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ournal of Infection and Public Health (2009) 2, 157—166

EVIEW

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anish Sinha ∗

enior Resident, Department of Neurology, Chhatrapati Shahuji Maharaj Medical University,ucknow 226003, India

eceived 9 June 2009; received in revised form 20 August 2009; accepted 27 August 2009

KEYWORDSSwine influenza;H1N1;Swine flu;Oseltamivir

Summary The recent outbreak of human infection with a novel Swine-OriginInfluenza A (H1N1) virus is spreading rapidly through sustained human-to-humantransmission in multiple countries. Human-to-human transmission occurs by inhala-tion of infectious droplets and droplet nuclei, and by direct contact, which isfacilitated by air and land travel and social gatherings. The most frequently reportedsymptoms are fever, cough, myalgia, and sore throat. Detailed contact and travelhistories and knowledge of viral activity in community are essential for prompt

case detection by the health personnel. Real-time Reverse Transcriptase-PolymeraseChain Reaction analysis of throat swabs or lower respiratory samples is a sensitivemeans of diagnosis. Use of oral oseltamivir may be warranted for the treatment ofsevere illness.© 2009 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

ontents

Introduction ................................................................................................ 158Clinical features ............................................................................................ 158

Transmission............................................................................................ 158Infectious period ....................................................................................... 158Incubation period ...................................................................................... 159Symptoms .............................................................................................. 159Complications .......................................................................................... 159

Mortality ............................................

Management .............................................Case detection ......................................Specimen collection.................................

∗ Tel.: +91 522 2756268.E-mail address: msinha1@yahoo.co.in.

876-0341/$ — see front matter © 2009 King Saud Bin Abdulaziz University for Health

oi:10.1016/j.jiph.2009.08.006

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................................................... 160

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Sciences. Published by Elsevier Ltd. All rights reserved.

158 M. Sinha

Virus detection......................................................................................... 160Real-time Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)............................ 160Viral culture ..................................................................................... 160Rapid antigen tests............................................................................... 160Immunofluorescent antibody testing ............................................................. 161

Case definition [13]..................................................................................... 161Hospitalization ......................................................................................... 161Antiviral agents ........................................................................................ 161

Oseltamivir ...................................................................................... 161Zanamivir ........................................................................................ 161Recommendations................................................................................ 162Post-exposure chemoprophylaxis ................................................................. 163

Antiviral resistance..................................................................................... 163Additional therapy ..................................................................................... 163

Prevention .................................................................................................. 163Immunization........................................................................................... 163Household and close contacts .......................................................................... 163Travel .................................................................................................. 164Public gathering........................................................................................ 164

Global efforts............................................................................................... 164Conclusions ................................................................................................. 164Conflict of interest.......................................................................................... 165

Acknowledgment.......................................................................................... 165.....

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Introduction

The recent outbreak of a novel Swine-OriginInfluenza A (H1N1) virus (S-OIV), which was firstdetected in April 2009 in California (USA) [1],has now migrated to other parts of the Americas,Europe, Australia, and Asia. S-OIV is a ‘triple-reassortment’ influenza virus, containing genesfrom human, swine, and avian influenza A viruses[2]. As of 19 August 2009, 210 countries haveofficially reported over 182,166 cases of S-OIVinfection, including 1799 deaths reported by over40 countries. The United States has reported themajority of fatal cases: 7511 laboratory-confirmedhuman cases, including 477 deaths. The othercountries reporting laboratory-confirmed cases areMexico, Canada, the United Kingdom, Australia,Thailand, Chile, Spain, Panama, Brazil, India, etc.[3]. On April 29, 2009 the World Health Organizationdesignated the outbreak a pandemic.

