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Types of Influenza Virus
Three types: A, B, C Influenza Type A can infect: People, birds, pigs, horses,
seals, whales and others Classified into subtypes
Influenza Type B: Human virus Not classified according to Subtype Cause human epidemics but not pandemics
Influenza Type C cause mild illness in humans Not classified according to subtype Do not cause epidemics or pandemics
Influenza Virus: Types A and BInfluenza Virus: Types A and BType A
(Seasonal and avian influenza)
Type B(Seasonal influenza)
Can cause significant disease
Generally causes milder disease but may also cause severe disease
Infects humans and other
species (e.g., birds; H5N1)Limited to humans
Classified according to subtypes
No classified according to subtypes
Can cause epidemics and pandemics (worldwide epidemics)
Generally causes milder epidemics
Influenza A Virus SubtypingInfluenza A Virus Subtyping
■ Influenza A subtypes are determined by two surface glycoproteins:
Hemagglutinin (HA)
Neuraminidase (NA)
■ 16 HA’s and 9 NA’s
Species Infected by Influenza A, HA
and NA Subtypes
H15,16H14H13H12H11H10
H3H2H1
H9H8H7H6H5H4
N9N8N7N6N5
N3N4
N2N1
Influenza: Epidemiologic Success
• The long-term epidemiologic success of influenza viruses is primarily due to antigenic variation that takes place in the two surface glycoproteins of the virus: HA and NA.
• Antigenic variation renders an individual susceptible to new Antigenic variation renders an individual susceptible to new strains despite previous infection by influenza viruses or strains despite previous infection by influenza viruses or previous vaccination.previous vaccination.
Influenza Epidemiologic Success: Antigenic Drift
■ Point mutations in the hemagglutinin gene cause minor antigenic changes to HA. Continuous process Immunity against one strain may be limited
■ These genetic changes often encode amino acid changes in the surface proteins and consequently in their antigenic properties.
■ Antigenic drift produces new virus strains that may not be recognized by antibodies to earlier influenza strains
Influenza Epidemiologic Success: Antigenic Drift
■ Antigenic drift is one of the main reasons why people can get the flu more than one time (Seasonal epidemics) and why the vaccine formulation has to be evaluated and modified every year.
■ One or two of the three virus strains included in the annual influenza vaccine are updated:
6-8 months process Targeted at high-risk (inactivated)
Influenza Epidemiologic Success: Antigenic Drift
• Global surveillance of influenza viruses has shown that antigenic variation and the consequent epidemiologic behavior of influenza A viruses follows a relatively uniform pattern.
• Each successive antigenic variant replaces its predecessor such that the co-circulation of distinct antigenic variants of a given subtype occurs for relatively short periods.
• During the past decade, new epidemic variants of influenza often are first detected in China before they spread to other locations.
Influenza Epidemiologic Success: Antigenic Shift
■ Gives rise to new influenza virus that can infect humans and has (new HA subtype ± NA) through:
Genetic reassortment (human and animal viruses) Direct animal (poultry) to human transmission
■ As most people have little or no protection against the new virus: Spread easily from person to person Pandemic (worldwide spread) may occur
