Fatal Flu
By DEAR
email: d34r123@yahoo.co.id
KOMUNITAS BLOGGER UNIVERSITAS SRIWIJAYA
Fatal Flu
Introduction
Human influenza pandemics over the last 100 years have been caused by H1, H2, and H3
subtypes of influenza A viruses.
More recently, avian influenza virus subtypes (that is, H5, H7) have been found to directly
infect humans from their avian hosts. The recent emergence, host expansion, and spread of
a highly pathogenic avian influenza (HPAI) H5N1 subtype in Asia have heightened concerns
globally, in regards to mortality from HPAI H5N1 infection in humans[1].
Swine influenza A subtypes H1N1, H1N2, H2N3, H3N1, and H3N2 in pigs are the most
common strains worldwide. In the United States, the H1N1 subtype was exclusively
prevalent among swine populations before 1998.
Influenza A viruses
Influenza A, B and C are the most important genera of the Orthomyxoviridae family, causing
both pandemic and seasonal disease in humans. Influenza A viruses are enveloped, singlestranded RNA viruses with a segmented genome (Table 1) [2]. They are classified into
subtypes on the basis of the antigenic properties of the hemagglutinin (HA) and
neuraminidase (NA) glycoproteins expressed on the surface of the virus. Influenza A viruses
are characterized by their pathogenicity, with highly pathogenic avian influenza (HPAI)
causing severe disease or death in domestic poultry. Molecular changes in the RNA genome
occur through two main mechanisms: point mutation (antigenic drift) and RNA segment
reassortment (antigenic shift) Point mutations cause minor changes in the antigenic
character of viruses.
Vaccination for influenza A is given yearly. Reassortment occurs when a host cell is infected
with two or more influenza A viruses, leading to the creation of a novel subtype. The
influenza subtypes of the 1957 (H2N2) and 1968 (H3N2) pandemics occurred through
reassortment, while the origins of the 1918 (H1N1) pandemic are unclear.
The HA glycoprotein mediates attachment and entry of the virus by binding to sialic acid
receptors on the cell surface. The binding affinity of the HA to the host sialic acid allows for
the host specificity of influenza A. Avian influenza subtypes prefer to bind to sialic acid linked
to galactose by α-2,3 linkages, which are found in avian intestinal and respiratory
epithelium (Table 2)[3]. Human virus subtypes bind to α-2,6 linkages found in human
respiratory epithelium. Swine contain both α-2,3 and α-2,6 linkages in their
respiratory epithelium, allowing for easy co-infection with both human and avian subtypes
(thus acting as a \'mixing vessel\' for new strains). Humans have been found to contain both
α-2,3 and α-2,6 linkages in their lower respiratory tract and conjunctivae, which
allows for human infections by avian subtypes. The HA glycoprotein is the main target for
immunity by neutralizing antibodies [3].
The NA glycoprotein allows the spread of the virus by cleaving the glycosidic linkages to
sialic acid on host cells and the surface of the virus. The virus is then spread in secretions or
other bodily fluids. The NA glycoprotein is not the major target site for neutralization of the
virus by antibodies [4].
Host range of influenza A viruses
Influenza A viruses infect a wide range of hosts, including many avian species, and various
mammalian species, such as swine, ferrets, felids, mink, whales, horses, seals, dogs, civets,
and humans.
Wild birds (ducks, geese, swans, and shorebirds) are important natural reservoirs of these
viruses, and all of the known 16 HA and 9 NA subtypes have been found in these birds. In
most cases, these subtypes are found within the gastrointestinal tract of the birds, are shed
in their feces, and rarely cause disease. Since 2002, however, HPAI H5N1 viruses
originating in Asia have been reported from approximately 960 wild bird species, causing
disease in some instances and asymptomatic shedding in others [5].
Epidemiology and pathogenicity in humans
Avian influenza
The incidence of avian influenza infections in humans has increased over the past decade.
In December of 2003, HPAI H5N1 surfaced in poultry in Korea and China, and from 2003 to
2006 the outbreak stretched worldwide in the largest outbreak in poultry history. Human
cases of HPAI H5N1 followed the poultry outbreak, with a total of 256 cases and 151
fatalities thus far. Other limited outbreaks have occurred, causing variable human disease
(Table 3).
However, HPAI H5N1 remains the largest and most significant poultry and human avian
influenza outbreak.
