H1N1 Influenza booklet

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H1N1 Influenza booklet

  1. 1. H1N1 INFLUENZA
  2. 2. Venkata Mattegunta Colin R Young Texas A&M University College Station TX USA
  3. 3. A. INFLUENZA VIRUS – STRUCTURE & PROPERTIES INTRODUCTION The H1N1 flu or Swine Flu as commonly referred to is a global pandemic caused by a novel strain of influenza virus A (H1N1). The virus was first identified in the Mexico in April 2009 and has thus far spread to almost all parts of the world with high infection rates. Though it was initially called Swine Flu, because the virus possessed genes from influenza viruses commonly affecting pigs in Europe and Asia, it has now been confirmed that the virus actually consists of a mixture of genes from different species. The virus is called a ‗quadruple reassortant‘ to indicate the fact that it is made up of genes found in influenza viruses infecting pigs, birds and humans. The letters H and N in H1N1 designate specific chemical structures expressed on the surface of the virus. STRUCTURE OF VIRUS The novel influenza A (H1N1) virus is similar in structure to the seasonal influenza virus that affects hundreds of thousands of people every year worldwide. In biological terms, organisms that share common features structurally and functionally are grouped together into classes known as Family, genera and species in decreasing hierarchical order. Influenza viruses are called RNA viruses since their genetic material is made up of Ribonucleic Acid. These viruses belong to the family Orthomyxoviridae. The family has five genera out of which three are most prominent - A, B and C. Influenza A virus is the most prominent genera among the three and has caused several epidemic outbreaks in the past. INFLUENZA A VIRUS This genus includes only one species: Influenza A virus. This virus causes influenza mostly in birds and occasionally in humans. The virus is a single stranded RNA virus. Several variations of the virus have been observed in nature based on two surface proteins hemagglutinin (H) and neuraminidase (N). These variations are called subtypes. Some of the prominent subtypes of Influenza A Virus are listed below. Fig 1. Influenza virus Fig 2. Microscopic structure
  4. 4.  H5N1 Subtype - Bird flu virus  H3N2 Subtype - Hong Kong flu pandemic of 1968  H5N2 Subtype - Highly pathogenic in chickens  H3N8 Subtype - Frequently found in horses  H2N2 Subtype - Asian flu pandemic of 1957  H7N7 Subtype - 2003 poultry epidemic  H1N1 Subtype - Spanish flu pandemic of 1918 and swine flu Subtypes There are 16 different subtypes of the virus based on the surface protein Hemagglutinin and 9 different subtypes based on Neuraminidase. The designation of the virus as H1N1 refers to the combination of these two surface proteins that make up the virus. The novel influenza A (H1N1) is an Influenza A virus made up of two different subtypes H1 and N1 of the proteins. The Novel influenza A (H1N1) Virus has mutated into various strains such as the Spanish Flu strain, mild human flu strains, endemic pig strains, and various strains found in birds. HA subtype designation NA subtype designation Avian influenza A viruses H1 N1 A/duck/Alberta/35/76(H1N1) H1 N8 A/duck/Alberta/97/77(H1N8) H2 N9 A/duck/Germany/1/72(H2N9) H3 N8 A/duck/Ukraine/63(H3N8) H3 N8 A/duck/England/62(H3N8) H3 N2 A/turkey/England/69(H3N2) H4 N6 A/duck/Czechoslovakia/56(H4N6) H4 N3 A/duck/Alberta/300/77(H4N3) H5 N3 A/tern/South Africa/300/77(H4N3) H5 N4 A/jyotichinara/Ethiopia/300/77(H6N6) H5 N9 A/turkey/Ontario/7732/66(H5N9) H5 N1 A/chick/Scotland/59(H5N1) H6 N2 A/turkey/Massachusetts/3740/65(H6N 2) H6 N8 A/turkey/Canada/63(H6N8) H6 N5 A/shearwater/Australia/72(H6N5) H6 N1 A/duck/Germany/1868/68(H6N1) H7 N7 A/fowl plague virus/Dutch/27(H7N7) H7 N1 A/chick/Brescia/1902(H7N1) H7 N3 A/turkey/England/639H7N3)
  5. 5. H7 N1 A/fowl plague virus/Rostock/34(H7N1) H8 N4 A/turkey/Ontario/6118/68(H8N4) H9 N2 A/turkey/Wisconsin/1/66(H9N2) H9 N6 A/duck/Hong Kong/147/77(H9N6) H10 N7 A/chick/Germany/N/49(H10N7) H10 N8 A/quail/Italy/1117/65(H10N8) H11 N6 A/duck/England/56(H11N6) H11 N9 A/duck/Memphis/546/74(H11N9) H12 N5 A/duck/Alberta/60/76/(H12N5) H13 N6 A/gull/Maryland/704/77(H13N6) H14 N4 A/duck/Gurjev/263/83(H14N4) H15 N9 A/shearwater/Australia/2576/83(H15N 9) Table 1: Avian influenza A virus strains INFLUENZA B VIRUS The virus belongs to the family Orthomyxoviridae. It is the only species in the genus Influenzavirus B. It is an RNA virus similar to the Influenza A virus. These viruses are known to infect humans and seals causing influenza. Compared to Influenza A virus, these viruses are limited in their ability to attack a wide variety of hosts. Hence they are not often associated with causing pandemics. Also, the virus mutates slowly as compared to Influenza A viruses. Influenza B virus progresses by causing localized outbreaks, predominantly in school children but sporadic cases are also reported in adults. It is very difficult to discern the level of antigenic variation in type B influenza viruses. The viruses isolated during some of the larger outbreaks possessed variations within the haemagglutinin molecule. These variations were not comparable to any other previous forms of influenza B virus. This seems to suggest that once one form of B strain virus emerges, it is highly unlikely that another strain with similar serological qualities will return. The slow antigenic drift of the influenza B virus, unlike that of type A, allows time for human populations to acquire immunity, and eventually halt the spread of the virus. INFLUENZA C VIRUS Influenza C virus belongs to the family Orthomyxoviridae, which includes those viruses which cause influenza. The only species in this genus is called "Influenza C virus". Influenza C viruses are known to infect humans and pigs with influenza. Flu due to the type C species is rare compared to types A or B, but can be severe and can cause local epidemics. Influenza type C differs from types A and B in some important ways. Type C infection usually causes either a very mild respiratory illness or no symptoms at all and does not have the severe public-health impact of influenza types A and B.
