220.1 🎓 醫孞生版

220.1.0.1 📌 䞀頁重點

220.1.0.1.1 Zika Virus
  • Virus: ssRNA flavivirus (same family as dengue, yellow fever, West Nile)
  • 2015-2016 Americas epidemic: Brazil + Caribbean + Latin America; 1.5M cases + 4000+ microcephaly cases
  • Vectors: Aedes aegypti + A. albopictus
  • Multiple transmission routes:
    • Mosquito bite (primary)
    • Sexual (semen for months after infection — unique among flaviviruses)
    • Vertical (in utero → congenital Zika syndrome)
    • Blood transfusion
    • Organ transplant
    • Saliva, urine, breast milk
  • Clinical:
    • 80% asymptomatic
    • Mild illness (when symptomatic): fever + rash (maculopapular, often pruritic) + arthralgia + non-purulent conjunctivitis + headache + retro-orbital pain
    • Self-limited 5-7 days
    • Mild compared to dengue + chikungunya
  • Major Concerns:
    • Congenital Zika Syndrome (CZS): 1st trimester maternal infection — microcephaly + brain calcifications + ocular defects + arthrogryposis + hypertonia
    • Guillain-Barré Syndrome (GBS) post-Zika
    • Sexual transmission longer than expected (semen 6+ months)
  • Diagnosis:
    • Zika PCR of blood (first 5 days) or urine (up to 14 days)
    • IgM serology — cross-reactive with other flaviviruses (dengue!) — interpret cautiously
    • PRNT (plaque reduction neutralization test) for confirmation
  • Treatment: supportive
  • Prevention:
    • Mosquito control + DEET
    • Travel advisories pregnant women (avoid endemic regions)
    • Sexual precautions (condoms) for ≥ 3 months post-Zika exposure
    • No vaccine yet (multiple candidates in trials)
220.1.0.1.2 Chikungunya Virus
  • Virus: ssRNA Togaviridae (alphavirus genus)
  • “Chikungunya” = Makonde language “to walk bent over” (joint pain)
  • Vectors: Aedes aegypti + A. albopictus
  • Geography: Africa + Asia + Caribbean + Americas; expanding
  • 2024 epidemic: severe in Brazil + Paraguay + Caribbean
  • Clinical:
    • Acute (days): fever + severe polyarthralgia (small joints, symmetric, debilitating) + maculopapular rash + myalgia + headache
    • Subacute/Chronic (weeks-years): persistent arthralgia in 30-60% — months to years
    • Distinguishes from dengue: more severe + prolonged joint pain
  • Severe: in neonates (vertical transmission), elderly, immunocompromise; encephalitis possible
  • Diagnosis:
    • PCR of blood (first 7 days)
    • IgM (after day 5)
    • IgG (lifelong post-infection)
  • Treatment:
    • Acute: paracetamol + NSAIDs (cautious — distinguish from dengue first), rest, hydration
    • Chronic arthralgia: NSAIDs, methotrexate / hydroxychloroquine / sulfasalazine for refractory
  • Vaccine:
    • Ixchiq (live attenuated, Valneva, FDA 2023) — first chikungunya vaccine — single dose 18+ yr
    • Vimkunya (Bavarian Nordic, FDA 2025) — VLP-based, alternative

