Loiasis (Loa loa infection)

INTRODUCTION — 

Loiasis, also known as African eye worm, is caused by the filarial nematode Loa loa. Loiasis is transmitted by the bite of the Chrysops fly; West and Central Africa are endemic regions. Manifestations of infection include subcutaneous swellings (known as Calabar swellings) and migration of the adult worm across the subconjunctiva of the eye.

The epidemiology, clinical features, diagnosis, and treatment of L. loa will be reviewed here. Other filarial infections, including onchocerciasis, lymphatic filariasis, and Mansonella infection, are discussed separately. (See "Onchocerciasis" and "Lymphatic filariasis: Epidemiology, clinical manifestations, and diagnosis" and "Lymphatic filariasis: Treatment and prevention".)

EPIDEMIOLOGY

●Transmission – Loiasis is transmitted by biting deerflies (Chrysops), which breed in the high-canopied rainforest of West and Central Africa, including the coastal plains of northern Angola, southeastern Benin, Cameroon, Central African Republic, Chad, Equatorial Guinea, Gabon, Nigeria, Sudan, the Democratic Republic of Congo, and Uganda.

●Disease burden – It is estimated that between 3 and 13 million people are infected [1]. Infection occurs most commonly among residents of endemic areas. It is unclear whether naturally acquired immunity develops after prolonged periods of exposure. Infection is occult in a large proportion of patients; therefore, in many areas, the epidemiology of loiasis has not been clearly defined. In endemic regions, the probability of infection increases with age and forest exposure [2]; the proportion of infected individuals varies depending on vector abundance, which in turn is dependent on local ecology [3].

Data suggest that loiasis is associated with significant morbidity in endemic areas (in rural Gabon, 413 morbidity-based disability-adjusted life-years per 100,000 people) [4]. Excess mortality has also been attributed to loiasis in several studies [5,6]. A study from rural Gabon suggests the monetary burden exceeds 3 million dollars annually [7].

Travelers to endemic regions can be infected. In one series including 150 patients diagnosed with loiasis in Belgium, 58 percent of cases were acquired by travel to endemic regions [8]. Usually, prolonged exposure (months to years) is required for infection; however, cases have been reported after as little as four days of exposure [9-11].

●Geographic distribution – Large-scale mapping of loiasis using a rapid assessment procedure for loiasis (based on community questionnaires to assess prevalence) has helped identify specific regions within ten countries in Africa where loiasis is endemic (figure 1) [12,13].

●Many of these regions are coendemic for onchocerciasis and/or lymphatic filariasis; this is important given the potential for complications arising from mass drug administration. One study predicted that in 2025, at least 31,000 individuals with loiasis-onchocerciasis coinfection would be at risk for serious adverse events due to loiasis microfilaremia as a result of mass treatment with ivermectin for onchocerciasis control [14].

LIFE CYCLE

●Vector – L. loa is spread via the bite of the female Chrysops fly, also known as the tabanid fly (horse fly or deer fly). This vector breeds in the canopy of rainforests and lays eggs in muddy swamps. The flies are attracted to movement and tend to bite humans during the daytime.

During a blood meal, an infected fly introduces third-stage filarial larvae onto the skin of the human host where they penetrate into the bite wound (figure 2).

●Human stages

•Maturation of larvae into adult worms – Larvae mature into adult worms over a period of three to six months. (See 'Adult worms' below.)

Adult worms cause clinical disease; they live in the subcutaneous tissue and can migrate to any area of the body, including the subconjunctival tissue of the eye. Adult worms can live for more than 20 years, but they do not replicate within the human host [11].

•Production of microfilariae by adult worms – After a period of 6 to 12 months from the time of initial infection (the prepatent period), the adult worms begin to produce thousands of microfilariae that are released into the bloodstream. If an infected individual leaves an endemic region, the microfilarial burden can continue to increase (due to ongoing production by adult worms).

Traditionally, microfilariae have not been viewed as contributors to pathology in patients with untreated loiasis; however, studies have demonstrated an association between high microfilarial levels and a range of effects, including arterial stiffness [15], proteinuria [16], and altered cognition [17]. Microfilarial death is also the main driver of complications in the context of treatment.

Microfilariae are responsible for transmission of infection, since they are taken up during the blood meal of female flies. Microfilariae are present in the blood in greater numbers during the daytime (diurnal periodicity), in accordance with the daytime biting habits of the Chrysops fly vector.