Clinical features

Transmission

Transmission of S-OIV is thought to occur in thesame way as seasonal flu [4,5]. Human-to-humantransmission occurs by inhalation of large infec-tious droplets and droplet nuclei as well as by

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irect contact with secretions or aerosols [6]. Pos-ibly, swine-to-human transmission may occur [7].t present, there is no evidence of spread of infec-ion by eating pork, or through water. Judging theandemic potential of S-OIV is difficult with limitedata, though recent epidemiological analyses sug-est its transmissibility is substantially higher thanhat of seasonal flu, and comparable with previousnfluenza pandemics [8].

nfectious period

ata regarding the estimated duration of S-OIVhedding by patients is limited and based uponeasonal influenza virus infection. In general, per-ons with S-OIV infection should be consideredotentially infectious from 1 day before to 7ays following illness onset or until symptomsesolve. Children, patients with lower respiratoryract infections, elderly and immunocompromisedatients might be infectious for up to 10 daysr longer [9,10]. This is due to low cytotoxic T-ymphocyte activity which is responsible for virallearance and recovery from infection [11]. Cyto-oxic T-lymphocyte activity declines in the elderly

s well as in immunocompromised individuals sohat viral shedding could persist longer in them12]. However, studies of viral shedding to definehe infectious period of S-OIV are needed. Theotential for persons with asymptomatic infection

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o be the source of infection to others is unknownut should be investigated.

ncubation period

he precise incubation period has not been estab-ished for S-OIV infection, it could range from 1o 7 days, and most likely from 1 to 4 days [13].his is comparable to the incubation period of avian

nfluenza A (H5N1) which is 1—8 days [14], butonger than that of seasonal human influenza (1—4ays) [15].

ymptoms

ovel S-OIV Investigation Team of Centers for Dis-ase Control and Prevention, United States ofmerica report a series of 642 cases from Unitedtates identified by enhanced surveillance andonfirmed by real-time RT-PCR, viral culture, oroth. The most frequently reported symptoms inhis series are fever (94%), cough (92%), and sorehroat (66%); 25% of patients report diarrhoea,nd a further 25% report vomiting [16]. Myal-ia and joint pains may also be present. Nineercent of patients in this series required hospi-alization. Of 22 hospitalized patients, 8 requireddmission to an intensive care unit, 4 had respi-atory failure, and two expired. Eleven patients50% of hospitalized patients in this series) hadadiologically confirmed pneumonia, including oneatient each of pneumomediastinum, necrotizingneumonia, and empyema. Radiographic changesn patents with pneumonia include diffuse, multifo-al, or patchy infiltrates, interstitial infiltrates, andegmental or lobular consolidation with air bron-hograms [17,18].

omplications

eople of any age with certain chronic medical con-itions, children less than 5 years, persons 65 orlder, and pregnant women might be at increasedisk for complications from S-OIV infection [19].omplications like pneumonia and dehydrationave required hospitalization in approximately—5% of confirmed cases in the United Statesnd 5—6% in Mexico [5,18]. Few bacterial infec-ions have been detected in patients with S-OIV;hese include empyema, necrotizing pneumonia,s well as ventilator-associated pneumonia due to

cinetobacter baumannii, Achromobacter xylosox-

dans, methicillin-resistant Staphylococcus aureus,nd Escherichia coli. Patients with ventilator-ssociated pneumonia have serious risk of deathup to 58%) mainly due to multi-organ failure [18].

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eurological complications in form of seizures iseported in four children in Texas with S-OIV devel-ped, though all four recovered fully [20].

There are few characteristics of this pandemichich appear unusual compared with a typical

nfluenza seasonal outbreak. First, the percentagef patients requiring hospitalization (2—6%) appearso be higher than would be expected during a typ-cal influenza season (0.4—1%) [21]. Second, theeed for hospitalisations for S-OIV infection haseen particularly high among persons aged betweenhe ages of 1.5 and 59 years [22], which is dif-erent than that of seasonal influenza, in whichevere infection requiring hospitalizations typicallyccurs in children aged less than 1 year and adultsged more than 65 years [21]. Why only few elderlyndividuals have been affected during the currentandemic is intriguing. This may be due to someegree of preexisting immunity in older individu-ls against antigenically similar influenza viruseshat circulated prior to 1957 [23]. Of five pregnantomen requiring hospitalization for S-OIV infec-

ion, one had spontaneous abortion (at 13 weeks ofestation) and one developed premature rupture ofembranes (at 35 weeks of gestation) [19].

ortality

s of August 19, 2009, there have been 182,166aboratory-confirmed cases of S-OIV worldwide,ncluding 1799 deaths (0.98%) [3]. Most of theeaths are reported by the Americas (1579 deaths).sian countries have reported 106 deaths. Europend Africa have reported fewer deaths.

