Laboratory diagnostics for viral haemorrhagic fever

Laboratory diagnostics were one of the six themes of the 2016 Berlin workshop. Because early VHF looks like malaria or typhoid, confirmation depends on laboratory tests – mainly RT-PCR during the acute phase and antibody tests later – carried out under strict biosafety conditions and backed by quality assessment.

Last reviewed: 7 October 2026 · Independent archive

Illustration of sample tubes in a biosafety cabinet and an RT-PCR amplification curve — Laboratory confirmation of VHF relies on molecular testing under strict biosafety. Illustration.

When VHF testing is considered

Testing is guided by exposure history: travel to or residence in an affected area, contact with a suspected or confirmed patient, contact with animal blood or ticks in CCHF-endemic regions, or laboratory exposure. Since malaria is far more common in the same regions, malaria testing is usually done in parallel – a positive malaria test does not automatically exclude a VHF.

Test methods

Main laboratory methods for VHF
Method	What it detects	When it is most useful
RT-PCR	Viral genetic material	Acute phase; standard method for confirmation
Antigen detection (ELISA, rapid tests)	Viral proteins	Acute phase; supplementary or field use
IgM / IgG antibody tests (ELISA)	Immune response	Later in illness and in survivors
Virus isolation in cell culture	Live virus	Reference and research use, high-containment laboratories only

During the Ebola response in the Democratic Republic of the Congo, cartridge-based PCR systems such as the GeneXpert Ebola assay were used close to treatment centres, shortening the time to results.

Biosafety

Viruses such as Ebola, Marburg, Lassa and CCHF virus require specialised containment. Work with live virus, including isolation, is restricted to high-containment (biosafety level 4) laboratories. In Germany, the Bernhard Nocht Institute for Tropical Medicine in Hamburg operates a BSL-4 laboratory and a WHO Collaborating Centre for arboviruses and haemorrhagic fever reference and research. The Robert Koch Institute's Centre for Biological Threats and Special Pathogens works on the same group of pathogens.

A consensus from the European networks EMERGE and EVD-LabNet on CCHF laboratory management addressed biosafety, the diagnostic algorithm and ways to improve laboratory capability, and stressed that frontline hospitals and reference laboratories must integrate laboratory, clinical and public-health responses.

Quality assessment and reference materials

External quality assessments test whether laboratories get the right answer. The European Network for Diagnostics of "Imported" Viral Diseases (ENIVD) organised the first international external quality assessment of molecular CCHF detection in 2011; the results showed a need to improve testing conditions and standardise protocols. A 2012 ENIVD survey of 31 laboratories in 28 countries examined case definitions, training needs, biosafety, quality assurance and test availability for CCHF.

WHO International Standards and other reference materials, assigned in International Units, allow assays to be calibrated and compared. Their production is complicated by the containment requirements of these viruses.

Frequently asked questions

Which test confirms Ebola, Lassa, Marburg or CCHF?

RT-PCR, which detects viral genetic material during the acute phase, is the main confirmatory test.

Can a normal hospital laboratory test for VHF?

Routine labs can perform safety-adapted basic tests, but confirmation and any work with live virus take place in specialised reference laboratories with appropriate containment.

What is a BSL-4 laboratory?

The highest biosafety containment level, required for work with live viruses such as Ebola, Marburg and Lassa.

Why is quality assessment important?

External quality assessments showed differences between laboratories in CCHF molecular testing and a need to standardise protocols, so that results are reliable everywhere.