●Fly stage

•Maturation of microfilariae into larvae – The life cycle is completed following maturation of microfilariae into infective third-stage larvae within the fly, which occurs over a period of 7 to 10 days [18].

CLINICAL MANIFESTATIONS

Signs and symptoms — Many individuals with L. loa infection are asymptomatic. The two cardinal clinical manifestations of loiasis are subcutaneous swellings (known as Calabar swellings) and migration of the adult worm across the subconjunctiva of the eye (known as eye worm).

Calabar swellings — Localized transient subcutaneous swellings (known as Calabar swellings) are a form of angioedema; they may represent hypersensitivity reactions to migrating adult parasites and/or released microfilariae (picture 1) [1].

The swellings are generally preceded by local pain or itching. They can occur anywhere on the body; they are observed most frequently on the face and extremities. Typical swellings are nonerythematous and measure 5 to 20 cm in diameter. Swelling can extend into nearby joints or compress peripheral nerves. Swellings usually resolve spontaneously after two to four days, but occasionally they last for several weeks. Recurrent episodes can develop at the same site or elsewhere.

Swellings occur more commonly among nonimmune visitors to endemic regions [19-21]. In one study, Calabar swellings were observed in 82 percent of individuals infected as visitors to endemic areas, compared with 50 percent of individuals infected within endemic areas [20].

Eye symptoms — The adult worm can migrate to the eye and crawl beneath the conjunctiva, causing transient inflammation and edema (picture 2). The adult worm typically migrates at a rate of 1 cm per minute. The worm may be visualized directly as it crosses the conjunctiva (eye worm), which usually takes 10 to 20 minutes. Symptoms resolve spontaneously after the worm has left the eye. Usually there are no sequelae; rarely, adult worms invade the eye, causing pain and intraocular inflammation [22,23].

Eye symptoms of loiasis can occur among individuals from endemic areas and among nonimmune individuals.

Eye symptoms of loiasis should not be confused with ocular disease due to onchocerciasis. (See 'Differential diagnosis' below.)

Other manifestations — Additional manifestations of loiasis include:

●Encephalopathy – Most cases of Loa-associated encephalopathy have been reported in patients with high microfilarial levels following microfilaricidal treatment with diethylcarbamazine or ivermectin. The precise risk threshold is not known; data from multiple studies suggest that the risk of encephalopathy following ivermectin is minimal in patients with microfilarial loads <20,000/mL of blood [24,25].

Encephalopathy has been reported in patients with low microfilarial levels (<5000/mL) following diethylcarbamazine treatment [26] and rarely can occur in untreated patients with microfilaremic loiasis [27,28]. Symptoms may include headache, insomnia, or coma; death can result.

The mechanism of post-treatment encephalopathy is incompletely understood. In individuals with high levels of blood microfilariae, microfilariae can be found in the cerebrospinal fluid following treatment with ivermectin [29]. Data from autopsy specimens and a study in nonhuman primates suggest that drug-induced paralysis or killing of these microfilariae can result in their entrapment in blood capillaries, where immune-mediated destruction causes local inflammation in the brain [30,31].

●Cardiomyopathy – Endomyocardial fibrosis leading to a secondary cardiomyopathy can develop in patients with loiasis and substantial eosinophilia [9,32].

●Nephropathy – Renal involvement (leading to hematuria or proteinuria) may occur in up to one-third of infected individuals, and may be transiently exacerbated during treatment [19,33]. The mechanism of renal involvement is not clear; the prevalence of proteinuria has been correlated with the level of circulating microfilariae [16]. Potential mechanisms of renal involvement include direct effects of microfilarial entrapment in the kidney and deposition of immune complexes [9,16]. Progression of nephropathy to renal failure is uncommon but has been reported.

●Other – L. loa adult worms can migrate to any subcutaneous site, occasionally resulting in arthritis or lymphadenitis. Entrapment neuropathy related to inflammation and angioedema involving peripheral nerves may be observed [1]. Splenic nodules have also been described [34].

Individuals from nonendemic areas — Nonimmune individuals who travel to endemic regions and acquire L. loa infection are more prone to allergic-type symptoms than local residents; these include urticaria, pruritus, Calabar swellings, and occasionally asthma [19,35,36]. Clinical manifestations can persist for prolonged periods even after the individual has left the endemic area, since adult worms can live for more than 20 years.