Epidemiological investigations of human cases of avian influenza show that the virus was
acquired by direct contact with infected birds. Influenza A is transmitted through the fecal-oral
and respiratory routes among wild birds and poultry. Human interaction with these infected
secretions and birds was the major mode of transmission, with contact including
consumption of undercooked or raw poultry products, handling of sick or dead birds without
protection, or food processing at bird cleaning sites. All birds were domesticated (chicken,
duck, goose) and no transmission from birds in the wild (migrating) or contaminated
waterways has been documented. In a few cases, limited human to human transmission has
been reported among health care workers and family members (Table 4) [6]. In each of these
cases, no personal protective equipment was used, which is the major factor in transmission
between humans.
Swine influenza
Transmission of influenza from swine to humans who work with swine was documented in a
small surveillance study performed in 2004 at the University of Iowa. This study among
others forms the basis of a recommendation that people whose jobs involve handling poultry
and swine be the focus of increased public health surveillance. Other professions at
particular risk of infection are veterinarians and meat processing workers, although the risk of
infection for both of these groups is lower than that of farm workers [7].
Interaction with avian H5N1 in pigs
Pigs are unusual as they can be infected with influenza strains that usually infect three
different species: pigs, birds and humans. This makes pigs a host where influenza viruses
might exchange genes, producing new and dangerous strains. In August 2004, researchers
in China found H5N1 in pigs [8].
Clinical manifestations in humans
Avian influenza
The clinical manifestations of avian influenza in humans has ranged from mild conjunctivitis
to severe pneumonia with multi-organ system failure . The median age of patients was 16
years in the 2003 to 2006 HPAI H5N1 outbreak in Southeast Asian cases (range 2 months to
90 years). The incubation period ranged from two to eight days from contact with sick or
dead birds to symptom onset. The predominant clinical findings appear to vary with each
influenza A subtype; for example, in 2003 during the Netherlands outbreak (H7N7) 92% (82
of 89) of patients presented with conjunctivitis and a minority with respiratory symptoms. Rye
syndrome, pulmonary hemorrhage, and predominant nausea, vomiting, and diarrhea
complicate these cases. Laboratory findings include both thrombocytopenia and
lymphopenia . Chest radiographic findings include interstitial infiltrates, lobar consolidation,
and air bronchograms. The clinical course of patients with HPAI H5N1 is rapid, with 68%
percent of patients developing ARDS and multiorgan failure within 6 days of disease onset.
The case fatality rate ranges form 67% to 80%, depending on the case series [9]. Once the
patients reached the critical care unit, however, the mortality rate was 90%.The average time
of death from disease onset was nine to ten days.
Avian influenza A infections in humans differ from seasonal influenza in several ways. The
presence of conjunctivitis is more common with avian influenza A infections than with
seasonal influenza. Gastrointestinal symptoms, as seen with HPAI H5N1, and reports of
primary influenza pneumonia and development of ARDS are also more common with avian
influenza A infections . Finally, the rapid progression to multi-organ failure and eventually
death occurs at a much higher rate with avian influenza A infections [10].
Swine influenza
According to the Centers for Disease Control and Prevention (CDC), in humans the
symptoms of the 2009 "swine flu" H1N1 virus are similar to those of influenza and
of influenza-like illness in general. Symptoms include fever, cough, sore throat, body aches,
headache, chills and fatigue. The 2009 outbreak has shown an increased percentage of
patients reporting diarrhea and vomiting. Because these symptoms are not specific to swine
flu, a differential diagnosis of probable swine flu requires not only symptoms but also a high
likelihood of swine flu due to the person\'s recent history [11].
The most common cause of death is respiratory failure. Other causes of death are
pneumonia (leading to sepsis)[12], high fever (leading to neurological problems), dehydration
(from excessive vomiting and diarrhea) and electrolyte imbalance. Fatalities are more likely
in young children and the elderly.
Diagnosis
The clinical diagnosis of avian influenza infection in humans is difficult and relies on the
epidemiological link to endemic areas, contact with sick or dead poultry, or contact with a
confirmed case of avian influenza. Since many infectious diseases present with similar
symptoms, the only feature significant to the clinician may be contact in an endemic area,
through travel or infected poultry, and the clinician should always elicit a detailed patient
history.
The definitive diagnosis is made from isolation of the virus in culture from clinical specimens.