Most of the deaths are related to respiratoryailure resulting from severe pneumonia and acuteespiratory distress syndrome [24]. Renal or multi-rgan failure occurs in 24% cases. In Mexico,ost of the deaths (54%) occurred in previously

ealthy individuals between the ages of 20 and 5924]. In other parts of world, most of the deathsccurred in individuals with underlying health prob-ems [25,26]. One death in Mexico and one deathn the US occurred in women who were in thehird trimester of pregnancy when they became ill19,24].

The number of deaths in US was highest amongeople 25—49 years of age (39%), followed by peo-le 50—64 year of age (25%) and people 5—24 year ofge (16%) [27]. This pattern is different from whats seen in seasonal influenza, where an estimated

0% of influenza-related deaths occur in people 65ears of age and older [21].

At present, the data seem to imply that this newirus is relatively mild, with case fatality ratiosround 1%, similar to or less than that seen for

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seasonal influenza [28]. However, simple interpre-tations of these crude figures at the beginning of apandemic may be misleading in terms of assessingseverity. This may occur due to bias in estimatesof the case fatality ratio (with time, efforts maybecome more focused on the most severe cases,leading to an overestimation of the case fatalityratio) and from the inevitable delay between symp-tom onset and death, which in the early phase ofthe epidemic can lead to underestimation of thecase fatality ratio if it is not adjusted for [29].

Management

Case detection

The possibility of S-OIV infection should be consid-ered in all patients with severe acute respiratoryillness in countries or territories with known S-OIV.Clinicians should consult their individual healthministries for information about incidence ofthe disease in their countries and guidelines forcase detection. Recommendations can also befound at the World health organization website(http://www.who.int/csr/resources/publications/swineflu/interim guidance/en/index.html) and theUnited States Centers for Disease Control and Pre-vention website (http://www.cdc.gov/swineflu).

As per United States Centers for Disease Controland Prevention guidelines [13], testing for S-OIVshould be considered in individuals with an acutefebrile respiratory illness (a measured tempera-ture of 37.8 ◦C or higher and recent onset of atleast one of the following: rhinorrhea, nasal conges-tion, sore throat, or cough) or sepsis-like syndrome.Priority for testing should be given to those whorequire hospitalization and those who are at highrisk for severe complications. In addition, patientshaving influenza-like illness developing within 7days of close contact with a person who is aconfirmed case of S-OIV infection, or who has trav-elled to areas with known S-OIV activity in past 7days, the possibility of S-OIV warrants consideration[30].

Not all individuals with suspected S-OIV infectionneed to have the diagnosis confirmed, particularly ifthe illness is mild [13]. Recommendations on whomto test may differ by state or country and cliniciansshould be aware of them. For countries with limitedlaboratory capacity, or limited access to laboratory

capacity, World Health Organization recommendsthat they should aim to test a number of samplesper week in order to verify that disease activity isstill largely due to S-OIV [30].

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M. Sinha

pecimen collection

o test for S-OIV, upper respiratory specimens, suchs a nasopharyngeal swab or aspirate, nasal wash,r tracheal aspirate should be collected with appro-riate personal protective precaution. Specimenshould be sent to the nearest laboratory which haseen equipped to test S-OIV. Swabs with a syn-hetic tip (e.g., polyester or Dacron) and aluminumr plastic shaft should be used. Swabs with cottonips and wooden shafts are not recommended. Theollection vial in which the swab is placed shouldontain 1—3 mL of viral transport media. Specimenshould be placed in viral transport media and placedn ice (4 ◦C) or refrigerated immediately for trans-ortation to the laboratory. Once the samples arriven the laboratory, they should be stored either in

refrigerator at 4 ◦C or in a −70 ◦C freezer. If a70 ◦C freezer is not available, they should be kept

efrigerated, preferably for ≤1 week. Specimenshould be shipped on dry ice to the state pub-ic health laboratory in clearly labeled containersnd should include all information requested by thetate health laboratory [13,30].

irus detection

eal-time Reverse Transcriptase-Polymerasehain Reaction (RT-PCR)he recommended test to confirm the diagnosis of-OIV is real-time RT-PCR for influenza A, B, H1,nd H3 [13,30]. The strain of H1N1 influenza A virusssociated with the 2009 pandemic tests positiveor influenza A and negative for H1 and H3 by real-ime RT-PCR.