220.1.0.2 1⃣ Zika Virus

220.1.0.2.1 Virology
  • ssRNA flavivirus
  • 2 main lineages: African + Asian
  • Asian lineage → American outbreak strain
  • Tropism for neural progenitor cells (basis of microcephaly)
220.1.0.2.2 2015-2016 Americas Epidemic
  • Brazil 2015 detection
  • Spread rapidly: Caribbean, Central + South America, Mexico, USA southern (local Florida + Texas)
  • Brazil 2015-2016: 1.5+ million Zika cases; 4000+ microcephaly cases
  • 2016-2017 declining cases (population immunity)
  • 2018+ low-level transmission ongoing
220.1.0.2.3 Transmission Routes
220.1.0.2.3.1 Mosquito Bite
  • Primary route
  • Aedes aegypti main; A. albopictus also
220.1.0.2.3.2 Sexual Transmission
  • Unique among flaviviruses
  • Semen contains Zika RNA for 6+ months (longer than blood)
  • Male-to-female, female-to-male, male-to-male reported
  • Recommendation: barrier protection ≥ 3 months post-Zika exposure (men + women); pregnancy planning delayed
220.1.0.2.3.3 Vertical Transmission
  • In utero (especially 1st trimester)
  • Congenital Zika Syndrome (CZS): microcephaly + brain malformations + ocular + arthrogryposis
  • Lifelong neurological impact
220.1.0.2.3.4 Other Routes
  • Blood transfusion (now screened in endemic)
  • Organ transplant
  • Saliva (theoretical, low risk)
  • Urine
  • Breast milk (theoretical, no documented cases)
220.1.0.2.4 Clinical (Postnatal Acquired)
  • 80% asymptomatic
  • Mild illness when symptomatic:
    • Low-grade fever
    • Maculopapular pruritic rash
    • Arthralgia (less severe than chikungunya)
    • Non-purulent conjunctivitis
    • Headache, retro-orbital pain
    • Myalgia
  • 5-7 days self-limited
  • Hospitalization rare
220.1.0.2.5 Severe Complications
220.1.0.2.5.1 Congenital Zika Syndrome (CZS)
  • 1st trimester maternal infection most severe risk (~ 10-20% have major fetal abnormalities)
  • 2nd-3rd trimester also possible
  • Features:
    • Microcephaly + craniofacial disproportion
    • Ventriculomegaly + brain calcifications
    • Cerebellar + brainstem hypoplasia
    • Arthrogryposis
    • Ocular: chorioretinal scarring, optic nerve hypoplasia
    • Hearing loss
    • Hypertonia, seizures, developmental delay
  • Long-term impact on growth + development
  • Multi-disciplinary care lifelong
220.1.0.2.5.2 Guillain-Barré Syndrome (GBS)
  • Post-Zika association documented
  • Increased GBS during epidemic
  • Likely molecular mimicry mechanism
  • Treatment: IVIG / plasmapheresis (standard GBS treatment)
220.1.0.2.5.3 Neurological
  • Encephalitis (rare)
  • Myelitis (rare)
  • Acute disseminated encephalomyelitis
220.1.0.2.6 Diagnosis
  • Zika PCR of blood (first 5 days; sensitivity declines after)
  • Zika PCR of urine (up to 14 days; sensitive)
  • IgM ELISA (after day 5; cross-reacts with dengue, yellow fever, JE, etc.)
  • PRNT (plaque reduction neutralization test) — for serologic confirmation
  • Distinguishing from dengue critical — both treated similarly but different prevention
220.1.0.2.7 Treatment
  • Supportive — no specific antiviral
  • Acetaminophen
  • NSAIDs after ruling out dengue
  • Hydration, rest
220.1.0.2.8 Prevention
220.1.0.2.8.1 Mosquito Control
  • Same as dengue
  • Aedes vector control
220.1.0.2.8.2 Personal Protection
  • DEET 20-30%
  • Picaridin 20%
  • Long sleeves + pants
  • Bed nets
220.1.0.2.8.3 Travel Advisories
  • Pregnant women should avoid travel to active Zika areas
  • Counsel before travel + after travel
  • Defer pregnancy 3-6 months post-Zika exposure
220.1.0.2.8.4 Sexual Transmission Prevention
  • Condoms ≥ 3 months post-Zika exposure (men + women)
  • Defer pregnancy 3-6 months
  • Pre-conception counseling
220.1.0.2.8.5 Vaccine
  • Multiple candidates in Phase 2-3 trials:
    • DNA vaccine (NIH)
    • mRNA vaccines
    • Whole-virus inactivated
  • No licensed Zika vaccine yet
220.1.0.2.9 Surveillance
  • 通報 in many countries
  • Pregnancy registries for Zika exposure outcome

