JOHNS HOPKINS
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Department of Pathology
600 N. Wolfe Street / Baltimore MD 21287-7093
(410) 955-5077 / FAX (410) 614-8087
Division of Medical Microbiology
THE JOHNS HOPKINS MICROBIOLOGY NEWSLETTER Vol. 26, No. 02
Tuesday, January 30, 2007
A. Provided by Sharon Wallace, Division of Outbreak Investigation, Maryland Department of
Health and Mental Hygiene.
There is no information available at this time.
B. The Johns Hopkins Hospital, Department of Pathology, Information provided by,
Justin A. Bishop, M.D.
Case presentation:
A 42-year-old woman presented to The Johns Hopkins Hospital in July 2006 for inability to
conceive for two years. Her past medical history was significant for symptomatic uterine fibroids
requiring two myomectomies. The patient was an immigrant from Cameroon in 1996. A review
of systems revealed only occasional pruritis. The patient underwent ultrasound-guided oocyte
retrieval in November 2006; intraoperatively, she was noted to have an adnexal cyst. The cyst
was aspirated and sent to the IVF lab, where multiple motile, “worm-like organisms” were
identified. These were ultimately identified as the microfilariae of Loa loa. Subsequent blood
samples examined by thick and thin smears stained with Giemsa revealed a worm burden
exceeding 10,000 microfilariae per mL.
Loa loa: 1,2,3
This organism is one of the microfilarial nematodes, a group that also includes the genera
Wuchereria, Brugia, Onchocerca, and Mansonella. All share a similar life cycle: an insect
vectors the third-stage larvae (L3) to a human host upon taking a blood meal. These larvae
mature into fourth-stage larvae (L4) and then to adult worms, which subsequently mate. After
mating, the adult female releases thousands of microfilariae (L1 or first-stage larvae). It is the
microfilariae that are ingested by the insect vector, inside of which the microfilariae undergo two
molts to become third-stage larvae, thus completing the life cycle. The insect vector for Loa loa
is the Mango fly (Chrysops dimidiata and C. silacea). It can take up to four years for third-stage
larvae to develop into mature adults; these adults can live in the human host for up to seventeen
years. Characteristically, the microfilariae of Loa loa demonstrate diurnal periodicity (i.e. the
microfilariae are found in the peripheral blood from 10 AM to 4 PM, when the Mango fly is
actively feeding). Loa loa is endemic only to a small region of sub-Saharan, Western Africa (an
area that includes Cameroon), where 13-17 million people are infected.
Diagnosis is traditionally made morphologically by observing the microfilariae directly from the
blood, or adults surgically removed from the skin or eye. The microfilariae of Loa loa are
distinguished from similar genera by possessing a sheath (which stains poorly with Giemsa), and
nuclei that extend, albeit irregularly, to the tip of the tail. Newer techniques for diagnosis
include indirect immunofluorescence, IgG4 serology, PCR, and antigen detection methods. These
modalities, which are not widely available, are most useful when the clinical diagnosis is highly
suspected, but microfilariae cannot be recovered from the patient.
Clinical Manifestations: 1,2
The most common manifestation of Loa loa infection is the so-called Calabar swelling, a localized
subcutaneous area of edema and inflammation from which adult worms can often be recovered.
The most alarming symptom is the identification of an adult worm migrating through the
subconjunctival space of the eye; the organism’s propensity to do this explains its nickname, “the
eye worm.” Unlike Onchocerca, however, blindness secondary to Loa loa is exceedingly rare.
Other rare complications include cardiomyopathy, nephropathy, pleural effusions, and
encephalopathy.
Pathogenesis: 1,2
Like the other microfilarial nematodes, Loa loa is able to survive by modulating its host’s immune
response through mechanisms which have not been entirely elucidated. However, upon the
organisms’ death, massive amounts of previously hidden antigens are released into the body,
leading to a vigorous host inflammatory response. It is for this reason that treatment, not the
infection itself, generally causes the most severe symptoms, including the most dreaded
complication, encephalitis. Interestingly, the endosymbiotic intracellular bacterium Wolbachia,
which seems to be responsible for a great amount of the inflammatory response to Wuchereria,
Brugia, and Onchocerca, has not been identified in Loa loa. 4
Treatment: 1,3,5
The chemotherapeutic drugs of choice for treatment of Loaisis are diethylcarbamazine (DEC) and
ivermectin. These agents are microfilaricidal, but not macrofilaricidal (i.e. they will not kill the
adult worms). Repeated administration is thought to render the adult female sterile, though.
Albendazole is an agent that has shown some activity against the adult worms; accordingly
combination therapy with DEC or ivermectin is often utilized. The untoward inflammatory effects
upon treatment mentioned above are most likely to occur when microfilarial loads are greater than
2,500 per milliliter in the peripheral blood. With levels greater than this, apheresis has been
effectively used to lower the host’s parasite burden prior to definitive chemotherapeutic treatment.
Adult worms in Calabar swellings or in the eye must be removed surgically.
References:
1. Despommier DD. Parasitic Diseases, 4th ed. Apple Trees Prod. New York: 2000.
2. Pion SDS, et al. Parasitology. 2006; 132(Pt 6):843-54.
3. Walker-Deemin A, et al. Parasitol Res. 2004; 92(2):128-32.
4. McGarry HF, et al. Filaria J. 2003 May 2; 2(1):9.
5. Bouree P, et al. Pathol Biol (Paris). 1993 Apr; 41(4):410-4.