iral culturevirus culture is diagnostic, but culture is usually

oo slow to help guide clinical management. A neg-tive viral culture does not exclude pandemic S-OIVnfection [13,31].

apid antigen testslinicians may consider using rapid influenza anti-en tests as part of rapid evaluation of patientsuspected of having S-OIV infection, but resultshould confirmed by real-time Reverse Transcrip-ase (RT)-PCR or culture [32]. The sensitivitynd specificity of rapid antigen testing for S-OIVnfection have not been established. Based onimited data, the sensitivity of rapid antigen test-

ng for detecting S-OIV is probably similar to, orower than, the sensitivity for detecting seasonalnfluenza [33]. A negative rapid influenza test doesot exclude infection [32].

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mmunofluorescent antibody testingpatient with a positive Immunofluorescent anti-

ody testing may be considered a probable case ife or she meets the other criteria. A negative testoes not exclude S-OIV infection since these testsave unclear sensitivity to detect this virus [34].

ase definition [13]

suspected case of S-OIV infection is defineds a person with acute febrile respiratory illnessfever = 37.8 ◦C) with onset:

(i) within 7 days of close contact with a personwho is a confirmed case of S-OIV infection, or

(ii) within 7 days of travel to areas where thereare one or more confirmed S-OIV cases, or

iii) resides in a community where there are one ormore confirmed swine influenza cases.

A probable case of S-OIV infection is defined asperson with an acute febrile respiratory illnessho:

(i) is positive for influenza A, but unsubtypable forH1 and H3 by influenza RT-PCR or reagents usedto detect seasonal influenza virus infection, or

(ii) is positive for influenza A by an influenza rapidtest or an influenza immunofluorescence assayplus meets criteria for a suspected case, or

iii) individual with a clinically compatible illnesswho died of an unexplained acute respiratoryillness who is considered to be epidemiologi-cally linked to a probable or confirmed case.

A confirmed case of S-OIV infection is defineds a person with an acute febrile respiratory illnessith laboratory-confirmed S-OIV infection by one orore of the following tests:

(i) Real-time RT-PCR(ii) Viral cultureiii) Four-fold rise in S-OIV specific neutralizing

antibodies.

ospitalization

ost cases of S-OIV infection tend to be mild andelf-limited and do not require visit to a healthare provider or hospitalization [16]. Patientsith severe illness and those at high risk foromplications from influenza should seek medicalare. Those with severe illness and complications

ay require prolong hospitalization, and in some

ases ventilatory support [5,18]. If patients areischarged early, both the patients and their fam-lies require education on personal hygiene andnfection-control measures.

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ntiviral agents

-OIV is susceptible to oseltamivir and zanamivir,euraminidase inhibitor antiviral medications,hich target the early phase of the infection. How-ver, this strain is resistant to adamantanes, suchs amantadine and rimantadine [35].

seltamivirseltamivir is a prodrug that is hydrolyzed by the

iver to its active metabolite, oseltamivir carboxy-ate, with an elimination half-life of about 6—10 h.seltamivir is a neuraminidase inhibitor, serving ascompetitive inhibitor of sialic acid, found on the

urface proteins of normal host cells. By blockinghe activity of the neuraminidase, oseltamivir pre-ents new viral particles from being released bynfected cells [36]. The therapeutic oral dosageor S-OIV infection in adults is 75 mg taken twiceaily for 5 days, starting within 48 h of the ini-ial symptoms to capture the early phase of viraleplication (Table 1). For chemoprophylaxis, theecommended dosage is 75 mg taken once dailyor 10 days after exposure. Therapeutic and pro-hylactic dosing schedules for children are similarabout 2 mg/kg twice a day for 5 days for treatment,nd 2 mg/kg once a day for 10 days for prophy-axis) [13]. Adverse effects of oseltamivir includesausea, vomiting and transient neuropsychiatricvents (self-injury or delirium). These dangerouside effects occur more commonly in children anddolescents [37]. Nausea and vomiting might be lessevere if oseltamivir is taken with food.

