swine influenza

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SWINE E INFLUEN NZA

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In 1743, when disease was presumed to be astral in origin, European newspapers reported on a contagious influence (influenza in Italian) that was being visited on the citizens of Rome. Two hundred years later, Wilson Smith and colleagues would isolate an influenza A virus, one of the members of the orthomyxovirus family. Swine influenza virus (SIV) or S-OIV (swine-origin influenza virus) is any strain of the influenza family of viruses that is endemic in pigs. As of 2009, the known SIV strains include influenza C and the subtypes of influenza A known as H1N1, H1N2, H3N1, H3N2, and H2N3. Swine influenza (also called Pig influenza, swine flu, hog flu and pig flu) is an infection by any one of several types of swine influenza virus. In all, 50 cases are known to have occurred since the first report in medical literature in 1958, which have resulted in a total of six deaths. Of these six people, one was pregnant, one had leukemia, one had Hodgkin disease and two were known to be previously healthy. Despite these apparently low numbers of infections, the true rate of infection may be higher, since most cases only cause a very mild disease, and will probably never be reported or diagnosed. This article presents the scenario of the 2009 H1N1 influenza, popularly known as “swine flu” and the data from inpatient admissions in Indraprastha Apollo Hospitals, Delhi, for the duration October 2009 to January 2010.

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Page 1: Swine Influenza

 

 

 

 

 

                  

 

                  

                       

                       

            

                             

SWINEE INFLUEN 

  

NZA

Page 2: Swine Influenza

Review Article

THE PRESENT SCENARIO-2009 H1N1

INFLUENZA (“SWINE FLU”)

2009 H1N1influenza, (sometimes called “swine flu”) isa new influenza virus causing illness in people. This newvirus was first detected in people in the United States inApril 2009. This virus is spreading from person-to-personworldwide, probably in much the same way that regularseasonal influenza viruses spread. On June 11, 2009, theWorld Health Organization (WHO) signaled that apandemic of 2009 H1N1 flu was underway.

This virus was originally referred to as “swine flu”because laboratory testing showed that many of the genes inthis new virus were very similar to influenza viruses thatnormally occur in pigs (swine) in North America [1]. Butfurther study has shown that this new virus is very differentfrom what normally circulates in North American pigs [2-4]. It has two genes from flu viruses that normally circulatein pigs in Europe and Asia and bird (avian) genes andhuman genes [5]. Scientists call this a “quadruplereassortant” virus [6] (Fig. 1).

Illness with 2009 H1N1 virus has ranged from mild tosevere. While most people who have been sick haverecovered without needing medical treatment,

hospitalizations and deaths from infection with this virushave occurred.The information analyzed by CDC supportsthe conclusion that 2009 H1N1 flu has caused greaterdisease burden in people younger than 25 years of age thanolder people [7]. At this time, there are relatively fewercases and deaths reported in people 65 years and older,

21 Apollo Medicine, Vol. 7, No. 1, March 2010

SWINE INFLUENZA

Suresh Chandra*and Neelam Bisht**

*Senior Consultant, **Associate Consultant, Department of Internal Medicine, Indraprastha Apollo Hospitals, Sarita Vihar,New Delhi 110076, India.

Correspondence to: Dr Suresh Chandra, Senior Consultant, Department of Internal Medicine, Indraprastha Apollo Hospitals,Sarita Vihar, New Delhi 110 076, India.

In 1743, when disease was presumed to be astral in origin, European newspapers reported on a contagiousinfluence (influenza in Italian) that was being visited on the citizens of Rome. Two hundred years later, WilsonSmith and colleagues would isolate an influenza A virus, one of the members of the orthomyxovirus family.Swine influenza virus (SIV) or S-OIV (swine-origin influenza virus) is any strain of the influenza family ofviruses that is endemic in pigs. As of 2009, the known SIV strains include influenza C and the subtypes ofinfluenza A known as H1N1, H1N2, H3N1, H3N2, and H2N3. Swine influenza (also called Pig influenza, swineflu, hog flu and pig flu) is an infection by any one of several types of swine influenza virus. In all, 50 cases areknown to have occurred since the first report in medical literature in 1958, which have resulted in a total of sixdeaths. Of these six people, one was pregnant, one had leukemia, one had Hodgkin disease and two wereknown to be previously healthy. Despite these apparently low numbers of infections, the true rate of infectionmay be higher, since most cases only cause a very mild disease, and will probably never be reported ordiagnosed. This article presents the scenario of the 2009 H1N1 influenza, popularly known as “swine flu” andthe data from inpatient admissions in Indraprastha Apollo Hospitals, Delhi, for the duration October 2009 toJanuary 2010.

