Transcript
Page 1: ARTICLE ORIGINAL/ORIGINAL ARTICLE INFLUENZAA (H1N1) …lebanesemedicaljournal.org/Articles/60-2/Original2.pdfARTICLE ORIGINAL/ORIGINAL ARTICLE INFLUENZAA (H1N1) 2009 PANDEMIA ... Noha

AARRTTIICCLLEE OORRIIGGIINNAALL//OORRIIGGIINNAALL AARRTTIICCLLEEINFLUENZA A (H1N1) 2009 PANDEMIATHE EXPERIENCE OF A TERTIARY CARE CENTER IN BEIRUThttp://www.lebanesemedicaljournal.org/articles/60-2/original2.pdfRania NAOUFAL1, Jihad IRANI2, Isabelle DJAFFAR JUREIDINI1, Noha HAKIME1, Eid AZAR3

George JUVELEKIAN4, Mona HADDAD5, Claude AFIF3,5

INTRODUCTION

Influenza A is a single-stranded RNA virus belonging tothe family Orthomyxoviridae. It is characterized by twotypes of glycoprotein spikes that project from its surface:hemaglutinin HA and neuraminidase NA [1-2]. InfluenzaA viruses are subtyped according to those two glycopro-

teins. New strains of influenza are the result of mutationsin the HA and NA genes, which occur via two mechanisms[3-4]. Antigenic drift occurs during replication of the influ-enza virus, with errors in progeny genes leading to fre-quent mutations. The second mechanism is the antigenic

Naoufal R, Irani J, Djaffar Jureidini I, Hakime N, Azar E,Juvelekian G, Haddad M, Afif C. Influenza A (H1N1) 2009pandemia : The experience of a tertiary care center in Beirut. J Med Liban 2012 ; 60 (2) : 70-76.

Naoufal R, Irani J, Djaffar Jureidini I, Hakime N, Azar E,Juvelekian G, Haddad M, Afif C. Influenza A (H1N1) : Expé-rience d’un hôpital universitaire libanais durant la pandémie de 2009. J Med Liban 2012 ; 60 (2) : 70-76.

ABSTRACT • INTRODUCTION : In March 2009, a newinfluenza virus strain emerged, currently known as the2009 pandemic H1N1 virus. The virus first appeared inMexico and rapidly spread globally to reach a pan-demic level in June of the same year. We describe herethe experience of one major referral center in Beirut,Lebanon.

MATERIALS AND METHODS : The Laboratory Depart-ment at St. George Hospital University Medical Centerreceived respiratory specimens from hospital wards,the Emergency Department, in addition to a consider-able proportion collected directly from “outpatients”in the lab. We used the real time RT-PCR as our maindiagnostic test. We collected data about the patientsfrom the Laboratory Information System and from theHospital Medical Records Department.

RESULTS : From mid-August 2009 till the end of Jan-uary 2010, a total of 1771 specimens were analyzed,with 948 (53.5%) returning positive for influenza A(H1N1) by RT-PCR. Only 79 patients with H1N1 in-fection required hospitalization. Most of H1N1 con-firmed patients were children and adolescents aged 5 to17 years and young adults between 25 and 44 years. The most common symptoms at presentation were:fever, cough, shortness of breath, chills, rhinorrhea ornasal congestion, as well as gastrointestinal symptoms.Twenty-three patients required ICU care and eight pa-tients died. The vast majority had an uncomplicatedcourse of illness and was managed in an outpatient setting.

CONCLUSION : The percentage of positive tests dur-ing the pandemia was significantly elevated, althoughfew patients experienced drastic clinical outcomes.

From the University of Balamand and Saint George Hospital University Medical Center, Beirut, Lebanon.Departments of • Laboratory Medicine1 • Medicine: Division of Family Medicine2, Division of Infectious Diseases3, Division ofPulmonary Medicine4 • Infection Control5.