anamiviranamivir is administered by inhalation with a dryowder inhaler. The bioavailability of the drug is0—20% by inhalation, compared with 2% by oraldministration. About 90% of the absorbed doses excreted unchanged in the urine. The elimi-ation half-life in serum of zanamivir is about—5 h [38]. The mechanism of action is similar toseltamivir. The therapeutic dose is 10 mg inhaledwice daily for 5 days starting within 48 h of the ini-ial symptoms. For chemoprophylaxis, the dose is0 mg inhaled once daily for 10 days after exposureTable 1). The recommended doses for children arehe same. Because zanamivir therapy requires theatient to voluntarily inhale through the device,

seltamivir may be preferred over zanamivir foroung children. Zanamivir is not recommended forreatment for patients with chronic airway diseaser asthma as it can induce bronchospasm [38].

162 M. Sinha

Table 1 Antiviral medication dosing recommendations for treatment or chemoprophylaxis of S-OIV infection.

Agent, group Treatment Chemoprophylaxis

OseltamivirAdults 75 mg capsule twice daily

for 5 days75 mg capsule once daily

Children ≥12 months 15 kg or less 60 mg per day divided into2 doses

30 mg once daily

15—23 kg 90 mg per day divided into2 doses

45 mg once daily

24—40 kg 120 mg per day dividedinto 2 doses

60 mg once daily

>40 kg 150 mg per day dividedinto 2 doses

75 mg once daily

ZanamivirAdults Two 5 mg inhalations

(10 mg total) twice dailyTwo 5 mg inhalations(10 mg total) once daily

Children Two 5 mg inhalations(10 mg total) twice daily

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RecommendationsDuring the current pandemic, patients with mildillness do not require antiviral agents unless theyhave risk factors for complications [13]. However,the decision of whether to initiate antiviral therapyfor each patient should be based upon the clin-ician’s judgment, especially in areas with limitedantiviral availability. Clinicians should consult withtheir ministries of health and/or the World HealthOrganization for specific recommendations.

The United States Centers for Disease Controland Prevention has released guidelines for the useof antivirals for patients with confirmed or sus-pected S-OIV infection and close contacts which areas follows [13].Adults. Antiviral therapy should be started in alladult hospitalized patients with confirmed, proba-ble, or suspected patients and in those at increasedrisk for complications. Therapy should be startedas soon as possible, since evidence of benefit isstrongest when treatment is started within 48 h ofillness onset. Some studies of hospitalized patientshave demonstrated benefit even when therapy forseasonal influenza is started >48 h after onset ofillness [5,17,18]. In patients with severe infection,therapy can be started even past 48 h of symptoms.Recommendations for use of antivirals may changeas data on antiviral effectiveness, clinical spectrumof illness, adverse events from antiviral use, andantiviral susceptibility data become available.

Pregnancy. Oseltamivir and zanamivir are Preg-nancy Category C drugs, reflecting that clinicalstudies have not been done to assess the safetyof their use during pregnancy [13,35]. Because of

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ore data about its safety in pregnancy, the usef oseltamaivir is preferred over zanamavir dur-ng pregnancy. Both oseltamivir and zanamivir areonsidered to be compatible with breastfeeding39]. Pregnant women who meet case definitions foronfirmed, probable, or suspected S-OIV infectionhould receive antiviral therapy with oseltamivir,ince the potential benefit outweighs the theoreti-al risk to the fetus. Treatment should be initiateds early as possible.

In addition to antiviral therapy, use ofcetaminophen is important when fever is present,ince hyperthermia during the first trimester haseen associated with neural tube defects and otherirth defects [40]. In addition, fever during labor isrisk factor for neonatal seizures, encephalopathy,erebral palsy, and neonatal death [41].hildren. All hospitalized children with con-rmed, probable, or suspected S-OIV infection andhose at higher risk of complications should receiventiviral agents. In addition, all children youngerhan 5 years of age, particularly those less than 2ears of age, are at increased risk for complicationsf influenza. Either oseltamivir or zanamivir can beiven in children, when indicated, during the cur-ent pandemic [13]. For children less than 1 yearf age, oseltamivir is the recommended drug. Chil-ren taking oseltamivir should be closely observedor serious neuropsychiatric events as described

Children who may have influenza infectionhould not take aspirin or aspirin-containing prod-cts, such as bismuth subsalicyclate due to thencreased risk of Reye syndrome [42].