Among travelers to endemic areas, microfilariae are less frequently detected in the peripheral blood compared with local residents of endemic areas (21 and 39 percent in travelers versus 59 and 68 percent in residents in two large studies, respectively) [37,38]. In contrast, symptoms more commonly observed in travelers include Calabar swellings, allergic symptoms (such as urticaria), and marked eosinophilia [19-21,36,39]. These observations may be due to a combination of factors including a heightened immune response to the parasite [20] and genetic factors [40].

Laboratory abnormalities — Nonspecific but characteristic laboratory abnormalities include a high eosinophil count, hypergammaglobulinemia, and a high immunoglobulin (Ig)E level. These findings are more common in nonimmune individuals than in residents of endemic areas.

In a study of 186 patients with imported loiasis, eosinophilia (≥500/microL) was observed in 84 percent of visitors to endemic areas (geometric mean absolute eosinophil count [AEC] 1532/microL) compared with 64 percent of permanent residents of endemic areas (geometric mean AEC 670/microL) [20].

DIAGNOSIS

Clinical approach

●Clinical suspicion and establishing a diagnosis – Loiasis should be suspected in an individual with relevant epidemiologic exposure, consistent clinical manifestations, and supportive laboratory findings.

A definitive diagnosis of loiasis can be established in either of the following ways [20,40]:

•Identifying a migrating adult worm in the subcutaneous tissue or conjunctiva

•Detection of L. loa microfilariae in the blood

●Evaluation for onchocerciasis coinfection – For patients with potential coinfection with onchocerciasis and loiasis (see 'Epidemiology' above), serologic testing and/or skin snips should be performed to assess for onchocerciasis; this is important because presence of coinfection influences the treatment approach. (See 'With onchocerciasis' below.)

Visualizing organisms

Adult worms — Adult worms are no more than 0.5 mm wide. Males range from 2.0 to 3.5 cm in length; females range from 5 to 7 cm in length. They are easily visualized in the subconjunctiva (picture 2).

Surgical removal of worms from the eye can be performed but is generally not necessary. Removal of a single adult is rarely curative, and the clinical finding of an eyeworm in a patient with an appropriate exposure history is diagnostic.

Adult worms characteristically migrate through the subcutaneous tissue, but they are rarely symptomatic. Occasionally, a serpiginous migratory swelling is visible just under the skin. This occurs more frequently following therapy with diethylcarbamazine. Removal of the worm is rarely indicated for diagnosis or treatment.

Microfilariae

●Periodicity – L. loa typically has diurnal periodicity; this means that microfilariae are more abundant in the bloodstream during the daytime (between 10 AM and 2 PM) than at night, coinciding with the vector feeding pattern in most settings – thereby potentiating transmission of infection. For patients within two weeks of travel from a different time zone, the time of the blood draw should be adjusted accordingly.

In general, diurnal periodicity differentiates L. loa microfilariae from the microfilariae of Wuchereria bancrofti (which are nocturnally periodic) in most settings in Africa. However, L. loa microfilariae have been demonstrated in blood smears collected at night in the Democratic Republic of Congo; periodicity testing in the context of this study demonstrated atypical patterns [41]. Therefore, species confirmation by other morphologic characteristics or polymerase chain reaction (PCR) may be necessary in some cases.

●Technique – Quantification of microfilariae on blood smear should be performed between 10 AM and 2 PM to capture the peak number of microfilariae circulating in the blood. For patients within two weeks of travel from a different time zone, the time of the blood draw should be adjusted accordingly.

Microfilariae of L. loa are sheathed and measure 230 to 250 mcm long in stained blood smears. The tail is tapered and nuclei extend to the tip of the tail (picture 3).

Microfilaremia may be determined by counting microfilariae on blood smears made from defined volumes of blood (eg, 50 microL) [13] or from larger volumes of blood (eg, 1 mL) concentrated through Nuclepore filters, using formalin (Knott's concentration), or saponin lysis; these concentration techniques increase the sensitivity of microscopy [42].

Role of serology

●Use in individuals from nonendemic areas – Serologic tests are most useful for diagnosis of loiasis among travelers. In endemic settings, serology is generally not useful since antibodies remain detectable for prolonged periods following infection and thus cannot distinguish between active and prior infection. However, a negative serologic test result can exclude the possibility of L. loa infection.