Correspondence to: Claude Afif, MD. University of Balamand, St George Hospital University Medical Center. PO Box 166378.Beirut. Lebanon.

e-mail: [email protected] Tel.: +961 1 566 781 Fax: +961 1 566 780

RÉSUMÉ • INTRODUCTION : En mars 2009, une nouvellesouche de virus influenza a émergé, couramment connuesous le nom de grippe pandémique du virus H1N1 2009.Apparu au Mexique, le virus s’est propagé rapidementdans le monde pour atteindre un niveau pandémique enjuin de la même année. Nous décrivons ici l’expérienced’un centre hospitalier universitaire à Beyrouth (Liban).

MATÉRIELS ET MÉTHODES : Le laboratoire de l’hôpi-tal St. Georges, centre médical universitaire, a collectéles échantillons respiratoires provenant des différentsservices de l’hôpital, des urgences en plus d’une pro-portion considérable prélevés en consultations externes.Nous avons utilisé la PCR en temps réel (RT-PCR)comme test de diagnostic principal. Les données despatients ont été recueillies à partir du système informa-tique du laboratoire et du département des archivesmédicales.

RÉSULTATS : De la mi-août 2009 jusqu’à fin janvier2010, un total de 1771 échantillons a été analysé, avec948 (53,5%) tests positifs pour la grippe A (H1N1) parRT-PCR. Seulement 79 patients infectés par le virusH1N1 ont dû être hospitalisés. La plupart des patientsatteints de grippe A H1N1/09 étaient des enfants et desadolescents âgés de 5 à 17 ans, et de jeunes adultes entre25 et 44 ans. Les symptômes les plus fréquents à l’ad-mission étaient : fièvre, toux, essoufflement, frissons,rhinorrhée ou congestion nasale, ainsi que des symp-tômes gastro-intestinaux. Vingt-trois patients ont néces-sité des soins intensifs et huit patients sont décédés.Dans la grande majorité des cas la maladie a suivi uncours normal, sans complications, et a été gérée enambulatoire.

CONCLUSION : Le pourcentage de tests positifs au coursde la pandémie était significativement élevé, bien que peude patients aient présenté un tableau clinique sévère aveccomplications.

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shift, which happens when a cell is co-infected with two ormore different influenza A subtypes, enabling exchange of full RNA segments. The 2009 pandemic H1N1 virus isa triple reassortant influenza virus containing genes fromavian, human, and swine influenza viruses. Since swinecells have receptors for both avian and human influenzastrains, co-infected swine cells served as mixing vesselsand allowed antigenic shift resulting in the emergence of anew influenza subtype [5-7].

In March 2009, an increased number of influenza-likeillnesses were reported in Mexico. In April 2009, a novelinfluenza A virus (H1N1) was identified, later on desig-nated as the 2009 pandemic virus. On June 11, the WorldHealth Organization (WHO) declared the 2009 H1N1influenza a phase 6 pandemic [8-9] characterized by com-munity level outbreaks in at least two continents.

The first cases of H1N1 in Lebanon were reported dur-ing the month of June. The Ministry of Public Health(MOPH) activated surveillance systems and kept track ofall reported cases. Several actions were undertaken by theMOPH: holding awareness campaigns, providing medicalcare in all health care systems; offering free testing in agovernmental hospital in Beirut, and distribution of anti-viral treatment. Saint George Hospital was one of the twomajor centers where diagnosis of H1N1/09 was available.Real time polymerase chain reaction was used (RT-PCR).Epidemiological data about the pandemic 2009 influenzaA virus in Lebanon is scarce, and no study have been pub-lished so far about the outbreak in Lebanon.

The objective of this study is to describe the experienceof one major center in Lebanon with the H1N1/09 influen-za A virus. It represents the first medical report aboutH1N1 pandemia in Lebanon. This will help drawing con-clusions and learning lessons for better preparedness dur-ing future pandemics.

MATERIALS AND METHODS

As of the third of August 2009, the Laboratory Depart-ment at Saint George Hospital University Medical Center(SGHUMC) started analyzing respiratory specimens forH1N1 influenza. Before that date, the Governmental Hos-pital of Beirut was the sole institution performing suchanalysis. We included in our review all analyzed speci-mens collected between that date and January 2010,excluding duplicates.

