Loa loa: A neglected NTD

Thomas B. Nutman, M.D.Head, Helminth Immunology Section andHead, Clinical Parasitology SectionLaboratory of Parasitic DiseasesNational 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

Loiasis - Clinical Manifestations

• Asymptomatic• Non-specific

– urticaria, pruritus, myalgias

• Calabar swellings• Eyeworm• Complications

– Endomyocardial fibrosis, renal disease, encephalopathy, entrapment neuropathy

•Episodic angioedema

•Most common on extremities

•Duration -1-4 days

Loiasis – Calabar Swellings

Parasite

Host

UnusualPathology

Immunity Pathology Infected

Hyper-responsive

Responsive(appropriate)

Responsive(inappropriate)

Hypo-responsive(tolerant/suppressed)

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•Amy Klion•Peter Burbelo•Susan Leitman•Jesica Christensen•Dan Fedorko•Gary Fahle

• Past and present LPD Clinical Staff– LPD Clinical Fellows– Kate Spates– Nicole Holland– Amara Pabon– Melissa Law– Cheryl Talar-Williams