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The diagnosis of loaisis should be considered in any patient with a history of travel in an endemic area who presents with eye worm, Calabar swellings, or unexplained peripheral eosinophilia. Additionally, any patient in whom therapy for lymphatic filariasis or onchocerciasis is anticipated who comes from a region of Africa co-endemic for loiasis should be screened for infection prior to initiating treatment because of the risk of fatal encephalopathy after treatment with diethylcarbamazine (DEC) or ivermectin.
The standard diagnostic test for the diagnosis of loiasis is demonstration of microfilariae on a daytime (10AM to 2PM) Giemsa-stained thin or thick blood smear. It is important to note that the timing of the blood smear should be adjusted to reflect local time at the point of origin of a traveler who is still experiencing jetlag. Concentration techniques such as Nuclepore™ filtration (Whatman Inc., Florham Park, NJ), Knott’s concentration, or saponin lysis may increase the diagnostic yield in persons with low numbers of circulating microfilariae. Identification of microfilariae on blood smear is sufficient for diagnosis of the infection. Quantification of the number of microfilariae per mL is needed to direct treatment.
Identification of the adult worm on physical exam in a patient with significant exposure history or by a pathologist after its extraction from subcutaneous or subconjunctival tissue would also be sufficient to make the diagnosis of infection. However, a blood smear would still need to be performed for quantification of microfilarial load prior to the initiation of antiparasitic agents.
Blood tests are available to assist in making the diagnosis in amicrofilaremic patients, though they are not widely available. There is a general screen for any filarial infection (including Wuchereria, Brugia, Onchocerca, and Mansonella infections) that is available in some specialty diagnostic labs. Because the test is highly sensitive, it is useful in determining if an individual has had filarial infection, but it is not specific enough to identify which filarial infection. As with any antibody test, the results indicate only that the patient has been exposed to the disease, but they do not indicate if the patient has an active infection. This distinction is less important in symptomatic travelers, but it limits the usefulness of the test in persons from endemic areas. One advantage of the test is that it can pick up evidence of infection in the pre-patent stage of infection. There are several Loa-specific serologic tests in existence, such as the tests for antibodies to the LlSXP-1 recombinant antigen which can be used in both an ELISA and a luciferase immunoprecipitation systems (LIPS) assay, but these are currently available only in the research setting and are not approved for diagnosis in the United States. There is one polymerase chain reaction (PCR) test for loiasis approved for diagnosis in the United States.
In general the diagnosis of L. loa infection should be made with blood smear. However, when blood smears are negative and clinical suspicion of infection is high, the general antibody test could be used in an attempt to exclude infection. If the general antibody test were positive, then it might be necessary to consider seeking additional diagnostic information by enlisting the assistance of researchers who perform specific antibody and/or PCR tests.
The treatment of loiasis is complex and is best undertaken after consultation with experts who have experience in the treatment of the disease and prevention of complications of treatment. Additionally, there may be times when it is best not to treat the infection.
Surgical excision of migrating adult worms is an effective treatment for symptoms localized to the migrating worm and provides an opportunity for diagnosis. Surgery is not curative. Antiparasitic medication is required for cure.
The drug of choice for the treatment of loiasis is diethylcarbamazine (DEC). Most patients will achieve cure, defined as resolution of symptoms, resolution of eosinophilia, and decreasing antifilarial antibody titers, with one or two courses of DEC. Some will require additional courses of DEC or a trial of albendazole. DEC is the treatment of choice because there is solid evidence that it kills both the microfilariae and the adult worms, resulting in quicker resolution of the infection. The risk of fatal encephalopathy or other severe adverse neurologic events is related to the microfilarial load. Quantitative blood smears are required before initiating treatment (see notes below). Prophylactic DEC (300 mg once a week) can be used to prevent infection in long-term travelers to endemic areas.