The specimens consisted of nasal and/or throat swabs,sputum, bronchoalveolar lavage fluids, and endotrachealtubes. The majority of specimens were collected from out-patients presenting to the Laboratory Department, the restwere sent from patients visiting the Emergency Depart-ment, and from hospitalized patients. We screened all thepatients for H1N1 positivity, but only those who werehospitalized were retained for further analysis retrospec-tively. Specimens were submitted to the Molecular Sec-tion of the Laboratory Department and were directly pro-cessed after collection during the working hours or storedat –80 ºC until processing. The results were reported with-

in 12-24 hours. The technique of choice was nucleic acidanalysis; we didn’t use the Rapid Antigen Test (RAT) as itwasn’t recommended due to high rates of false negative[10-13]. Viral nucleic acid was extracted using the HighPure Viral Nucleic Acid Kit (Roche Diagnostics). Foreach specimen, the screening for influenza A virus andinfluenza A pandemic H1N1 subtype was conducted inparallel by real time polymerase chain reaction (RT-PCR).A one-step RT-PCR using the Real-Time Ready RNAVirus Master and the Real-Time Ready Influenza A/H1N1detection set (Roche Diagnostics) was performed on theLight Cycler 2.0 Instrument according to the recommen-dations of the manufacturer. The detection of influenza Aviruses was done through Influenza A Matrix Protein 2gene M2, whereas that of the influenza pandemic H1N12009 strain relied on a specific H1N1 gene only present inthis new strain.

Specimens that were positive with both assays werereported as positive for the influenza pandemic H1N12009 strain, and those which were negative with bothassays as negative. A positivity with the H1N1 assay witha negative result with the Influenza A assay should not beinterpreted and the whole run should be repeated (situa-tion not encountered). A negative result with the H1N1together with a positive one for the influenza A wouldindicate an infection with a seasonal influenza A virus (notfound).

We used the Laboratory Information System (LIS) tocollect data about outpatients: date of testing, age, sex andresult; while data concerning the hospitalized patients wereretracted from the Archives Department. We designed aformat sheet to select the necessary information from eachpatient’s medical records: demographics, presenting symp-toms, workup, management and outcome.

The risk factors for severe disease from pandemicH1N1 2009 virus infection were assigned for each patientaccording to the WHO definition [14], and included thefollowing: infants and young children < 5 years; preg-nant women; persons with chronic pulmonary disease(bronchiectasis, asthma, hyper reactive airway disease, and chronic obstructive pulmonarty disease); persons withchronic cardiovascular disease (congestive heart failure,cardiomyopathy, congenital heart disease, valvulopathy,cardiac arrhythmia, and hypertension); persons with meta-bolic disorder and diabetes; persons with certain neu-rological conditions (neuromuscular, neurocognitive, andseizure disorders); persons with benign hematological diseases (paroxysmal nocturnal hemoglobinuria, autoim-mune hemolytic diseases), persons with malignancy(either solid tumor or hematological neoplasm); and per-sons aged 65 years and older.

We classified our patients according to specific age intervals, with emphasis on the extremes of age (high riskgroups). Infants and children < 5 years old were groupedtogether, and the other end included the elderly aged > 65 years.

Uncomplicated influenza was defined according to theWHO [14] as: an initial presentation with any influenza-

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like illness symptom but without dyspnea or shortness ofbreath, no signs of severe dehydration, no clinical or radio-logical signs of lower respiratory tract disease involvement,no secondary complication, no exacerbation of chronicunderlying disease and no signs of progressive disease.

We applied descriptive methods for the frequencies andpercentages of the different variables. The positivity ratewas defined as the number of individuals testing positivefor H1N1, out of all the tested individuals. We used the χ2 test or Fischer Exact Test for bivariate analysis. A

p-value < 0.05 was considered statistically significant. We used the SPSS 16.0 version for Windows® in the sta-tistical analysis.

