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Volume 17, Number 11—November 2011

Letter

Fatal Infectious Diseases during Pandemic (H1N1) 2009 Outbreak

Suggested citation for this article

To the Editor: Nonpandemic infectious diseases occur with usual incidence during pandemics even though clinical attention is often on the pandemic pathogen. Many of these other infectious diseases share similar clinical signs and symptoms and are sometimes fatal. During the outbreak of pandemic (H1N1) 2009, tissue specimens from case-patients with undiagnosed fatal respiratory illnesses were submitted to the Infectious Diseases Pathology Branch at the Centers for Disease Control and Prevention (Atlanta, Georgia, USA) for evaluation for pandemic (H1N1) 2009 virus infection (1).

All respiratory tissue specimens from 450 case-patients received during April 29, 2009–May 5, 2010, were screened by the Centers for Disease Control and Prevention real-time reverse transcription PCR (rRT-PCR) protocol for detection and characterization of swine influenza virus (2). Of these, specimens from 250 (56%) tested negative for pandemic (H1N1) 2009 virus and had no other confirmatory or prior influenza testing. Of these case-patients whose specimens tested negative for pandemic (H1N1) 2009 virus, a total of 139 (56%) were male, and the median age was 30 years (range 8 days to 81 years). The median duration from onset of illness to death was 7 days (range 1–40 days). Of the 164 case-patients with available medical records, 127 (77%) had >1 underlying or preexisting medical condition.

When compared with case-patients during the same time who had pandemic (H1N1) 2009 virus infection confirmed by rRT-PCR, case-patients who were not infected with pandemic (H1N1) 2009 virus were more likely to be young (<9 years of age; odds ratio [OR] 2.23, 95% confidence interval [CI] 1.38–3.61) and less likely to be obese (OR 0.6, 95% CI 0.36–0.92) or have asthma (OR 0.33, 95% CI 0.16–0.68). Fever, cough, and shortness of breath were less frequently reported in the case-patients without pandemic (H1N1) 2009.

On the basis of the histopathologic features observed in the respiratory tissues of the case-patients who were not infected with pandemic (H1N1) 2009, along with their clinical and epidemiologic information, the specimens were further evaluated by using special histochemical stains, immunohistochemical tests, and molecular assays. At least l etiologic agent was identified in specimens from 69 (28%) of the 250 specimens (Table). Bacterial pathogens were identified for 44 case-patients; Staphylococcus aureus and Streptococcus pneumoniae were the most frequently identified. Immunohistochemical tests and PCRs found evidence of viral agents in samples from 26 case-patients. Most of these were seasonal or unsubtypeable influenza A viruses; in a smaller subset, other respiratory viruses were detected, including respiratory syncytial virus and adenovirus. Multiple fungal pathogens were detected in specimens from 2 case-patients.

For many of the diseases caused by the pathogens subsequently identified, the clinical features are predominantly respiratory, and many nonspecific manifestations are similar to those of influenza. Nonetheless, >50% of the patients in this study who died of suspected influenza had negative test results for pandemic (H1N1) 2009 virus, and for >25% of these, other infectious causes were detected. Infections other than influenza should be considered during a pandemic and during an endemic influenza season to facilitate the diagnosis of illness and treatment of patients with complications or severe respiratory infections. Although we did not conduct a case–control study, these findings also support the results of other studies that previously reported the demographic characteristics of patients with pandemic influenza infections and the risk factors for severe or fatal pandemic influenza infections (3,4), especially with respect to obesity (5).

Evaluation of tissues collected during autopsy from patients with a suspected infectious process can provide an etiologic diagnosis that was not available from routine premortem and postmortem testing. Other etiologic agents detected in this study included reportable disease agents (e.g., Rickettsia rickettsii, Legionella pneumophila, dengue virus), vaccine-preventable diseases (e.g., pneumococcal, meningococcal diseases), and zoonotic agents (Leptospira and Capnocytophaga spp.). These findings underscore the need for autopsies for diagnosing fatal infectious diseases (6). They also confirm the need for coordinated surveillance programs that identify deaths potentially attributable to infectious causes, including the unexplained deaths program (7) and medical examiner infectious diseases death surveillance program (8). Partnerships of medical examiners and pathologists with local, state, and federal public health departments are crucial for detecting and monitoring pandemic diseases and for assessing the scope and magnitude of infectious agents that continuously affect human populations (9). These infections often result in sudden or unexplained death; thus, a standardized approach to death investigations is recommended.

