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Loa loa: A neglected NTD

Thomas B. Nutman, M.D.
Head, Helminth Immunology Section and
Head, Clinical Parasitology Section
Laboratory of Parasitic Diseases
National Institute of Allergy and Infectious
Diseases
Loiasis
• Ogranism-Loa loa
• Vector - Chrysops spp. (deerfly)
• Microfilariae: Blood-borne
• Adult worms: subcutaneous
• Prevalence - ?3-13 million
• Geographic Distribution - West and Central
  Africa
• Host range - Human
Geographic distribution of loiasis
Lifecycle of Loa loa

           (EGG)

                   L1
   ADULT




    L4             L2


            L3
Loiasis - Clinical Manifestations
• Asymptomatic
• Non-specific
  – urticaria, pruritus, myalgias
• Calabar swellings
• Eyeworm
• Complications
  – Endomyocardial fibrosis, renal disease,
    encephalopathy, entrapment neuropathy
Loiasis – Calabar Swellings



                   •Episodic angioedema
                   •Most common on
                   extremities
                   •Duration -1-4 days
Parasite


                             Host




Hyper-       Responsive         Responsive      Hypo-responsive
responsive   (appropriate)      (inappropriate) (tolerant/suppressed)



Unusual       Immunity          Pathology         Infected
Pathology
Loiasis: Diagnosis
• Definintive diagnosis
  – Detection of microfilariae in daytime blood
  – Identification of adult worm in the
    subconjunctiva or subcutaneous tissue
  – PCR using Loa loa repeat sequence
• Presumptive diagnosis
  – Compatible clinical picture + positive
    antifilarial antibodies
     • Problematic due to geographical, serologic and
       clinical overlap with other filarial infections
Loiasis: extraction of adult worm
Loiasis: treatment
• Diethylcarbamazine (DEC)
 – treatment of choice (8-10 mg/kg/d x 21
   days)
 – mechanism of action unknown
   • immune system dependent
   • macro- and microfilaricidal
 – associated with severe side effects in
   patients with high levels of circulating
   microfilariae
Loiasis: adjunct therapy
• Corticosteroids
  – decrease rate of microfilarial clearance
  – reduce severity of post-treatment reactions
  – DO NOT prevent severe CNS complications of
    treatment in patients with high microfilarial
    load
• Apheresis
  – transient reduction of microfilarial load
  – ?decreased incidence of severe side effects
Loiasis response to therapy

Median years of follow-up: 4.5 years (range 2-15 years)

Cure rates with DEC
   •1 course                       38% (12/32)
   • 2 courses                     54% (17/32)
   • ≥ 3 courses                   90% (23/32)

The remaining 3 patients were cured following a 3 week
course of albendazole.

          Klion A, Ottesen E, Nutman T. J Infect Dis. 1994 Mar;169(3):604-10.
Loiasis and ivermectin
• Between 1989 and 1998, 76 million doses of
  ivermectin were distributed with 84 SAEs
  reported by passive surveillance (1 case/million)
   – 65/84 (75%) from Southern Cameroon
   – 37/65 (60%) were neurologic, 25% of which had high
     levels of Loa microfilaremia
   – the encephalopathy was temporally related to
     Mectizan™ (<5 d post-rx) and occurred in previously
     healthy individuals
Acknowledgements
•Doran Fink           • Past and present LPD
•Amy Klion              Clinical Staff
•Peter Burbelo           – LPD Clinical Fellows
•Susan Leitman           – Kate Spates
•Jesica Christensen      – Nicole Holland
•Dan Fedorko             – Amara Pabon
•Gary Fahle              – Melissa Law
                         – Cheryl Talar-Williams
Loa Loa cope by Dr. Nutman

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Loa Loa cope by Dr. Nutman

  • 1. Loa loa: A neglected NTD Thomas B. Nutman, M.D. Head, Helminth Immunology Section and Head, Clinical Parasitology Section Laboratory of Parasitic Diseases National Institute of Allergy and Infectious Diseases
  • 2. Loiasis • Ogranism-Loa loa • Vector - Chrysops spp. (deerfly) • Microfilariae: Blood-borne • Adult worms: subcutaneous • Prevalence - ?3-13 million • Geographic Distribution - West and Central Africa • Host range - Human
  • 4. Lifecycle of Loa loa (EGG) L1 ADULT L4 L2 L3
  • 5. Loiasis - Clinical Manifestations • Asymptomatic • Non-specific – urticaria, pruritus, myalgias • Calabar swellings • Eyeworm • Complications – Endomyocardial fibrosis, renal disease, encephalopathy, entrapment neuropathy
  • 6. Loiasis – Calabar Swellings •Episodic angioedema •Most common on extremities •Duration -1-4 days
  • 7.
  • 8. Parasite Host Hyper- Responsive Responsive Hypo-responsive responsive (appropriate) (inappropriate) (tolerant/suppressed) Unusual Immunity Pathology Infected Pathology
  • 9. Loiasis: Diagnosis • Definintive diagnosis – Detection of microfilariae in daytime blood – Identification of adult worm in the subconjunctiva or subcutaneous tissue – PCR using Loa loa repeat sequence • Presumptive diagnosis – Compatible clinical picture + positive antifilarial antibodies • Problematic due to geographical, serologic and clinical overlap with other filarial infections
  • 10.
  • 12. Loiasis: treatment • Diethylcarbamazine (DEC) – treatment of choice (8-10 mg/kg/d x 21 days) – mechanism of action unknown • immune system dependent • macro- and microfilaricidal – associated with severe side effects in patients with high levels of circulating microfilariae
  • 13. Loiasis: adjunct therapy • Corticosteroids – decrease rate of microfilarial clearance – reduce severity of post-treatment reactions – DO NOT prevent severe CNS complications of treatment in patients with high microfilarial load • Apheresis – transient reduction of microfilarial load – ?decreased incidence of severe side effects
  • 14.
  • 15.
  • 16. Loiasis response to therapy Median years of follow-up: 4.5 years (range 2-15 years) Cure rates with DEC •1 course 38% (12/32) • 2 courses 54% (17/32) • ≥ 3 courses 90% (23/32) The remaining 3 patients were cured following a 3 week course of albendazole. Klion A, Ottesen E, Nutman T. J Infect Dis. 1994 Mar;169(3):604-10.
  • 17. Loiasis and ivermectin • Between 1989 and 1998, 76 million doses of ivermectin were distributed with 84 SAEs reported by passive surveillance (1 case/million) – 65/84 (75%) from Southern Cameroon – 37/65 (60%) were neurologic, 25% of which had high levels of Loa microfilaremia – the encephalopathy was temporally related to Mectizan™ (<5 d post-rx) and occurred in previously healthy individuals
  • 18. Acknowledgements •Doran Fink • Past and present LPD •Amy Klion Clinical Staff •Peter Burbelo – LPD Clinical Fellows •Susan Leitman – Kate Spates •Jesica Christensen – Nicole Holland •Dan Fedorko – Amara Pabon •Gary Fahle – Melissa Law – Cheryl Talar-Williams