  6. 6. A.2 GENETICS OF VIRUS VIRION STRUCTURE A single functional virus is known as a Virion. The Influenza A Virus is a globular particle about 100nm in diameter. Since the Influenza A virus is an RNA virus, it has RNA as the genetic material present along with proteins which make up the ribonucleoprotein core. This core is enveloped by a bi-layer of proteins. The virion is roughly spherical in shape. It is an enveloped virus – that is, the outer layer is a lipid membrane which is taken from the host cell in which the virus multiplies. Inserted into the lipid membrane are ‘spikes‘, which are glycoproteins that consist of protein linked to sugars – known as HA (hemagglutinin) and NA (neuraminidase). These are the proteins that determine the type of influenza virus (A, B, or C) and the subtype (A/H1N1, for example). Fig 3. Structure of a virion Beneath the lipid membrane is a viral protein called M1, or matrix protein. This protein, which forms a shell, gives strength and rigidity to the lipid envelope. Each RNA segment consists of RNA joined with several proteins: B1, PB2, PA, NP (Fig. 3). These RNA segments are the genes of influenza virus. The interior of the virion also contains another protein called NEP. A.3 INFLUENZA RECOMBINANTS Influenza viruses affect many different species in nature including humans, birds, pigs and other species (See Animal Reservoirs). These viruses are specific to the species in which
  7. 7. they cause infection. But on rare occasions, these viruses jump species and cause infection in a new host species. There are two possible mechanisms to explain such phenomena. They are Antigenic drift and antigenic shift which are explained in detail below. ANTIGENIC SHIFT The genetic change that enables a flu strain to jump from one animal species to another, including humans, is called ―antigenic shift‖. Antigenic shift is an abrupt, major change in the influenza A viruses, resulting in new hemagglutinin and/or new hemagglutinin and neuraminidase proteins in influenza viruses that infect humans. The shift results in a new influenza A subtype or a virus with a hemagglutinin or a hemagglutinin and neuraminidase combination. The new viral strain is so different from the same subtype in humans that most people do not have immunity to the new (e.g. novel) virus. Such a ―shift‖ occurred in the present case where a new H1N1 virus with a new combination of genes emerged to infect people and quickly spread, causing a pandemic. When this shift happens, most people have little or no protection against the new virus. While influenza viruses are changing by antigenic drift all the time, antigenic shift happens only happens occasionally. While Type A viruses undergo both kinds of changes, influenza type B viruses change only by the more gradual process of antigenic drift. Antigenic shift arises in three ways, and the following examples quoted for antigenic shift in avian influenza A viruses. Antigenic Shift 1  A duck or other aquatic bird passes a bird strain of influenza A to an intermediate host such as a chicken or pig.  A person passes a human strain of influenza A to the same chicken or pig.  When the viruses infect the same cell, the genes from the bird strain mix with genes from the human strain to yield a new strain.  The new strain can spread from the intermediate host to humans. Antigenic Shift 2  Without undergoing genetic change, a bird strain of influenza A can jump directly from a duck or other aquatic bird to humans. Antigenic Shift 3  Without undergoing genetic change, a bird strain of influenza A can jump directly from a duck or other aquatic bird to an intermediate animal host and then to humans. The new strain may further evolve to spread from person to person as in the case of H1N1 flu. If it happens, a flu pandemic may develop. ANTIGENIC DRIFT Small changes in the virus that happen continually over time lead to ―Antigenic drift‖. Antigenic drift produces new virus strains that may not be recognized by the body's immune system. The mechanism is as follows: a person infected with a particular flu virus strain develops antibody against that virus. As newer virus strains appear, the antibodies against the older strains no longer recognize the "newer" virus, and reinfection can occur. This is one of the main reasons
  8. 8. why people can contract flu on several different occasions. In most years, one or two of the three virus strains in the influenza vaccine are updated to keep abreast with the changes in the circulating flu viruses. Consequently, flu vaccines need to be given to individuals on a yearly basis. If two viruses infect the same cell simultaneously, during replication they may exchange genes. The new virus particles will then carry a combination of genetic material from both parental viral strains. Additionally, a cell is simultaneously invaded by strains of virus that normally originate from a different host species for example birds as well as humans. This can result in the exchange of genes between avian, human and pig viruses. This is thought to have occurred in 1957 and 1968, resulting in worldwide influenza pandemics. The influenza types responsible for those outbreaks arose through the exchange of genes between avian and human viruses. Flu viruses can transmit—albeit not easily—between different vertebrate hosts which gives theman opportunity to evolve further over time. A.4 ANTIGENIC STRUCTURE HEMAGGLUTTININ Hemagglutinin is a glycoprotein (a protein that has a carbohydrate chain) that helps in binding the virus to the cell being infected. As already mentioned earlier, there are 16 hemagglutinin antigenic subtypes which are numbered H1 through H16. The hemagglutinin molecule is actually a combination of three identical proteins that are bound together to form an elongated cylindrical shape. Fig 4. Hemagglutinin & Neuraminidase on the surface of a virus
  9. 9. NEURAMINIDASE Neuraminidase is an enzyme that helps the virus to breach the cell walls of infected cells. Neuraminidase is also known as sialidase because it breaks the linkages between sialic acid and cellular glycoproteins and glycolipids found in cell walls. There are 9 neuraminidase antigenic subtypes labeled N1 through N9. Neuraminidase can be easily recognized as it forms mushroom- like projections on the surface of the influenza virus. It is made up of four identical proteins with a roughly spherical shape. Fig 5. Virus attachment to a host cell A.5 VIRULENCE OF VIRUS Virulence is the ability of an infectious agent to produce disease. The virulence of a microorganism (such as a bacterium or virus) is a measure of the severity of the disease it is capable of causing. This current 2009 H1N1 virus spreads easily but it has a relatively low virulence. However it is possible that as waves of H1N1 Influenza spread globally, its virulence could change. Every year seasonal flu viruses cause more severe diseases and secondary complications, such as pneumonia than the H1N1 flu. Majority of people infected with H1N1 flu manifest only mild symptoms and recover fully within a few days. Only a very low percentage of the population (< 1%) develop severe symptoms which may need treatment by antiviral drugs or antibiotics. So although the H1N1 virus has high infection rates and spreads easily, the mortality rate is not as high indicating the low virulence of H1N1 flu virus.
  10. 10. A virus may have a very high virulence when it emerges with a completely new set of H antigens. There may be little or no pre- existing immunity or protection in the population when such an event occurs. Such events with ‗‗new‘‘ viruses have occurred 3 times in the last 100 years. Firstly with H1 in 1918/19, then H2 in 1950‘s (Asian flu) and then H3 in late 60‘s (Hong Kong flu). Two different types of Neuraminidases N1 and N2 have been found in animal viruses; 7 in other animals. The H1N1 flu strain is however not a ‗‗new‘‘ virus, it is just a repackaged H1 strain - variations of which have been circulating and re-infecting people yearly since 1918. Because this is not a new and completely different H strain of the influenza virus, some of the population has immunity to it. Older people are more likely to have been infected repeatedly with circulating influenza strains and consequently have more immunity. Even though young people are the most likely to have little or no immunity to H1 strains, infections with the H1N1 flu strain have been very mild. This again highlights the low virulence of this strain. NAME OF FLU / REGION OF ORIGIN YEAR VIRUS STRAIN Spanish Flu 1918 H1N1 Asian Flu 1957-58 H2N2 Hong Kong Flu 1968-69 H3N2 Russian Flu 1977 H1N1 Hong Kong 1997 H5N1 Hong Kong 1999 H9N2 Virginia 2002 H7N2 Worldwide 2003 to 2009 H5N1 Mexico 2009 H1N1 Table 2: Timeline of Human Influenza outbreaks
  11. 11. Pandemic Year Influenza virus type People infected (approximate) Estimated deaths worldwide Case fatality rate Spanish flu 1918–1919 A/H1N1 500 million 20–100 million >2.5% Asian flu 1956–1958 A/H2N2 Not Available 2 million <0.1% Hong Kong flu 1968–1969 A/H3N2 Not Available 1 million <0.1% Seasonal flu Every year A/H3N2, A/H1N1, and B 340 million – 1 billion 250,000–500,000 per year <0.1% Swine flu 2009 Pandemic H1N1/09 > 12,198 (lab- confirmed) 12,121 ( ECDC) ≥8,768 (WHO) 0.026% Table 3. Statistics of previous influenza pandemics In viral pandemics the viruses become less virulent with the passage of time. Roughly 50 million people died after the 1918 flu pandemic. However these deaths were not due to the direct effect of a flu virus that mutated and became more virulent with time. Secondary bacterial lung infections caused many of these deaths, especially pneumococcus, streptococcus and staphylococcus. Furthermore antibiotic resistance in bacteria is a continuing and rapidly growing global problem, especially in developing countries. Thus when 2009 swine flu strain spreads in the developing world there is also a possibility of a significant number of deaths arising from bacterial complications. While over 99% of the population will have mild symptoms similar to common cold, some will develop serious complications (e.g. pneumonia). However the incidence of serious complications is likely to be less than .01 percent of the infected population. Seasonal flu strains, circulating every year, cause proportionately more illness and deaths than the 2009 H1N1 flu strain.