●Limited specificity of assays measuring total IgG – Most antibody tests use crude antigen extracts from related animal filarial species. They have relatively good sensitivity but poor specificity, since they cross-react both with other filarial infections and with other nonfilarial helminthic parasites.

●Greater specificity of IgG4 assays – Assays which measure specific IgG4 antibodies rather than total IgG have been developed and are more specific for active infection with loiasis. However, these tests are not widely available.

One study evaluated an IgG4 antibody-based enzyme-linked immunosorbent assay (ELISA) using a crude extract of L. loa microfilariae and found that, in patients with microfilaremia, this method had a sensitivity and specificity of 80 and 78 percent, respectively [43]. Among patients with no detectable microfilariae on blood smear, 55 percent had significant levels of specific IgG4 antibodies against L. loa, suggesting they carried occult loiasis. The authors concluded that, despite the limited sensitivity and specificity of the test, IgG4 ELISA could be useful for estimating the real prevalence of loiasis in epidemiologic surveys and could help to confirm the diagnosis of L. loa in amicrofilaremic subjects with suggestive clinical signs.

Another study examined IgG4 in three groups: amicrofilaremic individuals with verified ocular passage of adult worms of L. loa, microfilaremic patients, and unexposed individuals [44]. The study showed that there was no significant difference in the level of parasite-specific IgG4 between amicrofilaremic individuals with occult infection and microfilaremic individuals. It also showed excellent specificity because there was no reactivity among unexposed individuals or among individuals exposed to filarial infections other than loiasis.

●Assays using recombinant antigens – Serologic assays using recombinant L. loa antigens have been developed, including a sensitive and specific rapid assay that uses a luciferase immunoprecipitation system to detect antibodies to the recombinant L. loa antigen LLSXP-1 [45].

Other tests — Tests that detect circulating L. loa antigens are in development [46]. A real-time PCR assay has been developed at the Laboratory of Parasitic Diseases, National Institutes of Health (LPD NIH), that can detect and quantitate L. loa microfilaremia [47]. This assay has been adapted for loop-mediated isothermal amplification, a point-of-care molecular diagnostic tool that can be used in field settings [48,49].

Other novel point-of-care tools for identification and quantification of L. loa microfilariae include an adaptation of a handheld automated cell counter and a mobile phone–based video microscope (termed a LoaScope) [24,50]. The LoaScope is designed to detect high levels of L. loa microfilaremia so that individuals at risk for adverse effects associated with mass administration of ivermectin for treatment of onchocerciasis or lymphatic filariasis can be excluded [24]. The tool is not designed for diagnosis of L. loa in individuals, as it is insensitive for detection of low levels of microfilaremia.

Assistance with serologic and other diagnostic tests is available from the LPD NIH (301-496-5398), and the United States Centers for Disease Control and Prevention (CDC).

DIFFERENTIAL DIAGNOSIS — 

The differential diagnosis of loiasis includes (table 1):

●Onchocerciasis – Patients with onchocerciasis typically present with a pruritic papular skin rash and deep subcutaneous nodules. Lymphedema that can occur as a result of lymph node involvement can sometimes be confused with Calabar swellings of loiasis. In contrast with the macroscopic "eyeworm" of loiasis, onchocercal eye involvement is characterized by visual impairment related to the presence of ocular microfilariae. The areas of onchocerciasis endemicity overlap with those of loiasis, and coinfection can occur, which is important for treatment decisions. The diagnosis of onchocerciasis is established based on epidemiology, clinical manifestations, and supportive laboratory evidence of infection. (See "Onchocerciasis".)

●Lymphatic filariasis – When localized, the lymphedema characteristic of lymphatic filariasis can be difficult to distinguish from angioedema. The areas of Wolbachia bancrofti endemicity overlap with those of loiasis, and coinfection can occur. False-positive antigen tests for W. bancrofti in the setting of L. loa microfilaremia may complicate the diagnosis of occult W. bancrofti in coinfected patients [41,51,52]. The diagnosis of lymphatic filariasis is established based on epidemiology, clinical manifestations, and supportive laboratory evidence of infection. (See "Lymphatic filariasis: Treatment and prevention".)