This method not only provides the definitive diagnosis, but the viral isolate is now available
for further testing, including pathogenicity, antiviral resistance, and DNA sequencing and
analysis. Alternatively, antibody testing can be performed, with a standard four-fold titer
increase to the specific subtype of avian influenza virus. Neutralizing antibody titer assays for
H5, H7 and H9 are performed by the micorneutralization technique. Western
blot analysis with recombinant H5 is the confirmatory test for any positive microneutralization
assay. More recently, rapid diagnosis can be performed with reverse transcription-PCR on
clinical samples with primers specific for the viral subtype. This test should be performed only
on patients meeting the case definition of possible avian influenza A infection [13].
Diagnosis of H1N1
Clinicians should consider the possibility of H1N1 influenza virus infections in patients who
present with febrile respiratory illness.
If H1N1 flu is suspected, the clinician should obtain a respiratory swab for H1N1 influenza
testing and place it in a refrigerator (not a freezer). Once collected, the clinician should
contact his or her state or local health department to facilitate transport and timely diagnosis
at a state public health laboratory.
A number of diagnostic tests are available to detect the presence of influenza viruses in
respiratory specimens. These tests differ in their sensitivity and specificity for detecting
influenza viruses, commercial availability, processing time, approved clinical setting, and
ability to distinguish between different influenza virus types (A versus B) and influenza A
subtypes (e.g., 2009 H1N1 versus seasonal H1N1 versus seasonal H3N2 viruses)[14].
Rapid influenza diagnostic tests (RIDTs) are widely available, advantages are that the test is
relatively easy to perform and results can be obtained as early as 30 minutes. Disadvantages
are its low sensitivity (10% to 70%) and inability to determine the subtype of influenza A. Also
negative result does not rule out H1N1 swine influenza infection.
Like RIDTs, direct immunofluorescence assays (DFAs) are widely available, have variable
sensitivity (range 47 – 93%) for 2009 H1N1 influenza virus, and a high specificity
(≥96%7). DFAs detect and distinguish between influenza A and B viruses but do not
distinguish among different influenza A subtypes.
When influenza viruses are circulating in a community, the positive predictive value of the
RIDT and DFA tests are generally high and a positive test result indicates that influenza virus
infection is likely. However, as stated above, a negative test does not rule out influenza virus
infection.
Nucleic acid amplification tests, including rRT-PCR, are the most sensitive and specific
influenza diagnostic tests, but they may not be readily available, obtaining test results may
take one to several days, and test performance depends on the individual rRT-PCR assay.
As with any assay, false negatives can occur. Not all nucleic acid amplification assays can
specifically differentiate 2009 H1N1 influenza virus from other influenza A viruses. If specific
testing for 2009 H1N1 influenza virus is required, testing with an rRT-PCR assay specific for
2009 H1N1 influenza or viral culture should be performed [15].
Treatment
Treatment of avian influenza infections in humans
It includes antiviral therapy and supportive care. Controlled clinical trials on the efficacy of
antivirals (NA inhibitors), supportive therapy, or adjuvant care have never been performed,
so current recommendations stem from the experiences of past avian influenza outbreaks
and animal models.
The adamantanes (rimantadine and amantadine) and NA inhibitors (oseltamivir and
zanamivir) are the antivirals used for treatment and prophylaxis of influenza infections in
humans. In avian influenza virus infections, adamantanes have no role due to widespread
resistance through a M2 protein alteration. In addition, over 90% of isolates of H1 and H3
human subtypes during seasonal influenza have had resistance to the adamantanes. Their
role has now been limited to prophylaxis in the community when the circulation strain is know
to be susceptible to the adamantanes[16]. NA inhibitors (oseltamivir and zanamivir) have
been studied for both treatment and prophylaxis with the human influenza A subtypes H1,
H2, and H3 as well as influenza B. In animal models with HPAI H5N1, their efficacy has been
well documented, with improved survival rates seen after infection. Oseltamivir has been
used in avian influenza outbreaks involving HPAI H5N1, and therapy with oseltamivir has
been shown to decrease the viral load in nasal secretions in patients infected with HPAI
H5N1. Resistance to oseltamivir has been documented in a HPAI H5N1 subtype in a
Vietnamese girl treated with 75 mg daily for 4 days as post-exposure prophylaxis. In one
study, the viral count of HPAI H5N1 in nasal secretions did not decrease with the
administration of oseltamivir when the H5N1 isolate carried this resistance mutation.
However, resistance produced by this change may be overcome with higher doses of
oseltamivir in vitro, and this change has not been documented to confer resistance to
zanamivir[17].