  12. 12. B. REPICATION, PATHOGENESIS & TRANSMISSION Influenza is a contagious, acute respiratory disease caused by infection of the host respiratory tract mucosa by an influenza virus. The influenza A viruses infect host epithelial cells by attaching to a cellular receptor (sialic acid) by the viral surface protein hemagglutinin (HA). The virus is subsequently released because of the action of another surface glycoprotein, the enzyme neuraminidase (NA), several hours after infection. B.1 Risk factors for infection Although anyone can be infected by H1N1 flu, certain sections of the population are more susceptible to developing infections. Statistics in the United States indicates that 99% of circulating influenza viruses in the United States are 2009 H1N1 influenza. Among people who become infected with 2009 H1N1, certain groups appear to be at increased risk of complications and may benefit most from early treatment with antiviral medications. Based on currently available data, approximately 70% of persons hospitalized with 2009 H1N1 influenza have had a recognized high risk condition. These groups are similar to those who are at increased risk for seasonal influenza-related complications:  Children younger than 2 years old;  Adults 65 years of age or older  Pregnant women and women up to 2 weeks postpartum (including following pregnancy loss)  Morbidly obese people (body mass index equal to or greater than 40) and perhaps people who are obese (body mass index 30 to 39) may be at increased risk of hospitalization and death due to 2009 H1N1 influenza infection.  Persons with the following conditions: o Chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, hematological (including sickle cell disease), or metabolic disorders (including diabetes mellitus); o Disorders that that can compromise respiratory function, or the handling of respiratory secretions, or that can increase the risk for aspiration (e.g., cognitive dysfunction, spinal cord injuries, seizure disorders, or other neuromuscular disorders) o Immunosuppression, including that caused by medications or by HIV; B.2 Replication Viruses replicate quickly inside the host cells. The Influenza virus gains access to the host cells through any of the three mentioned modes of transmission: (1) by direct contact with infected individuals; (2) by contact with contaminated objects such as toys, doorknobs, etc; and (3) by inhalation of virus-laden aerosols. The virus attaches to the outside of the host cell and its RNA enters into the cell. The viral genes are transcribed and translated by the cell's enzymes and ribosomes. By this process the host cell machinery is directed towards producing more virus particles. Now, instead of producing only new host cellular material, the cell produces hundreds of new virus particles. The new virus particles are eventually released from the cell and drift off, and can now further infect additional
  13. 13. cells of the host body. Sometimes the human body is able to produce antibodies preventing replication of the virus and hence arresting infection. Fig 6. Aerosols released during a normal sneeze Steps in Viral Replication The following steps take place during viral replication 1. Adsorption 2. Penetration 3. Uncoating 4. Viral genome replication 5. Maturation 6. Release Adsorption The virus attaches itself to the cell surface to gain access to the interior of the cell that it will infect. Receptors present on the cell surface are used by the virus for attachment. Cells possess various types of receptors which can be made up of glycoproteins, phospholipids or glycolipids. Receptors for some viruses may not be present on the cell surface. Such cells are resistant to attack by these viruses. The viral attachment can be blocked by antibodies that
  14. 14. bind to these receptors. Influenza viruses attach through glycoprotein spikes that are distributed over their surface. The spikes can be seen in the figure above. Fig 7. Life cycle of a virus Penetration After the virus attaches to the cell surface, it quickly enters the interior of the host cell and can no longer be recovered from the cell surface. The common method used for penetration is receptor mediated endocytosis. This is the same process used by many hormones and toxins to enter a cell. A cytoplasmic bubble called vacuole is formed around the virion inside the cell. Uncoating A change in the internal environment of the host cell due to an increase in acidic levels causes rearrangement of coat components of the virus resulting in an extrusion of the viral core into the cytoplasm of the cell. In Influenza virus, the core HA2 unit of the haemagglutinin is the acid-sensitive component.
  15. 15. Viral Nucleic Acid Replication The virus takes control of the host cell by shutting down the host cell‘s protein synthesis and disintegrating other key synthesis machinery resulting in a shift towards viral synthesis. The mechanism of protein synthesis shut down varies among different viruses within the same family. B.4 Pathogenesis When influenza virus infects the respiratory passage by aerosols or by contact with saliva or other respiratory secretions from an infected individual, it attaches to and replicates in cells lining the surface of the air passage. The virus replicates in both the upper and lower respiratory tract. Viral replication together with the immune response to infection leads to destruction and loss of cells lining the respiratory tract. As infection subsides, the surface cells are regenerated in a process that can take up to a month. Cough and weakness may persist for up to 2 weeks after infection. The incubation period for swine influenza virus ranges from 1 to 3 days. Transmission The main pathway that influenza viruses are thought to transmit from person to person is via respiratory droplets from coughs and sneezes. This can happen when droplets from a cough or sneeze of an infected person are propelled through the air and deposited on the mouth or nose of people nearby. Influenza viruses may also be transmitted between humans when the person touches an infected surface and then touches their own mouth and nose. This form of transmission can be prevented by people either disinfecting surfaces or washing their hands following contact with the surface. C. INFLUENZA – SYMPTOMS & DETECTION Diagnosis of Disease Identifying a disease from its signs and symptoms, also known as Diagnosis is very important. As H1N1 flu spreads rapidly, an awareness of symptoms of the flu among the general public will go a long way in taking precautionary action and preventing further spread. So far, the symptoms of H1N1 fu have been mild and very similar to seasonal flu. Rarely, serious symptoms have been developed in a small percentage of infected persons. If you or a member of your family has a fever or high temperature (over 38°C/100.4°F) and two or more of the following symptoms, you may have swine flu:  cough  sore throat  runny or stuffy nose  body aches  headache  chills  fatigue  diarrhea and vomiting It‘s important to note that not everyone with flu will have a fever.
