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Published Date: 2009-09-30 18:00:03
Subject: PRO/AH/EDR> Influenza pandemic (H1N1) 2009 (60): bacterial coinfection
Archive Number: 20090930.3410

INFLUENZA PANDEMIC (H1N1) 2009 (60): BACTERIAL COINFECTION
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Date: Tue 29 Sep 2009
Source: CDC. MMWR Morb Mortal Wkly Rep 2009; 58 (early release); 1-4 [edited]
<http://www.cdc.gov/mmwr/preview/mmwrhtml/mm58e0929a1.htm?s_cid=rr58e0929a1_e>

Bacterial coinfections in lung tissue specimens from fatal cases of 2009
pandemic influenza A (H1N1) - US, May-Aug 2009
----------------------------------------------------------
In previous influenza pandemics, studies of autopsy specimens have shown
that most deaths attributed to influenza A virus infection occurred
concurrently with bacterial pneumonia (1), but such evidence has been
lacking for the pandemic influenza A (H1N1) 2009 virus. To help determine
the role of bacterial coinfection in the current influenza pandemic, CDC
examined postmortem lung specimens from patients with fatal cases of
pandemic influenza A (H1N1) 2009 virus infection for bacterial causes of
pneumonia. During 1 May to 20 Aug 2009, medical examiners and local and
state health departments submitted specimens to CDC from 77 US patients
with fatal cases of confirmed 2009 pandemic influenza A (H1N1) virus
infection. This report summarizes the demographic and clinical findings
from these cases and the laboratory evaluation of the specimens. Evidence
of concurrent bacterial infection was found in specimens from 22 (29 per
cent) of the 77 patients, including 10 caused by _Streptococcus pneumoniae_
(pneumococcus). Duration of illness was available for 17 of the 22
patients; median duration was 6 days (range: 1 to 25 days). Of 18 patients
for whom information was available, 14 sought medical care while ill, and 8
(44 per cent) were hospitalized. These findings confirm that bacterial lung
infections are occurring among patients with fatal cases of 2009 pandemic
influenza A (H1N1) and underscore both the importance of pneumococcal
vaccination for persons at increased risk for pneumococcal pneumonia and
the need for early recognition of bacterial pneumonia in persons with
influenza.

CDC receives tissue specimens routinely from patients with confirmed or
suspected infectious diseases and provides histopathologic,
immunohistochemical, and molecular evaluations. Early in the 2009 influenza
A (H1N1) virus pandemic, CDC provided guidelines for submission of tissue
specimens for evaluation of influenza virus infections. Confirmed fatal
cases of 2009 pandemic influenza A (H1N1) were defined as influenza-like
illness or postmortem findings suggestive of viral pneumonia and
laboratory-confirmed 2009 pandemic influenza A (H1N1) virus infection by
real time reverse transcriptase-polymerase chain reaction (rRT-PCR).
Respiratory specimens (that is, lung, trachea, and large-airway specimens)
collected at autopsy were submitted to CDC by medical examiners, hospitals,
and local and state health departments for additional evaluation.

Specimens were received from 77 patients who had 2009 pandemic influenza A
(H1N1) virus infection confirmed before death (N = 41) or after death (N =
36). Of the 77 cases evaluated, 56 (72 per cent) had at least some clinical
information available, and 35 (45 per cent) had preliminary autopsy reports
submitted with the tissue specimens. All specimens were examined using
hematoxylin and eosin stain, Lillie-Twort tissue Gram stain, and
Warthin-Starry silver stain. Tissue specimens also were evaluated by
various immunohistochemical assays using antibodies that are specifically
reactive with _S. pneumoniae_, _Streptococcus pyogenes_, _Staphylococcus
aureus_, or _Haemophilus influenzae_. All bacteria were evaluated by a
broad-range PCR assay that targets a segment of the 16S ribosomal DNA gene
in DNA extracted from formalin-fixed, paraffin-embedded tissue (2). PCR for
lytA and spy genes and pneumococcal serotyping by multiplex PCR were
conducted to further characterize streptococcal coinfections.

Of the 77 confirmed cases evaluated, 22 had histopathologic,
immunohistochemical, and molecular evidence of coinfection with an
identified bacteria, including 10 cases with _S. pneumoniae_, 6 with _S.
pyogenes_, 7 with _S. aureus_, 2 with _Streptococcus mitis_, and 1 with _H.
influenzae_; 4 cases involved multiple pathogens [data tabulated in the
original text]. The median age of the 22 patients was 31 years (range: 2
months to 56 years); 11 (50 per cent) were male. The cases were reported
from 8 states: California, Hawaii, Illinois, New Jersey, New York, Texas,
Utah, and Virginia.

