Recognizing Zika Virus Infection

Distinguishing among Zika, Chikungunya and Dengue fever

The accessibility of aviation travel, coupled with globalization, has increased the transmission risk for various arboviruses, including Zika virus, Chikungunya virus and Dengue fever. It is important for NPs and PAs to distinguish among prospective arboviruses in clinical practice because of the potential for serious health manifestations. Clinicians must rely solely on history and physical findings to correctly diagnose the disease because diagnostic results are delayed and/or can be inaccurate. Therefore, the clinician must be well informed about distinguishing characteristics of prevalent arboviruses (Table 1).

Table 1


According to the Centers for Disease Control and Prevention (CDC), assessment is necessary for all patients who present with acute fever, rash and myalgia or arthralgia, and who have traveled in the prior 2 weeks to an area with ongoing transmission of Zika virus, Chikungunya virus and Dengue fever.1-4 Viral RNA can be identified in serum during the first 7 days of these illnesses, and reverse transcriptase polymerase chain reaction testing (RT-PCR) is the favored test for the three vector-borne viruses. Additionally, virus-specific IgM antibodies may be detectable 4 or more days after illness onset.4 Serologic cross-reactivity exists between flaviviruses, therefore current IgM antibody assays cannot reliably distinguish between Zika virus and Dengue virus infection. All of these specialized tests are performed at the CDC.4
The only FDA-cleared kit for commercial use identifies anti-DENV IgM antibodies, and results are typically not available for 5 to 7 days.4 The anti-DENV IgM antibodies kit can be obtained through the CDC. The clinician must take the appropriate next step if the testing result is suspicious for Dengue fever, including notifying the CDC promptly of the diagnosis of any of the arbor-borne viruses. Blood and urine samples must be sent to the CDC in accordance with their protocol of required laboratory testing.4Clinicians cannot rely on prolonged diagnostic interpretations in their diagnosis of patients with the suspected arbovirus. Thus, clinicians must be able to support their diagnosis solely on subjective and objective findings in order to initiate timely and appropriate treatment (Table 2).

Table 2

Why is it important to distinguish among suspected arboviruses?
Why is it important to correctly diagnose the arbovirus if the treatment generally consists of supportive care? Certain supportive care measure can be damaging for particular arboviruses. For example, aspirin and NSAIDs are contraindicated in Dengue fever due to risk for severe hemorrhage.2 But NSAIDs can be helpful to treat the rigorous arthralgia associated with Chikungunya virus. Each arbovirus can lead to unique and detrimental complications, as well as distinctive modes of transmission, if left undertreated or ignored. Dengue fever can lead to hypovolemic shock from plasma leakage, end-organ impairment due to prolonged shock, severe hemorrhage, and/or encephalopathy.2
Chikungunya virus can lead to debilitating joint pain that can persist for several months or even years. Zika virus can spread in utero and lead to spontaneous abortions, microcephaly, absent or poorly developed brain structures, defects of the eyes, and failure to thrive.5 Also of significance, Zika virus can be sexually transmitted and may lead to Guillain Barré syndrome.6 Only 1 in 5 people infected with Zika show overt symptoms.7,8 Therefore, it is crucial that clinicians be trained to correctly diagnose the arbor-borne illness. Zika virus, Chikungunya virus and Dengue fever all have similar manifestations, but each needs to be diagnosed correctly by a skilled clinician for the best patient outcome.

Taking the History

The hypothetical presentation of a patient with myalgia, retro-orbital pain, conjunctivitis, nausea, vomiting, fever and maculopapular rash aids in this discussion. Symptoms started 5 days ago and the patient traveled outside the United States within the last 2 weeks. In addition to general history questions, listed below are essential questions that must be asked during the initial patient interview to help differentiate among possible Zika virus, Chikungunya virus and Dengue fever:

  • Where exactly was your recent travel?
  • What are the exact dates of your travel?
  • When did your symptoms begin?
  • Can you describe your headache?
  • Do you have pain behind your eyes?
  • Can you describe your muscle aches?
  • How severe are your muscle aches?
  • Do you have joint pain?
  • Which time of day is the pain worst?
  • How severe is your joint pain?
  • Have you had any nosebleeds, bleeding gums, blood in your urine, or any small, non-blanching red dots?
  • How long have you had fever?
  • When did your fever start?
  • What have your temperatures been?
  • Are you sexually active?
  • Any chance that you are pregnant?
  • Have you had recent contact with someone who has had a known vector borne illness? If so, which one?

In addition to the answers to these questions, the clinician must obtain a full history of present illness and review of systems. Ask about use of all medications, immunization status, allergies, and past and current medical history.

Physical Examination

Patients with Dengue fever, Chikungunya virus or Zika virus will potentially experience the following symptoms: maculopapular rash that covers the trunk and arms; conjunctivitis; elevated temperature; and painful joints and muscles with palpation and active/passive range of motion.7 Distinguishing physical exam findings and varying degrees of severity will help guide the clinician in correctly diagnosing the illness. For example, a patient with Dengue fever may present with more hemorrhagic manifestations, such as petechiae or bleeding gums.2 A person affected with Chikungunya virus will have severe, debilitating arthralgia, especially with palpation, and decreased range of motion on examination.9 Lastly, a person affected by Zika virus may have exam findings that are fairly abnormal, such as nonpurulent conjunctivitis or mild decrease in ROM of joints related to minor pain in the small joints of the hands and feet.6 It is essential that the clinician perform their assessment in a cephalocaudal approach in order to not miss the appearance of serious findings or lack thereof (Table 3 and algorithm).