  16. 16. Fig 8. Figure showing systems that may show symptoms following infection by H1N1 flu Emergency warning signs that require urgent medical care are listed below. In children  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
  17. 17.  Fever with a rash In adults  Difficulty breathing or shortness of breath  Pain or pressure in the chest or abdomen  Sudden dizziness  Confusion  Severe or persistent vomiting Influenza Diagnostic Tests A diagnostic test is required to confirm the presence of influenza virus in respiratory specimens. Laboratory diagnostic tests that are presently used to detect the presence of influenza viruses in respiratory specimens fall under these categories:  Virus culture  Real-time reverse transcriptase-polymerase chain reaction (rRT-PCR)  Rapid Influenza diagnostic tests (RIDT‘s)  Direct Immunofluorescence essays (DFA‘s) These tests differ in their sensitivity and specificity in detecting influenza viruses as well as in their commercial availability, the amount of time needed from specimen collection until results are available, and the tests‘ ability to distinguish between different influenza virus types (A versus B) and influenza A subtypes (e.g. novel H1N1 versus seasonal H1N1 versus seasonal H3N2 viruses). At this time, there are only two FDA authorized assays for confirmation of novel influenza A(H1N1) virus infection, including the CDC rRT-PCR Swine Flu Panel assay; however, other rRT-PCR assays such as laboratory developed tests, not approved by FDA, may be able to detect novel influenza A (H1N1) viruses. Confirmation of novel influenza A(H1N1) infection may be necessary for surveillance purposes and for special situations, e.g. severely ill patients, patients with immune compromising conditions, and pregnant and breast feeding women. Rapid Influenza Diagnostic Tests Rapid influenza diagnostic tests (RIDTs) are used to detect the presence of viral antigens. The commercially available RIDTs can provide results within 30 minutes or less. Thus, results are available in a clinically relevant time period to make informed clinical decisions. Commercially available RIDTs can either:  detect and distinguish between influenza A and B viruses  detect both influenza A and B but not distinguish between influenza A and B viruses  detect only influenza A viruses None of the currently FDA approved RIDTs can distinguish between influenza A virus subtypes (e.g. seasonal influenza A (H3N2) versus seasonal influenza A (H1N1) viruses). Also, RIDTs cannot provide any information about antiviral drug susceptibility. Sensitivity For detection of seasonal influenza A virus infection in respiratory specimens, RIDTs have low to moderate sensitivity compared to viral culture or RT-PCR. The sensitivities of RIDTs to
  18. 18. detect influenza B viruses are lower than for detection of influenza A viruses. The sensitivities of RIDTs appear to be higher for specimens collected from children than specimens collected from adults. Although a positive RIDT result can be used in making treatment decisions, a negative result does not rule out infection with novel influenza A (H1N1) virus. Because of the limitations of RIDTs and until additional data are available, all results from RIDTs, both positive and negative, when used for clinical decision making in a patient with suspected novel influenza A (H1N1) virus infection, should be interpreted in the context of circulating influenza virus strains in the patient‘s community, level of clinical suspicion, severity of illness, and risk for complications. Influenza A H1N1 (2009) Real Time RT-PCR test The test uses reverse transcriptase polymerase chain reaction, or RT-PCR, to amplify viral RNA to make it detectable in a specimen. Most respiratory viruses are based on unstable RNA and are converted to complimentary DNA (cDNA) for testing due to DNA's better stability. It targets two separate regions of the hemagglutinin ("H1") gene of the 2009 H1N1 influenza virus to differentiate the presence of the pandemic virus from seasonal human influenza A virus. If RNA of Influenza A virus and the 2009 Influenza H1 gene are detected, the specimen is reported as positive for 2009 H1N1 influenza infection. Comparison between the tests Recent analytical studies indicate that commercially available RIDTs are reactive with the nucleoprotein of novel influenza A (H1N1) virus. Compared to RT-PCR, the sensitivity of RIDTs for detecting novel influenza A (H1N1) virus infections ranged from 10-70%. Therefore, a negative RIDT result does not rule out novel influenza A (H1N1) virus infection. Factors that might contribute to a lower sensitivity for influenza laboratory tests to detect novel influenza A (H1N1) virus infection include the type of respiratory specimen (i.e., nasal vs. nasopharyngeal swab), quality of the specimen, time from illness onset to specimen collection, the age of the patient, time from specimen collection to testing, and the storage and processing of the specimen prior to testing. TEST / PROCEDURE ACCEPTABLE SPECIMEN INFLUENZA TYPE DETECTED TIME FOR RESULTS RIDT Nasal swab A and B 15 minutes Virus culture NP* swab, throat swab, nasal wash, bronchial wash, nasal aspirate, sputum A and B 3-10 days
  19. 19. RT-PCR NP swab, throat swab, nasal wash, bronchial wash, nasal aspirate, sputum A and B 2-4 hours DFA NP swab, nasal wash, bronchial wash, nasal aspirate, sputum A and B 2-4 hours Table 5: Comparison between various diagnostic methods *NP – Nasopharyngeal COMMERCIAL AVAILABILITY Table: Comparison of various diagnostic tests available to detect influenza virus Fig 8. Nasopharyngeal swab
  20. 20. Fig 9. Nasal Wash Fig 10. Nasal aspirate D. IMMUNOLOGICAL RESPONSE TO VIRUS A viral infection is different from a bacterial infection with respect to the way our body reacts and responds to the infection. Normally, a virus infects the inner parts of a cell. After the virus gains entry into a host cell, it damages these infected cells from the inside. In order to eliminate the infection, the infected host cells should be destroyed. So the immune system should be able to differentiate between infected host cells and healthy cells. Viruses induce a strong immune response in humans. The immune response is of two types: 1. Antibody-mediated response 2. Cell-mediated response While immunity conferred by Antibodies is called Humoral immunity, a cell-mediated response results in Cellular immunity. Antibodies are proteins circulating in the blood that recognize and neutralize viruses and bacteria. They are produced by a special type of blood cells called B lymphocytes. The basis for these responses is two types of cells that form the basic units of immunity namely: B cells and T cells. The viral surface has distinct recognition particles called epitopes which are recognized by the B & T cells. Different people elicit different immune responses to the same virus depending on their genetic constitution. While humoral response is involved in blocking the infectivity of the virus using antibodies and thus neutralizes the virus, cellular response recognizes infected cells and destroys them. T lymphocytes play a major role in cell-mediated response. Humoral Response Our immune system produces proteins called antibodies or Immunoglobulins that help our bodies fight disease. They play an important role in body‘s natural defense system. They recognize any foreign entities within our body like viruses, bacteria, etc and bind to viruses or particular sites on cells and inhibit their ability to infect other cells. These antibodies bind to their
  21. 21. counterparts in a highly specific manner. Viral components present on both the surface and the interior of a virion are responsible for production of antibodies. Interaction of these antibodies with the viral surface components can occur in different ways producing a myriad of antibodies that differ from each other. There are five different types of antibodies, each performing a specific function. They are viz. Ig G, Ig A, Ig M, Ig D and Ig E. Functions of Antibodies These antibodies have specific functions within the human body. The most commonly found antibodies are IgG. They circulate in the body fluids like blood and give protection against invading bacteria and viruses. When IgG antibodies bind to bacterial or viral antigens, they activate other immune cells which engulf and destroy the pathogens. Saliva, mucus, tears, secretions of the respiratory, reproductive, digestive and urinary tracts contain IgA antibodies. These antibodies prevent the invading bacteria and viruses from entering the body and reaching internal organs. IgM is the largest antibody amongst all the 5 different classes of antibodies. It is Y-shaped with 5 units. Its function is similar to IgG. But unlike IgG which is produced in later stages of an infection, IgM is the first antibody to be produced following an infection by bacteria or viruses. IgD is found circulating in the blood in small quantities. It is found mostly o the surface of B cells. IgD helps B cells in recognizing specific antigens. IgE antibodies are found in small quantities in serum. They are responsible for allergic reactions. When an allergen (allergy causing substance) binds with IgE antibody, it triggers an allergic reaction by stimulating the release of vasoactive amines including Histamine. Histamine causes symptoms such as runny nose, sneezing and swollen tissues. Cell-mediated immunity As the name suggests, cell-mediated immunity is an immune response that does not involve antibodies. Rather, it uses specialized cells called macrophages, natural killer cells and cytotoxic T lymphocytes. These T lymphocytes seek infected cells and induce a process called Apoptosis (programmed cell death) in them and destroy the infected host cells. Macrophages and natural killer cells destroy pathogens present inside infected cells. Also, cytokines are released during cell-mediated immune response. These cytokines influence the function of other cells involved in an immune response.