Duration of illness was available for 17 of the 22 patients; median
duration was 6 days (range: 1 to 25 days). Of 18 patients with information
available, 14 sought medical care while ill, and 8 were hospitalized. Of
the 7 hospitalized patients with information available, all required
mechanical ventilation. Of 9 patients with information available on
antimicrobial therapy, 7 were treated with antibiotics. Of the 21 patients
for whom previous medical history was known, 16 had underlying medical
conditions that were known to increase the risk for influenza-associated
complications (16 patients) (3) or that were indications for vaccination
with 23-valent pneumococcal polysaccharide vaccine (PPSV23) (15 patients).

[reported by: J Louie, MD, C Jean, MPH, California Dept of Public Health.
T-H Chen, MD, S Park, MD, R Ueki, Hawaii State Dept of Health. T Harper,
MD, Stroger Hospital of Cook County; Chicago Dept of Public Health. E
Chmara, MD, Northern Region Medical Examiner Office; New Jersey Dept of
Health and Senior Svcs. J Myers, Erie County Medical Center; R Stoppacher,
MD, Onondaga County Medical Examiner's Office; C Catanese, MD, Orange
County Medical Examiner's Office; City of New York Office of the Chief
Medical Examiner; New York City Dept of Health and Mental Hygiene; New York
State Dept of Health. N Farley, MD, Valley Forensics, PLLC; Texas Dept of
State Health Svcs. E Leis, MD, Utah Office of the Medical Examiner; Utah
Dept of Public Health. C DiAngelo, MD, Northern District Office of the
Chief Medical Examiner, Virginia; Virginia Dept of Health. AM Fry, MD, L
Finelli, DrPH, Influenza Div, MG Carvalho, PhD, B Beall, PhD, M Moore, MD,
C Whitney, MD, Div of Bacterial Diseases, National Center for Immunization
and Respiratory Diseases; Infectious Diseases Pathology Br, National Center
for Zoonotic, Vector-Borne, and Enteric Diseases; DM Blau, DVM, PhD, EIS
Officer, CDC.]

MMWR editorial note
-------------------
During previous influenza pandemics, bacterial coinfections caused by _S.
pneumoniae_, _H. influenzae_, _S. aureus_, and group A _Streptococcus_ have
been important contributors to morbidity and mortality (1,4). However, 2
early reviews of severe cases of 2009 pandemic influenza A (H1N1) showed no
evidence of bacterial pneumonia among 30 hospitalized patients with
laboratory-confirmed cases in California (5) and 10 intensive-care patients
in Michigan (6). These reports might have led to a perception that
bacterial coinfections are playing a limited role or no role in influenza
deaths during the current pandemic. However, failure to document bacterial
lung infections might reflect the difficulty of establishing specific
bacterial diagnoses among persons with bacterial coinfections. Routine
clinical tests used to identify bacterial infections among patients with
pneumonia do not detect many of these infections. For example, less than 10
per cent of patients who are hospitalized with clinically diagnosed
pneumonia have blood cultures that are positive for bacterial infections
(7). Histopathologic evaluation and testing of lung tissue, especially
using PCR and immunochemistry methods, can detect many bacterial lung
infections missed by standard clinical methods (2). The findings in this
report indicate that, as during previous influenza pandemics, bacterial
pneumonia is contributing to deaths associated with pandemic H1N1 and that
histopathologic methods can be used to identify bacterial coinfections
after death.

Although the findings in this report confirm the presence of bacterial lung
coinfection, the results cannot be used to assess the prevalence of
bacterial pneumonia among patients who have died from pandemic H1N1. The
cases in this report do not come from a systematic sample and might not be
representative of all pandemic H1N1 deaths or all pandemic H1N1 deaths
associated with bacterial pneumonia. Systematic research is needed to
determine the incidence and outcome of bacterial lung coinfections among
patients with pandemic H1N1 virus infection and to quantify the role of
these infections in fatal cases.

Medical examiners and coroners have an important role in the surveillance
of deaths caused by the 2009 pandemic influenza A (H1N1) virus (8).
Histopathologic techniques can assist with postmortem diagnosis of
coinfections in patients in whom culture, antemortem or postmortem, does
not detect bacteria. When autopsies are performed for patients with
confirmed or suspected influenza who die after acute respiratory disease, a
pathological evaluation of respiratory tissues should be conducted and
should include testing for both viral and bacterial pathogens (8).

The findings in this report are subject to at least 3 limitations. First,
not all potential bacterial pathogens (such as, _Legionella_ species) were
evaluated. Second, the analysis of patient characteristics was based on
limited patient information. Because medical records and death certificates
generally were not available, no conclusion could be drawn about whether
the cause of death was influenza, bacterial infection, or both. Third,
because assessments of bacterial coinfections were conducted at autopsy,
inadequate sampling, collection of specimens from unaffected portions of
the lung, or prolonged illness and treatment before death might have
prevented identification of bacteria.

