Influenza Virus (social preventive pharmacy)

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Prevention 2. Christie, A.B. ( 1 9 8 0 ) . Infectious D i s e a s e : Epidemiology and Clinical

Practice, 3rd e d . , Churchill Livingstone.
VACCINATION: Highly effective live attenuated vaccine
3. Jawetz, E. et al (2007), Medical Microbiology, 24th e d . , Lange Medical
is now available for the prevention of mumps. Widely-used Book.

live attenuated mumps vaccine strains include the Jeryl­ 4. Stephen, J. McPhee et al (2008), Current Medical Diagnosis and

Lynn, RIT 4385, Leningrad-3, L-Zagreb and Urabe strains. Treatment, 4 7th e d . , A Lange Medical Book.

Live attenuated mumps vaccine strains used only on a 5. Feldman, Harry A ( 1 9 7 7 ) in Vira/Infections of Humans: Epidemiology

and Control, Evans Alfred, S. et al (eds), 2nd e d . , Plenum Medical,
limited scale include the Hoshino, Torii and NKM-46
New York and London.
strains. The WHO recommends that the Rubini
6. WHO ( 2 0 0 5 ) , Weekly Epidemiological Record No. 48, 2nd Dec. 2005.
mumps vaccine strain should not be used in national
7. Baum, S . G . and Litman N. ( 1979). in Principles and Practice of Infectious
immunization programmes because of its demonstrated low Diseases, Gerald L. Mandell et al (eds), John Wiley, New York.

effectiveness (6).

A single dose (0.5 ml) intramuscularly produces .INFLUENZA


detectable antibodies in 95 per cent of vaccinees. The

duration of long-term immunity is not known. It is Influenza is an acute respiratory tract infection caused by

recommended for routine immunization for children over influenza virus, of which there are 3 types – A, B and C. All

1 year of age, either alone or in combination with other virus known pandemics were caused by influenza A strains. The

vaccines, eg. in MMR vaccine or as a quadrivalent vaccine disease is characterized by sudden onset of chills, malaise,

with varicella. A second dose is recommended for children at fever, muscular pains and cough.

4-6 years of age i . e . , before starting the school. The current
Problem statement
mumps strain (Jeryl Lynm) has the lowest associated

incidence of post vaccine aseptic meningitis (from 1 in Influenza is truly an international disease. It occurs in all
1 5 0 , 0 0 0 to 1 in 1 . 8 m i l l i o n ) . There are no known cases of countries and affects millions of people every year. Its
long-term sequelae associated with mumps vaccination (4). behaviour is unpredictable. It may occur in several forms. It

may smoulder in a community without clinical recognition,
Countries including mumps vaccines in their national
being manifest only by serological surveys. It may occur in
immunization programme are advised by WHO to set
pandemics every 10-40 years due to major antigenic
disease control targets (control or elimination) and to design
changes, as occurred in 1918 (Spanish influenza), 1957
their mumps immunization strategy accordingly. Strategies
(Asian influenza) and 1968 (Hong Kong influenza) (1).
to achieve mumps elimination include very high coverage
In between pandemics, epidemics tend to occur at intervals
with the first dose of mumps vaccine, ensuring a second
of 2-3 years in case of influenza A and 3-6 years in the case
opportunity for vaccination and conducting catch-up
of influenza B – but the periodicity is not regular as in the
immunization of susceptible cohorts (6).
case of measles or whooping cough because several strains
As with most other live virus vaccines, mumps vaccine
of the virus may be in simultaneous circulation, which
should not be administered to pregnant women, patients
means that there may be outbreaks of influenza practically
receiving immunosuppressive therapy or those who are
every year, and sometimes even twice a year (2).
severely ill ( 7 ) .
Once an epidemic begins, the picture is quite

Mumps s u r v e i l l a n c e (6) characteristic. Preceded by a few early cases, there is a

sudden outburst of the disease. This may be indicated by
Case definitions : WHO recommends the following case
reports of increased febrile respiratory illness in children,
definitions for mumps surveillance :
followed by the same in adults. The next event is increased
a. Clinical mumps : acute onset of unilateral or bilateral
hospitalization of cases and sickness-absenteeism in schools
tender, self-limited swelling of the parotid or other and places of work. Attack rates tend to be high, varying
salivary gland, lasting 2 or more days and without from 5 to 10 per cent in adults and 20-30 per cent in
other apparent cause. children. The peak of the epidemic is reached in 3-4 weeks,

b. Laboratory confirmed mumps : a patient with clinical before tending to decline. The time scale is compressed for

mumps and laboratory confirmation by positive­ smaller geographic areas (1). The unique features of

mumps IgM antibody (without mumps immunization in influenza epidemics are the suddenness with which they

the previous 6 weeks) or; sero-conversion with arise, and the speed and ease with which they spread. The

4-fold or greater rise in mumps IgG titre; or isolation of short incubation period, large number of subclinical cases,

mumps virus from saliva, urine or cerebrospinal fluid. high proportion of susceptible population, short duration of

c. Epidemiologically-confirmed mumps : a patient with immunity, and absence of cross-immunity, all contribute to

clinical mumps who is epidemiologically linked to a its rapid spread. World-wide, the annual epidemics are

laboratory-confirmed mumps case. estimated to result in about 3-5 million cases of severe

illness and about 250,000 to 500,000 deaths (3). The fate of

Control the virus during inter-epidemic periods is not known (4).