  22. 22. E. ANIMAL RESERVOIRS E. Animal Reservoirs of Influenza Virus A reservoir is any person, animal, plant, soil or micro-organism that is used by the infectious agent (H1N1 virus in this case) for shelter and multiplication. Generally the infectious agent does not harm or cause infection to the reservoir. The reservoir serves as the source from which other individuals can be infected. Occasionally the infectious agent is transmitted to a human or other susceptible host from these reservoirs, which could result in devastating outbreaks in poultry or cause human influenza pandemics. Some of the common reservoirs in which the influenza virus resides are:  Aquatic birds (ducks, geese, swans, shorebirds, gulls, hawks, eagles, falcons, ravens, coots, pigeons, rails)  Pigs (Swine Influenza)  Sea mammals Animal Reservoirs Aquatic Birds Pigs Seals Chicken DogsHorses Civets Mink Wild Pikas
  23. 23.  Domestic poultry  Dogs (Canine Influenza)  Horses (Equine Influenza)  Civets  Mink  Wild Pikas (rabbit) Order Species Gaviiformes Arctic loon (Gavia arctica) Podicepediformes Pied-billed grebe (Podilymbus podiceps) Procellariiformes Wedge-tailed shearwater (Puffinus pacificus) Procellariiformes Short-tailed shearwater (P.tenuirostris) Ciconiiformes Gray heron (Ardea cinerea) Anseriformes Snow goose (Anser caerulescens) Anseriformes Canada goose (Branta canadensis) Anseriformes European wigeon (Anas penelope)
  24. 24. Anseriformes Common teal (A. crecca) Anseriformes Mallard (A. platyrhynchos) Anseriformes Northern Pintail (A. acuta) Anseriformes Greater scaup (Aythya marila) Anseriformes Black scoter (Melanitta nigra) Anseriformes Oldsquaw (Clangula hyemalis ) Anseriformes Red-breasted merganser (Mergus serrator) Gruiformes Eurasian coot (Fulica atra) Columbiformes Turtle dove (Streptopelia decaocto) Charadriiformes Common snipe (Gallinago gallinago) Charadriiformes Herring gull (Larus argentatus) Charadriiformes Lesser black-backed gull (L.fuscus) Charadriiformes Black-headed gull (L.ridibundus) Charadriiformes Black-tailed gull (L.crassirostris) Charadriiformes White-capped noddy tern (Anous minutus) Charadriiformes Black guillemot (Cepphus grylle) Charadriiformes Common murre (Uria aalge) Passeriformes Common crow (Corvus brachyrhynchos) Passeriformes Carrion crow (C. corone) Passeriformes House sparrow (Passer domesticus) Table 6: Free-living birds reported seropositive for Avian influenza virus Wild birds are the reservoirs of over 100 subtypes of Influenza A virus. These viruses replicate in the intestinal cells and are discharged in huge numbers in the feces. Avian influenza viruses spread easily among bird populations and although the infected birds don‘t show any symptoms
  25. 25. of the disease, it is invariably fatal. The virus prefers low temperatures and can survive for long periods in the tissues and feces of infected birds. The virus can survive indefinitely at freezing temperatures. As the temperature increases to 220 C, the survival time of the virus in water is reduced to 4 days. Many of the influenza A subtype viruses can be isolated from Southeast Asian bird populations. Close human contact with these infected birds poses a huge risk of transmission of these viruses to humans. The devastating avian flu that resulted in huge economic losses to the poultry industry was caused by influenza A virus belonging to the family Orthomyxoviridae. Canine flu, Swine flu and Horse flu have also been reported in dogs, pigs and horses respectively. Origin of H1N1 Influenza virus A reservoir may harbor viruses from more than one source at a time. Avian influenza virus cannot replicate well in humans. Hence the virus needs an intermediary host like pigs where it can reassemble itself and infect humans. Moreover pigs are a common reservoir for viruses from birds and humans. They serve as a mixing vessel where viruses from different species interact. Such an interaction creates the possibility of creation of a novel influenza virus having genes from birds, pigs and humans. The current H1N1 Influenza virus is thought to have been originated in pigs in this way resulting in a novel virus capable of causing human-human transmission through respiratory droplets. Influenza viruses from birds can infect humans when they attach to receptors on the cells lining the intestine. Receptors on cells are similar to locks. When a virus with a suitable key interacts with these receptors, it can unlock the cell and gain access to the cell and replicate. Although all viruses do not have the ability to attach to these receptors, those that succeed have a high chance of causing illness in humans. F. TREATMENT
  26. 26. A major concern with influenza virus is its rapid and unpredictable nature of evolution. This makes prevention using vaccines and treatment of the disease using medication extremely challenging. The vaccines used to prevent flu are produced from the viruses themselves. The vaccine components consists of either killed virus or components of live attenuated virus that are very similar the original disease causing virus. When injected into the body, these components illicit an immune response resulting in the production of antibodies against the virus. Thus the body is prepared in advance to fight against the virus in the event of an infection. These antibodies are extremely specific to the virus. . Immunological memory is a lifelong phenomenon. Thus vaccination provides long term immunity against infection The most common feature of Influenza viruses is their ability to mutate and modify themselves within short periods of time. This is a natural mechanism by which a virus escapes attack by the immune system of the host. Hence a prior vaccination against a specific subtype of virus does not protect the body from a mutated virus which is different from the earlier one. There are two kinds of H1N1 vaccines currently being produced. They are  Inactivated influenza vaccine  Live, attenuated vaccine Inactivated influenza vaccine The inactivated vaccine contains killed virus and is administered via an injection, usually in the arm. The flu vaccine (shot) is approved for use in humans aged 6 months or older, including healthy people, people with chronic medical conditions and pregnant women. Live, attenuated vaccine This vaccine is made with live, weakened viruses that do not cause the flu. It is sometimes called LAIV for "live attenuated influenza vaccine". It is intranasaly administered through the nasal passage. LAIV is approved for use in healthy people aged 2 years to 49 years of age and in women who are not pregnant. Both vaccines give protection against H1N1 influenza. Antibodies that provide protection against H1N1 influenza virus infection will develop 2 weeks post vaccination. The vaccines are manufactured in the same way as seasonal influenza vaccines. Hence they are not experimental and safe to use. Thimerosal, a mercury-containing preservative used in seasonal flu vaccine is also added in the 2009 H1N1 vaccine. People with severe allergies to chicken eggs or to any other substance in the vaccine should not be vaccinated. The H1N1 vaccine will not prevent seasonal flu and seasonal flu vaccine will not prevent H1N1 influenza. The table below provides information and relevant details about the current manufacturers of approved vaccines.
  27. 27. Supplier Vaccine Form Mercury µg/0.5 mL Age MedImmune (nasal spray) Live virus 0.2 mL (nasal spray sprayer) 0 2-49 yrs Sanofi (IM)a Inactivated 0.25 mL prefilled syringe 0.5 mL prefilled syringe 5 mL multidose vial 0 0 25 6-35 m > 36 m > 6 m Novartis (IM)a 5 mL multidose vial 0.5 mL prefilled syringe 25 < 1.0 ≥ 4 yrs > 4 yrs CSL Biotherapies, Inc (IM)a 0.5 mL prefilled syringe 5.0 mL multidose vial 0 24.5 > 18 yrs > 18 yrs Table 7: Approved Influenza A (H1N1) Vaccines Source: Department of Health and Environmental Control Younger children will require 2 doses separated by at least 21 days. Infants younger than 6 months are too young to be vaccinated against influenza. Guidelines for Inactivated influenza vaccine usage The inactivated H1N1 vaccine uses killed virus and is intended to prevent 2009 H1N1 (not seasonal flu) and is available in single dose or multidose vials. Children 6 months to 9 years of age should receive 2 doses separated by 3 weeks. Children 10 years and older and adults should receive 1 dose. The following groups should receive the vaccine as soon as it becomes available:  Pregnant women;  People who live with or care for infants younger than 6 months of age;  Healthcare workers and emergency medical personnel;  Persons aged 6 months to 24 years of age  Persons 25-64 years of age who have chronic diseases (including immunodeficiency states) that pose a risk for influenza. This includes persons who have chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, neurological/neuromuscular, hematological or metabolic distorders (including diabetes), immunosuppression (including immunosuppression caused by medications or by HIV) When more vaccine becomes available, the following persons should be vaccinated:  Healthy persons ages 25-64 years; and  Adults 65 years of age and older.