The Institutional Review Board (IRB) approval wasaccorded by the research committee at Saint GeorgeHospital to review the patients’ medical charts.

RESULTS

The outbreak was characterized by two waves. The firstwave occurred in August 2009 with the positivity ratereaching 69% during the last week of August. The viralactivity declined after, but reached new peaks duringNovember and December with up to 86% of positivecases (Fig. 1).

DemographicsFrom mid-August until the end of January, 1771 requestswere analyzed, with 948 (53.5%) testing positive forinfluenza A (H1N1) virus by RT-PCR. Of those 948 pos-itive patients, 869 (91.7%) were outpatients, and only 79 (8.3%) were hospitalized. The mean age was 24, rang-ing from newborns to 93 years; 48.6% were males and51.4% were females. The age groups with the highest pos-itive percentages of H1N1 were children aged 5-17 andadults between 25-44 years (Fig. 2). Table I describes thecharacteristics of the 79 hospitalized patients. The highesthospitalization rate was seen in children < 5 years, and inyoung adults between 25 and 44 years. The most commonrisk factors for complications recorded in our study popu-lation were age less than 5 in addition to having chroniccardiovascular diseases.

Hospitalized patientsPresenting symptoms – Symptoms at presentation includ-

ed fever (87%), cough (73%), shortness of breath(39%), chills (35%), rhinorrhea or nasal congestion(33%), myalgia (25%), fatigue and weakness (25%) andheadaches (18%). Gastrointestinal symptoms, i.e. nau-

350

300

250

200

150

100

50

01 3 5 7 9 11 13 15 17 19 21 23

Weeks starting August 3rd, 2009

FIGURE 1. H1N1 detection at St George Hospital University Medical Center from Aug 2009 to Jan 2010.

Total tests

Positive tests

TABLE IPATIENTS CHARACTERISTICS

VARIABLE N (%)

Gender Male 43 (54.4)Female 36 (45.6)

Age groups < 5 28 (35.4)5-17 8 (10.1)18-24 5 (6.3)25-44 17 (21.5)45-65 9 (11.4)> 65 12 (15.2)

Risk factors Age < 5 28 (35.4)Age > 65 12 (15.2)Chronic cardiovascular disease 16 (20.3)Chronic pulmonary disease 9 (11.4)Hematological neoplasm 7 (8.9)Chronic neurological disease 6 (7.6)Diabetes mellitus 6 (7.6)Solid tumor 6 (7.6)Benign hematological disease 5 (6.3)Prematurity 4 (5.1)Autoimmune disease 2 (2.5)Pregnancy 2 (2.5)Metabolic disease 1 (1.3)

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sea, vomiting and diarrhea were encountered in 32.9%of patients. The time between onset of symptoms andadmission to the hospital ranged between one day and45 days with a mean of 4.7 days. The admission diag-nosis was influenza-like illness in 61% of patients,while 13% had an admission diagnosis of pneumonia.

Diagnostic workup – The workup done upon presentationshowed a mean WBC count of 9,300/mm3 (range 300-36,100). Sixty-two percent had lymphopenia (absolutelymphocyte count < 1500/mm3); 62% were anemic and24% had thrombocytopenia. The mean highly sensitiveC-reactive protein (hs-CRP) was 9.2 (range 0.07 to43.54). The majority of patients had abnormal chestradiography findings: 48% had infiltrates and 11% hadevidence of consolidation. Other less occurring findingsincluded pneumothorax, pleural effusion and pneumo-mediastinum.

Management – Sixty-four out of the 79 patients receivedOseltamivir at the usual doses (75 mg twice daily) with22% among them receiving a double dose (150 mgtwice daily). Antibiotic therapy, either prophylactic ortherapeutic for bacterial super-infection was given to87% of patients. Thirty patients (38%) received a courseof corticosteroids.

