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Volume 8, Number 2—February 2002

Research

Surveillance for Unexplained Deaths and Critical Illnesses

Rana A. Hajjeh*Comments to Author , David Relman†, Paul R. Cieslak‡, Andre N. Sofair§, Douglas Passaro¶, Jennifer Flood¶, James Johnson#, Jill K. Hacker¶, Wun-Ju Shieh*, R. Michael Hendry¶, Simo Nikkari†, Stephen Ladd-Wilson‡, James Hadler§, Jean Rainbow#, Jordan W. Tappero*, Christopher W. Woods*, Laura Conn*, Sarah Reagan*, Sherif Zaki*, Bradley A. Perkins*, and for the Unexplained Deaths Critical Illness Working Group1
Author affiliations: *Centers for Disease Control and Prevention, Atlanta, Georgia, USA; †Stanford University, Stanford, California, USA; ‡the Emerging Infections Program, Portland, Oregon, USA; §the Emerging Infections Program, Hartford, Connecticut, USA; ¶the Emerging Infections Program, San Francisco, California, USA; #the Emerging Infections Program, Minneapolis, Minnesota, USA;

Main Article

Table 1

Classification of laboratory test results and cases,a surveillance for unexplained death and critical illness possibly due to infectious causes (UNEX), 1995-1998

A B C
1. Detection of organism by culture from involved siteb 1. Detection of organism by culture, IF, IHC, IEM, ISH, or PCRc in blood or clinically relevant sited 1. Detection of organism by culture, IF, IHC, IEM, ISH, or PCR from uninvolved, but nonmucosal, noncutaneous site
2. Detection of organism by direct immunologic staining (i.e., IF, IHC,IEM) at involved site 2. Positive serology: ≥4-fold change in IgG/IgA titer or significantly elevated IgM titer
3. Detection of organism by DNA/RNA ISH at involved site 3. Detection of organism by EMe at involved site
4. Detection of organism by PCRf at involved site 4. Detection of other specific microbial antigen at characteristic site (e.g., urine, CSF)

aCase classification: A case was considered to have a definite explanation if the organism was a well-recognized cause of syndrome and there was one test from column A or 2 from column B. A case was considered to have a probable explanation if the organism was a well-recognized cause of the syndrome and there was one test from column B, or if the organism was not a well-recognized cause of the syndrome and there was one test from column A or 2 from column B. A case was considered to have a possible explanation if the organism was not a well-recognized cause of the syndrome and there was one test from column B, or if there was one test from column C, regardless of whether organism is known to cause the syndrome.
b"Involved” refers to the presence of typical pathology.
cIF = immunofluorescence, IHC = immunohistochemistry, IEM = immunoelectronmicroscopy, ISH = in situ hybridization, PCR = polymerase chain reaction, Ig = immunoglobulin, EM = electron microscopy, CSF = cerebrospinal fluid.
dfor example, bronchoalveolar lavage in respiratory syndrome.
eEM is often nonspecific and may not permit reliable microbial identification without further characterization (e.g., IEM).
fSpecific or broad range PCR/reverse transcriptase-PCR; product must be characterized beyond size determination (e.g., sequencing, single-strand conformation polymorphism, restriction fragment-length polymorphism, or probe hybridization).

Main Article

1Divya Agrawal, William Bower, Richard Danila, Linda Duke, Mark Eberhard, Marc Fischer, Jeannette Guarner, Connie Heye, James Johnson, Rima Khabbaz, Fred Lopez, Ruth Lynfield, James Meek, Christopher Paddock, Arthur Reingold, Robert Ryder, Susan Smith, Deborah F. Talkington, Michael Virata, and Duc Vugia.

2Oregon used a different age cut-off because of limited resources.

3IHC was available at CDC for the following pathogens: Acanthamoeba culbertzoni; adenovirus; Bacillus anthracis; Balamuthia spp.; Bartonella henselae, Bartonella quintana; Brucella spp.; Chlamydia spp.; Coccidiodes spp; Coxiella burnetii; Crimean-Congo hemorrhagic fever virus; Cryptococcus spp.; Cytomegalovirus; Dengue virus; Eastern equine encephalitis virus; Ebola virus; Ehrlichia chaffeensis; Enterovirus (Pan-enterovirus); human enterovirus 71; Flavivirus; Japanese encephalitis serocomplex group (West Nile virus, St. Louis encephalitis virus [SLEV], Japanese encephalitis virus); Francisella tularensis; Group A streptococci; Guanarito virus (Venezuelan hemorrhagic fever virus); Hantavirus; Helicobacter pylori; Hendra virus; herpes simplex viruses 1 and 2; Histoplasma spp.; human granulocytic ehrlichiosis; Human herpesvirus 6; HIV-1; HIV-2; B19 virus (B19V); Influenza A virus (FLUA); Influenza B virus (FLUB); Junin virus (Argentine hemorrhagic fever); La Crosse virus; Lassa virus; Legionella pneumophila serogroups 1, 5, 6; Leptospira spp.; Listeria monocytogenes; Lymphocytic choriomeningitis virus (LCMV); Machupo virus (Bolivian hemorrhagic fever); Marburg virus; measles (Edmonston) virus (MeV); Mycobacterium spp.; Mycoplasma pneumoniae; Naegleria fowleri; Neisseria meningitidis C; Nipah virus; Human parainfluenza virus types 1 and 3 (HPIV 1,3); Rabies virus (RABV); Human respiratory syncytial virus (HRSV); Rickettsia spp. Orientia group; Rickettsia spp. spotted fever group; Rickettsia spp. Typhus group; Rift Valley fever virus; Rotavirus; Streptococcus pneumoniae; Toxoplasma gondii; Treponema pallidum; Trypanosoma cruzi; varicella-zoster virus (VZV); Venezuelan equine encephalitis virus; Western equine encephalomyelitis virus (WEEV); Yellow fever virus; and Yersinia pestis.

4The following viral tests were used at the CDHS Viral and Rickettsial Diseases Laboratory: IgG was detected by both EIA and IFA for adenovirus, HHV-6, HHV-8, herpes simplex virus, FLUAV, FLUBV, MeV, Mumps virus (MuV), HPIV-1-4, HRSV, Rubella virus (RUBV), VZV, SLEV, and WEEV. IgG was detected by EIA only for Hantavirus (Sin Nombre virus [SNV]) and B-19. IgG was detected by IFA only for Epstein-Barr virus (viral capsid antigen), LCV, and RABV. IgM was detected by both EIA and IFA for HHV-6, herpes simplex virus, MeV, MuV, HPIV-1-4, HRSV, RUBV, and VZV. IgM was detected by EIA only for enterovirus, hantavirus (SNV), and B19V. IgM was detected by IFA only for Epstein-Barr virus. PCR tests performed were Herpesvirus consensus PCR (6); enterovirus PCR, modified from (7) [Antisense primer (1R): 5’-ATT GTC ACC ATA AGC AGC CA, sense primer (1L): 5’-CCT CCG GCC CCT GAA TGC GGC TAA T]; and adenovirus PCR (8).

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