Influenza A Viruses in SwineInfluenza A Viruses in Swine
• Influenza viruses reported in swine:– H1N1 (swine classic)– H1N1 (avian and human like)– H3N2H3N2 (avian and human like)
Recent Transmissions Recent Transmissions of Swine Influenza in Humansof Swine Influenza in Humans
• 1998 at present:– Triple reassortant
(human, avian and swine genes)
– 2005-2009: 12 human cases in USA
PB2
PB1
PA
HA
NP
NA
M
NS
Avian N Am
Avian N Am
Seasonal H3N2
Classic swine N Am
Classic swine N Am
Classic swine N Am
Classic swine N Am
Classic swine N Am
Triple Reassortant Swine Triple Reassortant Swine
Recent Transmissions Recent Transmissions of Swine Influenza in Humansof Swine Influenza in Humans
• Novel Swine Origin Novel Swine Origin Influenza A H1N1Influenza A H1N1
• First reported:First reported:– California, April 15, 2009
• May 16: 36 countries May 16: 36 countries – 8,451 cases– 72 deaths (0.85 %)
PB2
PB1
PA
HA
NP
NA
M
NS
Avian N Am
Avian N Am
Seasonal H3N2
Classic swine N Am
Classic swine N Am
Eurasian swineEurasian swine
Eurasian swineEurasian swine
Classic swine N Am
Recent Transmissions Recent Transmissions of Swine Influenza in Humansof Swine Influenza in Humans
Novel Swine Origin Novel Swine Origin
Influenza A H1N1 (2009)Influenza A H1N1 (2009)Triple Reassortant Swine Triple Reassortant Swine
PB2
PB1
PA
HA
NP
NA
M
NS
Avian N Am
Avian N Am
Seasonal H3N2
Classic swine N Am
Classic swine N Am
Classic swine N Am
Classic swine N Am
Classic swine N Am
PB2
PB1
PA
HA
NP
NA
M
NS
Avian N Am
Avian N Am
Seasonal H3N2
Classic swine N Am
Classic swine N Am
Eurasian swineEurasian swine
Eurasian swineEurasian swine
Classic swine N Am
Novel Influenza A (H1N1)Novel Influenza A (H1N1)
• CDC developed a real time RT-PCR specific for novel influenza (H1N1)
PB2
PB1
PA
HA
NP
NA
M
NS
Avian N Am
Avian N Am
Seasonal H3N2
Classic swine N Am
Classic swine N Am
Eurasian swineEurasian swine
Eurasian swineEurasian swine
Classic swine N Am
PCR set up:
Univ Flu A
Sw Flu A
SW H1
RP
Novel influenza A (H1N1) Diagnostic Novel influenza A (H1N1) Diagnostic FlowchartFlowchart
Sw H1N1
Univ. Flu A = Pos
Sw Flu A = Pos
Sw H1 = Pos
Repeat reaction from extraction
Contact NAMRU-3 or CDC
Univ. Flu A = Pos
Sw Flu A = Pos
Sw H1 = Neg
Univ. Flu A = Pos
Sw Flu A = Neg
Sw H1 = Pos
Univ. Flu A = Pos
Sw Flu A = Neg
Sw H1 = Neg
RP = Pos
STOP:
Flu A virus
Seasonal Flu
Subtype specimen
Preserve remnant at -70C (if not available, then -20C)
Specimen: swabs in VTM
Nucleic Acid Extraction:
140 ul specimen
PCR Universal Flu A Negative:
Univ. Flu A Stop:
Non-Flu A virus
Positive: Univ. Flu A (continue with SwH1N1 primers)
Novel Influenza A (H1N1) Surveillance Novel Influenza A (H1N1) Surveillance ActivitiesActivities
• Objectives:Objectives:• Detect and confirm cases of novel influenza A (H1N1)
infections• Establish the extent of international spread• Assist in the early severity assessment of the disease.
Specimen meets criteria for
rRT-PCR Swine Flu Panel testing
Perform rRT-PCR Swine Flu Panel
Inf A (+)Universal SW InfA (+)Novel SW H1 (+)
Inf A (+)UniversalSW InfA (-)NovelSW H1 (-)
Inf A (-)UniversalSW InfA (-)NovelSW H1 (-)
Inf A (+)UniversalSW InfA (+)NovelSW H1 (-)
Inf A (+)UniversalSW InfA (-)NovelSW H1 (+)
Report Results
To CDC per normal
surveillance protocol
and send
specimens to CDC according to
current guidance.
Flu A positive specimens negative for human H1, H3, B , and swine H1
should be reported to CDC
immediately for priority testing.