Key words: Swine flu, H1N1 influenza, Apollo experience.

Fig.1. Electron microscope image of the reassorted H1N1influenza virus

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Apollo Medicine, Vol. 7, No. 1, March 2010 22

Review Article

getting sick to 5 to 7 days after. This can be longer in somepeople, especially children and people with weakenedimmune systems [10,11].

SIGNS AND SYMPTOMS

Mild or uncomplicated illness is characterized bytypical symptoms like fever (although not everyone withinfluenza will have a fever), cough, sore throat, rhinorrhea,muscle pain, headache, chills, malaise, sometimes diarrheaand vomiting, but no shortness of breath and little change inchronic health conditions [12].

Progressive illness is characterized by typicalsymptoms plus signs or symptoms suggesting more thanmild illness: chest pain, poor oxygenation (e.g., tachypnea,hypoxia, labored breathing in children), cardiopulmonaryinsufficiency (e.g., low blood pressure), CNS impairment(e.g., confusion, altered mental status), severe dehydration,or exacerbations of chronic conditions (e.g., asthma,chronic obstructive pulmonary disease, chronic renalfailure, diabetes or other cardiovascular conditions) [13].

Severe or complicated illness is characterized by signsof lower respiratory tract disease (e.g., hypoxia requiringsupplemental oxygen, abnormal chest radiograph,mechanical ventilation) (Fig. 2), CNS findings(encephalitis, encephalopathy), complications of low bloodpressure (shock, organ failure), myocarditis orrhabdomyolysis, or invasive secondary bacterial infection

which is unusual when compared with seasonal flu(Table 1). However, pregnancy and other previouslyrecognized high risk medical conditions from seasonalinfluenza appear to be associated with increased risk ofcomplications from this 2009 H1N1. These underlyingconditions include asthma, diabetes, suppressed immunesystems, heart disease, kidney disease, neurocognitive andneuromuscular disorders.

CDC laboratory studies have shown that no childrenand very few adults younger than 60 years old have existingantibody to 2009 H1N1 flu virus; however, about one-thirdof adults older than 60 may have antibodies against thisvirus. It is unknown how much, if any, protection may beafforded against 2009 H1N1 flu by any existing antibody.

EPIDEMIOLOGY

Spread of 2009 H1N1 virus is thought to occur in thesame way that seasonal flu spreads. Flu viruses are spreadmainly from person to person through coughing orsneezing by people with influenza [8]. Sometimes peoplemay become infected by touching something – such as asurface or object – with flu viruses on it and then touchingtheir mouth or nose [9]. The 2009 H1N1 virus is notzoonotic swine flu, as it is not transmitted from pigs tohumans, but from person to person.

People infected with seasonal and 2009 H1N1 flu shedvirus and may be able to infect others from 1 day before

Table 1. CDC estimates of 2009 H1N1 cases and related hospitalizations and deaths from April-November 14,

2009, by age group

2009 H1N1 Mid-level range* Estimated range *

Cases

0-17 years ~16 million ~12 million to ~23 million

18-64 years ~27 million ~19 million to ~38 million

65 years and older ~4 million ~3 million to ~6 million

Cases Total ~47 million ~34 million to ~67 million

Hospitalizations

0-17 years ~71,000 ~51,000 to ~101,000

18-64 years ~121,000 ~87,000 to ~172,000

65 years and older ~21,000 ~15,000 to ~29,000

Hospitalizations Total ~213,000 ~154,000 to ~303,000

Deaths

0-17 years ~1,090 ~790 to ~1,550

18-64 years ~7,450 ~5,360 to ~10,570

65 years and older ~1,280 ~920 to ~1,810

Deaths Total ~9,820 ~7,070 to ~13,930

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23 Apollo Medicine, Vol. 7, No. 1, March 2010

based on laboratory testing or clinical signs (e.g. persistenthigh fever and other symptoms beyond three days) [14].

People at high risk for developing flu-relatedcomplications

• Children younger than 5, but especially childrenyounger than 2 years old

• Adults 65 years of age and older

• Pregnant women

• People who have medical conditions including:

• Asthma

• Neurological and neurodevelopmental conditions[including disorders of the brain, spinal cord,

peripheral nerve, and muscle such as cerebralpalsy, epilepsy (seizure disorders), stroke,intellectual disability (mental retardation),moderate to severe developmental delay, musculardystrophy, or spinal cord injury].