Possible explanations include transmission of virus to extra­
The control of mumps is difficult because the disease is
human reservoirs (pigs, horses, birds), latent infection in
infectious before a diagnosis can be made. The long and
humans or continuous transfer from one human to another.
variable incubation period, and the occurrence of subclinical
This explains the occurrence of sporadic cases.
cases make the control of spread difficult. However, cases

should be isolated till the clinical manifestations subside. At present three types of influenza viruses are circulating

Steps should be taken to disinfect the articles used by the in the w o r l d : A ( H N A (H N ) and B viruses. WHO global
1 1), 3 2

patient. Contacts should be kept under surveillance. surveillance activities have identified human infection with a

new influenza virus called A (H N ) in Hong Kong in mid
5 1

References 1997. However, the possibility that the outbreak heralded

1. WHO ( 2 0 0 7 ) , Weekly Epidemiological Record, 16th Feb, No 7 , 2 0 0 7 .
a global influenza pandemic did not materialize. The threat


of a virus more easily transmitted between humans sexes. In general, the attack rate is lower among adults.

remains (5). More recently, influenza A (H N virus of swine Children constitute an important link in the transmission
1 1)

origin emerged in Mexico during the spring of 2009 and was chain. The highest mortality rate during an epidemic occurs

given name – pandemic influenza A (H N 2009 virus. It among certain high-risk groups in the population such as old
1 1)

spreads with travellers worldwide, resulting in the first people (generally over 65 years of age), children under

influenza pandemic since 1968. 18 months, and persons with diabetes or chronic heart

disease, kidney and respiratory ailments (7). (b) HUMAN

E p i d e m i o l o g i c a l determinants MOBILITY : This is an important factor in the spread of

infection. (c) IMMUNITY : Immunity to influenza is subtype­
Agent factors
specific. Antibodies against HA and NA are important in

(a) AGENT : Influenza viruses are classified within the immunity to influenza. Resistance to initiation of infection is

family Orthomyxoviridae. There are three viral subtypes, related to antibody against H A , . which neutralizes the virus,

namely influenza type A, type B and type C. These three whereas decreased severity of disease and decreased ability

viruses are antigenically distinct. There is no cross immunity to transmit virus to contacts are related to antibody directed

between them. Of importance are the influenza A and B against the NA. Antibodies against ribonucleoprotein are

viruses which are responsible for epidemics of disease type-specific and are useful in typing viral isolates as in

throughout the world (6). Influenza A virus has 2 distinct influenza A and B. Protection correlates with both serum

surface antigens – the haemagglutinin (H) and the antibodies and secretory lgA antibodies in nasal secretions.

neuraminidase (N) antigens. The H antigen initiates infection The local secretory antibody is probably important in

following attachment of the virus to susceptible cells. The N preventing infection. Serum antibodies persist for many

antigen is responsible for the release of the virus from the months, whereas secretory antibodies are shorter-lived

infected cell. The currently identified subtypes are 16 HA (usually only few months). Antibody also modifies the course

and 9 NA. Humans are generally infected by viruses of the of illness. A person with low titres of antibody may be infected

subtype H l , H2 or H3, and Nl or N2. Type B virus does not but will experience a mild form of illness. Immunity can be

incomplete as reinfection with the same virus can occur. The
exhibit antigenic shifts and is not divided into subtypes.
three types of influenza viruses are antigenically unrelated
The influenza A virus is unique among the viruses
and therefore induce no cross-protection. When a viral type
because it is frequently subject to antigenic variation, both
undergoes antigenic drift, a person with pre-existing antibody
major and minor. When there is a sudden complete or major
to the original strain may suffer only mild infection with the
change, it is called a shift, and when the antigenic change is
new strain (8). Antibodies appear in about 7 days after the
gradual over a period of time, it is called a drift. Antigenic
attack and reach a maximum level in about 2 weeks. After 8
shift appears to result from genetic recombination of human
to 12 months, the antibody level drops to pre-infection level.
with animal or avian virus, providing a major antigenic

change. This can cause a major epidemic or pandemic Environmental factors
involving most or all age groups. Antigenic drift involves
(a) Season : The seasonal incidence is striking, epidemics
“point mutation” in the gene owing to selection pressure by
usually occurring in winter months in the Northern
immunity in the host population. Antigenic changes occur to
Hemisphere and in the winter or rainy season in the
a lesser degree in the B group influenza viruses. Influenza C
Southern Hemisphere (6). In tropical countries, influenza
appears to be antigenically stable;
virus circulates throughout the year with one or two peaks

Since the isolation of the virus A in 1933, major antigenic during rainy season. (b) Overcrowding : Enhances

changes have occurred twice – once in 1957 (H N and transmission. The attack rates are high in close population
2 2)

again in 1968 (H N Strains occurring between 1946 and groups, e . g . , schools, institutions, ships, etc.
3 2).