The most common bacteria found in patients described in this report were
_S. pneumoniae_. This infection was documented in 10 of the 22 patients.
Although no data were available on the vaccination status of the 22
patients, one patient was aged less than 5 years and was therefore a
candidate for pneumococcal conjugate vaccine, and 15 others had underlying
medical conditions that were indications for PPSV23 vaccine (9,10). Persons
at greatest risk for invasive pneumococcal disease include young children,
older adults, and persons of any age with certain conditions, including
chronic lung or cardiovascular disease and immunosuppressive conditions.
All children aged less than 5 years should receive pneumococcal conjugate
vaccine according to current Advisory Committee on Immunization Practices
(ACIP) recommendations (9). In addition, PPSV23 is recommended for all
persons aged 2 to 64 years with certain health conditions and all persons
aged 65 years or more. Available vaccination coverage data indicate that
only a small proportion of persons aged 2 to 64 years in the United States
who are recommended by ACIP to receive pneumococcal vaccine have received
the vaccine. One study indicated that only 16 per cent of persons aged 18
to 49 years with indications for PPSV23 vaccine had received the vaccine.
Because of the higher rates of 2009 pandemic H1N1 illness and death among
persons aged 2 to 64 years, providers should target persons in this group
who have existing ACIP indications for PPSV23 to receive the vaccine.

The findings in this report also underscore the importance of managing
patients with influenza who also might have bacterial pneumonia with both
empiric antibacterial therapy and antiviral medications. In addition,
public health departments should encourage the use of pneumococcal vaccine,
seasonal influenza vaccine, and, when the vaccine becomes available,
pandemic influenza A (H1N1) 2009 monovalent vaccine.

References
----------
1. Morens DM, Taubenberger, Fauci AS. Predominant role of bacterial
pneumonia as a cause of death in pandemic influenza: implications for
pandemic influenza preparedness. J Infect Dis 2008; 198: 962-70 [available
at <http://www.journals.uchicago.edu/doi/full/10.1086/591708>].
2. Guarner J, Packard MM, Nolte KB, et al. Usefulness of
immunohistochemical diagnosis of _Streptococcus pneumoniae_ in
formalin-fixed, paraffin-embedded specimens compared with culture and gram
stain techniques. Am J Clin Pathol 2007; 127: 612-8 [available at
<http://ajcp.ascpjournals.org/content/127/4/612.full.pdf+html>].
3. CDC. Prevention and control of seasonal influenza with vaccines:
recommendations of the Advisory Committee on Immunization Practices (ACIP),
2009. MMWR 2009; 58(RR08); 1-52; available at
<http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5808a1.htm>.
4. Brundage JF, Shanks GD. Deaths from bacterial pneumonia during the
1918-19 influenza pandemic. Emerg Infect Dis 2008; 14(8): 1193-9 [available
at<http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18680641>].

5. CDC. Hospitalized patients with novel influenza A (H1N1) virus infection
- California, April-May, 2009. MMWR 2009; 58: 536-41; available at
<http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5819a6.htm>.
6. CDC. Intensive-care patients with severe novel influenza A (H1N1) virus
infection - Michigan, June 2009. MMWR 2009; 58: 749-52; available at
<http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5827a4.htm>.
7. Metersky ML, Ma A, Bratzler DW, Houck PM. Predicting bacteremia in
patients with community-acquired pneumonia. Am J Respir Crit Care Med 2004;
169: 342-7[available at
<http://ajrccm.atsjournals.org/cgi/reprint/169/3/342>].
8. Nolte KB, Lathrop SL, Nashelsky MB, et al. "Med-X": a medical examiner
surveillance model for bioterrorism and infectious disease mortality. Hum
Pathol 2007; 38(5): 718-25 [abstract available at
<http://www.humanpathol.com/article/S0046-8177(07)00090-1/abstract>].
9. CDC. Preventing pneumococcal disease among infants and young children:
recommendations of the Advisory Committee on Immunization Practices (ACIP).
MMWR 2000; 49(No. RR-9); available at
<http://www.cdc.gov/mmwr/preview/mmwrhtml/rr4909a1.htm>.
10. CDC. Prevention of pneumococcal disease: recommendations of the
Advisory Committee on Immunization Practices (ACIP). MMWR 1997; 46(No.
RR-8); available at <http://www.cdc.gov/mmwr/preview/mmwrhtml/00047135.htm>.

--
communicated by:
ProMED-mail rapporteur Brent Barrett

[These findings, in contrast to earlier reports, confirm that concurrent
bacterial infection can be an important factor affecting the outcome of
infection with the pandemic (H1N1) 2009 virus.

Bacterial coinfection was detected in specimens from 22 (29 per cent) of 77
patients investigated in detail. These included including 10 cases caused
by _Streptococcus pneumoniae_. This figure is considered to be a minimum
estimate, reinforcing the view that the outcome of infection with the
pandemic (H1N1) 2009 virus alone is rarely lethal. - Mod.CP]

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