• Chronic lung disease (such as chronic obstructivepulmonary disease [COPD] and cystic fibrosis)

• Heart disease (such as congenital heart disease,congestive heart failure and coronary arterydisease)

• Blood disorders (such as sickle cell disease)

• Endocrine disorders (such as diabetes mellitus)

• Kidney disorders

• Liver disorders

• Metabolic disorders (such as inherited metabolicdisorders and mitochondrial disorders)

• Weakened immune system due to disease ormedication (such as people with HIV or AIDS, orcancer, or those on chronic steroids)

• People younger than 19 years of age who arereceiving long-term aspirin therapy.

DIAGNOSIS

Case definition of H1N1 influenza

Suspected case

A suspected case of swine influenza A (H1N1) virusinfection is defined as: a person with acute febrilerespiratory illness (fever = 38ºC) with onset: within 7 daysof close contact with a person who is a confirmed case ofSwine influenza A (H1N1) virus infection, or within 7 daysof travel to areas where there is one or more confirmedSwine influenza A (H1N1) cases, orresides in a communitywhere there is one or more confirmed swine influenzacases.

Probable case

A probable case of swine influenza A (H1N1) virusinfection is defined as: a person with an acute febrilerespiratory illness who is positive for influenza A, butunsubtypable for H1 and H3 by influenza RTPCR orreagents used to detect seasonal influenza virus infection,or is positive for influenza A by an influenza rapid test orinfluenza immunofluorescence assay (IFA) plus meetscriteria for a suspected case, or an individual with aclinically compatible illness who died of an unexplainedacute respiratory illness who is considered to beepidemiologically linked to a probable or confirmed case.

Fig.2. The radiograph (A) shows bilateral alveolar opacitiesin the base of both lungs that progressed and becameconfluent. The specimen (B, hematoxylin and eosin)shows necrosis of bronchiolar walls (top arrow), aneutrophilic infiltrate (middle arrow), and diffuse alveolardamage with prominent hyaline membranes (bottomarrow).

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Confirmed case

A confirmed case of swine influenza A (H1N1) virusinfection is defined as: a person with an acute febrilerespiratory illness with laboratory confirmed swineinfluenza A (H1N1) virus infection at WHO approvedlaboratories by one or more of the following tests:Real timePCR,,Viral culture,Four-fold rise in swine influenza A(H1N1) virus specific neutralizing antibodies.

DIAGNOSTIC TESTS

This season CDC recommends that influenzadiagnostic testing be prioritized for (i) hospitalized patientswith suspected influenza, (ii) patients for whom a diagnosisof influenza will inform decisions regarding clinical care,infection control, or management of close contacts; and (iii)patients who died of an acute illness in which influenza wassuspected.

Most patients with a clinical illness consistent withuncomplicated influenza who reside in an area whereinfluenza viruses are circulating do not require diagnosticinfluenza testing for clinical management [15,16].

Rapid influenza diagnostic tests (RIDTs)

Rapid influenza diagnostic tests (RIDTs) are widelyavailable, commercial diagnostic tests that can detectinfluenza viruses in 30 minutes or less. Depending onwhich commercially available RIDT is used, the test caneither (i) detect and distinguish between influenza A and Bviruses; or (ii) detect both influenza A and B but notdistinguish between influenza A and B viruses. Rapidinfluenza diagnostic tests (RIDTs) are widely available buthave variable sensitivity (range 10-70%) for detecting 2009H1N1 influenza when compared with real-time reversetranscriptase polymerase chain reaction (rRT-PCR), and anegative RIDT result does not rule out influenza virusinfection. RIDTs have a high specificity (>95%).

Viral culture

Viral culture is available in certain laboratories butoften does not provide results in time to help with clinicaldecisions. However, viral culture is an important source ofpublic health virologic data on influenza antigeniccharacteristics and antiviral susceptibilities. Viral culture ishighly sensitive and specific.