1957 have been called (H N strains. The shift in 1968
1 1)

involved only the H antigen.
Mode of t r a n s m i s s i o n

Influenza is spread mainly from person to person by
(b) RESERVOIR OF INFECTION : It has become
droplet infection or droplet nuclei created by sneezing,
increasingly evident that a major reservoir of influenza virus
coughing or talking. The portal of entry of the virus is the
exists in animals and birds. Many influenza viruses have
respiratory tract.
been isolated from a wide variety of animals and birds ( e . g . ,

swine, horses, dogs, cats, domestic poultry, wild birds, etc).
I n c u b a t i o n period
Some of these include the major H and N antigens related to
18 to 72 hours.
human strains. It is hypothesized. There is an increasing

evidence that the animal reservoirs provide new strains of
Pathogenesis and c l i n i c a l features
influenza virus by recombination between the influenza
The virus enters the respiratory tract and causes
viruses of man, animals and birds.
inflammation and necrosis of superficial epithelium of the
(c) SOURCE OF INFECTION : Usually a case or
tracheal and bronchial mucosa, followed by secondary
subclinical case. During epidemics, a large number of mild
bacterial invasion. There is no viraemia. Both the viruses
and asymptomatic infections occur, which play an important
cause much the same symptoms – fever, chills, aches and
role in the spread of infection. The secretions of the
pains, coughing and generalized weakness. Fever lasts from
respiratory tract are infective.
1-5 days, averaging 3 days in adults. Frequent complications

(d) PERIOD OF INFECTIVITY : Virus is present in the are acute sinusitis, otitis media, purulent bronchitis and

nasopharynx from 1 to 2 days before and 1 to 2 days after pneumonia. The most dreaded complication is pneumonia,

onset of symptoms. which should be suspected if fever persists beyond 4 or 5

days or recurs abruptly after convalescence ( 1 ) .
Host factors
Reye syndrome (fatty liver with encephalopathy) is a rare

(a) AGE AND SEX : Influenza affects all ages and both and severe complication of influenza, usually B type,

in young children. It consists of rapidly concerns about activating replication


of HIV virus by the

progressive hepatic failure and encephalopathy, and there is immunogen appear to be exaggerated and may be less

about 30 per cent mortality rate. The pathogenesis is severe than the increase in HIV viral load associated with a

unknown, but the syndrome is associated with aspirin use in full influenza infection. Vaccination is less effective when

a variety of viral infections (9). CD4 counts are less than 100/mcL. False-positive assays for

HIV, HTLV-1, and HCV antibodies have been reported in

Laboratory d i a g n o s i s the wake of influenza vaccination ( 1 0 ) .

Since clinical diagnosis is difficult except during Prevention of exposure to avian influenza strains also

epidemics, laboratory methods are needed to confirm the includes hygienic practices during handling of poultry

diagnosis. These are (a) VIRUS ISOLATION products, including handwashing and prevention of cross­

Nasopharyngeal secretions are the best specimens for contamination, as well as thorough cooking, to more than

obtaining large amounts of virus-infected cells. The virus 70°C, of poultry products ( 1 0 ) .

can be detected by the indirect fluorescent antibody
Influenza vaccines
technique. However egg inoculation is required for virus

isolation and antigenic analysis. (b) SEROLOGY : Routine
serodiagnostic tests in use are based on haemagglutination
Most influenza vaccination programmes make use of
inhibition (HI) and ELISA. Paired acute and convalescent
inactivated vaccines. The recommended vaccine strains for
sera are necessary, because normal individuals usually have
vaccine production are grown in the allantoic cavity of
influenza antibodies. A fourfold or greater increase in titer
developing chick embryos, harvested, purified, killed by
must occur to indicate influenza infection. Human sera often
formalin or beta-propiolactone, and standardized according
contains non-specific mucoprotein inhibitors that must be
to the haemagglutinin content.
destroyed before testing by HI. The HI test reveals the strain

of virus responsible for infection only if the correct antigen is The vaccine is conventionally formulated in aqueous or

available for use. The ELISA test is more sensitive than other saline suspension. One dose of the vaccine contains

assays. approximately 15 micrograms of HA. The vaccine is

administered by the subcutaneous or intramuscular route.
Prevention of influenza A single inoculation (0.5 ml for adults and children over

3 years and 0.25 ml for children from 6 months to 36
All attempts to control influenza epidemics have so far
months of age) is usually given. However, in persons below
met with little success and the prospects of achieving control
9 years of age with no previous immunological experience
remain poor. Good ventilation of public buildings, the
(unprimed individuals), 2 doses of the vaccine, separated by
avoidance of crowded places during epidemics, encouraging
an interval of 3 to 4 weeks are considered necessary to
sufferers to cover their faces with a handkerchief when
induce satisfactory antibody levels. After vaccination, there
coughing and sneezing, and to stay at home at the first sign
is an increase in serum antibodies in about one week, which
of influenza are all sensible precautions. The vaccine is not
reaches a maximum in about 2 weeks. The protective value
recommended to control spread in the general population.
of the vaccine varies between 70-90 per cent (6) and
Immunization, in theory, offers the best prospect of
immunity lasts for only 6-12 months. Revaccination on an
controlling influenza at the present times. In view of the
annual basis is recommended.
changing antigenic characteristics of the virus (antigenic drift
The killed vaccine can produce fever, local inflammation
and antigenic shift) new vaccines are constantly required,
at the site of injection, and very rarely Guillain-Barre
and they should contain the H and N components of the
syndrome (an ascending paralysis). Since the vaccine strains
prevalent strain or strains to keep the vaccines upto date.
are grown in eggs, persons allergic to eggs may develop
The WHO makes recommendations every year as to what
symptoms and signs of hypersensitivity.
strains should be included in the vaccine. A number of field