The timing of treatment with NA inhibitors is paramount, as early therapy is directly related to
improved survival. The greatest level of protection was seen if the NA inhibitors were started
within 48 hours of infection, and protection rapidly dropped after 60 hours. These initial
studies, however, were performed with seasonal human influenza A and B, where the period
of viral shedding is approximately 48 to 72 hours. In HPAI H5N1 cases from Southeast Asia,
survival appeared to be improved in patients who received oseltamavir earlier (4.5 days
versus 9 days after onset of symptoms). Both of these time periods are much longer than
documented in animal models, so the window of optimal therapy is still unknown, particularly
if viral shedding exceeds the average 48 to 72 hour period seen in seasonal influenza A and
B infections. Combination therapy with influenza A viruses has not been studied. Ribavirin by
inhalation has been evaluated in vitro with some avian influenza A subtypes. Further animal
model studies are indicated to determine if there is a role for ribavirin or combination therapy
with avian influenza A viruses. Supportive care with intravenous rehydration, mechanical
ventilation, vasopressor therapy, and renal replacement therapy are required if multiorgan
failure and ARDS are a feature of disease. Due to the progression of pneumonia to ARDS,
non-invasive ventilation is not recommended, and early intubation may be beneficial before
overt respiratory failure ensues. Corticosteroids have been used in some patients with HPAI
H5N1, but no definitive role for steroids has been determined. Other immunomodulatory
therapy has not been reported [18].
Treatment of H1N1 in humans
Treatment is largely supportive and consists of bedrest, increased fluid consumption, cough
suppressants, and antipyretics and analgesics (eg, acetaminophen, nonsteroidal antiinflammatory drugs) for fever and myalgias. Severe cases may require intravenous hydration
and other supportive measures. Antiviral agents may also be considered for treatment or
prophylaxis (see Medications).
Patients should be encouraged to stay home if they become ill, to avoid close contact with
people who are sick, to wash their hands often, and to avoid touching their eyes, nose, and
mouth. The CDC recommends the following actions when human infection with H1N1
influenza (swine flu) is confirmed in a community [19]:
Home isolation
Patients who develop flulike illness (ie, fever with either cough or sore throat) should be
strongly encouraged to self-isolate in their home for 7 days after the onset of illness or at
least 24 hours after symptoms have resolved, whichever is longer.
To seek medical care, patient should contact their health care providers to report illness (by
telephone or other remote means) before seeking care at a clinic, physician\'s office, or
hospital.
Patients who have difficulty breathing or shortness of breath or who are believed to be
severely ill should seek immediate medical attention.
If the patient must go into the community (eg, to seek medical care), he or she should wear a
face mask to reduce the risk of spreading the virus in the community when coughing,
sneezing, talking, or breathing. If a face mask is unavailable, ill persons who need to go into
the community should use tissues to cover their mouth and nose while coughing.
While in home isolation, patients and other household members should be given infection
control instructions, including frequent hand washing with soap and water. Use alcoholbased hand gels (containing at least 60% alcohol) when soap and water are not available
and hands are not visibly dirty. Patients with H1N1 influenza should wear a face mask when
within 6 feet of others at home.
Household contacts who are not ill
Remain home at the earliest sign of illness.
Minimize contact in the community to the extent possible.
Designate a single household family member as caregiver for the patient to minimize
interactions with asymptomatic persons.
School dismissal and childcare facility closure
Strong consideration should be given to close schools upon a confirmed case of H1N1 flu or
a suspected case epidemiologically linked to a confirmed case.
Decisions regarding broader school dismissal within these communities should be left to
local authorities, taking into account the extent of influenzalike illness within the community.
Cancelation of all school or childcare related gatherings should also be announced.
Encourage parents and students to avoid congregating outside of the school if school is
canceled.
Duration of schools and childcare facilities closings should be evaluated on an ongoing basis
depending on epidemiological findings.
Consultation with local or state health departments is essential for guidance concerning
when to reopen schools. If no additional confirmed or suspected cases are identified among
students (or school-based personnel) for a period of 7 days, schools may consider
reopening.
Schools and childcare facilities in unaffected areas should begin preparation for possible
school closure.
Social distancing
Large gatherings linked to settings or institutions with laboratory-confirmed cases should be
canceled (eg, sporting events or concerts linked to a school with cases); other large
gatherings in the community may not need to be canceled at this time.
Additional social distancing measures are currently not recommended.
Persons with underlying medical conditions who are at high risk for complications of
influenza should consider avoiding large gatherings.
