Detlab diagnosis of viral infection
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CDC laboratory diagnosis viral infections PCR antigen antibody serology guidance
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https://archive.cdc.gov/www_cdc_gov/sars/guidance/f-lab/assa…
Laboratory diagnosis of viral infections
Laboratory diagnosis confirms the viral cause, helps guide antiviral therapy and infection-control measures, and supports surveillance. Clinical features alone are often nonspecific. Medical Microbiology, p. 447.
1. Appropriate specimen collection
Specimen choice depends on the site of disease and suspected virus.
| Clinical syndrome | Common specimens |
|---|---|
| Respiratory infection | Nasopharyngeal or throat swab, nasal aspirate |
| Viral meningitis/encephalitis | CSF, serum, throat swab, stool, lesion swab as appropriate |
| Gastroenteritis | Stool |
| Hepatitis | Serum or plasma |
| Vesicular/ulcerative lesions, HSV/VZV | Swab or scraping from fresh lesion |
| Congenital/perinatal infection | Maternal blood, neonatal blood/urine/saliva, placenta as indicated |
Collect samples early in illness, when viral shedding is highest. Delayed collection, poor sampling, inappropriate transport, or degradation can cause false-negative results. Medical Microbiology, p. 447.
2. Direct detection of the virus
A. Nucleic acid amplification tests (NAATs)
- PCR detects viral DNA.
- RT-PCR detects viral RNA.
- Real-time PCR gives rapid, sensitive, and specific results.
- Multiplex PCR can detect several viruses in one specimen.
- Sequencing can identify genotype, mutations, antiviral resistance, and transmission patterns.
This is the preferred method for many acute viral infections, for example influenza, SARS-CoV-2, HSV encephalitis, HIV viral load, hepatitis B/C, and enteroviruses.
B. Antigen detection
Detects viral proteins in clinical samples by:
- ELISA/EIA
- Immunofluorescence
- Rapid antigen tests
- Immunochromatographic tests
These tests are fast and inexpensive but are generally less sensitive than PCR. Examples include influenza, RSV, rotavirus, dengue NS1, hepatitis B surface antigen, and HIV p24 antigen.
C. Microscopy and cytology
Some viruses cause characteristic cellular changes:
- Multinucleated giant cells/syncytia: HSV, VZV, measles, RSV
- Inclusion bodies: CMV, HSV, rabies
- Tzanck smear: may support HSV or VZV, but it does not distinguish between them and has limited sensitivity.
3. Virus isolation and culture
Virus may be grown in cell culture and identified by cytopathic effect, immunofluorescence, neutralization, or PCR.
- Useful for selected viruses, outbreak investigation, vaccine work, and antiviral susceptibility studies.
- Slow, expensive, and requires specialized laboratories.
- Usually replaced by molecular tests for routine diagnosis.
- Culture of high-risk viruses must be done only in suitable containment laboratories.
4. Serology: antibody detection
Serology detects the host immune response rather than the virus itself.
| Antibody/test | Interpretation |
|---|---|
| Virus-specific IgM | Usually suggests recent or acute infection, but may persist or be falsely positive |
| Virus-specific IgG | Indicates past infection, vaccination, or immunity |
| Fourfold rise in IgG titre between acute and convalescent sera | Strong evidence of recent infection |
| Neutralization test | Highly specific confirmatory antibody test in reference laboratories |
Common uses include diagnosis of dengue, rubella, measles, hepatitis viruses, HIV, EBV, CMV, and many arboviral infections. A single positive IgG test usually does not prove acute infection. For rubella, definite diagnosis may rest on viral RNA detection, virus isolation, or seroconversion. Jawetz, Melnick & Adelberg’s Medical Microbiology, p. 617.
5. Interpretation by stage of infection
| Stage | Most useful tests |
|---|---|
| Early acute phase | PCR/RT-PCR, antigen detection, culture where appropriate |
| Later acute or convalescent phase | IgM, paired IgG titres |
| Past exposure/immunity | IgG serology |
| Chronic infection/monitoring | Quantitative viral nucleic acid testing, for example HIV RNA or HBV/HCV viral load |
6. Important precautions in interpretation
- A negative PCR does not exclude infection if the specimen was collected too late, from the wrong site, or handled poorly.
- A positive PCR can sometimes reflect residual viral nucleic acid rather than active, transmissible infection.
- Antibody results can cross-react, especially with related viruses such as flaviviruses.
- Interpret every result with symptoms, exposure history, vaccination status, timing of illness, and local epidemiology.
- When results are unexpected or high-consequence, confirm using a second specimen, an alternative assay, or a reference laboratory. CDC diagnostic guidance also emphasizes that PCR false results can arise from collection and transport problems, and results require clinical and epidemiologic interpretation.
In short: PCR/RT-PCR is the main test for acute viral infection; antigen tests provide rapid but less-sensitive detection; serology helps identify recent or past infection; and viral culture is now mainly reserved for specialized settings.
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