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Patients with Pandemic (H1N1) 2009 in Intensive Care Units, Israel

April 2010
Emerging Infectious Diseases 16(4):720-1

DOI:10.3201/eid1604.091696

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PubMed

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CC BY

Authors:

Eran Kopel

Ministry of Health (Israel)

Itamar Grotto

Ben-Gurion University of the Negev

Ehud Kaliner

Ministry of Health (Israel)

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To the Editor: We report results of an active surveillance system established by the Tel Aviv District Health Office in Israel. This surveillance system monitors the daily status of patients with laboratory-confirmed pandemic (H1N1) 2009 virus infection in each of the district's intensive care units (ICUs), including pediatric ICUs.

Figure. Number of intensive care unit (ICU) beds occupied by patients with pandemic (H1N1) 2009 infection in district ICUs during the described surveillance period, Tel Aviv, Israel. During this period, 5.7% of ICU beds, on average, were continuously occupied by patients with pandemic (H1N1) 2009 infection. The occupancy peak was 6.5 of 53.8 standardized ICU beds per million residents (12.1%) during the week ending August 28, 2009. Data are per million residents.

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LETTERS

was deﬁ ned by a >4-fold increase in

inﬂ uenza-speciﬁ c hemagglutinin inhi-

bition assay titer between baseline and

convalescent-phase serum samples

by using turkey erythrocytes and A/

TN/1560/2009(H1N1), a representa-

tive pandemic inﬂ uenza virus.

Of the 422 nurses included in the

analysis, 42 (10.0%) showed serocon-

version to pandemic (H1N1) 2009. Of

128 nurses who received the trivalent

inﬂ uenza vaccine, 9 (7.0%) showed

seroconversion vs. 33 (11.2%) of

those that did not (relative risk 0.63,

95% conﬁ dence interval 0.31–1.27, p

= 0.19).

Although the point estimate was

protective, the conﬁ dence interval is

wide and does not exclude an increase

in risk. Our sample size limits infer-

ences that can be drawn. Heterotypic

antibodies may have contributed to the

relatively high rate of seroconversion.

A rise in antibody titer is considered

by some as an outcome associated

with bias, unlike virus identiﬁ cation.

Nevertheless, these data suggest a pos-

sible positive effect of seasonal inﬂ u-

enza vaccine reducing risk of infection

with pandemic (H1N1) 2009.

This study was funded by the Public

Health Agency of Canada.

Mark Loeb, David J.D. Earn,

Marek Smieja,

and Richard Webby

Author afﬁ liations: McMaster University,

Hamilton, Ontario, Canada (M. Loeb, D.J.D.

Earn, M. Smieja); and St. Jude Children’s

Research Hospital, Memphis, Tennessee,

USA (R. Webby)

DOI: 10.3201/eid1604.091588

Reference

1. Loeb M, Dafoe N, Mahony J, John M,

Sarabia A, Glavin V, et al. Surgical mask

vs N95 respirator for preventing inﬂ uenza

among health care workers: a random-

ized trial. JAMA. 2009;302:1865–71.

DOI:10.1001/jama.2009.1466

Address for correspondence: Mark Loeb,

McMaster University, 1200 Main St W,

Hamilton, Ontario L8N 3Z5, Canada; email:

loebm@mcmaster.ca

Patients with

Pandemic (H1N1)

2009 in Intensive

Care Units, Israel

To the Editor: We report re-

sults of an active surveillance system

established by the Tel Aviv District

Health Ofﬁ ce in Israel. This surveil-

lance system monitors the daily status

of patients with laboratory-conﬁ rmed

pandemic (H1N1) 2009 virus infec-

tion in each of the district’s intensive

care units (ICUs), including pediatric

ICUs.

Follow-up is maintained by daily

phone conversations with medical

staff until disease outcome is con-

cluded by discharge, transfer to a

long-term rehabilitation facility, or

death. Medical records, as well as

daily laboratory reports, are collected

to conﬁ rm or to rule out pandemic

(H1N1) 2009 infection.

