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Lassa Fever
General Facts
• Viral hemorrhagic fever caused by the Arenavirus
  Lassa
• Transmitted from rodents to humans
• Discovered in Nigeria, 1969
• Endemic in portions of West Africa
• Seasonal clustering: Late rainy and early dry season
• Affects all age groups and both sexes
Arenaviridae
• Name derived from “arenosus” (Latin “sandy”) describing
  appearance of virions on examination by electron microscopy
• Enveloped virus, round or pleomorphic, 50-300 nm in diameter
• Single-stranded genome divided into 2 RNA segments: small
  (~3.4 kb) and large (~7.1 kb)
• 2 genes on each segment, arranged in unique “ambisense”
  orientation, encoding 5 proteins
• Inactivated by:
      –   heating to 56oF
      –   pH<5.5 or >8.5
      –   UV/gamma irradiation
      –   detergents
Arenaviridae
• Arenaviruses associated with human disease
  Virus        Origin of Name     Year   Distribution
  Lassa        Town, Nigeria      1969   West Africa
  Junin        Town, Argentina    1957   South America
  Machupo      River, Bolivia     1962   South America
  Guanarito    Area, Venezuela    1989   South America
  Sabia        Town, Brazil       1990   South America
  LCMV         Clinical disease   1933   Worldwide
Lassa Virus




Image source: C.S. Goldsmith and M. Bowen (CDC).
Epidemiology
• Endemic in areas of West Africa, including Nigeria,
  Liberia, Sierra Leone, and Guinea
• Estimated 300,000-500,000 infections/year, with 5000
  deaths
• Rodent-to-human transmission (the “multimammate rat”,
  Mastomys species-complex)
• Secondary human-to-human transmission with the
  potential for nosocomial outbreaks with high case-fatality
Known Distribution of Mastomys

                     MASTOMYS
                      MASTOMYS
                    DISTRIBUTION
                    DISTRIBUTION

                    LASSA 1969
                    LASSA 1969
Rodent Reservoir
        • Mastomys species
          complex
        • Taxonomy still unclear
          – M. huberti: more
            common in
            peridomestic habitat
          – M. erytholeucus: more
            common in brush
            habitat
          – Others
Transmission
• Rodent-to-human:
  – Inhalation of aerosolized virus

  – Ingestion of food or materials contaminated
    by infected rodent excreta
  – Catching and preparing Mastomys as a food
    source
Transmission
• Human-to-human:
  – Direct contact with blood, tissues,
    secretions or excretions of infected
    humans
  – Needle stick or cut

  – Inhalation of aerosolized virus
Pathogenesis
• Endothelial cell damage/capillary leak
• Platelet dysfunction
• Suppressed cardiac function
• Cytokines and other soluble mediators of
  shock and inflammation
Clinical Aspects
• Incubation period of 5-21 days
• Gradual onset of fever, headache, malaise and other non-specific
  signs and symptoms
• Pharyngitis, myalgias, retro-sternal pain, cough and
  gastrointestinal symptoms typically seen
• A minority present with classic symptoms of bleeding, neck/facial
  swelling and shock
• Case fatality of hospitalized cases: 15-20%
• Particularly severe in pregnant women and their offspring
• Deafness a common sequela
Clinical Signs and Symptoms
                         Fever
                     Headache
          Arthralgias/Myalgias
            Retro-sternal Pain
                    Weakness
                     Dizziness
       Sore throat/Pharyngitis
                       Cough
                     Vomiting
   Abdominal Pain/Tenderness
                      Diarrhea
Conjunctivitis/Sub-conjunctival
  Hemorrhage             Chills
                      Deafness
           Lymphadenopgathy
                    Bleeding
                   Confusion
         Swollen Neck or Face

