INFLUENZA

Influenza-Objectives
History Transmission Clinical Features Diagnosis Treatment Prevention

History
First described by Hippocrates in 412 BC Influenza-like outbreaks have been clearly documented since 1173 AD. Since 1580- 31 such possible influenza pandemics global epidemics 3 in this century: in 1918, 1957 & 1968.

 While pandemics can kill > 20 million people, more people have died this century from influenza complications that have occurred during a seasonal epidemic, than from a pandemic.

INFLUENZA PANDEMICS
Name of Pandemic Date Deaths Case Fatality rate 0.15 2 0.13 <.0.1 0.03 Subtype Pandemic Involved severity index Possibly H3N8 H1N1 H2N2 H3N2 H1N1 NA 5 2 2 NA

Asiatic ( Russian) Flu Spanish Flu Asian Flu Hong Kong Flu Swine Flu

18891890 19181920 19571958 19681969 20092010

1 million 20-100 million 1-1.5 million 0.75-1 million 18,000

History

SEASONAL EPIDEMICS
Worldwide, annual epidemics: 3-5 million cases of severe illness & about 250 000 - 500 000 deaths. Illnesses result in hospitalizations & deaths mainly among high-risk groups (the very young, elderly or chronically ill).

Most deaths associated with influenza in industrialized countries - people age 65 or older.

SEASONAL EPIDEMICS
Influenza epidemics occur yearly during autumn & winter in temperate regions. In some tropical countries, influenza viruses circulate throughout the year with one or two peaks during rainy seasons.

EPIDEMIOLOGY
Influenza update N 185 - May, 2013 (WHO):

Northern hemisphere: influenza season gradually coming to an end with inter seasonal levels in North America, Europe & northern Asia. A low level persistent transmission in a few countries: Canada and Egypt.

Associated with increasing numbers of influenza type B virus appearing late in the season across North America and parts of Europe

EPIDEMIOLOGY
Prior to this, most commonly detected virus: North America- influenza A(H3N2) Europe - A(H1N1)pdm09 Northern Asia - both viruses in varying proportions.

Number of specimens positive for influenza by subtype in the northern hemisphere

 Tropics & Southern hemisphere- Low levels of influenza activity, remains at inter-seasonal levels. Madagascar -epidemic since the beginning of April. In China- new cases of H7N9 have been reported with 131 cases & 32 deaths to date

Number of specimens positive for influenza by subtype in the Southern hemisphere

Number of specimens positive for influenza by subtype in the Tropical South America Transmission Zone

Epidemiology
Worldwide there have been more than 440,000 laboratory confirmed cases of pandemic Influenza H1N1 and over 5,700 deaths reported to the World Health Organization

Epidemiology
Trinidad and Tobago the most recent epidemiological reports indicate 210 confirmed H1N1 laboratory confirmed cases and five H1N1 deaths Males and females seem to be equally affected.

Epidemiology
57% of these cases fall within the 0-19 age group and 37% within the 20-49 age range

Epidemiology
Important to note persons who died presented with respiratory distress when admitted at the hospital and had serious underlying risk factors

Also the rest of the H1N1 cases treated in Trinidad and Tobago were relatively mild and the persons returned to their normal activities within seven to ten days

Etiology
There are three types of influenza viruses: A, B and C. The influenza A and B viruses that routinely spread in people (human influenza viruses) are responsible for seasonal flu epidemics each year. Influenza type C infections cause a mild respiratory illness and are not thought to cause epidemics.

Etiology
Influenza A viruses can be broken down into sub-types depending on the genes that make up the surface proteins; the hemagglutinin (H) and the neuraminidase (N). There are 17 different hemagglutinin subtypes and 10 different neuraminidase subtypes. Influenza A viruses can be further broken down into different strains

Etiology
CDC follows an internationally accepted naming convention for influenza viruses. The approach uses the following components: 1. The antigenic type (e.g., A, B, C) 2. The host of origin (e.g., swine, equine, chicken, etc. For human-origin viruses, no host of origin designation is given.) 3. Geographical origin (e.g., Denver, Taiwan, etc.) 4. Strain number (e.g., 15, 7, etc.) 5. Year of isolation (e.g., 57, 2009, etc.) 6. For influenza A viruses, the hemagglutinin and neuraminidase antigen description in parentheses (e.g., (H1N1), (H5N1)

Pathophysiology
Influenza viruses are encapsulated, negativesense, single-stranded RNA viruses of the family Orthomyxoviridae. The core nucleoproteins are used to distinguish the 3 types of influenza viruses: A, B, and C. Influenza A viruses cause most human and all avian influenza infections

Pathophysiology
The RNA core consists of 8 gene segments surrounded by a coat of 10 (influenza A) or 11 (influenza B) proteins. Immunologically, the most significant surface proteins include hemagglutinin (H) and neuraminidase (N).