  28. 28. Individuals with the highest priority listed above should be vaccinated first. Patients on the high- priority list should be vaccinated as soon as the vaccine becomes available. Pregnancy and breastfeeding are not contraindications for the inactivated vaccine to be administered. Guidelines for Live, attenuated vaccine usage The second vaccine is a live attenuated influenza (LAIV), which is given intranasally. LAIV does not contain thimerosal. It is produced the same way as the LAIV that is used for seasonal flu. It is expected that the LAIV for H1N1 influenza will be as safe and effective as the LAIV for seasonal flu. This vaccine will not prevent seasonal flu, and the seasonal flu vaccine will not prevent 2009 H1N1 influenza. Adults and children aged 10 years or older should receive should receive one dose of the vaccine. The LAIV for H1N1 is administered intranasally in a single dose. It is approved for people 2-49 years of age who do not have contraindications. Groups who should receive the LAIV include:  Persons 2-24 years of age;  Persons 25-49 years of age who live with or care for infants younger than 6 months; and  Persons 25-40 years of age who are Health Care Workers or emergency medical personnel.  LAIV is approved for use in healthy people 2-49 years of age who are not pregnant. When more vaccine becomes available it should be offered to healthy persons aged 25-49 years who do not have contraindications for the vaccine. The following people should not receive LAIV:  Persons who have chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, neurological/neuromuscular, hematological or metabolic distorders (including diabetes), immunosuppression (including immunosuppression caused by medications or by HIV)  Children 2-4 years of age with wheezing in the past 12 months  Children or adolescents receiving aspirin or other salicylate therapy  Pregnant women  People who have a severe allergy to chicken eggs or who are allergic to any LAIV components  Persons < 2 years or those >50 years Source: Center for Disease Control Side Affects Potential side effects of the H1N1 vaccines are expected to be similar to those of seasonal flu vaccines. The most common side effect for the injected vaccine is soreness at the injection site. Other side effects may include mild fever, body aches, and fatigue for a few days. The most common side effects for LAIV vaccine are runny nose or nasal congestion for individuals of all ages. Sore throats may be observed in adults and fever in children 2 to 6 years old. As with any medical product, unexpected or rare serious adverse events may occur. According to currently available information, children 6 months to 9 years of age have little or no protective antibodies to the H1N1 virus. So children 9 years of age and younger should be
  29. 29. administered two doses of the vaccine. Children and adults aged 10 years or older will require only one dose. Safety of 2009 H1N1 Vaccine Clinical studies show that the H1N1 vaccine has been well tolerated. The manufacturers are producing the vaccine using the well-established and licensed manufacturing process that is used for seasonal influenza vaccine. The regulatory authorities expect that the safety profile of the H1N1 vaccine will be similar to the seasonal influenza vaccine. Antiviral drugs Drugs are a second line of defense against H1N1 influenza. Oseltamivir and Zanamivir are two drugs presently being used against H1N1 influenza virus. They are available under the brand names Tamiflu and Relenza respectively. Tamiflu is available as a pill or liquid and Relenza is used in powder form. For Tamiflu to be effective, it must be taken within 48 hours of the development of flu symptoms. Although the drug does not cure the flu itself, it reduces the recovery time by one day. More importantly, it prevents the development of flu related complications such as chest infections. The drug has been approved for use in adults and children aged 1 year and above. Relenza is an antiviral drug used to treat influenza and prevent the spread of virus within the body. It is in powder form and has to be inhaled. It has been approved for use in adults and children aged 5 years and above. Zanamivir, the active drug in Relenza has been shown to reduce the duration of flu symptoms by one to one and a half days. It also prevents the virus from further replication within the individual. For Relenza to be effective, it should be taken within 48 hours of developing flu symptoms. How Antiviral drugs work Although antiviral drugs do not cure influenza, they reduce the recovery time and prevent the development of later flu related complication such as Pneumonia. Both the drugs Oseltamivir and Zanamivir restrict the viruses‘ ability to infect other cells. Every influenza virus has both Hemaggluttinin and Neuraminidase on the virus surface that enables it to infect host cells. These drugs block these chemicals and thus make the virus incapable of infecting new cells. Side Effects Although these approved drugs are safe to use, occasionally they produce unwanted side effects. One in 10,000 persons who take the drug shows side effects. The effects listed below vary from individual to individual.  Narrowing of the airways (bronchospasm)  Difficulty in breathing (dyspnoea)  Throat tightness  Rash or hives  Allergic reaction with swelling of the face or throat. Just because a side effect is stated here doesn‘t mean that the affected individual will have all these symptoms.
  30. 30. G. GEOGRAPHICAL DISTRIBUTION Geographical boundaries fail to contain the spread of influenza. Presently, there is no clear agreement on how to analyze and group according to geographic region. Geographic Information Systems (GIS) help a great deal in providing valuable information about the disease spread patterns within a localized region or a broad area. Fig 11. Number of H1N1 cases based on region
  31. 31. Virological surveillance data indicates that H1N1 virus has been predominantly present in all countries across the world. As of 1 December 2009, more than 199 countries have reported laboratory confirmed cases of pandemic H1N1 influenza. The death toll is estimated at more than 10,000 deaths. The actual number of individuals infected is estimated to be much higher since countries have stopped counting the number of people infected. Influenza Indicators Influenza activity is measured using certain indicators. The levels of influenza activity are based on two assessments. They are described below. 1. An indicator of the overall intensity of influenza activity in the country; 2. An indicator of the geographical spread of influenza in the country. Overall Intensity Indicators Low: no influenza activity or influenza activity is at baseline level Medium: level of influenza activity usually seen when influenza virus is circulating in the country based on historical data High: higher than usual influenza activity compared to historical data Very high: influenza activity is particularly severe compared to historical data Unknown: influenza activity is not known Geographical Spread Indicators Every country specifies geographical spread of influenza in terms of definitions defined by its own government. The definitions described below are based on the WHO global surveillance system – FluNet. Some terms that need to be defined are given below: ILI: Influenza like illness ARI: Acute respiratory infection Country: Countries may be made up of one or more regions Region: The population under surveillance in a defined geographical sub-division of a country. A region should not (generally) have a population of less than 5 million unless the country is large with geographically distinct regions No report: no report received No activity: reports indicate no evidence of influenza virus activity. Cases of ILI/ARI may be reported in the country but the overall level of clinical activity remains at baseline levels and influenza virus infections are not being laboratory confirmed. Cases occurring in people recently returned from other countries are excluded Sporadic: isolated cases of laboratory confirmed influenza infection in a region, or an outbreak in a single institution (such as a school, nursing home or other institutional setting), with clinical activity remaining at or below baseline levels. Cases occurring in people recently returned from other countries are excluded
  32. 32. Local outbreak: increased ILI/ARI activity in local areas (such as a city, county or district) within a region, or outbreaks in two or more institutions within a region, with laboratory confirmed cases of influenza infection. Levels of activity in remainder of region, and other regions of the country, remain at or below baseline levels Regional activity*: ILI/ARI activity above baseline levels in one or more regions with a population comprising less than 50% of the country's total population, with laboratory confirmed influenza infections in the affected region(s). Levels of activity in other regions of the country remain at or below baseline levels. * This term is not (generally) to be used in countries with a population of less than 5 million unless the country is large with geographically distinct regions Widespread activity: ILI/ARI activity above baseline levels in one or more regions with a population comprising 50% or more of the country's population, with laboratory confirmed influenza infections. Unknown: influenza geographical spread is not known The figures below present the geographical spread of influenza in a visual format.