Direct immunofluorescence assays (DFAs) and

Indirect immunofluorescence assays (IFAs)

Immunofluorescence (fluorescent antibody staining) isavailable at many hospital laboratories and can generallyyield test results in 2 to 4 hours, and sensitivities are

generally higher than rapid tests, but lower than viralculture or real-time reverse transcriptase polymerase chainreaction (rRT-PCR). Like RIDTs, direct immunofluore-scence assays (DFAs) are widely available and havevariable sensitivity for detecting 2009 H1N1 virus (range47-93%). DFAs detect and distinguish between influenza Aand B viruses but do not distinguish among differentinfluenza A subtypes.

Real-time reverse transcriptase polymerase chain

reaction (rRT-PCR)

Nucleic acid amplification tests, including rRT-PCR,are the most sensitive and specific influenza diagnostictests, but they may not be readily available, obtaining testresults may take one to several days, and test performancedepends on the individual rRT-PCR assay. As with anyassay, false negatives can occur. Table 2 summarises thediagnostic tests for influenza.

Hospitalized patients with suspected influenza shouldbe considered for testing with an available influenzadiagnostic test. Since a negative RIDT or DFA test resultdoes not exclude influenza virus infection, hospitalizedpatients with a negative RIDT or DFA result should havepriority for further testing with rRT-PCR, if influenzainfection is clinically suspected.

Specimens

The following specimens are generally appropriate forinfluenza virus diagnostic testing: nasopharyngeal swab;nasal aspirate, wash or swab; endotracheal aspirate;bronchoalveolar lavage (BAL); and combinednasopharyngeal or nasal swab with oropharyngeal swab.The performance of rRT-PCR assays specific for 2009H1N1 influenza has not been established forbronchoalveolar lavage and tracheal aspirates. If testingthese specimens for 2009 H1N1 influenza, consider testingin parallel with a nasopharyngeal, nasal, or oropharyngealswabs or a nasal aspirate.

TREATMENT

Antiviral drugs for treatment of influenza

The neuraminidase inhibitors are the drugs of choice fortreatment of 2009 H1N1 influenza and influenza-likeillness in both children and adults [17].

Oseltamivir: The neuraminidase inhibitor oseltamivirformulated as capsules or oral suspension (Tamiflu®) isFDA-approved for the treatment of uncomplicated acuteinfluenza in patients 1 year and older who have beensymptomatic for no more than 2 days.

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Definitive testing for 2009 H1N1 requires real-timereverse transcriptase-polymerase chain reaction (rRT-PCR)or viral culture. These tests should be prioritized forpersons with suspected or confirmed influenza requiringhospitalization and based on guidelines from local and statehealth departments.

Rapid influenza diagnostic tests (RIDTs) should not beused to rule out influenza because false negative results arecommon. The sensitivity of rapid tests in detecting 2009H1N1 has ranged from 10% to 70%. Clinicians should notwithhold treatment based on a negative rapid test result.

Zanamivir: The neuraminidase inhibitor zanamivirformulated for oral inhalation (Relenza®) is FDA-approved for the treatment of influenza in patients 7 yearsof age and older who, similar to approved uses foroseltamivir, have uncomplicated illness and have beensymptomatic for no more than 2 days.

Peramivir: A third neuraminidase inhibitor peramivirformulated for intravenous (IV) administration is aninvestigational product currently being evaluated in clinicaltrials. As of October, 2009, safety and/or efficacy data from1,891 patients with acute uncomplicated seasonalinfluenza A has been submitted to the FDA. Efficacy andsafety have not been evaluated in hospitalized patients [18].Even though the data are insufficient to allow FDAapproval,under the EUA, treatment of adult patients withIV peramivir is approved only if: (i) the patient has notresponded to either oral or inhaled antiviral therapy; (ii)drug delivery by a route other than IV is not expected to bedependable or is not feasible; or (iii) the clinician judges IVtherapy is appropriate due to other circumstances.

Initiation of treatment

Uncomplicated influenza illness

The algorithm for treating uncomplicated influenzaillness is as follows (Fig.3). Treatment should be startedempirically based on clinical judgment as early as possibleeven before definitive diagnostic test results becomeavailable, i.e., treatment should not wait for laboratoryconfirmation of influenza. Treatment is most effectivewhen started in the first 48 hours of illness. As noted above,however, evidence suggests treatment may benefit patientswith prolonged or severe illness even when started morethan 48 hours after the onset of illness (Table 3). Fig.3. Algorithm for treating uncomplicated influenza illness

Table 2. Diagnostic tests for influenza

Influenza diagnostic Method Availability Typical Sensitivity for Distinguishes 2009tests processing 2009 H1N1 H1N1 influenza

time influenza from otherinfluenza Aviruses?

