34. Emergence of Antigenic Subtypes of Influenza A Virus Associated with Pandemic or Epidemic Disease Mild pandemic H1N1 1977–78 c Moderate pandemic H3N2 1968–69 Severe pandemic H2N2 1957–58 Mild epidemic H1N1 1946–47 Mild epidemic H1N1 b (formerly H0N1) 1933–35 Severe pandemic H1N1 b (formerly HswN1) 1918–19 ?Moderate epidemic H3N8 a 1900–03 Severe pandemic H2N8 a 1889–90 Extent of Outbreak Subtype Years
35.
36.
37.
38. 1579 105,882 WHO Regional Office for the Americas (AMRO) 1,746 182,166 Total 3 1469 WHO Regional Office for Africa (AFRO) 8 2532 WHO Regional Office for the Eastern Mediterranean (EMRO) 106 13,172 WHO Regional Office for South-East Asia (SEARO) 50 27,111 WHO Regional Office for the Western Pacific (WPRO) Deaths Cases* Cumulative total as of 13 Aug 2009
56. Antiviral Treatment and Prophylaxis of Influenza Age 1–9, 5 mg/kg in 2 divided doses, up to 150 mg/d Prophylaxis, influenza A Not approved Treatment, influenza A Rimantadine c Age 1–9, 5 mg/kg in 2 divided doses, up to 150 mg/d Prophylaxis, influenza A Age 1–9, 5 mg/kg in 2 divided doses, up to 150 mg/d Treatment, influenza A Amantadinec Age 5–12, 10 mg qd by inhalation Prophylaxis, influenza A and B Age 7–12, 10 mg bid by inhalation Treatment, influenza A and B Zanamivir Age 1–12, dose varies by weight b Prophylaxis, influenza A and B Age 1–12, dose varies by weight a Treatment, influenza A and B Oseltamivir Children ( 12) Antiviral Drug Age Group (years)
Family Orthomyxoviridae Genera: Influenza A, B, and C viruses based on antigenic characteristics of the nucleoprotein (NP) and matrix (M) protein antigens. Subtypes: surface hemagglutinin (H) & neuraminidase (N) antigens 16 distinct H subtypes & 9 distinct N subtypes . Influenza outbreaks are recorded virtually every year, although their extent and severity vary widely. Localized outbreaks take place at variable intervals, usually every 1–3 years. Influenza A epidemics begin abruptly, peak over a 2- to 3-week period, generally last for 2–3 months, and often subside almost as rapidly as they began.
majority of the genes similar to swine influenza viruses 2 genes were similar genes of swine influenza viruses of the Eurasian lineage
The most extensive and severe outbreaks are caused by influenza A viruses, in part because of the remarkable propensity of the H and N antigens of these viruses to undergo periodic antigenic variation Antigenic Drift - minor antigenic changes & occur frequently. antigenic drifts result from point mutations involving the RNA segment that codes for the hemagglutinin , (The hemagglutinin is the site by which the virus binds to sialic acid cell receptors, ) - accumulation of point mutations in the HA is linear, with each strain replacing the previously circulating one These types of antigenic variation may involve the hemagglutinin alone or both the hemagglutinin and the neuraminidase. whereas the neuraminidase degrades the receptor and plays a role in the release of the virus from infected cells after replication has taken place.)
Antigenic Shift Major antigenic variations may be associated with pandemics and are restricted to influenza A viruses “ new” viruses to which the population has no immunity.
Hemagglutinin (HA) Antigenic sites and binds to sialic acid receptor cells. Neuraminidase (NA) enzyme that catalyzes the removal of terminal sialic acids ( N -acetyl neuraminic acid) or degrades the receptors to release of the virus from infected cells after replication has taken place.
a As determined by retrospective serologic survey of individuals alive during those years ("seroarcheology"). b Hemagglutinins formerly designated as Hsw and H0 are now classified as variants of H1. c From this time until the present (2006–2007), viruses of the H1N1 and H3N2 subtypes have circulated either in alternating years or concurrently. H1N1 viruses circulated from 1918 to 1956; thus, individuals born prior to 1957 would be expected to have some degree of immunity to H1N1 viruses. During most outbreaks of influenza A, a single subtype has circulated at a time. However, since 1977, H1N1 and H3N2 viruses have circulated simultaneously, resulting in outbreaks of varying severity only H1, H2, H3, N1, and N2 have been associated with epidemics of disease in humans. Influenza B and C viruses are similarly designated. Influenza A and B viruses most extensively studied morphologically similar major human pathogens 16 different HA antigens (H1 to H16) 9 different NA antigens (N1 to N9) three subtypes of HA (H1, H2, and H3) and two subtypes of NA (N1 and N2) – caused human disease. found in birds & pigs
17 May 2009, 39 countries have officially reported 8480 cases of influenza A(H1N1) infection. Mexico has reported 2895 laboratory confirmed human cases of infection, including 66 deaths. The United States has reported 4714 laboratory confirmed human cases, including four deaths. Canada has reported 496 laboratory confirmed human cases, including one death. Costa Rica has reported nine laboratory confirmed human cases, including one death. Current epidemiological models project that a pandemic could result in two to 7.4 million deaths globally.
