01Approach to the Critical Patient/attcp21

Immediate Risk Stratification

›Severity assessment on presentation

›Mild: uncomplicated febrile illness with rash, arthralgia, conjunctivitis — outpatient management

›Moderate: significant dehydration, inability to tolerate oral intake — observation

›Severe: neurologic complication (GBS with respiratory compromise), hemorrhagic manifestations, encephalopathy — admission

›Pregnancy with confirmed or suspected ZIKV exposure — urgent evaluation regardless of symptoms

Neurologic Emergency Recognition

›Progressive ascending weakness suggesting Guillain-Barre Syndrome

›GBS occurs in 2–3 per 10,000 ZIKV infections; onset typically 5–10 days after acute illness

›Bilateral facial paralysis in 50% of ZIKV-associated GBS cases

›Serial FVC monitoring: intubation threshold FVC less than 20 mL/kg or less than 1.0 L

›ICU admission if respiratory compromise or rapid neurologic deterioration

›Continuous telemetry for autonomic instability and cardiac arrhythmias

Stabilization Priorities

›Airway, breathing, circulation assessment in severe presentations

›Supplemental oxygen for respiratory insufficiency associated with GBS

›IV fluid resuscitation for dehydration; oral rehydration preferred in mild cases

›Avoid aspirin and NSAIDs until dengue is excluded — hemorrhage risk

›Acetaminophen for fever and pain management

Consult and Reporting Triggers

›Mandatory notifications and specialist activation

›Neurology consultation for any suspected GBS or CNS complication

›MFM/OB consultation for any pregnant patient with confirmed or suspected ZIKV exposure

›Infectious disease consultation for diagnostic uncertainty or complex serologic interpretation

›Report to state/local health department — nationally notifiable disease (ICD-10: A92.5)

02History/hx37

Travel and Exposure History

›Recent travel to or residence in ZIKV-endemic area

›Endemic regions: Latin America, Caribbean, Southeast Asia, Pacific Islands

›Incubation period 3–14 days after mosquito exposure

›Sexual contact with a partner who traveled to an endemic area even if asymptomatic

Symptom Characterization

›Classic symptom complex of acute ZIKV infection

›Acute onset maculopapular rash, often pruritic — most common presenting feature

›Low-grade fever, typically less than 38.5 degrees Celsius

›Arthralgia and myalgia — less severe and debilitating than chikungunya

›Non-purulent conjunctivitis — bilateral

›Headache and retro-orbital pain

›Duration up to 7 days, self-limited; 50–80% of infections asymptomatic

Alarm Symptoms Screening

›Red-flag symptoms requiring urgent evaluation

›Progressive or ascending limb weakness — GBS screening

›Facial droop, diplopia, dysphagia — cranial nerve involvement

›Difficulty walking or respiratory compromise

›Severe headache, altered mental status, seizures — meningoencephalitis

›Easy bruising, bleeding, petechiae — hemorrhagic manifestations; suspect dengue co-infection

Pregnancy and Reproductive History

›Pregnancy status — essential to determine immediately

›Both symptomatic and asymptomatic ZIKV infections pose vertical transmission risk

›Last menstrual period and gestational age

›Conception plans — defer conception per CDC guidance after exposure

›Prior adverse pregnancy outcomes

Sexual Transmission History

›Sexual exposure risk assessment

03Physical Exam/exam26

Vital Signs

›Hemodynamic and temperature assessment

›Low-grade fever typically less than 38.5 degrees Celsius

›Hemodynamically stable in uncomplicated infection

›Tachycardia or hypotension — consider dengue with plasma leakage, severe dehydration

Dermatologic Examination

›Skin findings characteristic of ZIKV infection

›Diffuse maculopapular rash, often pruritic and may be confluent

›Rash typically involves trunk and extremities; may involve palms and soles

›Petechiae or purpura — raises concern for dengue co-infection

Ophthalmologic Examination

›Eye findings

›Bilateral non-purulent conjunctivitis — distinguishes from bacterial conjunctivitis

›Fundoscopic examination if visual complaints — posterior uveitis reported

Lymph Node Examination

›Lymphadenopathy assessment

›Cervical and inguinal adenopathy may be present

›Generalized lymphadenopathy favors dengue or EBV

Musculoskeletal Examination

›Joint and muscle assessment

›Arthralgia without significant joint swelling — distinguishes from chikungunya

›Chikungunya presents with more severe and prolonged symmetric polyarthralgia

Neurologic Examination

›Comprehensive neurologic assessment — critical in all ZIKV presentations

›Cranial nerve examination — facial nerve palsy (CN VII), dysphagia (CN IX/X)