Clinical outcome – The mean length of stay was 11 days(SD 14; median 6; range: 2-71 days). Most of the pa-tients were discharged during the first week (Fig. 3).Only thirteen patients had an uncomplicated influenzacourse as per the WHO definition [14], whereas 66 pa-tients (83.5%) had at least one complication (Table II).

Special populationsPatients with nosocomial H1N1 – Five of our patients met

the criteria for nosocomial acquisition of the 2009H1N1 virus (onset of illness > 72 hours after hospitaladmission [15]); they all had good outcomes.

Patients with leukemia – Five children with leukemia had

the H1N1 virus. Two presented with febrile neutrope-nia, two had evidence of lower respiratory tract involve-ment and one had an uncomplicated course. They allshowed clinical improvement.

Patients admitted to ICU – Admission to the ICU wasrequired for 23 patients (39%); four out of those 23patients were previously healthy with no risk factors forcomplications from influenza A virus. Seventy percentof those admitted to ICU were less than 5 years old andonly two patients were older than 65 years.

DeathsThe mortality rate was 10% with a total of 8 deaths, 6 ofthem were in the extremes of age and/or had at least oneunderlying medical condition. The reported cause of deathwas H1N1 infection in 4 patients, cancer in 2 patients; onepatient died of heart failure and another of pulmonaryembolus. Of the 8 mortality patients, 5 were attributable to

TABLE IICLINICAL COURSE

N (%)Outcome

Uncomplicated influenza 13 (16.5)Complicated/severe influenza 66 (83.5)

ComplicationPresenting clinical and/or radiological signs 55 (69.6)

of lower respiratory tract infectionRespiratory failure/ ALI / ARDS 22 (27.8)Exacerbation of chronic disease 12 (15.2)Infectious complications and/or septic shock 10 (12.6)One single organ or multi-organ failure 7 (8.9)

Death 8 (10.1)

ALI : acute lung injury ARDS : adult respiratory distress syndrome

0 20 40 60 80Length of stay (days since admission)

FIGURE 3. Length of stay in the hospital.

Prop

ortio

n of

pat

ients

in th

e ho

spita

l

1.0

0.8

0.6

0.4

0.2

0.0

FIGURE 2. Patients who tested positive for H1N1 at St GeorgeHospital University Medical Center between Aug 2009 & Jan 2010.

450

400

350

300

250

200

150

100

50

0< 5 5 to 17 18 to 24 25 to 44 45 to 65 > 65

Age groups

Patients with positive H1N1 Hospitalized with positive H1N1 Percent admission

Survival FunctionCensored

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H1N1 illness and the other 3 were included in the totalmortality. With 8 patients not surviving the pandemicH1N1 influenza virus, the case fatality rate was 0.8%.

Postmortem studiesPostmortem studies were performed on two patients whosemortality was attributed to H1N1, and who died of multi-organ failure after having severe ARDS. The autopsy wassimilar in both patients, reporting severe viral pneumonitisas the cause of death and the main pathological finding inthe lung tissue was a diffuse alveolar damage.

Predictors of worst outcomeA correlation between having a risk factor for severe dis-ease from H1N1 influenza and ICU admission, length of stay > 5 days and dying was studied (Table III). Twostatistically significant parameters were found: young age < 5 years as a risk factor for ICU admission (p-value< 0.001) in addition to prematurity (p-value: 0.006).

DISCUSSION

By June 2009, the new influenza A (H1N1) virus hadreached Lebanon, three months after the first notificationof the infection in Mexico. As previous pandemics, the2009 outbreak is characterized by successive pandemicwaves [16]. Indeed Lebanon witnessed a first wave duringthe summer period and a second one, much more pro-nounced, in the fall. The viral activity started to declinetowards the end of December in accordance with the glob-al decrease in the 2009 H1N1 influenza activity reportedby the WHO. Very few sporadic cases were seen afterJanuary; but it was not until the 10th of August 2010 thatthe influenza virus was declared to have moved to thepost-pandemic period [17].