Rapid influenza diagnostic Antigen detection Wide 0.5 hour 10-70% Notests (RIDT)

Direct and indirect immuno- Antigen detection Wide 2-4 hours 47-93% Nofluorescence assays (DFAand IFA)

Viral isolation in tissue cell Virus isolation Limited 2-10 days – Yesculture

Nucleic acid amplification tests RNA detection Limited 48-96 hours 86-100% Yes(including rRT-PCR) (6-8 hours to

perform test)

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Treatment of influenza when oseltamivir-resistant

viruses are circulating

Oseltamivir resistance is common among seasonalinfluenza A (H1N1) viruses. These viruses typically remainsusceptible to zanamivir, rimantadine, and amantadine.However, since April 2009, very few seasonal H1N1viruses have circulated in the United States. Therefore,treatment, when indicated, with either oseltamivir orzanamivir is appropriate. However, if viral surveillancedata indicate that oseltamivir-resistant seasonal H1N1viruses have become more common or are associated withidentified community outbreaks, zanamivir or acombination of oseltamivir and rimantadine or amantadineshould be considered for use as empiric treatment forpatients who might have oseltamivir-resistant seasonalhuman influenza A (H1N1) virus infection (Table 4) [19].

Oseltamivir-resistant infection with the 2009 pandemicinfluenza A (H1N1) virus has so far been described only ina cluster in Vietnam and is conferred by the H275Ysubstitution in the neuraminidase enzyme. The resistant2009 H1N1 are transmissible and can replicate and causeillness in healthy people in the absence of selective drug

pressure. Although data are limited, it is likely that thedetected levels of oseltamivir resistance are clinicallyrelevant [20]. The risk of resistance is considered higher inpatients with severely compromised or suppressed immunesystems who have prolonged illness, have receivedoseltamivir treatment (especially for an extended duration),but still have evidence of persistent viral replication.

The risk of resistance is also considered higher inpeople who receive oseltamivir for so-called “post-exposure prophylaxis” following exposure to anotherperson with influenza, and who then develop illness despitetaking oseltamivir [21].

The loss of oseltamivir as a treatment option for severe2009 H1N1 infection could have profound consequences.To minimize this risk, the use of oseltamivir should berestricted to prophylaxis and treatment in high-riskpersons or the treatment of people with severe ordeteriorating illness, antiviral stockpiles should bediversified, and optimal dosages and combinationtherapies should be urgently studied. Close monitoring andreporting of resistance to neuraminidase inhibitors areessential [22].

Table 3. Antiviral medication dosing recommendations for treatment or chemoprophylaxis of 2009 H1N1 infection

Medication Treatment(5 days) Chemoprophylaxis(10 days)

OseltamivirAdults

75 mg twice daily 75 mg once daily

Children 12 months

Body weight (kg) Body weight (lbs)

15 kg 33lbs 30 mg twice daily 30 mg once daily

> 15 kg to 23 kg >33 lbs to 51 lbs 45 mg twice daily 45 mg once daily

>23 kg to 40 kg >51 lbs to 88 lbs 60 mg twice daily 60 mg once daily

>40 kg >88 lbs 75 mg twice daily 75 mg once daily

Children 3 months to < 12 months

3 mg/kg/dose twice daily 3 mg/kg/dose once per day

Children 0 to < 3 months

3 mg/kg/dose twice daily Not recommended unlesssituation judged critical due tolimited data on use in this agegroup

Zanamivir

Adults

10 mg (two 5 mg 10 mg (two 5 mg inhalations) once daily

inhalations) twice daily

Children ( 7 years or older for treatment, 5 years for chemoprophylaxis)

10 mg (two 5 mg inhalations) 10 mg (two 5 mg inhalations) once daily twice daily

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Antiviral chemoprophylaxis of exposed

individuals

Infectious period

One day before fever begins until 24 hours after feverends.

Who may be considered for antiviralchemoprophylaxis

The following persons who are a close contact of aperson with suspected or confirmed 2009 H1N1 influenzaduring the infectious period: Persons at high risk forcomplications of influenza, health care workers andemergency medical personnel, pregnant women.

Whom not to treat chemoprophylactically

Groups of healthy children or adults based on potentialexposures in the community, workplace, school, camp orother settings, if >48 hours have elapsed since the last closecontact, the close contact did not occur during theinfectious period .