During July 10–October 10,

2009, our prospective cohort included

17 patients with pandemic (H1N1)

2009 laboratory-conﬁ rmed infection

who were residents of the district; 12

(70.6%) were male patients. The me-

dian age was 44 years (interquartile

range 13–72 years). By October 10,

2009, six patients had been discharged,

7 had died, 2 had been transferred to

long-term rehabilitation facilities, and

2 remained hospitalized.

Twelve (70.6%) patients had an

underlying medical condition, mainly

chronic lung disease (6 patients) or

chronic cardiovascular disease (5 pa-

tients). Two patients were morbidly

obese (body mass index >35), and 1

patient was pregnant. Additionally, 3

patients (17.6%) were infected while

hospitalized.

Thirteen patients (76.5%) had

acute respiratory distress syndrome

caused by diffuse viral pneumonitis.

Other notable manifestations were

acute renal failure (6 patients), sepsis/

septic shock (5 patients), and neuro-

logic complications such as Guillain-

Barré syndrome, encephalitis, and sei-

zures (3 patients).

Documented nosocomial sepsis,

often of multiple gram-negative bacte-

ria (9 patients), was the most frequent

complication during the course of the

disease. Other frequent characteristics

were the use of high positive end-ex-

piratory pressure during mechanical

ventilation (4 patients) and the need

for tracheostomy (5 patients).

Average time from disease on-

set to hospital admission was 3 days.

Time from hospital admission to ICU

admission for those patients who died

was longer than for those who sur-

vived, with a median of 2 days com-

pared with 0.5 day, respectively, al-

beit not signiﬁ cant (p = 0.26). Average

hospitalization was 23.4 days; average

length of stay in the ICU was 16.7

days (71.4% of the average hospital-

ization time).

As mentioned previously, 7 pa-

tients (41.2%) died; 5 (71.4%) were

male, similar to their cohort’s pro-

portion. One signiﬁ cant difference (p

= 0.02) was found between the age

of survivors (mean 26.0 years, 95%

conﬁ dence interval 7.6–44.3) and the

age of nonsurvivors (mean 59.3 years,

95% conﬁ dence interval 39.6–79.0).

The most prominent case–fatality rate

was for elderly patients, >65 years of

age (3 of 4 patients) followed by pa-

tients between 20 and 64 years of age

(4 of 9 patients); these subgroups con-

stituted 23.5% and 52.9% of the co-

hort, respectively.

Estimated incidence rate was 13.8

patients and 5.7 deaths in ICUs per

million residents in the Tel Aviv dis-

trict. Again, the elderly subgroup was

720 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 16, No. 4, April 2010

LETTERS

dominant, with the highest estimated

rate of illness (23.1 per million resi-

dents) and death rate (17.3 per million

residents). The denominator of these

rates was calculated from the popula-

tion data published by the Israeli Cen-

tral Bureau of Statistics for 2007 and

2008. Upon that basis, the population

data for the end of the third quarter of

2009 was estimated.

During the described surveillance

period, 5.7% of ICU beds in the dis-

trict were, on average, continuously

occupied by patients infected with

pandemic (H1N1) 2009. The occupan-

cy peak was 6.5 of 53.8 standardized

ICU beds (12.1%) per million resi-

dents during the week ending August

28, 2009 (Figure).

In conclusion, our analysis of

patients having the most severe pan-

demic (H1N1) 2009 infection indi-

cates a need for prolonged periods of

hospitalizations, especially in ICUs,

for young adults and elderly patients.

Death or prolonged adverse com-

plications were frequent outcomes.

We found that the impact of patients

with pandemic (H1N1) 2009 on the

ICUs in our district during the sum-

mer wave was surprisingly similar in

length and intensity to the impact that

was recently reported in Australia and

New Zealand during the winter wave

(1). The maximum number of ICU

beds occupied per million residents,

reported for all regions of Australia

and New Zealand combined, was 7.4

during the week ending July 27, 2009

(vs. 6.5 as described above). We also

found that the mean age of those who

died was older than that in previous

reports (2–6).This ﬁ nding may present

a need for policymakers to reconsider

current vaccination priorities (7) while

facing the winter wave of inﬂ uenza in

the Northern Hemisphere.

Acknowledgments

We thank the medical team and ad-

ministrative staff of the intensive care

units in our district. We are grateful for the

daily ongoing cooperative effort because

it allows us to continuously monitor and

evaluate the evolving pandemic status.