WHO guidelines for H1N1
WHO guidelines recommend treating serious cases immediately [20].The guidelines
represent an international panel of experts who reviewed all available studies regarding
antiviral agents (with emphasis on oseltamivir and zanamivir). Evidence indicates that
oseltamivir, when properly prescribed, significantly decreases risk of pneumonia (a leading
cause of death for both pandemic and seasonal influenza) and the need for hospitalization.
For patients who initially present with severe illness or whose condition begins to deteriorate,
initiate oseltamivir as soon as possible. For patients with severe or deteriorating illness,
treatment should be provided even if started later. Where oseltamivir is unavailable or cannot
be used for any reason, zanamivir may be given. This recommendation applies to all patient
groups, including pregnant women, and all age groups, including young children and infants.
For patients with underlying medical conditions that increase the risk of more severe disease,
WHO recommends treatment with either oseltamivir or zanamivir. These patients should also
receive treatment as soon as possible after symptom onset, without waiting for the results of
laboratory tests. Pregnant women are included among groups at increased risk, and WHO
recommends that pregnant women receive antiviral treatment as soon as possible after
symptom onset.
At the same time, the presence of underlying medical conditions will not reliably predict all or
even most cases of severe illness. Worldwide, around 40% of severe cases are now
occurring in previously healthy children and adults, usually younger than 50 years. Some of
these patients experience a sudden and very rapid deterioration in their clinical condition,
usually on day 5 or 6 following the onset of symptoms.
Clinical deterioration is characterized by primary viral pneumonia, which destroys the lung
tissue and does not respond to antibiotics, and the failure of multiple organs, including the
heart, kidneys, and liver. These patients require management in intensive care units using
therapies in addition to antivirals .
Initiate antiviral agents within 48 hours
Prompt initiation of antiviral agents within 48 hours of symptom onset is imperative for
providing treatment efficacy against influenza virus. In studies of seasonal influenza,
evidence for benefits of treatment is strongest when treatment is started within 48 hours of
illness onset. However, some studies of treatment of seasonal influenza have indicated
benefit, including reductions in mortality or duration of hospitalization, even in patients in
whom treatment was started more than 48 hours after illness onset. The recommended
duration of treatment is 5 days.
*Prophylaxis with antiviral agents should also be considered in the following individuals (preexposure or postexposure):
-Close household contacts of a confirmed or suspected case who are at high risk for
complications (eg, chronic medical conditions, persons >65 y or <5 y, pregnant women)
-School children at high risk for complications who have been in close contact with a
confirmed or suspected case
-Health care providers or public health workers who were not using appropriate personal
protective equipment during close contact with a confirmed or suspected case
*In September 2009, the CDC updated recommendations concerning the use of antiviral
medications for prevention because of reported oseltamivir resistance; antivirals should not
be used for postexposure chemoprophylaxis in healthy children or adults to manage
outbreaks in the community, school, camp, or other settings.
*Pre-exposure prophylaxis can be considered in the following persons:
Any health care provider who is at high risk for complications (eg, persons with chronic
medical conditions, adults >65 y, pregnant women)
Pediatric considerations
Aspirin or aspirin-containing products (eg, bismuth subsalicylate [Pepto Bismol]) should not
be included in the treatment of confirmed or suspected viral infection in persons aged 18
years or younger because of the risk of Reye syndrome. For relief of fever, other antipyretic
medications (eg, acetaminophen, nonsteroidal anti-inflammatory drugs) are recommended.
Pregnant women
Oseltamivir and zanamivir are "Pregnancy Category C" medications, indicating
that no clinical studies have been conducted to assess the safety of these medications in
pregnant women.
Because of the unknown effects of influenza antiviral drugs on pregnant women and their
fetuses, oseltamivir or zanamivir should be used during pregnancy only if the potential
benefit justifies the potential risk to the embryo or fetus; the manufacturers\' package inserts
should be consulted. However, no adverse effects have been reported among women who
received oseltamivir or zanamivir during pregnancy or among infants born to women who
have received oseltamivir or zanamivir.
Pregnancy should not be considered a contraindication to oseltamivir or zanamivir use.
Because zanamivir is an inhaled medication and has less systemic absorption, some experts
prefer zanamivir over oseltamivir for use in pregnant women, when feasible [21] .Others
recommend that, because pregnant women may have a decreased ability to inhale
zanamivir, they should be given oseltamivir.
Antiviral Agents [21]
Drugs indicated for treatment of H1N1 influenza A virus include neuraminidase inhibitors (ie,
oseltamivir and zanamivir).