Subtype specimens
using rRT-PCR Flu Panel IVD
test or other approved
methods (as resources
permit and the prevalence of
other circulating
strains dictates)
Report results
To CDC per normal
surveillance protocol
Repeat results from the
extraction step in house, report
results
to CDC per normal
surveillance protocol, and
send
specimens
to CDC
according to
current guidance
Repeat results from the
extraction step in house, report
results
to CDC per normal
surveillance protocol, and
send
specimens
to CDC
according to
current guidance
Inf A (-)U. SW InfA (+)N. SW H1 (+)
Or Inf A (-)
U. SW InfA (-)N. SW H1 (+)
OrInf A (-)
U. SW InfA (+)N. SW H1 (-)
Report results
to CDC per normal
surveillance protocol
2009 Swine Influenza Testing: Testing Algorithm
Other Results
Repeat results from the
extraction step in house, report
results
to CDC per normal
surveillance protocol
* This algorithm assumes a positive RP result
Reassortment (in Animals and Humans)
Migratory birds
Reassortment in Swine
Human virus
Avian Virus
Avian Virus
Reassortment in humans
Human Pandemic Strain
Communicable Disease Surveillance, Forecasting and Response, CSR/EMRO)
Communicable Disease Surveillance, Forecasting and Response, CSR/EMRO)
The new virus must be efficiently transmitted from one human to another
The new virus must be efficiently transmitted from one human to another
Prerequisites for pandemic influenzaPrerequisites for pandemic influenza
A new influenza virus emerges to which the general population has little/no immunity
The new virus must be able to replicate in humans and cause disease
Phases of pandemic influenzaPhases of pandemic influenzaInter-pandemic period
Phase 1 No new influenza virus detected in humans. If a new influenza virus presents in animals, the risk of human infection is considered to be low
Phase 2 No human infections, but a circulating animal influenza virus poses a risk to humans
Pandemic alert period Phase 3
Human infection(s) with a new virus, but no (or very infrequent) human-to-human spread
Phase 4 Small cluster(s) with limited human-to-human transmission but spread is highly localized
Phase 5 Larger cluster(s) but human-to-human spread still localized
Pandemic period
Phase 6 Increased and sustained transmission in general population
Communicable Disease Surveillance, Forecasting and Response, CSR/EMRO)
Interpandemic phase"Animal influenza outbreaks"
Low risk for humans 1High risk for humans 2
Pandemic Alert
"New influenza subtype in humans"
No or only inefficient h2h transmission
3
Evidence for increased h2h transmission
4
Significant increase in h2h transmission
5
Pandemic 6
c
WHO Pandemic PhasesWHO Pandemic Phases
c
Way Forwards:Transparency
• The media are not your enemies– Need for a positive relationship
– Give early, regular, accurate and consistent information
– Get messages to the public (avoid confusion and panic)
– Let the world know what you are doingEarlyAccurateRegularConsistent
Media
Health Workers
The PublicGovernment
What is Swine Flu
• Swine influenza virus (referred to as SIV) refers to influenza cases that are caused by Orthomyxovirus endemic to pig populations. SIV strains isolated to date have been classified either as Influenza(virus C or one of the various subtypes of the genus Influenza virus A)
Different Strains circulate Periodically
• In the United States the H1N1 subtype was exclusively prevalent among swine populations before 1998; however, since late August 1998, H3N2 subtypes have been isolated from pigs. As of 2004, H3N2 virus isolates in US swine and turkey stocks were triple reassortants, containing genes from human (HA, NA, and PB1), swine (NS, NP, and M), and avian (PB2 and PA) lineages.
Swine Influenza (Flu)
• 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-to-human spread of swine flu viruses has been documented.
Swine Flu-Present Status
• From December 2005 through February 2009, a total of 12 human infections with swine influenza were reported from 10 states in the United States. Since March 2009, a number of confirmed human cases of a new strain of swine influenza A (H1N1) virus infection in the U.S. and internationally have been identified. An investigation into these cases is ongoing.
Swine Flu 2009
• In late March and early April 2009, cases of human infection with swine influenza A (H1N1) viruses were first reported in Southern California and near San Antonio, Texas. Other U.S. states have reported cases of swine flu infection in humans and cases have been reported internationally as well.
Update - Status Swine Flu
• The United States Government has reported seven confirmed human cases of Swine Influenza A/H1N1 in the USA (five in California and two in Texas) and nine suspect cases. All seven confirmed cases had mild Influenza-Like Illness (ILI), with only one requiring brief hospitalization. No deaths have been reported.
Swine Flu in Mexico
• In the Federal District of Mexico, surveillance began picking up cases of ILI starting 18 March. The number of cases has risen steadily through April and as of 23 April there are now more than 854 cases of pneumonia from the capital. Of those, 59 have died. In San Luis Potosi, in central Mexico, 24 cases of ILI, with three deaths, have been reported.
Swine Flu and Virus
• Swine Influenza (swine flu) is a respiratory disease of pigs caused by type A influenza virus that regularly causes outbreaks of influenza in pigs. Swine flu viruses cause high levels of illness and low death rates in pigs. Swine influenza viruses may circulate among swine throughout the year, but most outbreaks occur during the late fall and winter months similar to outbreaks in humans. The classical swine flu virus (an influenza type A H1N1 virus) was first isolated from a pig in 1930.