Eran Kopel, Ziva Amitai,

Itamar Grotto, Ehud Kaliner,

and Irina Volovik

Author afﬁ liations: Ministry of Health, Tel

Aviv, Israel

DOI: 10.3201/eid1604.091696

References

1. ANZIC Inﬂ uenza Investigators, Webb SA,

Pettilä V, Seppelt I, Bellomo R, Bailey M,

Cooper DJ, et al. Critical care services and

2009 H1N1 inﬂ uenza in Australia and New

Zealand. N Engl J Med. 2009;361:1925–

34. DOI: 10.1056/NEJMoa0908481

2. Kumar A, Zarychanski R, Pinto R, Cook

DJ, Marshall J, Lacroix J, et al. Criti-

cally ill patients with 2009 inﬂ uenza A

(H1N1) infection in Canada. JAMA.

2009;302:1872–9. DOI: 10.1001/

jama.2009.1496

3. Domínguez-Cherit G, Lapinsky SE, Ma-

cias AE, Pinto R, Espinosa-Perez L, de la

Torre A, et al. Critically ill patients with

2009 inﬂ uenza A (H1N1) in Mexico.

JAMA. 2009;302:1880–7. DOI: 10.1001/

jama.2009.1536

4. Jain S, Kamimoto L, Bramley AM,

Schmitz AM, Benoit SR, Louie J, et al.

Hospitalized patients with 2009 H1N1

inﬂ uenza in the United States, April–June

2009. N Engl J Med. 2009;361:1935–44.

5. Rello J, Rodríguez A, Ibañez P, Socias

L, Cebrian J, Marques A, et al. Intensive

care adult patients with severe respiratory

failure caused by inﬂ uenza A (H1N1)v

in Spain. Crit Care. 2009;13:R148. DOI:

10.1186/cc8044

6. Centers for Disease Control and Preven-

tion. Intensive-care patients with severe

novel inﬂ uenza A (H1N1) virus infection–

Michigan, June 2009. MMWR Morb Mor-

tal Wkly Rep. 2009;58:749–52.

7. Centers for Disease Control and Preven-

tion. Use of inﬂ uenza A (H1N1) 2009

monovalent vaccine: recommendations of

the Advisory Committee on Immunization

Practices (ACIP), 2009. MMWR Recomm

Rep. 2009;58:1–8.

Address for correspondence: Eran Kopel,

Ministry of Health, Tel Aviv District Health

Ofﬁ ce, 12 Ha’arba’ah, Tel Aviv 61203, Israel;

email: eran.kopf@telaviv.health.gov.il

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 16, No. 4, April 2010 721

Jul 10 Jul 17 Jul 24 Jul 31 Aug 7 Aug 14 Aug 21 Aug 28 Sep 4 Sep 11 Sep 18 Sep 25 Oct 2 Oct 9

No. ICU beds occupied/million residents

Surveillance week ending

Jul 10 Jul 17 Jul 24 Jul 31 Aug 7 Aug 14 Aug 21 Aug 28 Sep 4 Sep 11 Sep 18 Sep 25 Oct 2 Oct 9

No. ICU beds occupied/million residents

Surveillance week ending

Figure. Number of intensive care unit (ICU) beds occupied by patients with pandemic

(H1N1) 2009 infection in district ICUs during the described surveillance period, Tel Aviv,

Israel. During this period, 5.7% of ICU beds, on average, were continuously occupied

by patients with pandemic (H1N1) 2009 infection. The occupancy peak was 6.5 of 53.8

standardized ICU beds per million residents (12.1%) during the week ending August 28,

