influenza A(H1N1) Antiviral 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

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.

Swine Influenza A(H1N1) Vaccine Protection

Source: CDC

Swine Influenza A(H1N1): Face Mask and Respirator Protection

Setting Persons not at increased risk of severe illness from influenza

(Non-high risk persons)

Persons at increased risk of severe illness from influenza

(High-Risk Persons)

Community

No 2009 H1N1 in community Facemask/respirator not recommended Facemask/respirator not recommended

2009 H1N1 in community: not crowded setting Facemask/respirator not recommended Facemask/respirator not recommended

2009 H1N1 in community: crowded setting Facemask/respirator not recommended Avoid setting. If unavoidable, consider facemask or respirator

Home

Caregiver to person with influenza-like illness Facemask/respirator not recommended Avoid being caregiver. If unavoidable, use facemask or respirator

Other household members in home Facemask/respirator not recommended Facemask/respirator not recommended

Occupational (non-health care)

No 2009 H1N1 in community Facemask/respirator not recommended Facemask/respirator not recommended

2009 H1N1 in community Facemask/respirator not recommended but could be considered under certain circumstances

Facemask/respirator not recommended but could be considered under certain circumstances

Occupational (health care)

Caring for persons with known, probable or suspected 2009 H1N1 or influenza-like illness

Respirator Consider temporary reassignment. Respirator

Source: CDC

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

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

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

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

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.

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

Conclusion/Recommendations

1. 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%

2. 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

Conclusion/Recommendations

3. 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

4. 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

Conclusion/Recommendations

5. 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

6. 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

7. 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

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