Table 9 Definitive Diagnostics (Continued)
Pathogen Diagnostic test
Typhus fever (R. prowazekii) Serology: indirect microimmunofluorescence assay is the
most sensitive and specific, but is not usually positive
when the patient is acutely ill. PCR specific but not
sensitive. Real-time PCR both sensitive and specific.
Viral encephalitis [alphaviruses (e.g.,
Venezuelan equine encephalitis, EEE,
WEE)]
Direct detection (nucleic acid or virus isolation from acute-
phase serum or CSF); serologic assay (specific IgM in
CSF using capture ELISA or monoclonal antibody antigen
capture ELISA) at time of clinical encephalitis. Plaque
reduction neutralization test and ELISA can differentiate
the alphaviruses.
Viruses (noroviruses, hepatitis A virus) Norovirus: reverse transcription PCR, ELISA on stool
samples.
Hepatitis A: serology.
Water safety threats (e.g.,V. cholerae,
C. parvum)
V. cholerae: culture.
C. parvum: nested PCR on stool; modified acid-fast stain,
antibody staining, and other staining techniques on direct
stool smears; serum antibody response.
Protozoa (C. cayatanensis, G. lamblia,
Entameba histolytica, Toxoplasmaspp.,
Microsporidia)
Direct microscopy of stool (wet mounts, stained specimens,
and formal-ether concentrations), PCR; ELISA used to
detectE. histolyticaantigen in stool.
Category C pathogens
Emerging infectious diseases such as Nipah
virus and hantavirus; yellow fever virus,
tick-borne encephalitis complex
(Flaviviridae). Other viruses within the
same group are louping ill virus, Langat
virus, and Powassan virus.
Viral culture, PCR, and serology. Yellow fever: virus may
be isolated from blood during the first 3 days of illness.
Other methods of identification include antigen-capture
enzyme immunoassay, probe hybridization, and
immunofluorescence assay.Tick-borne hemorrhagic fever viruses
(Crimean-Congo hemorrhagic fever
(Nairovirus-a Bunyaviridae), Omsk
hemorrhagic fever, Kyasanur forest
disease and Alkhurma viruses.
Viral culture, PCR, serology (ELISA). Quantitative real-time
reverse transcription-PCR to measure viral load.Multidrug-resistantM. tuberculosis Culture and DNA probe. IFN-gamma-release assay that
measures the release of interferon after stimulation in
vitro byM. tuberculosisantigens for latent tuberculosis
and disease in immune compromised.
SARS virus (SARS-associated coronavirus) Viral detection via real-time PCR from respiratory
samples—only performed by the CDC, serology.
West Nile virus (a Flaviviridae)
Pandemic and avian influenza (H5N1
influenza)
Viral detection from oropharyngeal aspirate, swab, or lower-
respiratory sample. Viral subtyping by PCR by public
health laboratories. Rapid immunofluorescence or
enzyme immunoassay can differentiate between
influenza A and B strains.
Monkeypox virus (Orthopoxvirusof the
Poxviridae family)
Viral culture from skin lesions with real-time PCR to
differentiate from other poxviridae (smallpox)—only
performed by the CDC or WHO.
Genetically engineered biological weapons
Abbreviations: CDC, Centers for Disease Control; CSF, cerebrospinal fluid; DFA, direct fluorescent antibody; EEE,
eastern equine encephalitis; ELISA, enzyme-linked immunosorbent assay; IHA, indirect hemagglutination assay;
LAMP, loop-mediated isothermal amplification; MIF, microimmuno-fluorescent test; PCR, polymerase chain
reaction; RT-PCR, reverse transcription polymerase chain reaction; PCR-EIA, PCR-enzyme immunoassay; WEE,
western equine encephalitis; WHO, World Health Organization.
Source: From Refs. 1, 6, 11, and 58–71.
468 Cleri et al.