trials have shown that vaccines so constituted are highly
effective (70-90%). To be effective the vaccine must be

administered at least two weeks before the onset of an A trivalent, live-attenuated influenza vaccine

epidemic, or preferably 2 to 3 months before influenza is administered as a single dose intranasal spray is as effective

expected. Since epidemics of influenza are unpredictable, as inactivated vaccine in preventing the disease. It is

the hope of preventing influenza epidemics by prophylactic approved for use in otherwise healthy individuals between

mass vaccination is remote. age of 2 years and 49 years. Because the risk of transmission

of the live-attenuated vaccine virus to immunocompromised
Since influenza vaccines will not control epidemics, they
individuals is unknown, it should not be used in household
are recommended only in certain selected population groups
members of immunosuppressed individuals, health care
– e.g., in industry to reduce absenteeisms, and in public
workers, or others with close contact with
servants to prevent disruption of critical public services, such
immunosuppressed persons (9).
as the police, fire protection, transport and medical care.

Also, certain groups e . g . the elderly and individuals in any CONTRAINDICATIONS (11) : As a general rule,

age group who have a known underlying chronic or inactivated vaccines should not be administered to :

debilitating disease (e.g. disease of cardiovascular system, ( 1 ) People who have a severe allergy to chicken eggs;
metabolic disease like diabetes, cystic fibrosis, chronic (2) People with a history of anaphylactic reactions or other
respiratory disease and chronic renal insufficiency, life-threatening allergic reactions to any of the
congenital or acquired immunodeficiency) and their close constituents or trace residue of the vaccine;
contacts (persons living with them or their care givers), are
(3) People with history of a severe reaction to influenza
selectively immunized because of the high-risk of severe
complications, including death (6).
(4) People who developed Guillain-Barre syndrome (GBS)

HIV infected persons can be safely vaccinated, and within 6 weeks of getting an influenza vaccine;


(5) Children less than 6 months of age (inactivated influenza Based on knowledge about past pandemics, the (H N
1 1)

vaccine is not approved for this age g r o u p ) ; and 2009 virus is expected to continue to circulate as a seasonal

(6) People who have a moderate-to-severe illness with a virus for some years to come. While level of concern is now

fever (they should wait till they recover to get greatly diminished, vigilance on the part of national health

vaccinated). authorities remains important, when the behaviour of H N
1 1

virus as a seasonal virus cannot be reliably predicted (16).
Antiviral drugs
On 26th September 2 0 1 1 WHO has adapted a new nomen­

Because of limitations in the efficacy of influenza
clature as Influenza A ( H N pdm09 (17).
1 1)

vaccines antiviral drugs have been tried for the prophylaxis
Incubation period
and therapy of seasonal · influenza infections. Two

neuraminidase inhibitors (zanamivir and oseltamivir) are The incubation period appears to be approximately 2-3

available for prophylaxis and therapy of influenza A and B. days, but could range upto 7 days.

The dose of oseltamivir is 75 mg per day for prophylaxis and

Case definitions (18)
75 mg twice daily for 5 days for therapy. Zanamivir is

administered by inhaler (10 mg dose) and is given twice Suspected case : A suspected case of influenza A (H N
1 1)
daily for therapy and once daily for prophylaxis. The 2009 is defined as a person with acute febrile respiratory

duration of prophylaxis depends on the clinical setting. The illness (fever � 38°C) with onset (a) within 7 days of close

current recommendations are that influenza A be treated contact with a person who is a confirmed case of influenza

with zanamivir or a combination of oseltamivir and A (H N 2009 virus infection, or; (b) within 7 days of travel
1 1)

rimantadine. Influenza B can be treated with either to areas where there are one or more confirmed cases, or

oseltamivir or zanamivir (9). For chemoprophylaxis against (c) resides in a community where there are one or more

influenza A, zanamivir should be used. If this is confirmed influenza A ( H N 2009 cases.
1 1)

contraindicated, patients should be given rimantadine. In an
Probable case : A probable case of influenza A (H N
1 1)
outbreak associated with influenza B, either oseltamivir or
2009 virus i n f e c t i o n · is defined as a person with an acute

zanamivir can be used for prophylaxis (9).
febrile respiratory illness who : (1) is positive for influenza A,

but unsubtypable for H and H by influenza RT -PCR or
1 3
AVIAN INFLUENZA (12) reagents used to detect seasonal influenza virus infection, or;

