What are the differences in clinical presentations between Zika, Chikungunya, and Dengue in patients with suspected mosquito-borne illnesses?

Clinical Differentiation of Zika, Chikungunya, and Dengue

The key distinguishing features are: conjunctivitis and macular rash strongly suggest Zika; severe arthralgia with fever points to chikungunya; and retro-orbital pain, hemorrhagic manifestations, and thrombocytopenia indicate dengue. 1, 2, 3

Distinctive Clinical Features by Pathogen

Zika Virus

• Conjunctivitis and photophobia are the most specific features, occurring significantly more frequently than in dengue or chikungunya 1, 2
• Localized macular rash (rather than generalized) is characteristic 1
• Pruritus and peripheral edema are statistically associated with Zika infection 4, 3
• Patients are less likely to be febrile compared to dengue or chikungunya cases 2
• Milder clinical course with lower hospitalization rates (typically <3%) compared to dengue 2, 3
• Viremia levels are significantly lower (mean 4.70 log10 copies/mL) than chikungunya or dengue 2

Dengue Virus

• Retro-orbital pain is a hallmark feature not typically seen in Zika or chikungunya 5, 6
• Hemorrhagic manifestations including petechiae, mucosal bleeding, and positive tourniquet test distinguish dengue from other arboviruses 5, 6, 1
• Generalized non-macular rash (versus localized macular in Zika) 1
• Prostration and vomiting are more strongly associated with dengue than Zika 4
• Laboratory abnormalities are more pronounced: thrombocytopenia, lymphocytosis, elevated liver enzymes, and rising hematocrit with falling platelets 6, 4, 1
• Higher hospitalization rate (9.90%) and potential for progression to dengue hemorrhagic fever or shock syndrome 3, 6
• Thrombocytopenia can persist for up to 28 days 1

Chikungunya Virus

• Severe arthralgia combined with fever is the defining characteristic, more prominent than in dengue or Zika 7, 3
• Joint pain is typically polyarticular and can be debilitating 3
• Higher viremia levels (mean 6.42 log10 copies/mL) compared to Zika 2
• Hospitalization rate approximately 2.57% 3
• Risk of Guillain-Barré syndrome estimated at 1.70 per 10,000 cases 3

Temporal Patterns of Symptoms

• Dengue: Fever, rash, and petechiae persist beyond 10 days after symptom onset 1
• Zika: Conjunctivitis is the only feature that commonly persists beyond 10 days 1
• All three viruses: Share an incubation period of 4-8 days 6, 8

Critical Laboratory Distinctions

• Dengue-specific findings: Thrombocytopenia (platelets ≤100,000/mm³), rising hematocrit (>20% increase), leukopenia, and elevated ALT/total protein levels 6, 4, 1
• Zika: Minimal laboratory abnormalities; normal platelet counts and liver function tests are typical 4, 1
• Chikungunya: Generally normal laboratory parameters without the thrombocytopenia seen in dengue 3

Diagnostic Testing Algorithm

• For symptoms ≤7 days: Perform dengue, Zika, and chikungunya NAATs on serum simultaneously 5, 7, 9
• For symptoms >7 days: IgM antibody testing becomes the primary diagnostic modality 5, 9
• Pregnant women: Test by NAAT for both dengue and Zika viruses regardless of symptom duration due to risk of adverse fetal outcomes 5, 7, 9

Common Pitfalls to Avoid

• Do not rely on clinical presentation alone: Up to 67% of cases meeting probable Zika criteria remain unconfirmed and may be other etiologies 1
• Coinfections are common: 13.4-27% of patients may have concurrent dengue/Zika infection, with lower viremia levels in coinfections than monoinfections 4, 2
• Cross-reactivity in serology: IgM antibodies can cross-react between flaviviruses (dengue, Zika, yellow fever, Japanese encephalitis), making serologic diagnosis challenging 5, 6
• Never use NSAIDs or aspirin when dengue cannot be excluded due to hemorrhagic risk 6, 7

Severity Indicators Requiring Hospitalization

• Dengue warning signs: Persistent vomiting, severe abdominal pain, mucosal bleeding, rising hematocrit with falling platelets, lethargy, or restlessness 6, 7
• Higher viremia correlates with hospitalization: Hospitalized patients have mean viremia of 7.1 log10 copies/mL versus 4.1 in outpatients 2
• Zika in pregnancy: All pregnant women with confirmed Zika require close monitoring for fetal complications including microcephaly 5, 9