PREVENTION

Everyday steps to protect your health

• Cover your nose and mouth with a tissue when youcough or sneeze. Throw the tissue in the trash afteryou use it.

• Wash your hands often with soap and water. If soap

and water are not available, use an alcohol-based handrub. Avoid touching your eyes, nose or mouth. Germsspread this way.

• Avoid close contact (i.e., being within about 6 feet)with persons with influenza like illness.

• If you are sick with flu-like illness, CDC recommendsthat you stay home for at least 24 hours after yourfever is gone except to get medical care or for othernecessities. (Your fever should be gone without theuse of a fever-reducing medicine.) Keep away fromothers as much as possible to keep from making otherssick

• Chance of transmission is also reduced bydisinfecting household surfaces, which can be doneeffectively with a diluted chlorine bleach solution.Studies have shown that influenza virus can surviveon environmental surfaces and can infect a person for2 to 8 hours after being deposited on the surface.

Interim recommendations for facemask and

respirator use to reduce 2009 influenza A (H1N1)

virus transmission

Use of N95 respirators or facemasks generally is notrecommended for workers in non-healthcare occupationalsettings for general work activities. For specific workactivities that involve contact with people who haveILI(influenza like illness), such as escorting a person withILI, interviewing a person with ILI, providing assistance to

Table 4.When to consider the use of antibiotics in the treatment of 2009 H1N1 influenza–associated pneumonia

Indication Primary influenzal Secondary bacterial pneumonialower respiratory disease following influenza

Identification of influenza +++ ++; lower rate of recovery because later in illness

Fever +++ +++; secondary fever after a period ofdefervescence

Diagnostic specimen from lower Normal flora Gram's stain or culture shows pre-respiratory tract (sputum speci- dominant organism (Streptococcusmen, tracheal aspirate, specimen pneumoniae, Staphylococcus aureus,obtained on bronchoscopy of Streptococcus pyogenes, Hemophilusintubation) influenzae, Moraxella catarrhalis)

X-ray Diffuse process Lobar consolidation

White-cell count Normal to low Increased

Onset of respiratory compromise 1-2 days after initial symptoms 4-7 days after initial symptoms

ill contacts in family +++ +++

Underlying risk factors (particularly ++ ++neuromuscular, immunologic

++ denotes often found, and +++ usually found.

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an individual with ILI, the following are recommended:

• workers should try to maintain a distance of 6 feet ormore from the person with ILI;

• workers should keep their interactions with ill personsas brief as possible;

• the ill person should be asked to follow good coughetiquette and hand hygiene and to wear a facemask, ifable, and one is available;

• workers at increased risk of severe illness frominfluenza infection should avoid people with ILI(possibly by temporary reassignment); and,

• where workers cannot avoid close contact withpersons with ILI, some workers may choose to wear afacemask or N95 respirator on a voluntary basis.

• In the occupational healthcare setting, respiratoryprotection is recommended.

VACCINES

Vaccination is the best way to prevent influenzainfection and its complications. Seasonal influenzavaccines are highly effective in preventing influenzadisease [23]. The vaccines against 2009 H1N1 influenzaare expected to work in a similar fashion to the seasonalinfluenza vaccines. CDC and FDA believe that the benefitsof vaccination with the 2009 H1N1 influenza vaccine faroutweigh the risks.

• Killed, inactivated vaccines – Manufacturers areusing WHO recommended recombinant/re-assortantvaccine seed strains. This is most accepted type ofstrategy and is being followed by three Indianmanufacturers (Serum Institute of India, BharatBiotech and Panacea Biotech).

• Live attenuated nasal vaccines (LAIV)– Thesevaccines are based on the principle of production ofseasonal influenza vaccine originally manufacturedby Russians but now marketed in USA also.(Proposed by Serum Institute of India Ltd).

• Vaccines using virus like particles (VLP)– Theseare genetically engineered vaccines in which only theproteins are expressed which form non-infectiousvirus-like-particles. So far only one vaccinedeveloped this technology has been approved by theFDA (USA) – a vaccine for prevention of cervicalcancer. Cadila Pharmaceutical India Ltd. hasproposed production of an H1N1 vaccine using thistechnology in technical collaboration with a US based

company Novavax , in which Cadila has a majorityshare. The technology has been licensed to Cadila inIndia and it will set up a plant to manufacture thevaccine in India. This has already been assessed andapproved by Review Committee for genetically andEngineered Modified Organisms (RCGEM) of DBT.The merits of this technology are to be debated by ahigh-powered committee.