On April 29, 2009, the World Health Organization raised its pandemic alert level to phase 5, indicating that there is sustained person-to-person spread in at least two countries [ 8 ]. This designation implies that a pandemic is imminent and that the time to finalize the organization, communication, and implementation of the planned mitigation measures is short.
Pigs may play an important role in interspecies transmission of influenza virus. Susceptible pig cells possess receptors for both avian and human influenza strains, which allow for the reassortment of influenza virus genes from different species if a pig cell is infected with more than one strain
Manifestations of H1N1 influenza (swine flu) are similar to those of seasonal influenza. Patients present with symptoms of acute respiratory illness, including at least 2 of the following: Fever Cough Sore throat Body aches Headache Chills and fatigue Diarrhea and vomiting (possible) Persons with these symptoms should call their health care provider promptly. If an antiviral agent is warranted, it should ideally be initiated with 48 hours from the onset of symptoms (see Medications ). The duration of illness is typically 4-6 days. The infectious period for a confirmed case is defined as 1 day prior to the onset of symptoms to 7 days after onset. In children, signs of severe disease include apnea, tachypnea, dyspnea, cyanosis, dehydration, altered mental status, and extreme irritability. 13
Clinicians, patients, and those providing home-based care need to be alert to danger signs that can signal progression to more severe disease. As progression can be very rapid, medical attention should be sought when any of the following danger signs appear in a person with confirmed or suspected H1N1 infection: In children , danger signs include fast or difficult breathing, lack of alertness, difficulty in waking up, and little or no desire to play.
Immunocompromised Adults & children- cancer patients, HIV/ AIDS pt Adults and children who have required regular medical follow-up or hospitalization during the preceding year because of chronic metabolic diseases (including diabetes mellitus), renal dysfunction, hemoglobinopathies, or immunodeficiency (including immunodeficiency caused by medications or by HIV) Persons who live with or care for persons at high risk for influenza-related complications, including healthy household contacts of and caregivers for children from birth through 59 months of age Health care workers
a <15 kg: 30 mg bid; >15–23 kg: 45 mg bid; >23–40 kg: 60 mg bid; >40 kg: 75 mg bid. b <15 kg: 30 mg qd; >15–23 kg: 45 mg qd; >23–40 kg: 60 mg qd; >40 kg: 75 mg qd. c Amantadine and rimantadine are not currently recommended (2006–2007) because of widespread resistance in influenza A/H3N2 viruses. Oseltamivir (administered orally at a dose of 75 mg twice a day for 5 days) or zanamivir (which must be given by an oral inhalation device; 10 mg twice a day for 5 days) reduces the duration of signs and symptoms of influenza by 1–1.5 days if treatment is started within 2 days of the onset of illness.
WHO recommends prompt antiviral treatment for children with severe or deteriorating illness, and those at risk of more severe or complicated illness. This recommendation includes all children under the age of five years, as this age group is at increased risk of more severe illness.
oseltamivir has been associated with nausea and vomiting, whose frequency can be reduced by administration of the drug with food. Oseltamivir has also been associated with neuropsychiatric side effects in children.
Zanamivir may exacerbate bronchospasm in asthmatic patients
WHO recommends that pregnant women receive antiviral treatment as soon as possible after symptom onset.
The viruses in the vaccine change each year based on international surveillance and scientists' estimations about which types and strains of viruses will circulate in a given year.