(2) is positive for influenza A by an influenza rapid test or an
Avian influenza refers to a large group of different
influenza immunofluoresence assay (IFA) and meets criteria
influenza viruses that primarily affect birds. On rare
for a suspected case, or; (3) individual with a clinically
occasions, these bird viruses can infect other species,
compatible illness who died of an unexplained acute
including pigs and humans. The vast majority of avian
respiratory illness who is considered to be epidemiollogically
influenza viruses do not infect humans. However, avian
linked to a probable or confirmed case. ·
H N is a strain with pandemic potential, since it might
5 1
Confirmed case : A confirmed case of p a n d e m i c influenza
ultimately adapt into a strain that is contagious among

A (H N 2009 virus infection is defined as a person with an
humans. Once this adaptation occurs, it will no longer be a 1 1)

acute febrile respiratory illness with laboratory confirmed
bird virus – it will be a human influenza virus. Influenza

influenza A (H N 2009 virus infection at WHO approved
pandemics are caused by new influenza viruses that have 1 1)

laboratory by one or more of the following tests :
adapted to humans. Health experts have been monitoring a

new and extremely severe i n fl u e n z a virus – the H N strain – a. Real Time PCR
5 1

for almost 15 years. Fortunately, the virus does not jump
b. Viral culture

easily from birds to humans or spread readily and
c. Four-fold rise in influenza A (H N virus specific
1 1)
sustainably among humans. Once a fully contagious virus
neutralizing antibodies.

emerges, its global spread is considered inevitable.

C l i n i c a l features (19)

PANDEMIC INFLUENZA A ( H N 2009 A wide clinical spectrum of . disease ranging from non­
1 1)

febrile mild upper respiratory illness, febrile influenza like

The pandemic influenza A (H N 2009 virus differs in its illness (ILi), to severe or even fatal complications including
1 1)

pathogenicity from seasonal influenza in two key aspects. rapidly progressive pneumonia has been described . The

First, as the majority of human population has little or no case fatality rate is smilar to seasonal influenza i.e. about 0 . 5

pre-existing immunity to the virus, the impact of the per cent; however this could change (9). The clinical features

infection has been in a wider age range, in particular among are as described below :

children and young adults. Secondly, the virus can infect the
(a) Uncomplicated influenza
lower respiratory tract and can cause rapidly progressive
(1) IL i symptoms include : fever, cough, sore throat ,
pneumonia, especially in children and young to middle-aged
rhinorrhoea, headache, muscle pain, and malaise,
but no shortness of breath and no dyspnoea. Patients

Following its emergence in March 2009, pandemic
may present with some or all of these symptoms.

A (H N 2009 virus spread rapidly throughout the world,
1 1)
(2) G astrointestinal illness may also be pre s ent , such as
leading to the declaration of an inlfuenza pandemic by
diarrhoea and/or vomiting, especially in children ,
WHO on 11th June 2009 (14). The world is now in
but without evidence of dehydration.
post-pandemic period. Between September 2012 and

(b) Complicated or severe influenza
January 2013, all seasonal A (H N viruses detected were
1 1)

A (H N Pdm 09. In India it causes local outbreaks. During (1 ) Presenting clinical (e.g. short n ess of breath /
1 1)

2013, India reported 5,253 cases and 699 deaths, a case dyspnoea, tachypnea, hypoxia) and / or radiological

fatality rate of 1 3 . 3 per cent (15). signs of lower respiratory tract disease (e.g.


pneumonia), central nervous system (CNS) reported in individuals who are obese particularly in those

involvement (e.g. encephalopathy, encephalitis), who are morbidly obese.

severe dehydration, or presenting secondary

complications, such as renal failure, multiorgan
Laboratory d i a g n o s i s (19)

failure, and septic shock. Other complications can Laboratory diagnosis of pandemic influenza A (H N
1 1)

include rhabdomyolysis and myocarditis. 2009 virus, especially at the beginning of a new community

(2) Exacerbation of underlying chronic disease, outbreak or for unusual cases, has important implications for

including asthma, COPD, chronic hepatic or renal case managment, such as infection control procedures,

failure, diabetes, or other cardiovascular conditions. consideration of antiviral treatment options and avoiding

the inappropriate use of antibiotics. Currently, the diagnostic
(3) Any other condition or clinical presentation requiring
tests can be done by specialized laboratories in many
hospital admission for clinical management.
countries. Reverse transcriptase polymerase chain reaction
(4) Any of the signs of progressive disease.
(RT-PCR) will provide the most timely and sensitive

detection of the infection.
Signs and symptoms of progressive disease
Clinical specimens to be collected for laboratory
Patients who present initially with uncomplicated
diagnosis are respiratory samples. Samples from the upper
influenza may progress to more severe disease. Progression
respiratory tract, including a combination of nasal or
can be rapid ( i . e . within 24 h o u r s ) . The following are some
nasopharyngeal samples, and a throat swab are advised.
of the indicators of progression, which would necessitate an
Recent evidence supports viral replication and recovery of
urgent review of patient management.
pandemic A (H N)) 2009 virus from lower respiratory tract
(a) Symptoms and signs suggesting oxygen impairment or samples (tracheal and bronchial aspirates) in patients
cardiopulmonary insufficiency : presenting lower respiratory tract symptoms and in these