2009. Data are per million residents.

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Conference Paper

Oct 2012

Background: IVZ is a neuraminidase inhibitor in development for treatment of hospitalized patients with severe influenza. Methods: Hospitalized symptomatic patients with local laboratory-confirmed influenza within 7 days of illness onset received IVZ for 5-10 days at 600 mg twice daily adjusted for renal impairment or renal replacement therapy (RRT). Patients were assessed during treatment and for 23 days after treatment for safety and virology. Serial serum PK sampling was done with the first and a repeat IVZ dose (ClinicalTrials.gov NCT01014988). Results: 130 adults (56 female, 4 pregnant) from 8 countries were enrolled from November 2009 to August 2011. Median age was 48 years (range, 18-94), 75% were Caucasian, 33% were obese (BMI>30), 80% had received oseltamivir (median, 2 days). 75% had chronic medical conditions (respiratory 32%, immunocompromised 25%). Median time from influenza symptom onset to IVZ was 4.5 days (range, 1-7). At baseline, 89% had an infiltrate on chest X-ray, 48% required mechanical ventilation (MV) and 5% RRT. During the study 60% required MV, 83% required ICU care, and 3% ECMO. Median hospital stay was 15 days (range, 1-133) and median ICU stay was 11.5 days (range, 1-104). 14 and 28-day cumulative mortality was 13% and 17%. 94% of subjects had influenza A (71% H1N1pdm09, 12% H3N2, 11% subtype unknown), 2% influenza B and 4% not typed. Of 93 subjects with positive baseline nasopharyngeal PCR, median baseline viral load was 5.34 log10 c/mL (range, 2.86-8.17) and median change at Day 3 was –1.42 log10 c/mL (range, –3.38 to +1.08). Steady state PK data from 76 subjects with normal renal function (mean Cmax=35.3 µg/mL, AUC=90.3 h*µg/mL, Cmin= 0.82 µg/mL) were as expected for 600 mg and above the mean reported influenza IC50 (0.08-1.01 ng/mL) for IVZ. 85% of subjects experienced adverse events (AEs), 44% had a grade 3 or 4 AE and 34% a serious AE. 13% met protocol defined liver-event criteria (8% on-treatment, 5% post-treatment) with no correlation to PK. There were no clinically significant trends in labs, vital signs or ECGs. Potential causality of AEs was confounded by severity of illness and concomitant medications. Conclusion: No significant safety signals attributable to IVZ were identified in this population with severe influenza. A Phase 3 study of IVZ is underway.

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Article

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J INFECT DIS

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The role of pneumonia and secondary bacterial infection in fatal and serious outcomes of pandemic influenza a(H1N1)pdm09

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Dec 2018

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Background The aim of this study was to estimate the prevalence of pneumonia and secondary bacterial infections during the pandemic of influenza A(H1N1)pdm09. Methods A systematic review was conducted to identify relevant literature in which clinical outcomes of pandemic influenza A(H1N1)pdm09 infection were described. Published studies (between 01/01/2009 and 05/07/2012) describing cases of fatal or hospitalised A(H1N1)pdm09 and including data on bacterial testing or co-infection. Results Seventy five studies met the inclusion criteria. Fatal cases with autopsy specimen testing were reported in 11 studies, in which any co-infection was identified in 23% of cases (Streptococcus pneumoniae 29%). Eleven studies reported bacterial co-infection among hospitalised cases of A(H1N1)2009pdm with confirmed pneumonia, with a mean of 19% positive for bacteria (Streptococcus pneumoniae 54%). Of 16 studies of intensive care unit (ICU) patients, bacterial co-infection identified in a mean of 19% of cases (Streptococcus pneumoniae 26%). The mean prevalence of bacterial co-infection was 12% in studies of hospitalised patients not requiring ICU (Streptococcus pneumoniae 33%) and 16% in studies of paediatric patients hospitalised in general or pediatric intensive care unit (PICU) wards (Streptococcus pneumoniae 16%). Conclusion We found that few studies of the 2009 influenza pandemic reported on bacterial complications and testing. Of studies which did report on this, secondary bacterial infection was identified in almost one in four patients, with Streptococcus pneumoniae the most common bacteria identified. Bacterial complications were associated with serious outcomes such as death and admission to intensive care. Prevention and treatment of bacterial secondary infection should be an integral part of pandemic planning, and improved uptake of routine pneumococcal vaccination in adults with an indication may reduce the impact of a pandemic.