                                  0   10   20   30   40     50      60   70   80   90   100
                                                          Percent
Lassa Fever in Pregnancy
• Increased maternal mortality in third trimester
  (>30%)
• Increased fetal and neonatal mortality (>85%)
• Increased level of viremia in pregnant women
• Placental infection
• Evacuation of uterus improves mother’s chance
  of survival
Sensorineural Hearing Deficit in
            Lassa Fever
• Typically appears during early
  convalescence
• Not related to severity of acute illness
• Occurs in one-third of cases
• May be bilateral or unilateral
• May persist for life in up to one-third of those
  affected
Lassa Fever in Children and Infants
• Significant cause of pediatric hospitalizations in
  some areas of West Africa
• Signs and symptoms most often similar to
  adults
• “Swollen Baby Syndrome”
     - Edema/Anasarca
     - Abdominal distension
     - Bleeding
     - Poor prognosis
Differential Diagnosis of
                  Lassa Fever
• Malaria               • Bacterial sepsis
• Typhoid fever         • Bacterial meningitis
• Streptococcal         • Arboviral infection
  pharyngitis           • Anicteric hepatitis
• Leptospirosis         • Enterovirus infection
                        • Bacterial or viral
                          conjuctivitis
Diagnostics
• Clinical diagnosis often difficult
• ELISA (Enzyme-linked immunosorbent
  assays) for antigen, IgM, and IgG
• As research tools:
  – Virus isolation
  – Immunohistochemistry (for post-mortem
    diagnosis)
  – RT-PCR (Reverse transcription-polymerase
    chain reaction)
Treatment
• Supportive measures
• Ribavirin
  – Most effective when started within the first 6 days
    of illness
  – Major toxicity: mild hemolysis and suppression of
    erythropoesis. Both reversible
  – Presently contraindicated in pregnancy, although
    may be warranted if mother’s life at risk
  – Does not appear to reduce incidence or severity
    of deafness
Associated with Poor Prognosis in
          Lassa Fever
 • High viremia
 • Serum AST level >150 IU/L
 • Bleeding
 • Encephalitis
 • Edema
 • Third trimester of pregnancy
Prevention and Control

• Village-based programs for rodent control
  and avoidance

• Hospital training programs to avoid
  nosocomial spread: barrier nursing manual

• Diagnostic technology transfer

• Specific antiviral chemotherapy (ribavirin)
Rodent Control

• Proper storage of food in rodent-proof
  containers
• Cleaning around homes
• Trapping and killing rodents with proper and
  safe disposal of carcasses
• Avoid rodents as a food source