– Shortness of breath (with activity or at rest), difficulty patients, such samples have higher diagnostic yields than

in breathing, turning blue, bloody or coloured sputum, samples from the upper respiratory tract.

chest pain, and low blood pressure;
When influenza viruses are known to be circulating in a

– In children, fast or laboured breathing; and community, patients presenting with features of

– Hypoxia, as indicated by pulse oximetry. uncomplicated influenza can be diagnosed on clinical and

epidemiological grounds. All patients should be instructed to
(b) Symptoms and signs suggesting CNS complications:
return for follow-up, should they develop any signs or
– Altered mental status, unconsciousness, drowsiness, or symptoms of progressive disease or fail to improve within
difficult to awaken and recurring or persistent 72 hours of the onset of symptoms.
convulsions (seizures), confusion, severe weakness, or
Diagnostic testing, when available, should be prioritized
for patients in whom confirmation of influenza virus
(c) Evidence of sustained virus replication or invasive infection may affect clinical management, including patients
secondary bacterial infection based on laboratory testing considered at-risk and/or those with complicated, severe, or
or clinical signs (e.g. persistent high fever and other progressive respiratory illness. In addition, results of
symptoms beyond 3 days). diagnostic testing may also be valuable in guiding infection

(d) Severe dehydration, manifested as decreased activity, control practices and management of a patient’s close

dizziness, decreased urine output, and lethargy. contacts. Under no circumstances should influenza

diagnostic testing delay initiation of infection control

Risk factors for severe d i s e a s e (19) practices or antiviral treatment, if pandemic influenza

A (H N 2009 disease is suspected clinically and
1 1)
Risk factors for severe disease from pandemic influenza
epidemiologically ( 1 9 ) .
A (H N 2009 virus infection reported to date are considered
1 1)

similar to those risk factors identified for complications from Several rapid influenza diagnostic tests including (so­

called point-of-care diagnostic tests) are commercially
seasonal influenza. These include the following groups :
available. However, studies indicate that rapid diagnostic
( 1 ) Infants and young children, in particular <2 years
tests miss many infections with pandemic ( H N 2009 virus
1 1)
(2) Pregnant women
and, therefore, negative results cannot rule out disease, and
(3) Persons of any age with chronic pulmonary disease ( e . g . should not be used as grounds to withhold therapy or lift
asthma, COPD) infection control measures.

(4) Persons of any age with chronic cardiac disease (e.g.
Infection control
congestive cardiac failure)

(5) Persons with metabolic disorders ( e . g . diabetes) Evidence to date suggests that pandemic (H N 2009
1 1)

virus is transmitted similarly as seasonal influenza A and B
(6) Persons with chronic renal disease, chronic hepatic
viruses. Appropriate infection control measures (standard
disease, certain neurological conditions (including
plus droplet precautions) should be adhered to at all times,
neuromuscular, neurocognitive, and seizure disorders),
which includes strict adherence to hand hygiene with soap
haemoglobinopathies, or immunosuppression, whether
and water or an alcohol based hand sanitizer, and to cover
due to primary immunosuppressive conditions, such as
mouth and nose with tissue or handkerchief when coughing
HIV infection, or secondary conditions, such as
or sneezing. If ill persons must go into the community e.g. to
immunosuppressive medication or malignancy
seek medical care, they should wear a face mask to reduce
( 7 ) Children receiving chronic aspirin therapy
the risk of spreading the virus in the community.
(8) Persons aged 65 years and older.
Whenever performing high-risk aerosol-generating

A higher risk of severe complications from pandemic procedures (for example, bronchoscopy or any procedure

influenza A (H N 2009 virus infection has also been involving aspiration of the respiratory tract) use a particulate
1 1)
II ·——–


respirator (N95, FFP2 or equivalent), eye protection, gown, CONTRAINDICATIONS (11) : As a general rule,

and gloves, and carry out the procedure in an adequately inactivated vaccines should not be administered to certain

ventilated room, either naturally or mechanically. category of people. For details please refer to page 155.

The duration of isolation precautions for hospitalized
patients with influenza symptoms should be continued for
Pandemic influenza vaccine does not give 100 per cent
7 days after onset of illness or 24 hours after the resolution
protection against the disease but they greatly reduce the
of fever and respiratory symptoms, whichever is longer,
risk of disease. Influenza vaccine only becomes effective
while a patient is in a health-care facility. For prolonged
about 14 days after vaccination. Those infected shortly
illness with complications (i.e. pneumonia), control
before (1-3 days) or shortly after immunization can still get
measures should be used during the duration of acute illness
the disease (11). Vaccinated individuals can also get
(i.e. until the patient has improved clinically). Special
influenza caused by a different strain of influenza virus, for
attention is needed in caring for immunosuppressed patients
which the vaccine does not provide protection ( 1 1 ) .
who may shed virus for a longer time period and are also at

increased risk for development of antiviral resistant virus.