Table 3

Click the thumbnails to download the algorithms:

Before beginning the full head-to-toe assessment, the clinician must take close note of vital sign abnormalities and overall appearance of the patient. Certain symptoms may warrant sending the patient to the emergency department for further evaluation and management of serious complications. These red flag symptoms include: mentation changes; dehydration; significant fever; neurologic irritability; enlargement of the spleen or liver; severe hemorrhagic manifestations such as gastrointestinal bleeding; heart murmur/gallop; respiratory distress; abdominal irritability; and/or systematic musculoskeletal involvement.2

Differential Diagnoses

Based on the subjective and objective information you have obtained, you must come up with a focused differential diagnosis list. Knowledge and understanding of the three threats is the primary way to correctly diagnose the arbovirus. The clinician must then take steps to stop the transmission, be aware of related potential complications, and correctly treat the illness. Lack of experience and knowledge with these arboviruses may cause the clinician to misdiagnose cases, fail to initiate proper treatment, and/or fail to accurately educate the patient on potential transmission and complications.
If a 29-year-old woman were not correctly diagnosed with Zika virus, she would not be informed of her potential risks of conceiving a fetus born with microcephaly and/or other harmful effects to the fetus.5 If she thought she only had influenza, she could sexually transmit the virus to others, or become pregnant and have harmful effects on the fetus.5 Conducting a thorough history, including a history of present illness, review of systems, and physical examination, will allow the clinician to come up with a focused list of differential diagnoses.
Because these arboviruses are similar in clinical presentation, the differential diagnoses are closely related:2,10

  • Rubella
  • Influenza
  • Measles
  • Group A Streptococcus
  • Leptospirosis
  • Malaria
  • Scarlet fever
  • Rocky Mountain spotted fever
  • West Nile virus
  • Erythema Infectiosum (Fifth Disease),
  • Roseola Infantum (Sixth Disease)
  • Rickettsial Disease
  • Chagas Disease
  • Leptospirosis
  • Epstein Barr virus
  • Parvovirus
  • Enterovirus
  • Adenovirus
  • Chikungunya virus, Zika virus, Dengue fever and yellow fever should also be included in the differential diagnoses 2,10

Additional Diagnostics for Suspected Dengue Fever

As previously mentioned, laboratory confirmation of arbovirus differentiation (RT-PCR and ELISA) is time-consuming. However, samples should be collected and initiated for proper laboratory testing for the eventual confirmation of diagnosis by CDC. Dengue fever can yield severe hemorrhagic complications that could potentially be prevented, if the clinician has an early, watchful eye. If Dengue fever is suspected, certain diagnostic tests need to be done to facilitate both diagnosis and severity determination. The following laboratory tests should be ordered:2

  • Complete blood count
  • Metabolic panel
  • Serum protein
  • Liver profile
  • Disseminated intravascular coagulation (DIC) panel
  • Urinalysis (UA)
  • Stool for occult blood.2,3,11

The following results are consistent with Dengue fever:

  • Thrombocytopenia
  • Leukopenia
  • Mild to moderate elevation aspartate aminotransferase/alanine aminotransferase
  • (+) Occult blood guaiac testing
  • (2+) Blood in urine.2,3,11

Education for Advanced Practice

Although treatment is primarily in the form of supportive measures, it is essential for clinicians to be skilled in distinguishing among Zika virus, Chikungunya virus and Dengue fever based on history and physical examination, due to the potential for serious complications. Clinicians should be up-to-date on arbovirus outbreak locations and obtain a thorough travel history from the patient. Clinicians must also be aware of distinctive symptoms associated with each illness.

Connecting a strong patient history and pertinent physical exam findings will allow the clinician to accurately diagnose the patient and take precautions to prevent complications.

Educating Patients before they Travel

Although no vaccinations for these illnesses are available, it is important to share prevention information with patients prior to travel. Both species of mosquito that can transmit the arbor-borne illnesses mentioned bite outdoors (Aedes aegypti and Aedes albopictus), but Aedes aegypti will also bite people indoors.9 Protect against mosquito bites using the following techniques:

  • Wear DEET-containing insect repellent at all times while outside.
  • Protect the body with long sleeves and long pants.
  • Wear light-colored clothing.
  • Be vigilant about applying insect repellent during the morning hours and late afternoon/evening hours (time frame when Aedes mosquito is most likely to bite).10
  • Apply physical barriers, such as window screens and closed doors and windows.
  • Regularly empty, clean or cover containers that store water.8-10


  1. Centers for Disease Control and Prevention. Chikungunya Virus Geographic Distribution.
  2. Centers for Disease Control and Prevention. Dengue Clinical Case Management.
  3. Centers for Disease Control and Prevention. Division of Vector-Borne Diseases.
  4. Centers for Disease Control and Prevention. Revised Diagnostic Testing for Zika, Chikungunya, and Dengue Viruses in US Public Health Laboratories.
  5. Oduyebo T, et al. Update: Interim Guidelines for Health Care Providers Caring for Pregnant Women and Women of Reproductive Age with Possible Zika Virus Exposure—United States, 2016. MMWR. 2016;65:122-127.
  6. World Health Organization. Zika Virus.
  7. Dengue Fever, Chikungunya and Zika Virus in the Pacific Islands.
  8. Zika Virus.
  9. World Health Organization. Chikungunya.
  10. Medscape. Chikungunya Virus Differential Diagnosis.
  11. Medscape. Dengue Workup.

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