Dianna M. BlauComments to Author , Amy M. Denison, Julu Bhatnagar, Marlene DeLeon-Carnes, Clifton Drew, Christopher Paddock, Wun-Ju Shieh, Sherif R. Zaki, and Infectious Diseases Pathology Branch Working Group
Author affiliations: Centers for Disease Control and Prevention, Atlanta, GA, USA

Acknowledgment

We thank the state and local public health departments, the state and local public health laboratories, and all the pathologists and medical examiners who submitted specimens to the Infectious Diseases Pathology Branch.

References

  1. Shieh WJ, Blau DM, Denison AM, Deleon-Carnes M, Adem P, Bhatnagar J, 2009 Pandemic influenza A (H1N1): pathology and pathogenesis of 100 fatal cases in the United States. Am J Pathol. 2010;177:16675. DOIPubMed
  2. Denison AM, Blau DM, Jost HA, Jones T, Rollin D, Gao R, Diagnosis of influenza from respiratory autopsy tissues: detection of virus by real-time reverse transcription-PCR in 222 cases. J Mol Diagn. 2011;13:1238. DOIPubMed
  3. Centers for Disease Control and Prevention. Intensive-care patients with severe novel influenza A (H1N1) virus infection—Michigan, June 2009. MMWR Morb Mortal Wkly Rep. 2009;58:74952.PubMed
  4. Jain S, Kamimoto L, Bramley AM, Schmitz AM, Benoit SR, Louie J, Hospitalized patients with 2009 H1N1 influenza in the United States, April–June 2009. N Engl J Med. 2009;361:193544. DOIPubMed
  5. Louie JK, Acosta M, Samuel MC, Schechter R, Vugia DJ, Harriman K, A novel risk factor for a novel virus: obesity and 2009 pandemic influenza A (H1N1). Clin Infect Dis. 2011;52:30112. DOIPubMed
  6. Hanzlick R. Medical examiners, coroners, and public health: a review and update. Arch Pathol Lab Med. 2006;130:127482.PubMed
  7. Hajjeh RA, Relman D, Cieslak PR, Sofair AN, Passaro D, Flood J, Surveillance for unexplained deaths and critical illnesses due to possibly infectious causes, United States, 1995–1998. Emerg Infect Dis. 2002;8:14553. DOIPubMed
  8. Nolte KB, Lathrop SL, Nashelsky MB, Nine JS, Gallaher MM, Umland ET, “Med-X”: a medical examiner surveillance model for bioterrorism and infectious disease mortality. Hum Pathol. 2007;38:71825. DOIPubMed
  9. Nolte KB, Fischer M, Reagan S, Lynfield R. Guidelines to implement medical examiner/coroner-based surveillance for fatal infectious diseases and bioterrorism (“Med-X”). Am J Forensic Med Pathol. 2010;31:30812. DOIPubMed

Table

Suggested citation for this article: Blau DM, Denison AM, Bhatnagar J, DeLeon-Carnes M, Drew C, Paddock C, et al. Fatal infectious diseases during pandemic (H1N1) 2009 outbreak [letter]. Emerg Infect Dis [serial on the internet]. 2011 Nov [date cited]. http://dx.doi.org/10.3201/eid1711.110429

DOI: 10.3201/eid1711.110429

1Infectious Diseases Pathology Branch Working Group members were Patty Adem, Jeanine Bartlett, Brigid Batten, Reema Dedania, Amy Green, Pat Greer, Tara Jones, Lindy Liu, Jeltley Montague, Mitesh Patel, Dominique Rollin, Chalanda Smith, and Libby White.

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Table of Contents – Volume 17, Number 11—November 2011

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Dianna M. Blau, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mailstop G32, Atlanta, GA 30333, USA

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