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ost-exposure chemoprophylaxisost-exposure chemoprophylaxis should be consid-red for both close contacts of cases and healthare personnel who have had a recognized, unpro-ected close contact exposure to a confirmed,robable or suspected case during the infectiouseriod of that patient. Close contact is defined aserson who has cared for or lived with a person whos a confirmed, probable or suspected case of S-OIVnfection, or having been to a setting where thereas a high likelihood of contact with respiratoryroplets and/or body fluids of such a patient. Exam-les of close contact include kissing or embracing,haring eating or drinking utensils, physical exami-ation, or any other contact between persons likelyo result in exposure to respiratory droplets. Closeontact typically does not include activities such asalking by an infected person or sitting across fromsymptomatic patient in a waiting room or office

43].For antiviral chemoprophylaxis of S-OIV infec-

ion, either oseltamivir or zanamivir can be givenTable 1). Antiviral post-exposure chemoprophy-axis should be given for 10 days after the lastnown exposure to S-OIV.

ntiviral resistance

s with other antiviral agents, resistance tohe agent is expected with widespread use ofseltamivir and zanamivir. At least five isolatesf S-OIV with resistance to oseltamivir have beenetected from patients in Denmark, Japan, Hongong, and Canada [44,45]. Mutations conferringesistance are single amino acid residue substitu-ions (His274Tyr) in the neuraminidase enzyme [46].

However, in locations where oseltamivir-esistant virus is circulating, zanamivir may beiven. In such a setting, for patients who arenable to take zanamivir, rimantadine, amantadiner ribavarine may be added to oseltamivir [47].ne recent study has reported reduced zanamivirusceptibility in nine influenza A (H1N1) viruses iso-ated between 2006 and early 2008 from Australasiand South East Asia which contained a previouslyndescribed Gln136Lys (Q136K) neuraminidaseutation [48].

dditional therapy

dditional therapy such as antibiotics should be

sed at the discretion of the clinicians if theatient’s clinical condition warrants. Patients withandemic S-OIV infection who develop pneumoniahould be treated empirically for community-cquired pneumonia [49]. In patients with severe

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ommunity-acquired pneumonia requiring inten-ive care unit admission who also have either necro-izing/cavitary infiltrates or empyema, pathogensike methicillin-resistant S. aureus (MRSA), A. bau-annii, A. xylosoxidans and E. coli infection shoulde suspected and treated aggressively as mortalityay be high among them [18].Role of corticosteroids in the management of

everely ill patients with novel S-OIV infections unclear, and routine corticosteroid use is notecommended. Low doses of corticosteroids maye considered for patients in septic shock whoequire vasopressors and have suspected adrenalnsufficiency. Prolonged use of or high dose corti-osteroids can result in serious adverse events innfluenza virus-infected patients, including oppor-unistic infection and possibly prolonged viraleplication [50].

revention

mmunization

accines are the most powerful public health toolor control of influenza. Seasonal influenza vaccinesre not expected to provide protection against-OIV infection because this novel strain hemagglu-inin is different from seasonal influenza A (H1N1)51]. Around 20 vaccine manufacturers are prepar-ng to make S-OIV vaccine, and it is expected toe available as early as September 2009 [52]. Asaccines available initially will not be sufficient, atep-wise approach to vaccinate particular groupsay be considered. The Strategic Advisory Group of

xperts of the World Health Organization suggestedhe following groups for consideration, noting thatountries need to determine their order of prior-ty based on country-specific conditions: healthcareroviders; pregnant women; those aged above 6onths with one of several chronic medical condi-

ions; healthy young adults of 15—49 years of age;ealthy children; healthy adults of 50—64 years ofge; and healthy adults of 65 years of age andbove. Since the S-OIV vaccine is not intended toeplace the seasonal flu vaccine, individuals shoulde encouraged to get their seasonal flu vaccinelong with it [52].

ousehold and close contacts

ousehold contacts of persons with confirmed casesf S-OIV should receive post-exposure prophylaxiss described above. Contacts of a patient withroven or suspected virus should monitor their tem-