In Saint George Hospital, a total of 948 cases were con-firmed during the two waves. It is important to note thatnone of our isolates tested positive with the Influenza Aassay and negative with the H1N1/09 assay, confirmingthe true pandemic nature of this period. The true incidenceof infection might be considerably underestimated sincetesting was not uniformly performed. The Center forDisease Control (CDC) published guidelines limiting lab-oratory testing to hospitalized patients having influenza-like illness, to patients having high risk of complications,to patients whom a PCR diagnosis would affect the courseof treatment, and to those who have died of an acute ill-ness in which influenza was suspected [18]. Thereafter inJuly 2009, the WHO stopped requiring countries to reportthe number of cases [3].

The patients’ age distribution in this study was similarto what has been described elsewhere. The WHO reportedthat most patients worldwide were teenagers and youngadults in contrast to the seasonal influenza where older persons are the most affected [14, 19-21]; 84% of ourstudy group fell within this range. Serologic studies sug-gest that elderly persons may have cross-protective anti-bodies [5, 7, 22-23], due to the similarity with viruses thatcirculated before 1957.

Our analysis only addressed the 79 hospitalized pa-tients, thus the hospitalization rate was 8.3%, a comparablerate to that in Mexico (8%) and higher than that fromCanada and the USA [3]. Almost half of our patients wereyounger than 18 years; this finding is similar to that seen inthe USA from April to June 2009 [24]. 26.6% of our hos-pitalized patients had no risk factors for influenza relatedcomplications. The remaining 73.4% patients had one ormore underlying co-morbidity including age extremes. Ina study of 272 hospitalized patients with H1N1 in theUSA, 73% were at risk for complications [1].

TABLE III ASSOCIATION BETWEEN RISK FACTORS AND SELECTED OUTCOMES

RISK FACTORS ADMISSION TO ICU LENGTH OF STAY > 5 DAYS DEATH

Frequency (%) p-value* Frequency (%) p-value Frequency (%) p-value

Sex Male 12 (27.9) 0.796 29 (67.4) 0.278 4 (9.3) 1.000Female 11 (30.6) 20 (55.6) 4 (11.1)

Age < 5 16 (57.1) < 0.001 ** 20 (71.4) 0.233 2 (7.1) 0.705Age > 65 2 (16.7) 0.492 9 (75) 0.520 3 (25) 0.098Chronic lung disease 1 (11.1) 0.271 6 (66.7) 1.000 2 (22.2) 0.225Chronic cardiac disease 4 (25) 0.768 12 (75) 0.231 2 (12.5) 0.661Chronic neurologic disease 3 (50) 0.350 4 (66.7) 1.000 1 (16.7) 0.485Benign hematologic disease 0 0.314 1 (20) 0.066 0 1.000Solid tumor 1 (16.7) 0.666 4 (66.7) 1.000 2 (33.3) 0.110Hematologic neoplasm 1 (14.3) 0.667 6 (85.7) 0.243 1 (14.3) 0.541Diabetes 0 0.173 3 (50) 0.668 0 1.000Metabolic disease 100 0.291 1 (100) 1.000 0 1.000Autoimmune disease 1 (50) 0.500 2 (100) 0.523 1 (50) 0.193Prematurity 4 (100) 0.006 ** 3 (75) 1.000 0 1.000

* p-values calculated based on χ2 test, or Fisher Exact Test. ** Significant result

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The clinical picture was similar to that of seasonalinfluenza. The most striking laboratory finding was lym-phopenia. Comparatively, Cao et al. reported 68% ofChinese patients having lymphopenia [25]; in Mexico61% had lymphopenia [26].

Antiviral treatment with Oseltamivir was administeredeither upon hospitalization or after a positive PCR forH1N1 influenza A. The early initiation of antiviral thera-py proved to be associated with better outcomes [14];nonetheless, a delayed initiation to more than 48 hoursafter onset of illness was FDA approved [9, 14, 24, 27]. Adouble dose of Oseltamivir was given to those who had acomplicated course and those who didn’t show major clin-ical improvement. The WHO issued guidelines [28] rec-ommending the use of higher doses (up to 150 mg twicedaily) and longer duration of treatment, depending on theclinical response.