  33. 33. Epidemiology The total number of illnesses, hospitalizations and deaths due to H1N1 virus is difficult to assess accurately. The table below gives a situation update on reported and confirmed cases of H1N1 infection across different regions. REGION DEATHS* WHO Regional Office for Africa (AFRO) 109 WHO Regional Office for the Americas (AMRO) At least 6335 WHO Regional Office for the Eastern Mediterranean(EMRO) 572 WHO Regional Office for Europe (EURO) At least 1654 WHO Regional Office for South-East Asia (SEARO) 892 WHO Regional Office for the Western Pacific (WPRO) 1020 Total** At least 10582
  34. 34. Table 8. Data showing number of confirmed deaths in different regions. * The reported number of fatal cases is an under representation of the actual numbers as many deaths are never tested or recognized as influenza related. Country Cumulative total Cases Deaths Algeria 78 0 Angola 13 0 Botswana 23 0 Burundi 6 0 Cameroon 4 0 Cape Verde 62 0 Congo 8 0 Cote d‘Ivoire 3 0 Democratic Republic of Congo 13 0 Ethiopia 6 0 Gabon 1 0 Ghana 18 0
  35. 35. Kenya 417 0 Lesotho 54 0 Madagascar1 698 1 Malawi 4 0 Mauritius2 69 8 Mozambique 101 2 Namibia 72 1 Nigeria 1 0 Rwanda 279 0 Sao Tome & Principe 41 0 Seychelles 33 0 South Africa3 12620 91 Swaziland 2 0 Tanzania 561 1 Uganda 227 0 Zambia 77 0
  36. 36. Zimbabwe 12 0 TOTAL 15503 104 Source: WHO Table 9. Data showing number of deaths in African nations. 1: Data received from previous epidemiological weeks. Average of 100 cases reported weekly. 2: Is monitoring the pandemic but is no longer reporting individual cases. 3: Data reported on a weekly basis. Week ending at November 15, 2009. H. PANDEMIC PLANNING For any pandemic planning program to be successful, the foundation lies in anticipating future events with reasonable accuracy and having effective plans and guidelines in place. It is important to understand that guidelines provided by the respective governments of a country can only be implemented successfully with the cooperation of its citizens. Also implementing prevention strategies at the individual level is vital to keep the pandemic from growing. Guidelines at the individual level are given below. 1. Get vaccinated Vaccination is the best way to get protection against H1N1 flu. Seasonal flu vaccine is different from H1N1 flu vaccine. Hence they require separate vaccinations. 2. Cover your mouth and nose Coughing and sneezing are the most common ways of spreading infection to others around us. Use a tissue or your sleeve when coughing or sneezing. 3. Wash hands often Hands are often a source of influenza causing viruses. Wash your hands often with soap and water, especially after you cough or sneeze. Alcohol-based hand cleaners are effective. 4. Avoid touching eyes, nose and mouth Eyes, mouth and nose contain moist mucus membranes which provide easy passage ways for the virus to enter your body. Avoid touching these regions. 5. Stay home if ill An infected person can infect others around him. If you are sick with flu-like symptoms, stay home for at least a day after the fever subsides. Phases of a pandemic Three conditions should be met for a pandemic to start. These conditions are: 1. A virus subtype to humans emerges, 2. It infects humans, causing serious illness, and
  37. 37. 3. It spreads easily and sustainably among humans. Once a pandemic is in place, it passes through different stages of intensity and infection rates. The World Health Organization has laid down detailed guidelines to help countries identify the different stage of a pandemic. WHO has defined the pandemic in six phases. They are described below. PHASE 1 No animal influenza virus circulating among animals has been reported to cause infection in humans. PHASE 2 An animal influenza virus circulating in domesticated or wild animals is known to have caused infection in humans and is therefore considered a specific potential pandemic threat. PHASE 3 An animal or human-animal influenza reassortant virus has caused sporadic cases or small clusters of disease in people, but has not resulted in human-to-human transmission sufficient to sustain community-level outbreaks. PHASE 4 Human-to-human transmission (H2H) of an animal or human-animal influenza reassortant virus able to sustain community-level outbreaks has been verified. PHASE 5 The same identified virus has caused sustained community level outbreaks in two or more countries in one WHO region. PHASE 6 In addition to the criteria defined in Phase 5, the same virus has caused sustained community level outbreaks in at least one other country in another WHO region. POST-PEAK PERIOD Levels of pandemic influenza in most countries with adequate surveillance have dropped below peak levels. POSSIBLE NEW WAVE Level of pandemic influenza activity in most countries with adequate surveillance rising again.
  38. 38. POST- PANDEMIC PERIOD Levels of influenza activity have returned to the levels seen for seasonal influenza in most countries with adequate surveillance. Table 10: WHO pandemic phases Fig 14. Diagrammatic representation of revised WHO phases Pandemic Planning Pandemic influenza preparedness is a process. It is not an isolated event. Specific capabilities must be developed through preparedness activities before the pandemic occurs. While all sectors of society are involved in pandemic preparedness and response, the national government is the leader for overall coordination and communication efforts. It should lay down detailed guidelines for all the concerned departments on taking specific actions during a pandemic. World Health Organization has suggested five components of preparedness and response which serve as a blueprint upon which national guidelines should be built. The action plan includes five components which are described below briefly. 1. Planning and coordination 2. Situation monitoring and assessment 3. Reducing the spread of disease 4. Continuity of health care provision 5. Communications
  39. 39. Planning and coordination These efforts are aimed:  to provide leadership and coordination across sectors, and  to integrate pandemic preparedness into national emergency preparedness frameworks Situation monitoring and assessment These efforts are aimed:  to collect, interpret, and disseminate information on the risk of a pandemic before it occurs, and  to monitor pandemic activity and characteristics Monitoring the infectious agent and its infection rates and disease spread patterns will be necessary to assess if the risk of a pandemic is rising. It is important to collect data on influenza viruses, the genetic changes taking place and consequent changes in biological characteristics, and to rapidly investigate and evaluate outbreaks. Once a pandemic influenza virus begins to circulate, it will be vital to assess the effectiveness of the response measures.  Find out when and where influenza activity is occurring  Track influenza-related illness  Determine what influenza viruses are circulating  Detect changes in influenza viruses  Measure the impact influenza is having on deaths in the nation Reducing the spread of disease Reducing the spread of disease is a vital component of pandemic planning. It depends to a large extent on increasing the ‗social distance‘ between people. Measures at individual/household level, societal-level, international travel measures and the use of antiviral drugs, other pharmaceuticals and vaccines will be important.  Individual/household level measures include risk communication, individual hygiene and personal protection, and home care of the ill and quarantine of contacts.  Societal-level measures are applied to societies or communities rather than individuals or families. These measures require a behavioral change in the population, multiple sector involvement, and mobilization of resources, strong communication, and media support.  International travel measures aim to delay the entry of pandemic disease into not-yet- affected countries and will have an impact on international traffic and trade. Countries should balance reducing the risks to public health and avoiding unnecessary interference with international traffic and trade.  The use of pharmaceutical interventions to prevent or treat influenza encompasses a range of approaches. Additionally, the successful prevention and treatment of secondary or pre-existing conditions will be a key factor in many settings for reducing the overall burden of illness and death.
  40. 40. During a pandemic, health systems should provide health care services while attending to the increasing number of patients with influenza illness. The goal of planning and coordination efforts is to provide leadership and coordination across sectors and to determine the extent to which the existing health system can expand to manage the additional patient load. Health care facilities will need to maintain adequate infection control measures to protect health care workers, patients, and visitors. Communications These efforts are aimed:  to provide and exchange relevant information with the public, partners, and stakeholders to allow them to make well informed decisions, and  to take appropriate actions to protect health and safety. During a pandemic, the ability to communicate effectively about the risks related to the influenza is very crucial and forms the basis of effective risk management. Clear and detailed information about the outbreak and recommendations should be communicated to the public, partners and other groups involved. Along with these, core risk communication strategies should be developed to deal with any public health emergency that may arise. Early detection of a pandemic virus Since new viruses with pandemic potential emerge periodically, continuous global surveillance of influenza is necessary to detect these new strains before they cause pandemic situations. With 120 National Influenza Centers in more than 90 countries, WHO is monitoring the activity of influenza viruses around the world. These centers isolate influenza viruses in each region and report any ―unusual‖ influenza virus to WHO Global Influenza Program. Stockpiles of Antiviral drugs A stockpile of antiviral drugs in each country combined with an international stockpile at WHO are essential components of comprehensive international pandemic preparedness. During a pandemic, supplies are severely constrained. Hence countries stockpiling antiviral drugs or vaccines should decide in advance on priority groups and have guidelines in place for administering these drugs. Without any guidelines in place, the situation could become worse during a pandemic as mass administration of antiviral drugs to healthy individuals would speed up the process of development of drug resistance. National Influenza Centers in Africa The World Health Organization has established a network of influenza laboratories in some African countries through its Regional Office for Africa. Rapid and reliable diagnosis of influenza viruses can be performed in these laboratories. More information on these laboratories is given below.
