Last reviewed: 20 Sep 2021
Last updated: 28 Jul 2020



History and exam

Key diagnostic factors

  • presence of risk factors
  • acute onset of fever
  • headache
  • myalgia
  • arthralgia

Other diagnostic factors

  • retro-orbital pain
  • tachypnoea
  • tachycardia
  • chills
  • altered mental status
  • nausea/vomiting
  • seizures
  • gastrointestinal bleeding
  • rhinorrhoea
  • cough
  • diarrhoea
  • rash
  • sore throat
  • hemiparesis
  • lethargy, drowsiness, or confusion
  • paraesthesias
  • ataxia/gait abnormalities
  • behavioural abnormalities
  • stupor, somnolence, or coma
  • neck stiffness (nuchal rigidity)
  • jaundice
  • papilloedema

Risk factors

  • living and/or working in or near tropical forests in Central or South America
  • fishing in or near tropical forests in Central or South America
  • age <15 years
  • occupational exposure (laboratory)
  • bioterrorism

Diagnostic investigations

1st investigations to order

  • reverse transcription-polymerase chain reaction (RT-PCR)
  • enzyme-linked immunosorbent assay (ELISA)

Investigations to consider

  • plaque reduction neutralisation test (PRNT)
  • viral isolation
  • cerebrospinal fluid cell count, chemistries (glucose, protein), and viral isolation
  • FBC (including haematocrit)
  • LFTs
  • chest x-ray
  • head CT
  • brain MRI
  • rapid malaria antigen test or malaria smear
  • electroencephalogram

Treatment algorithm



Amy Vittor, MD, PhD

Assistant Professor

Division of Infectious Disease and Global Medicine

University of Florida




AV is funded by the National Institute of Allergy and Infectious Diseases (NIAID) for work on host susceptibility and emerging alphaviruses (2016-2021); however, the funding supports new insights in the field only, it does not directly impact any articles produced. AV is a recipient of an NIH NIAID K08 award. AV is also the author of a reference cited in this topic.

Peer reviewers

Miguel G. Madariaga, MD, MSc, FACP

Infectious Diseases Consultant

Naples Community Hospital




MGM declares that he has no competing interests.

Stalin Vilcarromero, MD

Research Physician

US Naval Medical Research Unit 6 (NAMRU-6)




SV declares that he has no competing interests.

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