Pandemic influenza A ( H N 2 0 0 9 vaccine Live attenuated vaccines are given via a nasal spray, and
1 1)

can commonly cause runny nose, nasal congestion, cough
In response to the pandemic, over 30 pandemic (H N
1 1)
and can less frequently cause sore throat, low grade fever,
2009 vaccines were licensed worldwide. These include live
irritability and muscle-aches and headache. Wheezing and
attenuated vaccines; inactivated unadjuvanted vaccines
vomiting episodes have been described in children receiving
(split, subunit virion or whole virion); and inactivated
live influenza vaccines ( 1 1 ) .
adjuvanted vaccines (split or subunit virion) (20). Pandemic

A (H N viruses were antigenically and genetically similar to Since the spread of the pandemic virus is unstoppable
1 1)

A/California/7 /2009 like viruses. Vaccines containing and there is limitation of vaccine availability, WHO

NCalifornia/7/2009 antigen stimulated anti-HA antibodies recommends that all the countries should immunize their
of similar titres against the vaccine virus and recent health care workers as a first priority to protect the essential
pandemic A (H N viruses ( 1 4 ) . health infrastructure, and to prevent initiation of nosocomial
1 1)

spread of disease to vulnerable patients. Furthermore, WHO
suggests the following groups for vaccination according to

It is a monovalent vaccine containing antigen equivalent their order of priority : (a) pregnant women; (b) individuals

to NCalifornia/7/2009 ( H N V – like strain, 15 micrograms aged more than 6 months with one of the several chronic
1 1)

of haemagglutinin per 0.5 ml dose ( 2 1 ) . Inactivated vaccines medical conditions; (c) healthy young adults between age

contain thiomersal if they are supplied in multidose vials 15-49 years, (d) healthy children; (e) healthy adults

(10 dose of 0.5 ml). It is a commonly used vaccine between age 49-65 years; and (f) healthy adults aged more

preservative to prevent vaccine contamination by bacteria than 65 years (22).

during use.
Though the vaccine can be used within 7 days after
Key principles for clinical management include basic
opening the vial, it is preferred that the open vial is used
symptomatic care, early use of antiviral drugs if available,
completely in a given session day. This will minimize the risk
for high risk populations, antimicrobials for co-infections,
of adverse effects of immunization due to programmatic
and proactive observation for progression of illness.
errors and also reduce vaccine wastage. To facilitate tracking

and timely disposal of multidose vials, it is suggested that the Hospital care requires early supplemental oxygen therapy

date of opening be clearly written on the label ( 2 1 ) . to correct hypoxaemia, with saturation monitoring at triage

and during hospitalization, if possible, careful fluid
The vaccine should be stored between 2°C-8°C. It
replacement, antimicrobials, and other supportive care. It is
should not be frozen.
important to provide appropriate antimicrobials for other
The vaccine is administered as single dose intramuscular
infections which also present with severe respiratory distress.
injection in the upper arm. In infants aged more than
A number of severely ill patients with pandemic (H N ) 2009
.6 months and young children thigh is the preferred site for
disease develop respiratory distress requiring mechanical
vaccination. Inactivated influenza vaccine can be given at
ventilation and intensive care support.
the same time as other injectable, non-influenza vaccines,

but the vaccine should be administered at different injection Antiviral therapy (19)

site. Seasonal influenza and pandemic influenza vaccines
Pandemic influenza A (H N 2009 virus is currently
1 1)
can be administered together, and there is a public health
susceptible to the neuraminidase inhibitors (NAis)
value in doing so. Clinical studies on this area of vaccination
oseltamivir and zanamivir, but resistant to the M2 inhibitors
are continuing ( 1 1 ) .
amantadine or rimantadine.

SIDE-EFFECTS : Inactivated vaccines, administered by
The following is a summary of treatment
injection, commonly cause local reactions such as soreness,
swelling and redness at the injection site, and less often can
( 1 ) Patients who have severe or progressive clinical illness
cause fever, muscle or joint-aches or headache. These
should be treated with oseltamivir. Treatment should be
symptoms are generally mild and do not need medical
initiated as soon as possible.
attention, and last for 1-2 days. Fever, aches and headaches

can occur more frequently in children compared to elderly (a) This recommendation applies to all patient groups,

people. Rarely, these inlfuenza vaccines can cause allergic including pregnant women, and young children

reactions such as hives, rapid swelling of deeper skin layers <2 years, including neonates.

and tissues, asthma or a severe multisystem allergic reaction (b) In patients with severe or progressive illness not

due to hypersensitivity to certain components. responding to normal treatment regimens, higher

doses of oseltamivir and longer duration of Zanamivir

treatment may be appropriate. In adults, a dose of
Zanamivir is indicated for treatment of influenza in adults
150 mg twice daily is being used in some situations.
and children (>5 years}. The recommended dose for
(c) Where oseltamivir is not available or not possible to
treatment of adults and children from the age of 5 years is
use, or if the virus is resistant to oseltamivir, patients
two inhalations (2 x 5 mg} twice daily for 5 days.
who have severe or progressive clinical illness should

be treated with zanamivir. C h e m o p r o p h y l a x i s (18)