Pathophysiology
Major typing of influenza A occurs through identification of both N and H. Sixteen N and 9 H types have been identified. All hemagglutinins and neuraminidases infect wild waterfowl, and the various combinations of H and N results in 144 combinations and potential subtypes of influenza. The most common subtypes of human influenza virus identified to date contain only hemagglutinins 1, 2, and 3 and neuraminidases 1 and 2.

Pathophysiology
The variants are used to identify influenza A virus subtypes. For example, influenza A subtype H3N2 expresses hemagglutinin 3 and neuraminidase 2. H3N2 and H1N1 are the most common prevailing influenza A subtypes that infect humans.

Pathophysiology
The viral RNA polymerase lacks error-checking mechanisms and, as such, the antigenic drift from year to year is sufficient to ensure a significant susceptible host population. However, the segmented genome also has the potential to allow re-assortment of genome segments from different strains of influenza in a co-infected host.

Pathophysiology
In addition to humans, influenza also infects a variety of animal species. More than 100 types of influenza A infect most species of birds, pigs, horses, dogs and seals. Influenza B has also been reported in seals, and influenza C, rarely, in pigs.

Pathophysiology
Influenza A is a genetically labile virus, with mutation rates as high as 300 times that of other microbes.[14] Changes in its major functional and antigenic proteins occur by means of 2 well-described mechanisms: antigenic drift and shift.

Pathophysiology
Antigenic drift is the process by which inaccurate viral RNA polymerase frequently produces point mutations in certain error-prone regions in the genes. These mutations are ongoing and are responsible for the ability of the virus to evade annually acquired immunity in humans. Drift can also alter the virulence of the strain. Drift occurs within a set subtype (eg, H2N2). For example, AH2N2 Singapore 225/99 may reappear as with a slightly altered antigen coat as AH2N2 New Delhi 033/01.

Pathophysiology
Antigenic shift is less frequent than antigenic drift. In a shift event, influenza genes between 2 strains are reassorted, presumably during co-infection of a single host. Segmentation of the viral genome, which consists of 10 genes on 8 RNA molecules, facilitates genetic reassortment. Antigenic shift is less frequent than antigenic drift. In a shift event, influenza genes between 2 strains are reassorted, presumably during co-infection of a single host. Segmentation of the viral genome, which consists of 10 genes on 8 RNA molecules, facilitates genetic reassortment.

Pathophysiology
Such an antigenic shift can result in a virulent strain of influenza that possesses the triad of infectivity, lethality, and transmissibility and can cause a pandemic. Three such influenza pandemics have occurred in recorded history: the 1918 Spanish influenza (H1N1) pandemic and the pandemics of 1957 (H2N2) and 1968 (H3N2). Smaller outbreaks occurred in 1947, 1976, and 1977.

Pathophysiology
To date, the vast majority of cases of avian influenza have been acquired from direct contact with live poultry in emerging nations. Hemagglutinin type H5 attaches well to avian respiratory cells and thus spreads easily among avian species. However, attachment to human cells and resultant infection is more difficult. The reasons why humans can be infected with H5 are poorly understood.

Pathophysiology
To date, avian influenza remains a zoonosis, with no sustained human-to-human transmission. Family clusters have been reported but appear to be almost always related to common exposures; however, limited human-to-human spread through close proximity could not be officially ruled out. In September 2004, one case in Thailand probably involved daughter-to-mother transmission; the mother died.

Pathophysiology
The pathophysiology of avian influenza differs from that of normal influenza. Avian influenza is still primarily a respiratory infection but involves more of the lower airways than human influenza typically does. This is likely due to differences in the hemagglutinin protein and the types of sialic acid residues to which the protein binds.

Pathophysiology
Although this results in a more severe respiratory infection, it probably explains why few, if any, definite human-to-human transmissions of avian influenza have been reported: infection of the upper airways is probably required for efficient spread via coughing and sneezing.

