Yellow Fever Flashcards

(25 cards)

1
Q

What’s the causative agen for yellow fever? And family?
Major mode of transmission

A

Yellow Fever (YF) Overview

  • Causative Agent: Yellow fever virus (Flavivirus, RNA virus)
  • Vector: Aedes mosquitoes (mainly Aedes aegypti)
  • Reservoirs: Humans and monkeys
  • Transmission: Mosquito bite
  • Risk Areas: Tropical and subtropical regions of South America and Sub-Saharan Africa
  • At-Risk Group: Unvaccinated individuals in endemic areas
  • Mortality (severe cases): 20–50%
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2
Q

Historical Highlights

  • Origin: Africa
  • First outbreak: 1648 in the New World
  • Introduced via: Slave-trading ships carrying infected mosquitoes
  • Major outbreaks:
    • 1793, Philadelphia: 10% of city died
    • 1878, Mississippi Valley: \~100,000 cases

When was vaccine breakthrough made?

A
  • Vaccine breakthrough: 1930s by Max Theiler (17D vaccine)
    • Nobel Prize: 1950
  • Vaccine usage: Still incomplete in endemic regions ➡️ periodic outbreaks
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3
Q

There are how many genotype of this virus?
Which is found in Nigeria?

A

Epidemiology

  • Genotypes: 7 total
    • 5 in Africa: Angola, Central Africa, East Africa, West Africa I & II
    • West Africa Genotype I: Found in Nigeria — highly virulent
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4
Q
  • Seasonal Pattern:
    • South America: Jan–Mar (peak rainfall & humidity)
    • Africa: Late rainy to early dry season.
A
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5
Q
  • WHO Data:
    • 84,000–170,000 severe cases yearly in Africa
    • 29,000–60,000 deaths

Yellow Fever in Nigeria

  • Among 47 high-risk African countries
  • Vaccine introduced: 2004 via routine immunization
  • Problem: Low coverage ➡️ accumulation of susceptibles ➡️ outbreaks

2020 Outbreak (Nigeria)

  • Reported: Nov 1, 2, 8 by Delta, Enugu, and Bauchi States
  • Demographics: Mostly males, 1–55 years
  • Symptoms:
    • Fever, jaundice, vomiting (± blood), abdominal pain, epistaxis, hematuria, convulsion, unconsciousness
  • Response:
    • Nov 7: National Yellow Fever Emergency Operations Centre (EOC) activated

Outbreak Data (as of Nov 18, 2020)

State Suspected Confirmed Deaths
Bauchi | 89 | 8 | 8
Delta | 162 | 8 | 67
Enugu | 141 | 19 |75
Benue | 28 | 3 | 22

A
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6
Q

What are the Transmission Cycles of Yellow Fever?

A

Transmission Cycles of Yellow Fever

  1. Sylvatic (Jungle) Cycle
  • Occurs: Tropical rainforests
  • Vector:
    • Haemagogus (South America)
    • Aedes africanus (Africa)
  • Reservoir: Monkeys
  • How it spreads:
    • Infected monkeys ➡️ forest mosquitoes → humans who enter forest
  1. Intermediate Cycle (Africa only)
  • Occurs: Humid/semi-humid savannahs
  • Vector: Semi-domestic mosquitoes
  • Reservoir: Both monkeys and humans
  • Features: Small outbreaks in rural communities
  1. Urban Cycle
  • Occurs: Densely populated areas
  • Vector: Aedes aegypti
  • Transmission: Infected person from jungle/savannah introduces virus to urban population ➡️ epidemic
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7
Q

What’s the family and genus of yellow fever? And it’s related viruses

A

Virology of Yellow Fever Virus (YFV)

  • Family: Flaviviridae
  • Genus: Flavivirus (“flavus” = yellow in Latin)
  • Related viruses: Dengue, Japanese Encephalitis, Tick-borne encephalitis
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8
Q

What is the **Structure of YFV **

A

YFV Structure

  • Size: \~50 nm
  • Capsid: Icosahedral
  • Envelope: Yes
  • Surface Proteins:
    • M, E glycoproteins
    • E protein: mediates host cell entry, fusion, and antibody neutralization

Genome

  • Type: ssRNA (+) strand, infectious
  • Size: \~11 kb
  • Encodes:
    • Structural: C, M, E
    • Non-structural: NS1 to NS5
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9
Q

Stability

  • Sensitive to: Heat, UV light, disinfectants, acidic pH
  • Unstable outside host
A
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10
Q

What’s the Pathogenesis of Yellow Fever?
General pathology and organ specific pathology