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perature and symptoms. Medical attention shouldbe sought if they have fever greater than 37.8 ◦Cplus one or more of the following: rhinorrhea ornasal congestion; sore throat; cough. All peopleof patient’s family, including patient, should covertheir cough and wash hands often. People withinfluenza-like illness should remain at home untilat least 24 h after they are free of fever (37.8 ◦C),or signs of a fever without the use of fever-reducingmedications [53]. In community and home settings,the use of facemasks and respirators are not rec-ommended, except for persons at increased risk ofsevere illness from influenza. However, healthcareproviders caring for persons with confirmed, prob-able or suspected S-OIV infection should wear N-95respirator [54].

Travel

People with symptoms of flu should not leave homeor travel. If symptoms develop during flight or pub-lic transport vehicle, the person with illness shouldprotect others by wearing a facemask if tolera-ble to reduce the number of droplets coughed orsneezed into the air or use a tissue to cover theirnose and mouth when coughing or sneezing. Theperson with illness should sit at least 6 feet apartfrom others without compromising flight safety. Ifthe person with illness is travelling to a differentcountry, the captain of the plane should report theillness to quarantine officials in the jurisdiction ofthe airport where the plane is expected to landprior to arrival or as soon as illness is noted. Quar-antine officials will work with the airline and localand state health departments to assist with medicaltransportation of the patient upon arrival, diseasecontrol and containment measures, passenger andcrew notification and surveillance activities, andairline disinfection procedures [55].

Public gathering

In public gatherings, it is difficult to maintain phys-ical distance between people. As a result, theremay be increased risk for spread of S-OIV. Suchgatherings can include school or college classes,church services, sporting events, concerts, socialand cultural celebrations, weddings, conferences,and other similar activities attended by relativelylarge groups of people. It is recommended that per-sons with influenza-like illness should avoid such

gatherings and stay at home for 7 days after theonset of illness or at least 24 h after symptoms haveresolved, whichever is longer [56]. Persons who areat high risk of complications from S-OIV infectionshould consider staying away from public gather-

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ngs in communities where S-OIV is circulating. Allersons should be reminded to use appropriate res-iratory and hand hygiene precautions.

Further, large public gatherings offer a goodpportunity for public health officials and eventrganizers to deliver key educational messagesbout measures attendees can take to help reducehe spread of S-OIV infection. Other measures likeand washing facilities with soap and running water,and sanitizer, tissues, and on-site medical assess-ent can be provided by event organizers to help

educe the risk for infection. [57].School closures are not universally recom-

ended due to ethical concerns, though policiesay vary in different countries [58]. However, it

s pertinent to mention that the current pandemicpread to United States from Mexico in March—April009 after some students of a New York school con-racted S-OIV infection during a visit to Mexico overpring break [1].

lobal efforts

orld Health Organization (WHO) is actively mon-toring the progress of the pandemic throughonsultations with its Regional Offices and mem-er states. WHO has teamed up with agenciesike United States Centers for Disease Controlnd Prevention, the Pan-American Health Orga-ization/(PAHO/WHO), Global Outbreak Alert andesponse Network, European Centre for Diseaserevention and Control, and the China Centreor Disease Prevention and Control to betternderstand the outbreak, including clinical illnesseverity and transmission patterns, and to facilitatehe production and distribution of S-OIV vaccine.

onclusions

lthough it has been just over four month sincehe first few cases were identified, the outbreakf human infection with a novel S-OIV is spread-ng rapidly through sustained human-to-humanransmission in multiple countries. The spread ofnfection has been facilitated by air and land travelnd social gatherings. The better understanding ofoutes of transmission, clinical features, pathogen-sis, and perhaps, response to treatment is required

o check the spread of infection. Detailed contactnd travel histories and knowledge of viral activ-ty in community are essential for prompt caseetection by the health personnel. Real-time RT-CR analysis of throat swabs or lower respiratory

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amples may offer sensitive means of diagnosis.se of oral oseltamivir may be warranted for thereatment of severe illness. Above all, there is anrgent need for global coordination in clinical andpidemiologic research to control this outbreak.

onflict of interest

unding: None.Competing interests: None declared.Ethical approval: Not required.

cknowledgment

one.

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