›Motor strength — proximal and distal, bilateral; ascending pattern of weakness

›Deep tendon reflexes — areflexia or hyporeflexia suggests GBS

›Sensory examination — paresthesias, glove-and-stocking distribution

04Differential Diagnosis/ddx32

Arboviral Infections

›Dengue fever — most critical diagnosis to exclude

›ICD-10: A90 (dengue fever), A91 (dengue hemorrhagic fever)

›Overlapping geography and presentation; higher fever, severe myalgia, retro-orbital pain

›Thrombocytopenia, leukopenia, elevated hematocrit more prominent

›Risk of hemorrhagic manifestations and dengue shock syndrome

›Tourniquet test positive in dengue hemorrhagic fever

›Chikungunya virus

›ICD-10: A92.0

›More prominent, debilitating, and prolonged symmetric polyarthralgia

›Rash similar; conjunctivitis less common than in ZIKV

Other Infectious Mimics

›Malaria

›ICD-10: B50-B54

›Cyclical fevers, rigors, hepatosplenomegaly; diagnosis via thick and thin smear or RDT

›Rubella

›ICD-10: B06

›Similar rash and lymphadenopathy; critical to distinguish in pregnancy

›Measles

›ICD-10: B05

›Cephalocaudal rash progression, Koplik spots, cough, coryza, conjunctivitis triad

›Parvovirus B19

›ICD-10: B97.6

›Slapped-cheek rash, arthralgias; arthropathy prominent in adults

Less Common Infectious Differentials

›Leptospirosis, rickettsiosis, oropouche virus

›Leptospirosis: conjunctival suffusion, jaundice, renal failure; ICD-10: A27

›Rickettsiosis: eschar, petechial rash; ICD-10: A77

05Laboratory Tests/lt25

Nucleic Acid Amplification Testing

›RT-PCR (NAAT) on paired serum and urine — preferred diagnostic modality

›Perform within first 1–2 weeks of symptom onset; highest yield in first week

›For symptomatic pregnant women: NAAT on serum and urine as soon as possible, up to 12 weeks after symptom onset

›Urine RT-PCR detects virus longer than serum RT-PCR

›Positive NAAT on a single sample should be re-extracted and re-tested to confirm; rule out false positive

›Per updated IDSA/ASM guidance 2024: NAAT is the recommended first-line test

Serology

›IgM serology — secondary role with significant limitations

›Develops end of first week of illness; persists months to years

›Cross-reacts with dengue, yellow fever, and other flaviviruses — limited specificity

›No longer recommended for pregnant women per updated CDC/IDSA guidance

›PRNT (plaque reduction neutralization test) for serologic confirmation — reference lab required

›PRNT still subject to cross-reactivity in secondary flavivirus infections

›Concurrent dengue NAAT and IgM testing recommended given overlapping geography

Complete Blood Count

›Hematologic assessment

›Mild leukopenia — common in ZIKV; moderate-to-severe leukopenia raises dengue concern

›Thrombocytopenia — may be mild in ZIKV; marked thrombocytopenia below 100 × 10^9/L raises dengue concern

›Elevated hematocrit with thrombocytopenia — dengue with plasma leakage

Metabolic and Hepatic Panel

›Biochemical evaluation

›Renal function (creatinine, electrolytes) — for dehydration assessment and leptospirosis exclusion

›Liver enzymes (AST, ALT) — transaminase elevation more prominent in dengue

›Serum glucose — baseline in febrile illness

CSF Analysis

›Lumbar puncture if GBS or meningoencephalitis suspected

›Albuminocytologic dissociation: elevated protein with normal cell count — classic GBS finding

06Diagnostic Tests/dt29

Scoring Systems

›Clinical prediction and severity tools

›No validated ZIKV-specific clinical prediction score exists

›Brighton Collaboration criteria for GBS case classification — useful for ZIKV-associated GBS

›GBS disability scale (0–6): score greater than or equal to 3 (unable to walk unaided) — strong consideration for IVIG or therapeutic plasma exchange

›Tourniquet test for dengue co-infection: 10 or more petechiae per square centimeter indicates positive result