A

Pathogenesis of Yellow Fever

  • Entry: Bite from infected mosquito
  • Initial replication: Regional lymph nodes
  • Viraemia: Peaks between days 3–6
  • Cytokines: ↑ TNF-α, IL-1RA, mild ↑ IL-6
  • Systemic Spread: Liver, kidney, lungs, adrenal gland, spleen, bone marrow

Pathology
General Findings

  • Widespread hemorrhages: Skin, mucosa, GI tract
  • Hematemesis: From gastric mucosa erosion + petechial hemorrhage
  • Bleeding Diathesis: Due to:
    • ↓ clotting factors (liver failure)
    • Thrombocytopenia
    • Endothelial + platelet dysfunction
    • DIC (Disseminated Intravascular Coagulation)

Organ-Specific Pathology

  • Liver:
    • Lobular necrosis
    • Glycogen depletion
    • Fatty change (steatosis)
    • Councilman bodies (eosinophilic apoptotic cells)
  • Kidneys:
    • Acute tubular necrosis
  • CNS:
    • Cerebral oedema
    • Hemorrhages
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11
Q

What’s the incubation period of yellow fever?
How’s the onset?

Spectrum:

Ranges from:

  • Mild febrile illness
  • To severe hemorrhagic fever (fatal in up to 50% of severe cases)
A

Clinical Features of Yellow Fever

  • Incubation period: 3–6 days
  • Asymptomatic cases: 5–50%
  • Onset: Abrupt
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12
Q

What are the clinical features of yellow fever?

A

Three Classic Phases:

  1. Period of Infection
  • Features: Fever, Faget sign (fever + bradycardia), chills, malaise, headache, flushing, nausea, dizziness
  • Viraemia present — patient can infect mosquitoes
  • Duration: Few days
  1. Period of Remission
  • Features: Temporary improvement, fever subsides
  • Duration: 2–48 hours
  • May lead to full recovery or progress to next phase
  1. Period of Intoxication (15% of cases)
  • Features:
    • Return of high fever
    • Nausea, vomiting
    • Epigastric and lumbosacral pain
    • Jaundice, renal failure, bleeding
  • No viraemia
  • Death: 7–10 days after symptom onset
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13
Q

Recovery:

  • Convalescence: Prolonged fatigue and weakness for weeks
  • Immunity: Lifelong after infection (due to neutralizing antibodies)
A
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14
Q

What are the possible complications of yellow fever?
And differential diagnosis?

A

Complications

  • Bacterial superinfections: Pneumonia, sepsis
  • Cardiac: Myocarditis, arrhythmias, heart failure

Differential Diagnosis

Consider in any patient with:

  • Fever + jaundice + bleeding tendency

Infectious causes:

  • Malaria
  • Typhoid fever
  • Dengue fever
  • Viral hepatitis
  • Lassa fever
  • Marburg virus
  • Ebola virus
  • Hantavirus
  • Leptospirosis
  • Influenza

Non-infectious causes:

  • Surgical/obstructive jaundice
  • Toxic hepatitis
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15
Q

What are the Laboratory Diagnosis of Yellow Fever (YF)?

A

Direct Detection

  • RT-PCR: Detects viral RNA
  • Best within first 10 days of illness
  • Viral culture: Samples from week 1
  • Antigen detection: In tissue samples
  • Immunohistochemistry: Post-mortem tissues for YF Ag

Serology (ELISA)

  • IgM and IgG:
  • Sample ≥ 3 days after symptom onset
  • Positive = presumptive case
  • PRNT (Plaque Reduction Neutralization Test):
  • Confirms neutralizing antibodies to YF virus

Ancillary Labs

  • FBC:
  • Leukopaenia
  • Relative neutropenia
  • Thrombocytopenia
  • Clotting profile:
  • Prolonged PT
  • ⬇️ clotting factor levels
  • LFT:
  • ⬆️ AST > ALT
  • ⬆️ Serum bilirubin
  • Renal:
  • Proteinuria
  • ⬆️ BUN, creatinine
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16
Q

YF Testing Algorithm (Nigeria). How’s it done?

And reference labs in 9ja

A
  1. ELISA IgM
  • Positive = Presumptive
  • Indeterminate = Inconclusive
  • Negative = Negative
  1. All presumptive/inconclusive ➡️ Sent to reference labs for RT-PCR within 3 days

Reference Labs (6 total)

  • Abuja (2)
  • Kaduna (1)
  • Lagos (1)
  • Enugu (1)
  • Edo (1)
17
Q

How’s Management of Yellow Fever done?

A

No specific antiviral. Supportive care only.