Pathophysiology
In contrast to human influenza, most deaths associated with avian influenza have been due to primary viral pneumonia, with no evidence of secondary bacterial infection.

Pathophysiology
Reservoirs for avian influenza A Waterfowl, including ducks and geese, are considered to be the natural reservoirs for avian influenza A. Most infections in these birds are believed to be asymptomatic. However, because these viruses can also infect and cause disease in domestic poultry and because of the potential economic implications, substantial attention has been given to avian influenza.

TRANSMISSION

Transmission
Transmission of influenza from poultry or pigs to humans appears to occur predominantly as a result of direct contact with infected animals. The risk is especially high during slaughter and preparation for consumption; eating properly cooked meat poses no risk. Avian influenza can also be spread through exposure to water and surfaces contaminated by bird droppings.[23]

Transmission
Influenza viruses spread from human to human via aerosols created by coughs or sneezes of infected individuals. Influenza virus infection occurs after inhalation of the aerosol by a person who is immunologically susceptible. If not neutralized by secretory antibodies, the virus invades airway and respiratory tract cells.

Transmission
Once within host cells, cellular dysfunction and degeneration occur, along with viral replication and release of viral progeny. Systemic symptoms result from inflammatory mediators, similar to other viruses. The incubation period of influenza ranges from 1872 hours.

Transmission
Viral shedding occurs at the onset of symptoms or just before the onset of illness (0-24 h). Shedding continues for 5-10 days. Young children may shed virus longer, placing others at risk for contracting infection with the virus. Shedding may persist for weeks to months in highly immunocompromised persons.[5]

Direct Transmission

Airbone route

Contaminated objects
Hand to mouth Hand to nose Hand to eyes

HISTORY
Sore throat Cough Headache Fever, chills and rigors Myalgia Dyspnoea Weakness and Fatigue Vomiting Diarrhoea

 Ask about contacts with the disease History of travel travel to places with outbreaks

EXAMINATION
Febrile to touch, Fever >38 oC
Patient looks unwell

Altered mental status

RHINITIS, EYES WATERY AND RED

PHARYNGITIS

TACHYCARDIA

LUNGS CLEAR

Complications
Reyes Syndrome In children
2-12 days after onset of infection Severe fatty infiltration of the liver Cerebral edema Risk enhanced by use of salicylates Confusion LOC seizures

Other complications
Myositis Myocarditis Pericarditis CNS dysfunction

Differential Diagnoses

 Accurately diagnosing influenza A or B infection based solely on clinical criteria is difficult because of the overlapping symptoms caused by the various viruses associated with upper respiratory tract infection (URTI). In addition, several serious viruses, including adenoviruses, enteroviruses, and paramyxoviruses, may initially cause influenza like symptoms. The early presentation of mild or moderate cases of flavivirus infections (eg, dengue) may initially mimic influenza. For example, some cases of West Nile fever acquired in New York in 1999 were clinically misdiagnosed as influenza.

Differential Diagnoses
Acute Respiratory Distress Syndrome Adenoviruses Arenaviruses Cytomegalovirus Dengue Fever Echoviruses Hantavirus Pulmonary Syndrome HIV Disease Legionnaires Disease Parainfluenza Virus

Diagnostics

RIDT
Rapid influenza diagnostic test (RIDT) used to detect the virus in nasal secretions and one of the most common methods used to diagnose this infection. It can help differentiate influenza from other viral and bacterial infections with similar symptoms that may be serious and must be treated differently.

 Rapid flu tests are best used within the first 48 hours of the onset of symptoms to help diagnose influenza and determine whether or not antiviral drugs are a treatment option.

Sometimes rapid tests are ordered to help identify outbreaks.

Rapid tests vary in their ability to detect influenza. Some types can only detect influenza A; others can detect both A and B but not distinguish between the two.

Still others can detect and distinguish between influenza A and B. However, none of them are able to differentiate between the strains of influenza A, such as H1N1.

Viral culture
Viral culture has been considered the "gold standard" for diagnosing influenza, but it can take up to 3 to 10 days for results.
It can be used for confirmation of a positive rapid test result. In this test, the influenza virus is actually grown and identified in the laboratory. It has the advantage of identifying which viruses (A, B, or another respiratory virus) and which strains of virus are present.

Disadvantages
The main disadvantages of the rapid influenza antigen test are: 1) It will miss up to 30% of influenza cases, may only detect 10-70% of 2009 H1N1 influenza infections. 2) It will occasionally be positive when someone does not actually have the flu.