MRI

›MRI indications in ZIKV-associated neurologic complications

›MRI spine with gadolinium for suspected acute myelitis or extensive GBS

›Nerve root and cauda equina enhancement on gadolinium-enhanced MRI — supports GBS diagnosis

›MRI brain for encephalopathy or meningoencephalitis evaluation

›Fetal MRI for confirmed congenital ZIKV — more sensitive than ultrasound for cortical malformations

›Congenital findings: simplified gyral pattern, pachygyria, heterotopia, cerebellar hypoplasia

CT

›CT indications in ZIKV presentations

›CT head — not routinely indicated in uncomplicated ZIKV infection

›CT head for altered mental status, suspected encephalopathy, or to exclude hemorrhage

›Congenital Zika syndrome: periventricular and subcortical calcifications on neonatal head CT

›Cerebral volume loss, ventriculomegaly, cortical malformations in severe congenital disease

Ultrasound

›Ultrasound applications in ZIKV

›Fetal ultrasound at 18–22 weeks gestation in confirmed or suspected maternal ZIKV infection

›Serial fetal ultrasound every 3–4 weeks to monitor for microcephaly, ventriculomegaly, intracranial calcifications

›Amniocentesis not routinely recommended — risk of false negatives and iatrogenic loss

›Newborn head ultrasound by 1 month of age in congenital Zika syndrome

Neurophysiology

›Nerve conduction studies and EMG for suspected GBS

›ZIKV-associated GBS — AIDP subtype most common; AMAN subtype also reported

07Disposition/dispo25

Discharge Criteria

›Uncomplicated ZIKV infection suitable for outpatient management

›Adequate oral hydration and tolerating PO intake

›No progressive neurologic symptoms

›Non-pregnant, or pregnancy with urgent OB/MFM follow-up arranged within 24–48 hours

›Reliable follow-up and clear return precautions provided

›Dengue testing sent or excluded; no hemorrhagic manifestations

Observation Indications

›Patients requiring monitoring or IV therapy

›Dehydration requiring IV fluid resuscitation

›Pregnant patients awaiting urgent NAAT results

›Borderline neurologic findings requiring repeat examination

Admission Criteria

›Hospital admission indications

›Progressive neurologic deficits consistent with GBS

›Respiratory compromise or FVC less than 20 mL/kg

›Severe thrombocytopenia or hemorrhagic manifestations

›Encephalopathy or meningoencephalitis

›Autonomic instability requiring telemetry

Specialist Consultation

›Consultation triggers by clinical scenario

›Neurology: any suspected GBS, CNS complication, or myelitis

›MFM/OB: any pregnant patient with confirmed or suspected ZIKV exposure

›Infectious disease: diagnostic uncertainty, complex serologic interpretation, rare manifestations

›Pediatric neurology or developmental specialist: congenital Zika syndrome

›Ophthalmology: uveitis or ocular complaints in adults or congenital disease

Public Health Reporting

›Mandatory reporting obligations

08Treatment/t37

Supportive Care

›Mainstay of management for uncomplicated ZIKV infection

›Acetaminophen 650 mg orally every 6 hours or 1000 mg every 8 hours for fever and pain

›Maximum dose 4 g per 24 hours in adults without hepatic impairment

›Maximum dose 2 g per 24 hours in patients with hepatic disease or alcohol use

›Oral hydration — primary fluid management strategy for mild disease

›IV normal saline 0.9% for dehydration when oral intake insufficient

›No specific antiviral therapy approved for ZIKV infection

›No approved vaccine currently available; multiple candidates in clinical trials

NSAID and Aspirin Avoidance

›Analgesic restriction until dengue exclusion

›Avoid aspirin and all NSAIDs until dengue is definitively excluded

›Rationale: dengue-associated thrombocytopenia combined with platelet inhibition increases hemorrhage risk

›Once dengue excluded, NSAIDs may be used for arthralgia if clinically indicated

GBS Treatment

›Immunomodulatory therapy for ZIKV-associated GBS — same protocol as idiopathic GBS

›IVIG 0.4 g/kg/day IV for 5 days (total 2 g/kg)

›Administer over 2–5 hours per dose depending on formulation and tolerability

›Preferred in patients with IgA deficiency exclusion

›Class I recommendation per AAN guidelines for GBS

›Therapeutic plasma exchange (TPE) — equivalent efficacy to IVIG

›5 exchanges over 7–14 days (total 200–250 mL/kg)

›Preferred when IVIG contraindicated (IgA deficiency, prior IVIG reaction, renal failure)