  41. 41. Country Center Location Contact Algeria Algiers Fax:+213 21 390257 Central African Republic Bangui Fax: +236 (61) 01 09 Côte d'Ivoire Abidjan Fax: + 225 22 48 53 05 Egypt Cairo Fax: +(202) 227942034 Madagascar Antananarivo Fax: +261 (20) 22 415 34 Morocco Rabat Fax: +212 (37) 772 067 Nigeria Ibadan Fax: +234 (02) 241 1768 South Africa Cape Town Fax: +27 (21) 448 4110 Sudan Khartoum - Syrian Arab Republic Damascus Fax: +963 114442153 Tunisia Tunis Fax: +216 (71) 56 87 44 Uganda Entebbe - Table 11. List of National Influenza Centers in Africa Priority actions for African nations 1. Build strong collaboration between various health service sectors 36 African countries have surveillance and reporting systems on priority systems in place through district health personnel. These systems serve as a backbone which supports local surveillance and response capabilities. Frequent exchange of information along with provision for jointly investigation any outbreaks will help establish a network.
  42. 42. 2. Existing national coordinating bodies should expand their role to include pandemic influenza. National, regional and district level committees on Pandemic preparedness and response are present throughout Africa. Additionally, these committees need to bring accountability and responsibility within each sector. If possible, a panel of national experts should be assigned the responsibility of leading these committees. 3. Improve the capacity of surveillance systems to detect cases and ensure a rapid response. African countries, with assistance from the WHO Regional Office, have strengthened their surveillance, preparedness and response capacity for outbreaks. Priority diseases have standard definitions defined by these countries. Other approaches that need to be incorporated include an early warning system supported by a staff trained and equipped to perform diagnostic tests and confirm diseases. 4. Develop strategies for the rapid communication of information to the public and the media. Efforts at individual and community level to stop the spread of infection may be the most effective tools to prevent a pandemic from growing further in Africa. This requires efficient communication of messages to the public to increase awareness about a developing disease. GLOSSARY Antibody: Proteins generally found in the blood that detect and destroy invaders, like bacteria and viruses. B Cells: B cells are lymphocytes that play a large role in the humoral immune response. The principal function of B cells is to make antibodies against soluble antigens. Body mass index: A measurement of the relative percentages of fat and muscle mass in the human body, in which mass in kilograms is divided by height in meters squared and the result used as an index of obesity. CDC: Centers for Disease Control and Prevention Cognitive dysfunction: The loss of intellectual functions (such as thinking, remembering, and reasoning) of sufficient severity to interfere with daily functioning. Contraindications: a condition or factor that increases the risks involved in using a particular drug, carrying out a medical procedure or engaging in a particular activity.
  43. 43. Cytokines: Chemicals made by the cells that act on other cells to stimulate or inhibit their function. Cytotoxic T lymphocytes: A T cell that is antigen-specific and is able to search out and kill specific types of virus-infected cells. Diabetes Mellitus: Diabetes mellitus is a condition in which the pancreas no longer produces enough insulin or cells stop responding to the insulin that is produced, so that glucose in the blood cannot be absorbed into the cells of the body. Symptoms include frequent urination, lethargy, excessive thirst, and hunger. DNA: Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms. Epidemic: Affecting or tending to affect an atypically large number of individuals within a population, community, or region at the same time. Epitopes: An epitope is the part of a macromolecule that is recognized by the immune system, specifically by antibodies, B cells, or T cells. FDA: Food and Drug Administration. Flu: Any of several diseases caused by bacteria or viruses and marked especially by respiratory or intestinal symptoms. Glycoprotein: Any of a group of conjugated proteins that contain a carbohydrate as the nonprotein component. Glycolipid: A lipid containing carbohydrate groups, often galactose but also glucose, inositol or others. Hemagglutinin: An important surface structure protein of the influenza virus, an essential gene for the spread of the virus throughout the respiratory tract, enables the virus to attach itself to a cell in the respiratory system and penetrate it. Hypertension: Hypertension is high blood pressure. Blood pressure is the force of blood pushing against the walls of arteries as it flows through them. Hematological: pertaining to or emanating from blood cells. HIV: A transmissible retrovirus that causes AIDS in humans. Immunosupression: Suppression of the immune response, as by drugs or radiation, in order to prevent the rejection of grafts or transplants or control autoimmune diseases.
  44. 44. Influenza: Any of several acute highly contagious respiratory diseases caused by strains of three major orthomyxoviruses now considered to comprise three species assigned to three separate genera: Influenza A, Influenza B or Influenza C. Mucosa: The thin layer which lines body cavities and passages. Mutation: A sudden structural change within a gene or chromosome of an organism resulting in the creation of a new character or trait not found in the parental type. Natural Killer Cell: Cell that can react against and destroy another cell without prior sensitization to it. Natural killer (NK) cells are part of our first line of defense against cancer cells and virus-infected cells. Neuraminidase: An important surface structure protein of the influenza virus, an essential enzyme for the spread of the virus throughout the respiratory tract, enables the virus to escape the host cell and infect new cells. Orthomyxoviridae: A family of RNA viruses that includes five genera: Influenzavirus A, Influenzavirus B, Influenzavirus C, Isavirus and Thogotovirus. Pandemic: Occurring over a wide geographic area and affecting an exceptionally high proportion of the population. Phospholipid: Any of various phosphorous-containing lipids that are composed mainly of fatty acids, a phosphate group, and a simple organic molecule. PCR: Polymerase Chain Reaction; a rapid technique for in vitro amplification of specific DNA or RNA sequences. Pneumococcus: A nonmotile, gram-positive bacterium (Streptococcus pneumoniae) that is the most common cause of bacterial pneumonia and is associated with meningitis and other infectious diseases. Postpartum: Referring to the time period following childbirth. Reassortant virus: A virion containing deoxyribonucleic acid from one virus species and a protein coat from another. Ribosome: A minute round cytoplasmic particle composed of RNA and protein that is the site of protein synthesis as directed by mRNA. RT-PCR: A laboratory technique used to simultaneously quantify and amplify a specific part of a given DNA molecule Respiratory tract: the passages through which air enters and leaves the body
  45. 45. RNA: A nucleic acid that is generally single stranded (double stranded in some viruses) and plays a role in transferring information from DNA to protein-forming system of the cell. Serologic: related to serum; the clear portion of any liquid separated from its more solid elements. Streptococcus: A genus of gram-positive, anaerobic, often pathogenic bacteria having an ovoid or spherical appearance and occurring in pairs or chains, including many erythrocytolytic and pathogenic species that cause erysipelas, scarlet fever, and septic sore throat in humans. Staphylococcus: A genus of spherical, gram-positive bacteria tending to occur in grapelike clusters; they are normal flora on the skin and in the upper respiratory tract and are the most common cause of localized infections. Transcription: The synthesis of RNA using a DNA template catalyzed by RNA polymerase. Translation: Transfer of information from mRNA to proteins. T Cells: T cells belong to a group of white blood cells known as lymphocytes and play a central role in cell-mediated immunity. Virus: The causative agent of an infectious disease. Vaccination: Vaccination is the administration of antigenic material to produce immunity to a disease. Vasoactive: Causing constriction or dilation of blood vessels.

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