• Recombinant fusion protein subunit vaccine usingtoll like receptors (TLR) in E coli expressionvector– Biological E Ltd. Hyderabad, has proposedproduction of an H1N1 vaccine using this technologyplatform in technical collaboration with Vaccinate (aUS based biotech company). The technology is beingtransferred to Biological E and the vaccine would bemanufactured at Hyderabad. Approval of theRCGEM is being sought. Further details of the time-lines of preclinical and human studies are awaited.

2009 H1N1 ACIP vaccination recommendations

CDC’s Advisory Committee on Immunization Practices(ACIP), a panel made up of medical and public healthexperts, met July 29, 2009, to make recommendations onwho should receive the 2009 H1N1 vaccine [24]. Thegroups recommended to receive the 2009 H1N1 influenzavaccine include:

• Pregnant women because they are at higher risk ofcomplications and can potentially provide protectionto infants who cannot be vaccinated;

• Household contacts and caregivers for childrenyounger than 6 months of age because younger infantsare at higher risk of influenza-related complicationsand cannot be vaccinated. Vaccination of those inclose contact with infants younger than 6 months oldmight help protect infants by “cocooning” them fromthe virus;

• Healthcare and emergency medical servicespersonnel because infections among healthcareworkers have been reported and this can be a potentialsource of infection for vulnerable patients. Also,increased absenteeism in this population could reducehealthcare system capacity;

• All people from 6 months through 24 years of age;

• Children from 6 months through 18 years of agebecause cases of 2009 H1N1 influenza have beenseen in children who are in close contact with eachother in school and day care settings, which increasesthe likelihood of disease spread;

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• Young adults 19 through 24 years of age becausemany cases of 2009 H1N1 influenza have been seenin these healthy young adults and they often live,work, and study in close proximity, and they are afrequently mobile population; and,

• Persons aged 25 through 64 years who have healthconditions associated with higher risk of medicalcomplications from influenza.

The 2009 H1N1 vaccine is not intended to replace theseasonal flu vaccine. It is an additional influenza vaccinefor this influenza season. Many people will berecommended to get both vaccines. So the best advice is,get the seasonal flu vaccine as soon as it is available in yourcommunity, and if you are in one of the recommendedgroups, get the 2009 H1N1 vaccine when it becomesavailable .

The 2009 H1N1 influenza vaccine is showing a similarsafety profile to seasonal flu vaccines, which have a verygood safety track record [24]. The most common sideeffects following flu vaccinations are mild, such assoreness, redness, tenderness or swelling where the shotwas given.

In 1976, there was a small risk of GBS followinginfluenza (swine flu) vaccination (approximately 1additional case per 100,000 people who received the swineflu vaccine). That number of GBS cases was slightly higherthan what is normally seen in the population, whether or notpeople were vaccinated. Since then, numerous studies havebeen done to evaluate if other flu vaccines were associatedwith GBS. In most studies, no association was found, buttwo studies suggested that approximately 1 additionalperson out of 1 million vaccinated people may be at risk forGBS associated with the seasonal influenza vaccine [25-26]. FDA and CDC are closely monitoring reports ofserious problems following the 2009 H1N1 influenzavaccines, including GBS. Flu antiviral drugs taken from 48hours before through 2 weeks after getting LAIV can loweror prevent the vaccinated person from responding to thevaccine and the person may not get immune protectionfrom the vaccine.

Contraindication for vaccination

People who have a severe (life-threatening) allergy tochicken eggs or to any other substance in the vaccineshould not be vaccinated.

APOLLO EXPERIENCE OF 2009 H1N1 DISEASE

Starting from October 2009 till January 2010,therewere 94 admissions for suspected H1N1 disease. Of

these,72 were confirmed to be H1N1 influenza by throatswab RTPCR test. The mean age of presentation was 32yrs, and 21% of patients were less than 18 years of age. Themale and female ratio was 1:1, and the median time ofpresentation to our hospital was 6 days.

Symptomatology

Fever was present in all the patients, while theoccurrence of other symptoms were as follows-cough 88%,sore throat 55.6%, shortness of breath 58.3%, diarrhea22.2% and vomiting 13.9% (Fig. 4).