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Oct 2009
NEW ENGL J MED

During the spring of 2009, a pandemic influenza A (H1N1) virus emerged and spread globally. We describe the clinical characteristics of patients who were hospitalized with 2009 H1N1 influenza in the United States from April 2009 to mid-June 2009. Using medical charts, we collected data on 272 patients who were hospitalized for at least 24 hours for influenza-like illness and who tested positive for the 2009 H1N1 virus with the use of a real-time reverse-transcriptase-polymerase-chain-reaction assay. Of the 272 patients we studied, 25% were admitted to an intensive care unit and 7% died. Forty-five percent of the patients were children under the age of 18 years, and 5% were 65 years of age or older. Seventy-three percent of the patients had at least one underlying medical condition; these conditions included asthma; diabetes; heart, lung, and neurologic diseases; and pregnancy. Of the 249 patients who underwent chest radiography on admission, 100 (40%) had findings consistent with pneumonia. Of the 268 patients for whom data were available regarding the use of antiviral drugs, such therapy was initiated in 200 patients (75%) at a median of 3 days after the onset of illness. Data suggest that the use of antiviral drugs was beneficial in hospitalized patients, especially when such therapy was initiated early. During the evaluation period, 2009 H1N1 influenza caused severe illness requiring hospitalization, including pneumonia and death. Nearly three quarters of the patients had one or more underlying medical conditions. Few severe illnesses were reported among persons 65 years of age or older. Patients seemed to benefit from antiviral therapy.

Intensive care adult patients with severe respiratory failure caused by Influenza A (H1N1)v in Spain

Article

Full-text available

Sep 2009

Patients with influenza A (H1N1)v infection have developed rapidly progressive lower respiratory tract disease resulting in respiratory failure. We describe the clinical and epidemiologic characteristics of the first 32 persons reported to be admitted to the intensive care unit (ICU) due to influenza A (H1N1)v infection in Spain. We used medical chart reviews to collect data on ICU adult patients reported in a standardized form. Influenza A (H1N1)v infection was confirmed in specimens using real-time reverse transcriptase-polymerase-chain-reaction (RT PCR) assay. Illness onset of the 32 patients occurred between 23 June and 31 July, 2009. The median age was 36 years (IQR = 31 - 52). Ten (31.2%) were obese, 2 (6.3%) pregnant and 16 (50%) had pre-existing medical complications. Twenty-nine (90.6%) had primary viral pneumonitis, 2 (6.3%) exacerbation of structural respiratory disease and 1 (3.1%) secondary bacterial pneumonia. Twenty-four patients (75.0%) developed multiorgan dysfunction, 7 (21.9%) received renal replacement techniques and 24 (75.0%) required mechanical ventilation. Six patients died within 28 days, with two additional late deaths. Oseltamivir administration delay ranged from 2 to 8 days after illness onset, 31.2% received high-dose (300 mg/day), and treatment duration ranged from 5 to 10 days (mean 8.0 +/- 3.3). Over a 5-week period, influenza A (H1N1)v infection led to ICU admission in 32 adult patients, with frequently observed severe hypoxemia and a relatively high case-fatality rate. Clinicians should be aware of pulmonary complications of influenza A (H1N1)v infection, particularly in pregnant and young obese but previously healthy persons.

Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2003

Article

Jan 2003

Critical care services and 2009 H1N1 influenza in Australia and New Zealand.

Jan 2009
1925

ANZIC Influenza Investigators

ANZIC Infl uenza Investigators, Webb SA, Pettilä V, Seppelt I, Bellomo R, Bailey M, Cooper DJ, et al. Critical care services and 2009 H1N1 infl uenza in Australia and New Zealand. N Engl J Med. 2009;361:1925–

Intensive-care patients with severe novel infl uenza A (H1N1) virus infection– Michigan

Jul 2009
749-52

Disease Centers
Control
Prevention

Centers for Disease Control and Prevention. Intensive-care patients with severe novel infl uenza A (H1N1) virus infection– Michigan, June 2009. MMWR Morb Mortal Wkly Rep. 2009;58:749–52.

Critically ill patients with 2009 infl uenza A (H1N1) in Mexico DOI: 10.1001/ jama

1880-7

G Domínguez-Cherit
Se Lapinsky
Ae Macias
R Pinto
Espinosa
L Perez
De
A Torre

Domínguez-Cherit G, Lapinsky SE, Macias AE, Pinto R, Espinosa-Perez L, de la Torre A, et al. Critically ill patients with 2009 infl uenza A (H1N1) in Mexico. JAMA. 2009;302:1880–7. DOI: 10.1001/ jama.2009.1536