Antivirals reduce the length of illness by an average of 1.5 days. (In a subgroup of high-risk
patients, illness was reduced by 2.5 d.) In addition, the severity of symptoms is also reduced.
On October 23, 2009, the FDA announced emergency-use authorization of the
investigational intravenous neuraminidase inhibitor, peramivir.
Oseltamivir (Tamiflu)
Inhibits neuraminidase, which is a glycoprotein on the surface of influenza virus that destroys
an infected cell\'s receptor for viral hemagglutinin. By inhibiting viral neuraminidase,
decreases release of viruses from infected cells and thus viral spread. Effective to treat
influenza A or B Start within 40 h of symptom onset. Available as 30-mg, 45-mg, and 75-mg
oral capsules and as a powder for suspension that contains 12 mg/mL after reconstitution.
Precautions in renal impairment, chronic cardiac or respiratory disease, and breastfeeding;
(preclinical trials have demonstrated death in young animals, possibly related to immature
blood brain barriers); postmarketing reports (mostly from Japan) of self-injury and delirium in
patients with influenza (reports primarily among children), unknown if oseltamivir directly
contributes to this behavior (monitor for abnormal behavior throughout treatment period.
Pediatric dosing:
Treatment for acute illness and age <1 year:
<3 months: 12 mg PO bid for 5 d
3-5 months: 20 mg PO bid for 5 d
6-11 months: 25 mg PO bid for 5 d
Treatment for acute illness and age >1 year:
<15 kg: 30 mg PO bid for 5 d
15-23 kg: 45 mg PO bid for 5 d
23-40 kg: 60 mg PO bid for 5 d
>40 kg: Administer as in adults
Prophylaxis and age <1 year:
<3 months: Data limited; not recommended unless situation judged critical
3-5 months: 20 mg PO qd
6-11 months: 25 mg PO qd
Prophylaxis and age >1 year:
<15 kg: 30 mg PO qd for 10 d
15-23 kg: 45 mg PO qd for 10 d
23-40 kg: 60 mg PO qd for 10 d
>40 kg: Administer as in adults
Zanamivir (Relenza)
Inhibitor of neuraminidase, so release of viruses from infected cells and viral spread are
decreased. Effective against both influenza A and B. Inhaled through Diskhaler oral
inhalation device. Circular foil discs containing 5-mg blisters of drug are inserted into
supplied inhalation device.
Individuals with asthma or other respiratory conditions that may decrease ability to inhale the
drug should be given oseltamivir (eg, asthma, pregnancy). Severe respiratory failure caused
by H1N1 influenza has been reported in the southern hemisphere during July and August
2009; therefore, in severely ill patients, the ability to inhale zanamivir may be impaired.
Pediatric dosing:
Treatment for acute illness:
<7 years: Not established
>7 years: Administer as in adults
Prophylaxis in household contact:
<5 years: Not established
>5 years: Administer as in adults
Prophylaxis in community outbreak:
Adolescents 12-16 years: Administer as in adults
Peramivir (investigational)
Is an investigational neuraminidase inhibitor. Also Peramivir IV is an unapproved drug and is
still being evaluated in phase 3 clinical trials. Limited phase 2 and 3 safety and efficacy data
for Peramivir IV are available, but not sufficient to constitute an adequate basis to establish
safety and efficacy that is required for full marketing approval. The data are sufficient to allow
approval for emergency use of Peramivir IV in certain patients The dose not to exceed 600
mg IV qd for 5-10 days, dilute with 0.45% or 0.9% NaCl and infuse IV over 60 min.
Emergency-use authorization issued by US FDA for use of peramivir in hospitalized adult
and pediatric patients with suspected or laboratory-confirmed 2009 H1N1 influenza
unresponsive to oseltamivir or zanamivir, unable to take PO or inhaled drugs (or delivery
route not dependable or feasible), or other circumstances determined by clinician .
* Do not use Peramivir IV for the treatment of seasonal influenza A or B virus infections, for
outpatients with acute uncomplicated 2009 H1N1 virus infection or for pre- or post-exposure
chemoprophylaxis (prevention) of influenza.[22]
Vaccination
Vaccines of H5N1
Human vaccination for avian influenza viruses has not been widely used, although multiple
vaccination trials are underway. Prior avian vaccines in humans have been poorly
immunogenic and thus have limited use. An inactivated H5N3 has been tested and was
tolerated but with limited immunogenicity. Other H5 vaccines have resulted in the
development of neutralizing antibodies, but to a limited degree. Recently, a large randomized
trial looked at an H5N1 attenuated vaccine from the Vietnam strain [23].