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Lassa fever

  • 2. General Facts • Viral hemorrhagic fever caused by the Arenavirus Lassa • Transmitted from rodents to humans • Discovered in Nigeria, 1969 • Endemic in portions of West Africa • Seasonal clustering: Late rainy and early dry season • Affects all age groups and both sexes
  • 3. Arenaviridae • Name derived from “arenosus” (Latin “sandy”) describing appearance of virions on examination by electron microscopy • Enveloped virus, round or pleomorphic, 50-300 nm in diameter • Single-stranded genome divided into 2 RNA segments: small (~3.4 kb) and large (~7.1 kb) • 2 genes on each segment, arranged in unique “ambisense” orientation, encoding 5 proteins • Inactivated by: – heating to 56oF – pH<5.5 or >8.5 – UV/gamma irradiation – detergents
  • 4. Arenaviridae • Arenaviruses associated with human disease Virus Origin of Name Year Distribution Lassa Town, Nigeria 1969 West Africa Junin Town, Argentina 1957 South America Machupo River, Bolivia 1962 South America Guanarito Area, Venezuela 1989 South America Sabia Town, Brazil 1990 South America LCMV Clinical disease 1933 Worldwide
  • 5. Lassa Virus Image source: C.S. Goldsmith and M. Bowen (CDC).
  • 6.
  • 7.
  • 8. Epidemiology • Endemic in areas of West Africa, including Nigeria, Liberia, Sierra Leone, and Guinea • Estimated 300,000-500,000 infections/year, with 5000 deaths • Rodent-to-human transmission (the “multimammate rat”, Mastomys species-complex) • Secondary human-to-human transmission with the potential for nosocomial outbreaks with high case-fatality
  • 9. Known Distribution of Mastomys MASTOMYS MASTOMYS DISTRIBUTION DISTRIBUTION LASSA 1969 LASSA 1969
  • 10. Rodent Reservoir • Mastomys species complex • Taxonomy still unclear – M. huberti: more common in peridomestic habitat – M. erytholeucus: more common in brush habitat – Others
  • 11. Transmission • Rodent-to-human: – Inhalation of aerosolized virus – Ingestion of food or materials contaminated by infected rodent excreta – Catching and preparing Mastomys as a food source
  • 12. Transmission • Human-to-human: – Direct contact with blood, tissues, secretions or excretions of infected humans – Needle stick or cut – Inhalation of aerosolized virus
  • 13. Pathogenesis • Endothelial cell damage/capillary leak • Platelet dysfunction • Suppressed cardiac function • Cytokines and other soluble mediators of shock and inflammation
  • 14. Clinical Aspects • Incubation period of 5-21 days • Gradual onset of fever, headache, malaise and other non-specific signs and symptoms • Pharyngitis, myalgias, retro-sternal pain, cough and gastrointestinal symptoms typically seen • A minority present with classic symptoms of bleeding, neck/facial swelling and shock • Case fatality of hospitalized cases: 15-20% • Particularly severe in pregnant women and their offspring • Deafness a common sequela
  • 15. Clinical Signs and Symptoms Fever Headache Arthralgias/Myalgias Retro-sternal Pain Weakness Dizziness Sore throat/Pharyngitis Cough Vomiting Abdominal Pain/Tenderness Diarrhea Conjunctivitis/Sub-conjunctival Hemorrhage Chills Deafness Lymphadenopgathy Bleeding Confusion Swollen Neck or Face 0 10 20 30 40 50 60 70 80 90 100 Percent
  • 16. Lassa Fever in Pregnancy • Increased maternal mortality in third trimester (>30%) • Increased fetal and neonatal mortality (>85%) • Increased level of viremia in pregnant women • Placental infection • Evacuation of uterus improves mother’s chance of survival
  • 17. Sensorineural Hearing Deficit in Lassa Fever • Typically appears during early convalescence • Not related to severity of acute illness • Occurs in one-third of cases • May be bilateral or unilateral • May persist for life in up to one-third of those affected
  • 18. Lassa Fever in Children and Infants • Significant cause of pediatric hospitalizations in some areas of West Africa • Signs and symptoms most often similar to adults • “Swollen Baby Syndrome” - Edema/Anasarca - Abdominal distension - Bleeding - Poor prognosis
  • 19. Differential Diagnosis of Lassa Fever • Malaria • Bacterial sepsis • Typhoid fever • Bacterial meningitis • Streptococcal • Arboviral infection pharyngitis • Anicteric hepatitis • Leptospirosis • Enterovirus infection • Bacterial or viral conjuctivitis
  • 20. Diagnostics • Clinical diagnosis often difficult • ELISA (Enzyme-linked immunosorbent assays) for antigen, IgM, and IgG • As research tools: – Virus isolation – Immunohistochemistry (for post-mortem diagnosis) – RT-PCR (Reverse transcription-polymerase chain reaction)
  • 21. Treatment • Supportive measures • Ribavirin – Most effective when started within the first 6 days of illness – Major toxicity: mild hemolysis and suppression of erythropoesis. Both reversible – Presently contraindicated in pregnancy, although may be warranted if mother’s life at risk – Does not appear to reduce incidence or severity of deafness
  • 22. Associated with Poor Prognosis in Lassa Fever • High viremia • Serum AST level >150 IU/L • Bleeding • Encephalitis • Edema • Third trimester of pregnancy
  • 23. Prevention and Control • Village-based programs for rodent control and avoidance • Hospital training programs to avoid nosocomial spread: barrier nursing manual • Diagnostic technology transfer • Specific antiviral chemotherapy (ribavirin)
  • 24. Rodent Control • Proper storage of food in rodent-proof containers • Cleaning around homes • Trapping and killing rodents with proper and safe disposal of carcasses • Avoid rodents as a food source