›Combination IVIG and TPE not superior to either alone — do not combine

GBS Supportive Management

›Monitoring and supportive measures in GBS

›Serial FVC every 4–6 hours during acute phase

›Intubation and mechanical ventilation if FVC less than 20 mL/kg, PaO2 less than 70 mmHg, or rapid decline

09Special Populations/sp34

Pregnancy

›Zika virus in pregnancy — highest clinical priority population

›Both symptomatic and asymptomatic maternal ZIKV infection pose fetal risk

›Congenital Zika syndrome: microcephaly, parenchymal and periventricular calcifications, ventriculomegaly, arthrogryposis, ocular anomalies, low birth weight

›Vertical transmission risk highest in first trimester; severe brain anomalies reported in all trimesters

›Pregnant women should avoid travel to ZIKV-endemic areas per CDC and AFP guidance

›Diagnostic approach in pregnancy

›Urgent NAAT on serum and urine for all pregnant patients with ZIKV symptoms or endemic area exposure

›Concurrent dengue NAAT and IgM testing

›IgM serology no longer recommended for routine prenatal ZIKV screening per updated IDSA/CDC guidance

›Serial fetal ultrasound every 3–4 weeks for confirmed or suspected maternal infection

›Amniocentesis not routinely recommended — risk of false negatives and pregnancy loss

›Management priorities in pregnancy

›OB/MFM co-management for all confirmed or suspected exposures

›Acetaminophen preferred for analgesia; NSAIDs contraindicated in pregnancy beyond 20 weeks

›Defer conception: CDC guidance recommends delay after ZIKV exposure

Geriatric

›Older adult considerations in ZIKV infection

›Dehydration risk increased — lower physiologic reserve; lower threshold for IV hydration

›Polypharmacy: verify acetaminophen dose does not exceed 2 g per 24 hours if hepatic impairment or chronic alcohol use

›GBS in older adults associated with more severe course and longer recovery

›IVIG volume load may exacerbate heart failure — consider slower infusion rate and cardiac monitoring

›Atypical presentation risk

›Fever may be blunted or absent in elderly — low threshold to test despite absent fever

›Altered mental status may mask or present as the dominant symptom

Pediatrics

›Pediatric ZIKV infection and congenital disease

›Acute ZIKV in children is generally mild and similar to adult presentation

10Background/b30

Epidemiology

›Global burden and transmission patterns of ZIKV

›Mosquito-borne flavivirus transmitted primarily by Aedes aegypti and Aedes albopictus

›Epidemic transmission documented in Micronesia (2007), French Polynesia (2013–2014), and the Americas (2015–2016)

›More than 80 countries reported mosquito-borne ZIKV transmission during the 2015–2016 pandemic

›50–80% of ZIKV infections are asymptomatic

›Symptomatic illness is typically mild and self-limited, lasting up to 7 days

›GBS incidence: approximately 2–3 per 10,000 ZIKV infections

›Sexual transmission documented in multiple countries — both heterosexual and same-sex male transmission

›Blood transfusion transmission documented — rare route

›Current (2026) transmission: low-level endemic in parts of Southeast Asia and the Pacific; travel-associated cases in non-endemic countries

›ICD-10 code: A92.5 (Zika virus disease)

Pathophysiology

›Mechanisms of ZIKV disease and teratogenicity

›ZIKV is a positive-sense single-stranded RNA virus in the Flaviviridae family

›Primary vector: Aedes aegypti; secondary vector: Aedes albopictus with wider geographic range

›Viral tropism includes skin keratinocytes, dendritic cells, and neural progenitor cells

›Neural progenitor cell infection causes apoptosis — mechanism of microcephaly and cortical malformation

›Fetal blood-brain barrier more permeable than adult — increased CNS vulnerability

›GBS pathogenesis: molecular mimicry — ZIKV antigens cross-react with peripheral nerve gangliosides

›AIDP subtype most common in ZIKV-associated GBS; AMAN subtype also documented

›Viral persistence in semen for up to 3 months explains sexual transmission window

›Congenital Zika syndrome differs from acquired infection: CNS destruction pattern with calcifications, cortical malformations, and cerebellar hypoplasia

Therapeutic Considerations

›Evidence base and treatment landscape for ZIKV

›No approved antiviral therapy exists; management remains entirely supportive for acute infection

›No licensed ZIKV vaccine as of 2026; multiple mRNA and subunit vaccine candidates in Phase 2/3 trials