Only a modest immune response was seen, with microneutralization antibodies being
developed at 12 times the dose used in the seasonal influenza vaccine. The side effects
were minimal. A number of other industry trials with adjuvant vaccines are currently ongoing.
Although promising, human vaccination against avian influenza viruses is still under
development. Underscoring this development is the uncertainty of a pandemic strain, which
may have vastly different antigenic properties from any developed H5 vaccine [1].
Vaccines of H1N1[24]
Four manufacturers are supplying the H1N1 vaccine. The vaccine is available as an
Intramuscular injection and as an intranasal product.
Influenza A virus vaccine (H1N1)
Available as monovalent, inactivated influenza A virus vaccine (H1N1) for IM injection.
Indicated for active immunization against influenza caused by pandemic (H1N1) 2009 virus.
Stimulates active immunity to influenza virus infection by inducing production of specific
antibodies.
Adult
IM injection: 0.5 mL IM in deltoid muscle of upper arm (1 dose)
Pediatric
IM injection (Sanofi Pasteur vaccine)
6-35 months: 0.25 mL IM; administer 2 injections approximately 4 wk apart
3-9 years: 0.5 mL IM; administer 2 injections approximately 4 wk apart
10-17 years: Administer as in adults
IM injection (Novartis vaccine)
4-9 years: 0.5 mL IM; administer 2 injections approximately 4 wk apart
10-17 years: Administer as in adults
Administer IM injection in anterolateral aspect of thigh for infants, and administer in deltoid
muscle of upper arm in toddlers and children.
Avoid gluteal region or areas with major nerve trunk,
Precautions
Guillain-Barré syndrome has occurred within 6 wk of previous influenza vaccination;
immunocompromised persons may have a diminished immune response to vaccine;
common injection site adverse effects (≥10%) include tenderness, pain, redness, and
swelling; common systemic adverse effects (≥10%) include headache, malaise, and
myalgia; multidose vial contains thimerosal, a mercury derivative.
*Trivalent seasonal influenza immunization is recommended for all children aged 6 months
through 18 years. Healthy children aged 2 through 18 years can receive either TIV or LAIV
[25].
Also the combination of A (H1N1) vaccine with trivalent seasonal vaccine would have
significant regulatory implications. [26]
Influenza A virus vaccine (H1N1), intranasal
Available as monovalent live virus vaccine for intranasal administration. Indicated for active
immunization against influenza caused by pandemic (H1N1) 2009 virus. Stimulates active
immunity to influenza virus infection by inducing production of specific antibodies.
Dose:
Adult
Intranasal (10-49 years): 0.2 mL/dose (0.1 mL per nostril) intranasally (1 dose)
Pediatric
Intranasal (MedImmune vaccine)
2-9 years: 0.2 mL/dose (0.1 mL per nostril) intranasally; administer 2 doses approximately 4
wk apart
>9 years: Administer as in adults
Precautions
Guillain-Barré syndrome has occurred within 6 wk of previous influenza vaccination;
adverse effects include rhinitis, nasal congestion, fever >100°F in children aged 2-6
y, and sore throat in adults; administer intranasal vaccine with caution to individuals with
asthma or recurrent wheezing; intranasal vaccine has potential for viral transmission to
immunocompromised household contacts.
References:
1-Christian Sandrock, Terra KellyCritical Care 2007, 11:209 (doi:10.1186/cc5675).
2. World Health Organization Expert Committee: A revision of the
system of nomenclature for influenza viruses: a WHO Memorandum.
Bull WHO 1980, 58:585-591.
3-Couceiro JN, Paulson JC, Baum LG: Influenza virus strains
selectively recognize sialyloligosaccharides on human respiratory
epithelium: the role of the host cell in selection of
hemagglutinin receptor specificity. Virus Res 1993, 29:155-165
4-Matrosovich MN, Matrosovich TY, Gray T, Roberts NA, Klenk HD:
Human and avian influenza (AI) viruses target different cell
types in cultures of human airway epithelium. Proc Natl Acad
Sci USA 2004, 101:4620-4624
5-Webster RG, Bean WJ, Gorman OT, Chambers TM, Kawaoka Y:
Evolution and ecology of influenza A viruses. Microbiol Rev
1992, 56:152-179.