DFA
Direct fluorescent antibody stain (DFA) detects influenza A or B virus in samples of nasal secretions. This method of testing is more specific than RIDT but requires specialized equipment to perform and special training to interpret, so it is usually not performed in a doctor's office.

Samples are typically sent to a laboratory for testing. A negative result with this test does not rule out influenza.

Viral culture
A rapid culture method, known as shell vial culture, may detect the presence of a respiratory virus in 24 to 48 hours, however, a traditional viral culture performed in a large test tube may require several days before the virus can be detected. Growing the virus in culture is useful for documenting which strains of influenza are circulating in the community and which antiviral agents are effective in treating these viruses.

Viral Culture
Identifying these outbreaks can assist health care workers in the prevention and treatment of the flu throughout a community. Influenza virus grown in culture can be sent to a public health laboratory to determine if the strain of influenza A is the antigenic type (H5N1) found in birds and chickens or the 2009 H1N1 influenza virus. Viral cultures can also be used to identify other viral infections that cause clinical symptoms similar to the flu.

RT-PCR
Real-time polymerase chain reaction (RT-PCR) molecular testing is available that detects viral genetic material in nasal secretions and is the most sensitive test for influenza virus. However, this test is not widely available and results can take from one to several days. These tests may be ordered to diagnose influenza A infection, especially in those who are seriously ill (hospitalized) and to help track influenza outbreaks.

Disadvantage of RT-PCR
Some false negatives can occur with this method. A new version of this test with specific reagents directed toward the 2009 H1N1 influenza virus was developed in April 2009 to allow the detection of this novel flu virus.

Antibody Tests
Influenza A or B antibody tests these are blood tests performed to detect the body's immune response to an influenza infection. Acute and convalescent samples are required to help confirm that a recent infection was due to the flu. Antibody testing on single blood samples is not useful. These tests are not done routinely and are most often done for public health or research purposes.

Treatment
Mild illness: Basic supportive care : antipyretics, such as paracetamol or acetaminophen for fever or pain fluid rehydration and can be provided as needed. Plenty rest Counseling pts- signs of progressive disease, when to seek medical attention Antiviral treatment is not necessary for people have uncomplicated, or mild, illness and are not in a high risk group for severe illness.

ANTIVIRALS
WHO and CDC Recommendations Antiviral treatment is recommended as soon as possible for patients with confirmed or suspected influenza who have severe, complicated, or progressive illness or who require hospitalization regardless of previous health or vaccination status

outpatients with confirmed or suspected influenza who are at higher risk for influenza complications on the basis of their age or underlying medical conditions; clinical judgment should be an important component of outpatient treatment decisions During 2009 H1N1 pandemic empiric neuraminidase inhibitor treatment for all persons with suspected or confirmed H1N1 virus infection who are at increased risk for influenza complications.

ANTIVIRALS
Persons at higher risk for influenza complications children aged younger than 2 years; adults aged 65 years and older; persons with chronic pulmonary (including asthma), cardiovascular (except hypertension alone), renal, hepatic, hematological (including sickle cell disease), metabolic disorders (including diabetes mellitus) or neurologic and neurodevelopment conditions (including disorders of the brain, spinal cord, peripheral nerve, and muscle such as cerebral palsy, epilepsy, stroke, mental retardation persons with immunosuppression, e.g. HIV, including that caused by medications women who are pregnant or postpartum (within 2 weeks after delivery); persons aged younger than 19 years who are receiving long-term aspirin therapy; persons who are morbidly obese (i.e., BMI is 40 or greater) residents of nursing homes and other chronic-care facilities

ANTIVIRALS
2 classes available for treatment and prevention of influenza 1. ADAMANTANES

Include: amantadine and remantadine MOA: inhibits the function of the M2 protein by blocking the ion channel and thus stops the replication process virus to infect other cells - Act against influenza A virus only. - Come in a capsule or syrup form side effects: The most frequent reactions are nausea, dizziness and insomnia

ANTIVIRALS
2. NEURAMINIDASE INHIBITORS Includes: oseltamivir and zanamivir MOA: bind to the active site on the viral neuraminidase, blocking its activity. Thus, virus particles cannot exit the cells as easily, and they tend to clump and not disperse. This impedes their ability to infect more cells and attenuates the patient's infection. -effective against both influenza A and B infections. -Zanamivir inhaled powder -Osetalmivir- capsules Side effects: zanamivir may be associated with bronchospasm and may exacerbate asthma in some patients-. not recommended for persons with underlying airway disease oseltamivir causes mild nausea and vomiting , which can be reduced by taking it with food