›IVIG and therapeutic plasma exchange for ZIKV-associated GBS: evidence extrapolated from idiopathic GBS trials; Class I recommendation per AAN guidelines

11Patient Discharge Instructions/pdi25

copy discharge instructions

›Discharge instructions for Zika Virus Infection

›Your diagnosis is Zika virus infection, a mosquito-borne viral illness usually lasting 5–7 days

›Take acetaminophen (Tylenol) for fever and pain as directed; do not exceed the dose on the label

›Do not take aspirin, ibuprofen, naproxen, or other anti-inflammatory medications until your doctor confirms you do not have dengue fever

›Drink plenty of fluids; oral rehydration solutions (e.g., Pedialyte, Gatorade) are recommended if you have difficulty eating or drinking

›Rest is recommended during acute illness

›Mosquito bite prevention

›Use insect repellent containing at least 20–30% DEET when outdoors for at least 1 week after illness onset

›Wear long sleeves and pants; use permethrin-treated clothing if available

›Stay in air-conditioned or well-screened environments to prevent spreading Zika to mosquitoes and then to others

›Sexual transmission prevention

›If you are male: use condoms or avoid sex for 3 months after symptom onset to prevent sexual transmission

›If you are female: use condoms or avoid sex for 2 months after symptom onset

›These precautions apply even if you feel fully recovered

›Pregnancy and family planning

›If you are pregnant or your partner is pregnant, follow up with your obstetrician immediately

›If you are planning a pregnancy, discuss timing with your doctor before attempting conception

›Return to the Emergency Department immediately if you develop

›Weakness or numbness in your arms or legs

›Difficulty walking, facial drooping, or trouble swallowing

›Difficulty breathing or shortness of breath

›Severe headache, confusion, or difficulty speaking

›Bleeding from gums, nose, or skin; blood in urine or stool

›High fever not controlled with acetaminophen

›Vomiting preventing oral fluid intake

12References/r22

Guidelines and Key Sources

›Musso D, Ko AI, Baud D. Zika Virus Infection After the Pandemic. N Engl J Med. 2019

›Comprehensive review of ZIKV epidemiology, diagnostics, clinical manifestations, and management

›Covers GBS association, congenital Zika syndrome, and sexual transmission evidence

›CDC Yellow Book 2025. Zika. Martin SW, Meaney-Delman D, Staples JE

›Current CDC guidance on travel risk, diagnostics, prevention, and public health reporting

›Recommendations for avoiding aspirin/NSAIDs and mosquito bite prevention during illness

›Miller JM, Binnicker MJ, Campbell S, et al. IDSA/ASM Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update. Clin Infect Dis. 2024

›Current recommendations: NAAT preferred; IgM serology not recommended for pregnant women

›Guidance on concurrent dengue testing in co-endemic settings

Landmark Studies and Society Recommendations

›Parra B, Lizarazo J, Jimenez-Arango JA, et al. GBS Associated with ZIKV Infection in Colombia. N Engl J Med. 2016

›Established causal association between ZIKV infection and GBS; characterized AIDP predominance

›Identified 50% bilateral facial palsy rate in ZIKV-associated GBS

›Krauer F, Riesen M, Reveiz L, et al. Zika Virus Infection as a Cause of Congenital Brain Abnormalities and GBS: Systematic Review. PLoS Med. 2017

›Systematic review confirming teratogenicity and GBS association

›Sharp TM, Fischer M, Munoz-Jordan JL, et al. Dengue and Zika Virus Diagnostic Testing for Patients With Clinically Compatible Illness. MMWR Recomm Rep. 2019

›Guideline for concurrent dengue and ZIKV diagnostic testing algorithm

›Baud D, Gubler DJ, Schaub B, Lanteri MC, Musso D. An Update on Zika Virus Infection. Lancet. 2017

›Comprehensive update on pathogenesis, clinical spectrum, and therapeutic landscape

›Shahrizaila N, Lehmann HC, Kuwabara S. Guillain-Barre Syndrome. Lancet. 2021

›Current GBS management review supporting IVIG 2 g/kg and TPE as equivalent Class I treatments

›Freitas DA, Souza-Santos R, Carvalho LMA, et al. Congenital Zika Syndrome: A Systematic Review. PloS One. 2020

›Systematic review of congenital manifestations: neuroimaging findings, ophthalmologic anomalies, audiology

Evidence & Review

Evidence & Review