Mechanical ventilation with lung protective strategywas adopted to manage patients with respiratory failureand/or ARDS. The non-invasive ventilation strategy wasadopted in two of our patients; one of them survived, theother died of massive pulmonary embolus. Namendys-Silva et al. [29] did not recommend non-invasive ventila-tion for patients with pandemic influenza A (H1N1) virusinfection complicated by pneumonia, acute lung injury orARDS because it was not shown to alter the natural courseof the disease.

The H1N1 virus had such a high transmissibility thatnosocomial outbreaks were to be expected. Four out of thefive patients who acquired H1N1 infection during theirhospital stay were infants in the neonatal ICU. The viruscan easily spread in closed units. Neonates in NICUs aresubject to a high risk for severe disease because of theirimmature immunity and prolonged hospitalization [30].Fortunately all survived and were cured from H1N1.

Even though seasonal influenza is rarely associatedwith severe disease in acute leukemia patients on chemo-therapy regimens [31], data about the severity of the pan-demic H1N1 disease in hematological neoplasms is limit-ed. In our study, all patients with H1N1 known to haveacute leukemia had a manageable course. Ten acute lym-phoblastic leukemia patients were diagnosed with pan-demic H1N1 influenza A in a single Spanish institution[32], and none of them died. Moreover, in a study con-ducted on hospitalized children in Argentina, patients withcancer on chemotherapy were less likely to be admitted toICU [15].

Most of those who did not survive the H1N1 infectionhad a severe underlying disease; only two patients had norisk factor for complication. A surveillance study from theBritish Medical Journal [33] showed that high risk pa-tients were nine times more likely to die from pandemicA (H1N1) than patients with no risk factor for severe ill-ness despite having received antiviral therapy. The casefatality rate in Saint George Hospital was 0.8%; this rateranged from 0.1% to 0.9% in different regions of theworld [5, 34-35].

In the two patients on whom autopsy was performed,

diffuse alveolar damage was seen similar to what wasreported from Sao Paulo [36]. Zhang et al. [16] showedthat the pandemic influenza virus has a greater capacityto replicate in human lung tissues than does the season-al virus and a similar pathogenicity to that of H5N1viruses.

In our study, premature newborns and patients underthe age of 5 years were at risk for ICU admission (p-value:0.006 and < 0.001 respectively). The other high riskgroups had no statistically significant correlation withICU admission, or a prolonged length of stay or death.Excluding children less than 5 years old, poor outcomecould not be predicted.

Our study has several limitations; it is a retrospectivereview of a limited number of patients with a confirmeddiagnosis of Influenza A (H1N1) in a single medical center.However, a limited number of centers in Lebanon per-formed a PCR for accurate diagnosis. Therefore we believethat this study represents the first report from Lebanon withdetailed review on patients’ characteristics with highlightson several points. First, the clinical presentation was indis-tinguishable of any other viral infection and it had variablemanifestations: gastrointestinal, hematological, neurologi-cal, in addition to the classical lower and/or upper respira-tory tract disease. Second, patients at higher risk of havingworst outcomes were children less than 5 years old. Finally,the vast majority of patients had an uncomplicated courseof disease. The mass state of alert was somehow inflated.This reaction was misled by the media that tended toemphasize on mortality cases.

CONCLUSION

Today the pandemic virus has replaced the circulatingstrain. The test of choice for H1N1 remains the PCR.However, this is a quite expensive technique; but the ratiocost/benefit is justified if testing is reserved only to theseverely sick patients and to patients at risk of having com-plicated H1N1 disease. The majority can be treated em-pirically and on an outpatient basis. Antiviral therapyshould not be indicated systematically; it should be pre-scribed only to patients belonging to high risk groups, andto patients showing signs of severe or progressive illness.Emergence of resistance should be considered upon decid-ing on the therapeutic option.

Lessons learned from this outbreak should help themedical body to be fully prepared for future pandemics.

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