ANTIVIRALS
Treatment is most effective when given within 48hours after the onset of illness, and the earlier the better. Recommended duration of treatment for uncomplicated illness is 5 days. Patients with suspected influenza should complete antiviral treatment for a full treatment course regardless of negative initial test results unless an alternative diagnosis can be established and clinical judgment suggests that influenza is unlikely Supportive care such as oxygen therapy, intravenous fluids, and parenteral nutrition may be needed. Severe cases may require ventilatory support with intubation

TREATMENT
a pulmonary specialist, a critical care specialist, an infectious disease specialist, and the staff of the local public health department may all be consulted. Clinical laboratory personnel should also be informed before potential isolates are sent to them. hospital infection-control officers should be involved early in the care of any patient who might have virus. Early involvement of the local public health department and hospital infection control is necessary to contain any outbreaks.

Treatment
Patients with influenza are at high risk for such secondary bacterial complications Antibacterial therapy plus antiviral treatment are recommended for patients with communityacquired pneumonia when influenza also is suspected. likely bacterial pathogens associated with influenza: S. pneumoniae, S. pyogenes, and S. aureus- including MRSA, especially for hospitalized patients .

Treatment algorithm

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC139319/figure/f2-25/

Viral Resistance
Patients receiving antiviral medications who do not respond to treatment might have an infection with an antiviral-resistant influenza virus. In 2007-2008, a significant increase in the prevalence of oseltamivir resistance was reported among influenza A (H1N1) viruses worldwide. During the influenza season, 10.9% of H1N1 viruses tested in the United States were resistant to oseltamivir. Oseltamivir resistance has been reported particularly among immunocompromised patients with 2009 H1N1 virus infection. has made this class of medications less useful clinically Infection-control measures are especially important for patients who are immunocompromised to reduce the risk for transmission of oseltamivir-resistant viruses In 2011 H3N2was found to be resistant to adamantanes

Post exposure
Postexposure chemoprophylaxis with neuraminidase inhibitors generally should be reserved for those who have had recent close contact with a person with influenza. -family or other close contacts of a person with a suspected or confirmed case who are at higher risk for influenza complications but have not been vaccinated against the influenza virus strains circulating at the time of exposure -Unvaccinated health-care workers who have occupational exposures and who did not use adequate personal protective equipment at the time of exposure are also potential candidates for chemoprophylaxis typically administered for a total of no more than 10 days after the most recent known exposure to a close contact known to have influenza.

Prevention

Definitions
Vaccine any preparation intended to produce immunity to a disease by stimulating the production of antibodies Immunization process whereby a person is made immune or resistant to an infectious disease, typically by the administration of a vaccine

Who should get vaccinated?

High risk of having serious flu related complications People who live with or care for people at high risk for developing flu-related complications.

 Age : 6mths -4 yrs , >50 yrs

Children aged 6 months to 18 years on long-term ASA therapy Reye syndrome after infection Immunosuppression medication/ HIV Chronic pulmonary ( + asthma), cardiovascular (hypertension), renal, hepatic, neurologic, hematologic, or metabolic disorders (+ diabetes mellitus)

 Health-care personnel
Household contacts & caregivers of :
Children < 5yrs (esp. <6/12) & adults > 50 yrs people with medical conditions with higher risk of severe complications from influenza

Women who are pregnant People who are morbidly obese(BMI> 40)

Vaccine for children

Recommended 6 months 19th birthday 2009 H1N1 was not added to the seasonal vaccine until 2010-2011 flu season If did not get the 2009 H1N1 vaccine in 20092010 / seasonal flu vaccine in 2010-2011 or later not fully protected from 2009 H1N1 virus until they receive 2 doses of the 2012-2013 flu vaccine.