  • Hospital admission
  • IV fluids for rehydration
  • Paracetamol for pain (avoid aspirin/NSAIDs)
  • Ventilation for respiratory failure
  • Dialysis for renal failure
  • Transfusions for bleeding
18
Q

Infection Prevention & Control (IPC)

  • No human-to-human transmission
  • Isolate for differential diagnoses
  • Use mosquito nets to prevent spread
  • Standard precautions mandatory
19
Q

How’s yellow fever **Prevented and Controled? **

A

1. Vector Control

  • Reduce mosquito breeding
  • Insecticide use

2. Vaccination: 17D Live-Attenuated Vaccine

  • >90% protected in 10 days
  • \~99% protected in 30 days
  • Single dose = lifelong immunity
  • Part of EPI in endemic zones
20
Q

Vector Control (Nigeria)

Entomologic Survey (NAVRC 2007–2014)

  • Identified 9 Aedes species in 19 states + FCT
  • States: Kwara, Kogi, Benue, Edo, Cross River, Rivers, Akwa Ibom, Delta, Anambra, Imo, Enugu, Abia, Ebonyi, Ondo, Kaduna, Kebbi, Katsina, Zamfara, Taraba
21
Q

Control Measures

  • Eliminate mosquito breeding sites around homes, clinics, worksites
  • Empty/cover water containers
  • Proper waste disposal
  • Use mosquito nets
  • Plant water-retaining crops away from homes
  • Apply biological/chemical larvicides
22
Q

Yellow Fever Vaccine (17D)

Routine Immunization

  • Single dose = lifelong protection
  • Given at _____ month (introduced in Nigeria in 2004)

Tell me what you can about supplementary immunization

A

9 months

Supplemental Immunization

  • “Catch-up” doses for those who missed routine vaccination

Mass Vaccination Campaigns

  • PMVC (Preventive): Age 9 months–44 years
  • Targets \~85% of population
  • RMVC (Reactive): Same age group
  • Deployed after outbreak confirmation to rapidly boost immunity.
23
Q

What can you say about the EYE Strategy?

A

EYE Strategy (Eliminating Yellow Fever Epidemics)

Background

  • Developed in 2016 after YF outbreaks in Angola, DRC, Brazil
  • Global strategy covering 2017–2026

Objectives

  1. Protect at-risk populations
  2. Prevent international spread
  3. Contain outbreaks quickly

Vision:

A world without yellow fever epidemics

Mission:

Coordinate global support to help countries prevent, detect, and respond to outbreaks

Goal:

Minimize suffering, loss, and spread via early detection and timely response

24
Q

What’s the Outbreak Response at Health Care Facility for YF

A

Outbreak Response at Health Care Facility

  • Detect & manage cases; report and collect samples
  • Train HCWs for high suspicion index
  • Preposition supplies for outbreak response
  • Follow YF-specific guidance for surveillance and epidemic control
  • Activate case management protocols
  • Use standard case definitions for diagnosis and reporting
  • Report to LGA Disease Surveillance and Notification Officer (DSNO)
  • Conduct active case search + blood sampling
  • Send samples to designated lab for confirmation.

-

25
What's the **Case Definitions of Yellow Fever**?
**Case Definitions of Yellow Fever** **1. Suspected Case** * Acute fever **± weakness**, **vomiting**, **bleeding**, or **jaundice** * Jaundice appears **within 14 days** of symptom onset **2. Probable Case** * A **suspected case** who **died** without laboratory confirmation **3. Presumptive Positive Case** * YF **IgM positive** in **non-vaccinated** patient (no YF vaccine in **last 30 days**) * **OR** epidemiological link to a confirmed case/outbreak * **OR** positive **post-mortem liver histopathology** **4. Confirmed Case** A presumptive case with **any of the following**: * **Serology:**   * YF-specific **IgM detection**   * **≥4-fold rise** in IgM/IgG titres (acute ⏩ convalescent)   * Detection of **neutralizing Ab** * **AND** no YF immunization in **last 30 days** **OR** * **Molecular/Direct detection:**   * YFV **RNA by PCR** in blood/liver/organ   * YFV **antigen by immunoassay**   * **Isolation** of YF virus   * **AND** no YF immunization in **last 14 days** **Alert and Outbreak Thresholds** * **Alert Threshold:** 1 suspected case * **Outbreak Alert:** 1 presumptive positive case * **Outbreak Threshold:** 1 confirmed case (by **reference lab/PCR**) **YF Notification Network (Nigeria)** ```text Health Facility      ⬇️ LGA DSNO ⏩ National Lab      ⬇️ ⬆️ State Epidemiologist      ⬇️     NCDC    ⬇️ ⬇️ NHMIS NPHCDA ``` --- **Conclusion** * YF is **vaccine-preventable**, yet fatal in **>50%** of severe cases * Increasing **community awareness** and **vaccination uptake** is essential for **herd immunity**