Coexisting illnesses

Coexisting illness were present in 75% patients-hypertension (9), diabetes mellitus (11), allergic bronchitis(3), COPD (2), bronchial asthma (6), dyslipidemia (2),pulmonary tuberculosis (1), coronaryartery disease(4),hypothyroidism (2), pregnancy (2), obesity (1), psoriasis(1), post op meningioma (1), old splenic infarct (1), postAVR (1), Wegener’s disease (1), polycystic ovarian disease(1), post renal transplant (2), CLL (1), CVA (1) (Fig.5).

Laboratory abnormalities

Laboratory abnormalities observed in the patients were-leucopenia 19.4%, leucocytosis 16.7%, deranged liverfunction tests 38.9%, deranged renal profile 27.8% andthrombocytopenia 8.3%. Two patients had positive dengueserology, and the coinfection of H1N1 influenza anddengue fever has not been reported elsewhere till now.

Fig. 4. Symptomatology of patients (A-fever, B-cough,C-shortness of breath, D-sore throat, E-diarrhea,F-vomiting).

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Chest X ray revealed varied findings like few infiltrates,bronchopneumonia and ARDS in 56.9% patients and44.4% patients required non invasive ventilation.33.3%patients required invasive ventilation and mortality washigh in this group 23.6% (Fig. 6).

During the period October 2009 to January 2010,therewere 94 admissions with suspected swine flu,however,72of them were confirmed with RTPCR assay.Majority of thepatients presented within 6 days of illness and fever,coughand shortness of breath were the most commoncomplaints.An overwhelming 75% of these patients hadvaried preexisting medical or surgical illnesses. Patientswith an abnormal Chest X Ray were more likely to receiveventilatory support.Multiorgan dysfunction was commonin patients with ARDS and this group carried a highmortality as expected.There were two patients with acoinfection with Dengue virus,a phenomenon which hasnot been reported yet.

Swine flu’s lesson for the medical professionals

Other than humility and a familiar lesson about thedangers of hubris, what can we learn from the soberingrealities presented by these latest developments? First,preparation is an important and necessary activity, but in noway is it protective. One might even argue that it can havethe negative consequence of lulling us into thinking wehave a problem covered, when clearly we never do. Indefense of this panic-driven approach, the product may notbe entirely useless: preparation, albeit for the wronginvader, sharpens reflexes and can have at least some

minimal practical yield, such as stockpiles of protectivegear for health care workers.

Second, we should marvel at the raw, restless power ofmicrobes. They have the numbers – trillions andquadrillions and more that replicate wildly, inaccurately,and disinterestedly. Nothing microbes do, whether underthe duress imposed by antimicrobials or from some lessevident pressure, should surprise us. It’s their world; weonly live in it. In this regard, it is perhaps fitting that ourmost successful incursion against them – Fleming’sdiscovery of penicillin on a nearly discarded culture plate –is immortalized as a fluke, an accident, the product ofsloppy laboratory hygiene, anything but a headlongManhattan Project–like assault against the enemy.

Finally, and perhaps most important, doctors should bereminded against profligate use of antimicrobial agents.Once again, it seems that our message against profligate useof antimicrobial agents has crept over into the realm ofmorality, that comic-book world of good guys and badguys. Yes, over prescribing of antibiotics is an enormousproblem that must be curtailed. It causes predictableproblems, and its interruption results in predictable relief ofdrug resistance. Just as we must watch our waistlines andour bottom lines and not drink to excess and never exceedthe speed limit, in the same spirit we must control runawayantibiotic use because it will help people’s health and savemoney–but not because such restraint is holy or somehowseparates good people from bad. In the future, we mustresolve to keep fire and brimstone out of public healthdecisions. Otherwise, good judgment, necessary alertness,and scientific doubt also may go up in smoke.

Fig. 5. Coexisting illnesses in the patients (A-hypertension,B-diabetes mellitus, C- allergic bronchitis, D-COPD, E-bronchial asthma, F-dyslipidemia, G-pulmonarytuberculosis, H-coronary artery disease, I-hypothyroidism, J-pregnancy, K-obesity, L-psoriasis, M-post op meningioma, N-old splenic infarct, O-post AVR,P-Wegener’s disease, Q-polycystic ovarian disease, R-post renal transplant, S-CLL, T-CVA ).

Fig. 6. Laboratory abnormalities in the patients (A-leucopeniaB-leucocytosis, C-deranged liver function tests,D-deranged renal profile, E-thrombocytopenia,F-abnormal Chest X-ray).

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