Cause by Reassortment of different strains
• Like all influenza viruses, swine flu viruses change constantly. Pigs can be infected by avian influenza and human influenza viruses as well as swine influenza viruses. When influenza viruses from different species infect pigs, the viruses can reassort (i.e. swap genes) and new viruses that are a mix of swine, human and/or avian influenza viruses can emerge
Swine Flu differs from Human Flu
• The H1N1 swine flu viruses are antigenically very different from human H1N1 viruses and, therefore, vaccines for human seasonal flu would not provide protection from H1N1 swine flu viruses
Out breaks among Pigs• Outbreaks among pigs
normally occur in colder weather months (late fall and winter) and sometimes with the introduction of new pigs into susceptible herds. Studies have shown that the swine flu H1N1 is common throughout pig populations worldwide, with 25 percent of animals showing antibody evidence of infection.
Present Swine Flu strains
• At this time, there are four main influenza type A virus subtypes that have been isolated in pigs: H1N1, H1N2, H3N2, and H3N1. However, most of the recently isolated influenza viruses from pigs have been H1N1 viruses.
How man is exposed
• Most commonly, these cases occur in persons with direct exposure to pigs (e.g. children near pigs at a fair or workers in the swine industry). In addition, there have been documented cases of one person spreading swine flu to others.
How Swine Flu presents in Humans
• The symptoms of swine flu in people are expected to be similar to the symptoms of regular human seasonal influenza and include fever, lethargy, lack of appetite and coughing. Some people with swine flu also have reported runny nose, sore throat, nausea, vomiting and diarrhea
Is the eating Pork infects ?• No. Swine influenza viruses
are not transmitted by food. You can not get swine influenza from eating pork or pork products. Eating properly handled and cooked pork and pork products is safe. Cooking pork to an internal temperature of 160°F kills the swine flu virus as it does other bacteria and viruses
Close proximity with PIGS spread the Infections
• Influenza viruses can be directly transmitted from pigs to people and from people to pigs. Human infection with flu viruses from pigs are most likely to occur when people are in close proximity to infected pigs, such as in pig barns and livestock exhibits housing pigs at fairs. Human-to-human transmission of swine flu can also occur.
How Swine flu spread among Pigs
• Swine flu viruses are thought to be spread mostly through close contact among pigs and possibly from contaminated objects moving between infected and uninfected pigs. Herds with continuous swine flu infections and herds that are vaccinated against swine flu may have sporadic disease, or may show only mild or no symptoms of infection.
Seek emergency medical care.IF - in Children
• In children emergency warning signs that need urgent medical attention include:
• Fast breathing or trouble breathing Bluish skin color.Not drinking enough fluids
• Not waking up or not interacting • Being so irritable that the child does not want to be
held • Flu-like symptoms improve but then return with
fever and worse cough • Fever with a rash
Adults Need attention if Present with
• Difficulty breathing or shortness of breath • Pain or pressure in the chest or abdomen • Sudden dizziness • Confusion • Severe or persistent vomiting
Diagnosis• To diagnose swine influenza
A infection, a respiratory specimen would generally need to be collected within the first 4 to 5 days of illness (when an infected person is most likely to be shedding virus). However, some persons, especially children, may shed virus for 10 days or longer. Identification as a swine flu influenza A virus
CDC helps in Diagnosis
• Requires sending the specimen to CDC for laboratory testing as many laboratories in Developing world do not have facilities
Drugs which are effective in Swine Flu
• There are four different antiviral drugs that are licensed for use in the US for the treatment of influenza: Amantidine, rimantadine, oseltamivir and zanamivir. While most swine influenza viruses have been susceptible to all four drugs
Drugs proved resistant at Present
• Most recent swine influenza viruses isolated from humans are resistant to Amantidine and Rimantadine
CDC recommends at Present
• CDC recommends the use of oseltamivir or zanamivir for the treatment and/or prevention of infection with swine influenza viruses
Treatment of serious cases
OseltamivirReduce significantly the risk of
pneumonia( leading case of death for pandemic & seasonal influenza ,
Reduce the need for hospitalization
Cont,,,
If Oseltamivir is unavailable or can’t be used , zanamavir may be given.
This recommendation applies to all patient groups( pregnant women, young children, and infants).