2 dose vaccination
1st dose
as soon as vaccine avaliable

2nd dose
28 days after 1st

reduced /no protection from a single dose of vaccine. Approx. 2 weeks after the 2nd dose for protection to begin. Protection lasts approx. 1 yr

Who should not be vaccinated

1. Allergy to chicken eggs 2. Previous severe reaction to an influenza vaccine 3. Children age < 6/12 4. Moderately / severely ill with or without fever after recovery then administer vaccine 5. Hx of Guillain-Barre Syndrome (GBS) within 6 weeks following receipt of influenza vaccine

Vaccination with egg allergy

2012-2013 season CDC administration of both full doses and split doses of TIV have been tolerated by people with egg allergies, without serious reactions The Advisory Committee on Immunization Practices (ACIP) experienced only hives from consuming eggs can receive TIV IM as long as they are treated by a health care provider

 familiar with the potential manifestations of egg allergies & can be observed by a health care professional for at least 30 minutes after receiving each dose. LAIV should not be used in these patients

Trivalent inactivated vaccine (TIV)

Injected muscle of the upper arm or thigh. Used for healthy people*
aged > 6/12 chronic medical conditions women who are pregnant * Healthy people people who do not have an underlying medical condition that predisposes them to influenza complications.

Live attenuated intranasal vaccine (LAIV)

Eg. FluMist Adult 0.2 mL intranasally once /season
1 mL in each nostril

Peads
2-8 yrs NOT previously vaccinated with intranasal influenza vaccine: as adult then repeat dose in 4674 d >8 years: Administer as in adults

Seasonal Influenza vaccine safety

2012-2013 seasonal influenza vaccine
Available August 2012
protects against
influenza A H3N2 virus an influenza B virus & the 2009 (Influenza A) H1N1 virus

Seasonal LAIV & TIV contain all 3 strains .

Adverse effects - TIV

Injection site reactions pain , redness, swelling resolve <2 days without treatment Fever, malaise, myalgia & other systemic symptoms no previous exposure to the influenza virus antigens in the vaccine e.g. young children. Ocular or respiratory symptoms (e.g., red eyes, hoarse voice, cough etc) mild , resolve without treatment Immediate hypersensitivity reactions urticaria, angioedema, anaphylaxis

Adverse Effect - LAIV

runny nose /nasal congestion (all ages) fever >100F age 2-6 yrs sore throat ( adults)

Screening for Vaccine

Ask about:
Egg allergy Adverse events(eg. GBS) to prior doses of influenza vaccine Current Health status

Children age 2- 4 years:

Presence of wheeze / asthma in the past 12 months
USE TIV (NOT LAIV)

2013- 2014 Influenza season

Approved Feb.21st 2013 by ACIP TIV
inactivated influenza vaccines replaced with the abbreviation IIV
egg-based and cell culture-based trivalent inactivated influenza vaccine (IIV3); and egg-based quadrivalent inactivated influenza vaccine (IIV4).

2013-2014 Influenza season

RIV
recombinant hemagglutinin influenza vaccine available as a trivalent formulation (RIV3) Produced in insect cells

LAIV
live, attenuated influenza vaccine, available as a quadrivalent formulation (LAIV4)

numeric suffix # of influenza virus antigens contained in the vaccine.

Everyday preventative action to stop the spread of germs

1. Try to avoid close contact with sick people. 2. If you are sick with flu-like illness, CDC recommends that you stay home for at least 24 hours after your fever is gone except to get medical care or for other necessities. (Your fever should be gone without the use of a fever-reducing medicine.)

3. While sick, limit contact with others as much as possible to keep from infecting them. 4. Cover your nose and mouth cough or sneeze. Throw the tissue after use. 5. Wash hands often with soap and water / use alco. Based hand rub.

6. Avoid touching your eyes, nose and mouth. 7. Clean and disinfect surfaces and objects that may be contaminated .

Public Health
Enhanced surveillance
with daily temperature taking prompt reporting with isolation Influenza update weekly

Thank You

References
Seneca H. Influenza: epidemiology, etiology, immunization and management. J Am Geriatr Soc. 1980 Jun;28(6):241-50 Palese P (January 2006). Making better influenza virus vaccines? Emerging Infect. Dis. 12 (1): 615 Government of Trinidad and Tobago.

http://www.news.gov.tt/index.php?news=2346. 04 November, 2009 02:27:00

References
http://www.cdc.gov/flu/professionals/antivira ls/antiviral-use-influenza.htm#indications http://www.who.int/csr/resources/publication s/swineflu/clinical_management/en/ http://www.ncbi.nlm.nih.gov/pmc/articles/P MC3430703/ http://emedicine.medscape.com/article/2195 57-clinical#a0256

References
http://www.cdc.gov/flu/about/disease/spread .htm http://cid.oxfordjournals.org/content/37/8/10 94.full.pdf