H1N1 Influenza booklet

H1N1 INFLUENZA

Venkata Mattegunta

Colin R Young

Texas A&M University

College Station

TX

USA

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

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)


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)


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)

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.

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

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

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 them an 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

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.

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

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.

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

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

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.

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.

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

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

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

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

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

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.

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

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)

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

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 220C, 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

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.

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


5 mL multidose vial

0

0

25

6-35 m

> 36 m

> 6 m

Novartis (IM)a

5 mL multidose vial


25

< 1.0

≥ 4 yrs

> 4 yrs

CSL Biotherapies, Inc (IM)a


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.

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

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.

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

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

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.

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

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

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

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

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.

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

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


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.

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


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.

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.

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.

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.

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

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.

H1N1 Influenza booklet

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