Vaccines to prevent the 2009 H1N1 virus have not yet been licensed; however, initial doses of licensed vaccine are expected to be available by mid-October 2009
Activities at WHO Collaborating Centers Identification of a new virus: network surveillance-, laboratories around the world routinely collect samples of circulating influenza viruses and submit these to WHO Collaborating Centres for Reference and Research on Influenza for analysis. The first step towards the production of a pandemic vaccine starts when a Centre detects a novel influenza virus that differs significantly from circulating strains and reports this finding to WHO. Vaccine virus is grown in eggs because the flu virus grows well in them, and eggs are readily available. 2. Preparation of the vaccine strain (called vaccine virus): To make the vaccine virus less dangerous and better able to grow in hen’s eggs (the production method used by most manufacturers), the virus is mixed with a standard laboratory virus strain and the two are allowed to grow together. After a while, a hybrid is formed which contains the inner components of the laboratory strain, and the outer components of the pandemic strain. It takes roughly three weeks to prepare the hybrid virus. 3. Verification of the vaccine strain: the hybrid virus needs to be tested to make sure that it truly produces the outer proteins of the pandemic strain, is safe and grows in eggs. Upon completion of this process, which takes roughly another three weeks , the vaccine strain is distributed to vaccine manufacturers. 4. Preparation of reagents to test the vaccine (with reference reagents): In parallel, WHO Collaborating Centres produce standardized substances (called reagents) that are given to all vaccine manufacturers to enable them to measure how much virus they are producing, and to ensure they are all packaging the correct dose of vaccine. This requires at least three months and often represents a bottleneck for manufacturers. Activities at vaccine manufacturers 1. Optimization of virus growth conditions: The vaccine manufacturer takes the hybrid vaccine virus that it has received from the WHO laboratories, and tests different growth conditions in eggs to find the best conditions. This process requires roughly three weeks . 2. Vaccine bulk manufacture: For most influenza vaccine production, this is performed in nine to twelve-days old fertilized hen's eggs . The vaccine virus is injected into thousands of eggs, and the eggs are then incubated for two to three days during which time the virus multiplies. The egg white, which now contains many millions of vaccine viruses, is then harvested, and the virus is separated from the egg white. The partially pure virus is killed with chemicals. The outer proteins of the virus are then purified and the result is several hundred or thousand liters of purified virus protein that is referred to as antigen, the active ingredient in the vaccine. Producing each batch, or lot, of antigen takes approximately two weeks, and a new batch can be started every few days. The size of the batch depends on how many eggs a manufacturer can obtain, inoculate and incubate. Another factor is the yield per egg. When one batch has been produced, the process is repeated as often as needed to generate the required amount of vaccine. 3. Quality control: This can only begin once the reagents for testing the vaccine are supplied by WHO laboratories, as described above. Each batch is tested and the sterility of bulk antigen is verified. This process takes two weeks . 4. Vaccine filling and release: The batch of vaccine is diluted to give the desired concentration of antigen, and put into vials or syringes, and labeled. A number of these are then tested: for sterility to confirm the protein concentration and for safety by testing in animals. This process takes two weeks . 5. Clinical studies: In certain countries, each new influenza vaccine has to be tested in a few people to show that it performs as expected . This requires at least four weeks . In some countries this may not be required as many clinical trials were done with similar annual vaccine preparation, and the assumption is that the new pandemic vaccine will behave similarly. Activities at regulatory agencies - regulatory approval Before the vaccine can be sold or administered to people, regulatory approval is required. Each country has its own regulatory agency and rules. If the vaccine is made with the same processes as the seasonal influenza vaccine, and in the same manufacturing plant, this can be very rapid (one to two days). Regulatory agencies in some countries may require clinical testing before approving the vaccine, which adds to the time before the vaccine is available. The full process, in a best case scenario, can be completed in five to six months. Then the first final pandemic vaccine lot would be available for distribution and use.
While influenza outbreaks can happen as early as October, most of the time influenza activity peaks in January or later.
Home isolation Patients who develop flulike illness (ie, fever with either cough or sore throat) should be strongly encouraged to self-isolate in their home for 7 days after the onset of illness or at least 24 hours after symptoms have resolved, whichever is longer. To seek medical care, patient should contact their health care providers to report illness (by telephone or other remote means) before seeking care at a clinic, physician's office, or hospital. Patients who have difficulty breathing or shortness of breath or who are believed to be severely ill should seek immediate medical attention. If the patient must go into the community (eg, to seek medical care), he or she should wear a face mask to reduce the risk of spreading the virus in the community when coughing, sneezing, talking, or breathing. If a face mask is unavailable, ill persons who need to go into the community should use tissues to cover their mouth and nose while coughing. While in home isolation, patients and other household members should be given infection control instructions, including frequent hand washing with soap and water. Use alcohol-based hand gels (containing at least 60% alcohol) when soap and water are not available and hands are not visibly dirty. Patients with H1N1 influenza should wear a face mask when within 6 feet of others at home. Household contacts who are not ill Remain home at the earliest sign of illness. Minimize contact in the community to the extent possible. Designate a single household family member as caregiver for the patient to minimize interactions with asymptomatic persons. School dismissal and childcare facility closure Strong consideration should be given to close schools upon a confirmed case of H1N1 flu or a suspected case epidemiologically linked to a confirmed case. Decisions regarding broader school dismissal within these communities should be left to local authorities, taking into account the extent of influenzalike illness within the community. Cancelation of all school or childcare related gatherings should also be announced. Encourage parents and students to avoid congregating outside of the school if school is canceled. Duration of schools and childcare facilities closings should be evaluated on an ongoing basis depending on epidemiological findings. Consultation with local or state health departments is essential for guidance concerning when to reopen schools. If no additional confirmed or suspected cases are identified among students (or school-based personnel) for a period of 7 days, schools may consider reopening. Schools and childcare facilities in unaffected areas should begin preparation for possible school closure. Social distancing Large gatherings linked to settings or institutions with laboratory-confirmed cases should be canceled (eg, sporting events or concerts linked to a school with cases); other large gatherings in the community may not need to be canceled at this time. Additional social distancing measures are currently not recommended. Persons with underlying medical conditions who are at high risk for complications of influenza should consider avoiding large gatherings.
Increase body resistance: -have at least 8 hrs of sleep. -be physically active -drink plenty of fluids. -eat nutritious foods.
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