(2) Patients at higher risk of developing severe or
Oseltamivir is the drug of choice for chemoprophylaxis to
complicated illness, but presenting with uncomplicated
health care personnels and close contacts of suspected,
illness due to influenza virus infection, should be treated
probable or confirmed case of pandemic influenza A ( H N
1 1}
with oseltamivir or zanamvir. Treatment should be
2009. It should be given till 1 0 days after last exposure. The
initiated as soon as possible following onset of illness.
dose by body weight is a follows :
(3) Patients not considered to be at higher risk of developing
Weight less than 15 kg – 30 mg OD
severe or complicated illness and who have
15-23 kg – 45 mg OD
uncomplicated illness due to confirmed or strongly
24-40 kg – 60 mg OD
suspected influenza virus infection need not be treated

with antivirals. > 40 kg – 75 mg OD

If used, antiviral treatment should ideally be started early For infants

following the onset of symptoms, but it may also be used at < 3 months – not recommended unless

any stage of active disease when ongoing viral replication is situation is critical

anticipated or documented. Recent experience strongly 3-5 months – 20mgOD
indicates that earlier treatment is associated with better
6-11 months – 25mgOD
outcomes. Therefore, antiviral treatment should be initiated

immediately and without waiting for laboratory confirmation References

of diagnosis.
1. WHO (2012), Weekly Epidemiological Record No. 47, 23 Nov. 2012.

In patients who have persistent severe illness despite 2. Maxine A. Papadakis, Stephen J. McPhee, Current Medical Diagnosis

and Treatment, 53rd Ed. 2014, Lange Publication.
oseltamivir treatment, there are few licensed alternative
3. WHO 2014, Fact Sheet, March 14, 2014.
antiviral treatments. In these situations, clinicians have
4. Douglas, R.G. and R.F. Betts ( 1 9 7 9 ) . in Principles and Practice of
considered intravenous administration of alternative
Infectious Diseases, Mandell, G.L. et al (eds), John Wiley, New York.
antiviral drugs such as zanamivir, peramivir, and ribavirin.
5. WHO (1998) World Health Report 1998, life in the 21st century, A
The use of such treatments should be done only in the vision for all.

context of prospective clinical and virological data collection 6. WHO ( 1 9 8 0 ) . Techn.Rep.Ser., No.642.

and with regard to the following cautions: 7. WHO (1985) Bull. WHO 63 ( 1 ) 5 1 .

8. Jawetz, et al (2001) Medical Microbiology, 22nd ed., A Lange Med.
– ribavirin should not be administered as monotherapy;
– ribavirin should not be administered to pregnant
9. Stephen J. Mcphee et al (2010), Current Medical Diagnosis and
women; and Treatment, 49th Ed., A Lange & Med. Publication.

– zanamivir formulated as a powder for inhalation 10. Lawrence, et al (2006). Current Medical Diagnosis and Treatment,

45th Ed., A LangeMed. Publication.
should not be delivered via nebulization due to the
11. WHO ( 2 0 1 0 ) , Safety of pandemic (H N 2009 vaccines, 30th Oct,
presence of lactose, which may compromise ventilator 1 1)

12. WHO (2005). Weekly Epidemiological Record, No.49/50, Oct 14,

S t a n d a r d antiviral treatment regimens (19)
13. WHO (2012), Weekly Epidemiological Record, No. 13, 30th March,

14. WHO (2009), Weekly Epidemiological Record, No. 4 1 , 9th Oct, 2009.
Oseltamivir is indicated for treatment of influenza. For
15. Govt. of India (2014), National Health Profile 2013, Central Bureau of
adults the recommended oral dose is 75 mg oseltamivir Health Intelligence, Ministry of Health and Family Welfare, New Delhi.

twice daily for 5 days. 16. WHO (2010), WHO Recommendations for the post-pandemic,

Pandemic (H N 2009 briefing note 23.
1 1)
For infants less than 1 year of age recommended oral
17. WHO ( 2 0 1 1 ) , Weekly Epidemiological Record, No. 43, 21st Oct, 2 0 1 1 .
doses are as follows:
18. Govt. of India ( 2 0 1 0 ) , Guidelines for Swineflu (Influenza A H N
1 1),

Ministry of Health and Family Welfare, New Delhi.
>3 months to 12 months 3 mg/kg, twice daily for 5 days
19. WHO (2009), Clinical Management of human infection with

> 1 month to 3 months 2.5 mg/kg, twice daily for 5 days pandemic, (H N 2 0 0 9 : revised guidance, November, 2009.
1 1)

20. WHO (2010), Weekly Epidemiological Record, No. 30, 23rd July,
Oto 1 month* 2 mg/kg, twice daily for 5 days

21. Govt. of India ( 2 0 1 0 ) , Guidance on pandemic vaccination, DGHS,
* There are no data available regarding the adminstration
Ministry of Health and Family Welfare, Emergency Medical Relief, New
of oseltamivir to infants less than one month of age.

22. WHO (2009), Weekly Epidemiological Record, No. 30, 24th July,
For older children the recommended oral doses according
2009. .
to body weight are as follows:

15 kg or less 30 mg twice a day for 5 days DIPHTHERIA

15-23 kg 45 mg twice a day for 5 days

Diphtheria is an acute infectious disease caused by
24-40 kg 60 mg twice a day for 5 days
toxigenic strains of Corynebacterium diphtheriae. Three
>40kg 75 mg twice a day for 5 days major clinical types have been described : anterior nasal,