220.1.0.3 2⃣ Chikungunya Virus

220.1.0.3.1 Virology
  • ssRNA alphavirus
  • Togaviridae family
  • Single serotype
  • 3 main genotypes: West African, East/Central/South African (ECSA), Asian
  • Tropism for fibroblasts + macrophages + endothelial cells
220.1.0.3.2 Epidemiology
  • Africa + Asia historically
  • Caribbean 2013-2014 outbreak
  • Americas 2014-2024 ongoing
  • 2024 Brazil + Paraguay severe epidemic
  • Aedes aegypti main; A. albopictus expanding (Europe)
  • Local outbreaks Italy + France (2007-2017+ sporadic) due A. albopictus
220.1.0.3.3 Transmission
  • Mosquito bite (primary)
  • Vertical (occasionally) — neonatal severe disease
  • Blood transfusion (rare)
  • Person-to-person: NOT direct
220.1.0.3.4 Clinical
220.1.0.3.4.1 Acute Phase (Days)
  • 3-7 day incubation
  • Sudden onset fever (39-40°C)
  • Severe symmetric polyarthralgia — small joints especially hands + wrists + ankles + knees + elbows
  • “Bent over” walking due joint pain (origin of name)
  • Maculopapular rash (50%)
  • Myalgia
  • Headache
  • Fatigue
  • GI symptoms
  • 5-10 days fever resolves
220.1.0.3.4.2 Subacute / Chronic Phase
  • 30-60% develop chronic arthralgia
  • Persistent joint pain weeks to years
  • Often disabling
  • Mimics RA in some
  • Inflammatory markers can be elevated
  • Imaging: synovitis + erosions in severe chronic
  • Quality of life impact significant
220.1.0.3.4.3 Severe / Atypical
  • Neonatal vertical transmission — severe disease (encephalopathy, myocarditis, hemorrhage)
  • Elderly + immunocompromise more severe
  • Encephalitis, myocarditis (rare adult)
  • Hepatitis
  • Bullous dermatitis (rare)
220.1.0.3.5 Diagnosis
  • PCR first 5-7 days (most sensitive acute)
  • IgM after day 5 (acute marker)
  • IgG lifelong (post-infection)
  • Distinguish from dengue + Zika clinically + serologically
220.1.0.3.6 Treatment
220.1.0.3.6.1 Acute
  • Supportive
  • Paracetamol + cautious NSAIDs (after ruling out dengue)
  • Rest + hydration
  • No antiviral
220.1.0.3.6.2 Chronic Arthralgia
  • NSAIDs + analgesia
  • DMARDs if persistent severe:
    • Methotrexate
    • Hydroxychloroquine
    • Sulfasalazine
    • Anti-TNF in refractory
  • Physical therapy
  • Joint injections occasionally
220.1.0.3.7 Vaccines
220.1.0.3.7.1 Ixchiq (Valneva, FDA 2023)
  • First chikungunya vaccine licensed
  • Live attenuated (deletion mutant)
  • Single dose IM, 18+ yr
  • Efficacy ~ 99% generating neutralizing antibodies (correlate of protection)
  • Indications: travel to endemic areas; outbreak control
  • Caveats: live attenuated — caution in immunocompromise; pregnancy precaution
  • USA + EU + UK approved
220.1.0.3.7.2 Vimkunya (Bavarian Nordic, FDA 2025)
  • VLP-based (recombinant)
  • Alternative
  • Non-live, may be option for some populations
220.1.0.3.7.3 Other Candidates
  • VLP, mRNA in Phase 2
220.1.0.3.8 Prevention
  • Mosquito control
  • DEET + protective clothing + bed nets
  • Vaccine for travelers + outbreak areas (Ixchiq)
  • Surveillance