There is some evidence that albendazole given twice daily for 21 days may be an effective treatment for loiasis that is refractory to DEC treatment. It also may be used to reduce microfilarial load prior to initiation of DEC treatment. The response to albendazole is slow so close, frequent monitoring would be needed to determine when it is safe to treat with DEC. Albendazole does not appear to be prone to cause encephalopathy, though published data are limited.
Treatment of loiasis with antiparasitic agents may result in a brief increase of symptoms, such as Calabar swelling or pruritus. Some authors suggest that these symptoms might be attenuated with the concomitant use of antihistamines or corticosteroids during the first seven days of treatment. There is also the risk of fatal encephalopathy with DEC treatment; this risk has not been shown to be eliminated by corticosteroid treatment. More details on this are given below the treatment table.
Loa loa do not contain Wolbachia so doxycycline is not an effective treatment.
|Treatment||Indication||Adult Dose||Pediatric Dose|
|Diethylcarbamazine (DEC)||Symptomatic loiasis with MF/mL <8,000||8–10 mg/kg/day orally in 3 divided doses daily for 21 days||8–10 mg/kg/day orally in 3 divided doses daily for 21 days|
|Albendazole||Symptomatic loiasis, with MF/mL <8,000 and failed 2 rounds DEC
Symptomatic loiasis, with MF/ml ≥8,000 to reduce level to <8,000 prior to treatment with DEC
|200 mg orally twice daily for 21 days||200 mg orally twice daily for 21 days|
|Apheresis* followed by DEC||Symptomatic loiasis, with MF/mL ≥8,000||N/A||N/A|
MF = microfilariae of L. loa
* Apheresis should be performed at an institution with experience in using this therapeutic modality for loiasis. Oral albendazole is available for human use in the United States.
Note on risk of fatal encephalopathy when treating loiasis:
Available data demonstrate that the risk of fatal encephalopathy in patients treated with DEC with microfilarial loads <8,000 microfilariae per mL approaches zero. In those patients with microfilarial loads ≥8,000 microfilariae per mL, apheresis can be used in specialized centers to reduce the load below the 8,000 threshold prior to beginning treatment. Some authors suggest a more conservative threshold of 2,500 microfilariae per mL for the initiation of treatment of loaisis. This lower threshold would need to be balanced with the risk associated with apheresis. There are some data available that suggest treating the patient with albendazole, 200mg twice daily for 21 days, may reduce the microfilarial load to acceptable levels, though re-measurement of levels after albendazole treatment would be required prior to treatment with DEC.
Note on treatment in patients with O. volvulus co-infection:
DEC is contraindicated in persons with onchocerciasis because of the risk of blindness and/or severe exacerbation of skin disease. Please see the onchocerciasis web pages for treatment recommendations.
Note on obtaining the medication:
Diethylcarbamazine (DEC) has been used worldwide for more than 50 years. Because this infection is rare in the United States, the drug is no longer approved by the U.S. Food and Drug Administration (FDA) and cannot be sold in the United States. Physicians can obtain the medication from CDC after confirmed positive lab results.
Albendazole is pregnancy category C. Data on the use of albendazole in pregnant women are limited, though the available evidence suggests no difference in congenital abnormalities in the children of women who were accidentally treated with albendazole during mass prevention campaigns compared with those who were not. In mass prevention campaigns for which the World Health Organization (WHO) has determined that the benefit of treatment outweighs the risk, WHO allows use of albendazole in the 2nd and 3rd trimesters of pregnancy. However, the risk of treatment in pregnant women who are known to have an infection needs to be balanced with the risk of disease progression in the absence of treatment.
Pregnancy Category C: Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal, or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.
It is not known whether albendazole is excreted in human milk. Albendazole should be used with caution in breastfeeding women.
The safety of albendazole in children less than 6 years old is not certain. Studies of the use of albendazole in children as young as one year old suggest that its use is safe. According to WHO guidelines for mass prevention campaigns, albendazole can be used in children as young as 1 year old. Many children less than 6 years old have been treated in these campaigns with albendazole, albeit at a reduced dose.