6-Buxton Bridges C, Katz JM, Seto WH, Chan PK, Tsang D, Ho W,
Mak KH, Lim W, Tam JS, Clarke M, et al.: Risk of influenza A
(H5N1) infection among health care workers exposed to
patients with influenza A (H5N1), Hong Kong. J Infect Dis
2000, 181:344-348
7- Gray GC, McCarthy T, Capuano AW, Setterquist SF, Olsen CW, Alavanja MC (December
2007). "Swine workers and swine influenza virus infections". Emerging Infectious
Diseases 13 (12): 1871–8. PMID 18258038
8- World Health Organization (28 October 2005). "H5N1 avian influenza:
timeline".
9. Tran TH, Nguyen TL, Nguyen TD, Luong TS, Pham PM, Nguyen
VC, Pham TS, Vo CD, Le TQ, Ngo TT, et al.: Avian influenza A
(H5N1) in 10 patients in Vietnam. N Engl J Med 2004, 350:
1179-1188
10. Gruber PC, Gomersall CD, Joynt GM: Avian influenza (H5N1):
implications for intensive care. Intensive Care Med 2006,32:823-829
11- "Swine Flu and You". CDC. 2009-04-26. Retrieved 2009-04-26.
12-http://www.cdc.gov/h1n1flu/guidance/rapid_testing.htm.
13-Payungporn S, Phakdeewirot P, Chutinimitkul S, Theamboonlers
A, Keawcharoen J, Oraveerakul K, Amonsin A, Poovorawan Y:
Single-step multiplex reverse transcription-polymerase chain
reaction (RT-PCR) for influenza A virus subtype H5N1 detection.
Viral Immunol 2004, 17:588-593.
14-CDC. Guidance for Clinicians & Public Health Professionals.
http://www.cdc.gov/swineflu/guidance/. Available at http://www.cdc.gov/swineflu/guidance.
15-http://bestpractice.bmj.com/best-practice/monograph/1178/diagnosis/tests.html
16-. Jefferson TO, Demicheli V, Di Pietrantonj C, Jones M, Rivetti D:
Neuroaminidase inhibitors for preventing and treating
influenza in healthy adults. Cochrane Databse Syst Rev 2006,
Jul 19:3CD001265
17-Le QM, Kiso M, Someya K, Sakai YT, Nguyen TH, Nguyen KH,
Pham ND, Ngyen HH, Yamada S, Muramoto Y, et al.: Avian flu:isolation of drug-resistant
H5N1 virus. Nature 2005, 437:1108.
18-Nicholson KG, Colegate AE, Podda A, Stephenson I, Wood J,
Ypma E, Zambon MC: Safety and antigenicity of non-adjuvanted
and F59-adjuvanted influenza A/Duck/Singapore/97
(h5N3) vaccine: a randomized trial of two potential vaccines
against H5N1 influenza. Lancet 2001, 357:1937-1943
19-CDC. Interim Guidance for Clinicians on the Prevention and Treatment of Swine-Origin
Influenza Virus Infection in Young Children. Centers for Disease Control and Prevention.
Available at http://www.cdc.gov/swineflu/childrentreatment.htm
20-WHO guidelines for pharmacological management of pandemic (H1N1) 2009 influenza
and other influenza viruses. August 20, 2009. World Health Organization. Available at
http://www.who.int/csr/resources/publications/swineflu/h1n1_use_antivirals_20090820/en/ind
ex.html Accessed September 1, 2009.
21-CDC. Interim Guidance on Antiviral Recommendations for Patients with Confirmed or
Suspected Swine Influenza A (H1N1) Virus Infection and Close Contacts. Centers for
Disease Control and Prevention. Available at
http://www.cdc.gov/swineflu/recommendations.html
22-Peramivir EUA, Fact Sheet for HCP Authorized by FDA on October 23, 2009
23-Treanor JJ, Campbell JD, Zangwill KM, Rowe T, Wolff M: Saftey
and immunogenicity of an inactivated subviron influenza A
(H5N1) vaccine. New Engl J Med 2006, 354:1343-1351.
24- http://www.pediatrics.org/cgi/doi/10.1542/peds.2009-1806 Policy
Statement—Recommendations for the
Prevention and Treatment of Influenza in Children,
2009 –2010
25-http://emedicine.medscape.com/article/1673658-overview.
26- Recommendations of the Strategic Advisory Group of Experts (SAGE) on Influenza A
(H1N1) vaccines .19 May 2009
DOWNLOAD