Pregnant women & patients with underlying medical conditions recommended to receive AVT as soon as possible after symptom onset.
Worldwide, around 40% of severe cases are occurring in previously health children & adults, ( < 50 yrs.)
Some of these patients experience a sudden & very rapid deterioration in their clinical condition, usually day 5 or 6 following the onset of symptoms.
Clinical deterioration
• Primary viral pneumoniaWhich destroys the lung tissue & does not
respond to antibiotics• Failure of multiple organs ( heart , kidney &
liver)
Clinicians, patients, and those providing home based care need to:
• Be alert to warning signals that indicate to more severe illness.
• To take urgent action which should include treatment with oseltamivir
• In case of sever illness, clinicians may consider using higher doses of oseltamivir for longer duration.
AVT for children
WHO recommends prompt AVT to children o With severe or deteriorating illness o Those at risk of more severe or complicated
illness. o These recommendation includes all children
under the age of 5 yrs. o Children older than 5yrs need NOT be given
AVT unless their persist or worsense
Danger signs in children :• Fast or difficult breathing• Lack of alertness• Difficulty in waking up • Little or no desire to play.
How long can an infected person spread swine flu to others?
• People with swine influenza virus infection should be considered potentially contagious as long as they are symptomatic and possible for up to 7 days following illness onset. Children, especially younger children, might potentially be contagious for longer periods.
How long can viruses live outside the body?
• We know that some viruses and bacteria can live 2 hours or longer on surfaces like cafeteria tables, doorknobs, and desks. Frequent hand washing will help you reduce the chance of getting contamination from these common surfaces.
No Vaccines to HumansBut available to PIGS
• Vaccines are available to be given to pigs to prevent swine influenza. There is no vaccine to protect humans from swine flu. The seasonal influenza vaccine will likely help provide partial protection against swine H3N2, but not swine H1N1 viruses.
Avoid close contact
• Avoid close contact with people who are sick. When you are sick, keep your distance from others to protect them from getting sick too.
• Aerosols spread the virus in any environment
Stay home when you are sick.
• If possible, stay home from work, school, and errands when you are sick. You will help prevent others from catching your illness.
Cover your mouth and nose.
• Cover your mouth and nose with a tissue when coughing or sneezing. It may prevent those around you from getting sick
Clean your hands.
• Washing your hands often will help protect you from germs.
• Hand washing proved to be best procedure in prevention of Majority of Communicable diseases.
Avoid touching your eyes, nose or mouth.
• Germs are often spread when a person touches something that is contaminated with germs and then touches his or her eyes, nose, or mouth.
Practice other good health habits.
• Get plenty of sleep, be physically active, manage your stress, drink plenty of fluids, and eat nutritious.
• Unnecessary Migration of people from epidemic and endemic areas to be reduced.
Is eating Pork meat safe during Epidemics
• Swine influenza viruses are not spread by food. You cannot get swine influenza from eating pork or pork products. Eating properly handled and cooked pork products is safe.
Simple measures carry get good Benefits
• Cover your mouth and nose. Use a tissue when you cough or sneeze and drop it in the trash. If you don’t have a tissue, cover your mouth and nose as best you can.
Clean Hands saves you
• Clean your hands often. Clean your hands every time you cough or sneeze. Hand washing stops germs. Alcohol-based gels and wipes also work well.
Distribution of Pandemic H1N1/09 cases by Age group
from first case 10/6 to 26/8 of onset of outbreak
Age group ( year) No. of cases %
< 1 1 0.8 %
1-4 12 9.8 %
5-9 17 13.8 %
10-19 32 26 %
20-29 25 20.3 %
30-39 15 12.2 %
40-49 16 13 %
> 50 5 4.1 %
Total 123 100%
Distribution of cases by District
District No. of cases %
Hebron 1 1 %
Jenin 1 1 %
Al-Quds 12 10 %
Bethlehem 14 11 %
Ramallah 75 61 %
Nablus 17 14 %
Tulkarm 3 2 %
Total 123 100%
Distribution of cases by Nationality
Nationality No. of cases %
Palestinian 101 82 %
Germany 1 0.8 %
USA 20 10.3 %
Italy 1 0.8 %
Total 123 100%
Distribution of Pandemic H1N1/09 Cases by Source of Infection
Source No. of cases %
Imported 48 39 %
Local 71 58 %
Unknown 4 3 %
Total 123 100%