●Gnathostomiasis – Migratory subcutaneous swellings in gnathostomiasis can be identical to Calabar swellings; gnathostomiasis is most common in Asia, while loiasis is restricted to Africa. Filarial serology based on crude antigen recognition may be cross-reactive in gnathostomiasis. The diagnosis of gnathostomiasis is established based on epidemiology, clinical manifestations, and supportive laboratory evidence of infection. (See "Skin lesions in the returning traveler", section on 'Gnathostomiasis'.)

●Zoonotic infections – Human infection with a variety of zoonotic helminths, including Dirofilaria repens, Dirofilaria tenuis, Loaina, and Baylisascaris procyonis, occasionally presents with subconjunctival migration of a worm that may be clinically indistinguishable from the "eyeworm" of loiasis. Intraocular involvement has also been reported with a number of species [22]. Geography may be helpful in some cases. For example, the natural host for B. procyonis is the raccoon, which is not endemic in Africa. In other cases, removal of the worm may be necessary to make a definitive diagnosis.

●Cutaneous larva migrans – Cutaneous larva migrans consists of a pruritic erythematous serpiginous lesion that develops at the site of penetration by nematode larvae that are not natural human parasites (picture 4). Inflammation due to migration of adult L. loa worms under the skin is typically minimal and transient (especially following treatment), in contrast with the intense pruritus and persistence of an inflammatory track characteristic of cutaneous larva migrans [53]. (See "Hookworm-related cutaneous larva migrans".)

●Strongyloidiasis – Strongyloidiasis most often presents with asymptomatic eosinophilia or nonspecific symptoms, including urticaria, abdominal discomfort, and malaise. Larva currens, an evanescent serpiginous skin lesion due to larval migration, is sometimes seen but differs in clinical appearance from the migratory skin lesion of L. loa. Since strongyloidiasis overlaps considerably with loiasis in geography, and available serologic testing is hampered by cross-reactivity between the two nematodes, empiric treatment with albendazole or ivermectin (if no L. loa microfilariae are detected) may be appropriate in patients with loiasis and positive serologic testing for strongyloidiasis. (See "Strongyloidiasis".)

TREATMENT OF MONOINFECTION

Rationale for universal treatment — We treat all patients with L. loa infection, given data demonstrating associations between microfilaremia and excess mortality [5,6], measures of arterial stiffness [15], proteinuria [16], and altered cognition [17]. In a retrospective study in Cameroon including more than 3000 individuals with loiasis followed between 2001 and 2016, high-grade microfilaremia (>30,000 microfilariae per mL) was associated with increased risk of death (adjusted time ratio 0.67, 95% CI 0.48-0.95) [6].

For patients with high levels of microfilaremia, the risks and benefits of treatment should be considered carefully; the incidence and severity of adverse effects associated with treatment increases with increasing microfilarial levels.

Treat based on microfilarial level — Blood microfilaremia must be quantified prior to initiating treatment for loiasis. (See 'Microfilariae' above.)

Patients with detectable microfilariae should be monitored closely during the first few days of treatment.

For patients with L. loa microfilaremia ≥2500/mL, an attempt should be made to reduce the blood microfilarial level prior to definitive treatment with diethylcarbamazine (DEC), which can provoke serious adverse effects in patients with high microfilarial load. For patients with microfilaremia levels >2500/mL, hospitalization may be warranted.

A threshold of 2500/mL has been suggested, although supporting data are lacking. In patients with lower levels of microfilaremia, serious side effects of DEC are uncommon but can occur.

Apheresis has been used to lower microfilarial levels successfully but is not feasible in most cases [54-56].

≥20,000 microfilariae/mL — Patients with ≥20,000 microfilariae/mL should be hospitalized when initiating treatment.

For these patients, microfilaremia may be reduced with albendazole (200 mg orally twice daily for 21 days). In some cases, multiple courses of albendazole may be necessary (algorithm 1) [57].

Microfilarial counts should be rechecked at least six weeks (and up to six months) after albendazole therapy to ensure that the microfilarial load is <2500/mL prior to DEC therapy. If microfilarial levels remain ≥20,000/mL, a repeat course of albendazole should be administered.

Once microfilaremia levels are 2500 to 20,000/mL, ivermectin may be administered as outlined below. (See '2500 to 20,000 microfilariae/mL' below.).

Use of ivermectin in patients with high microfilarial load can provoke serious adverse effects. While large scale treatment trials demonstrated no serious adverse effects in patients with <20,000 microfilariae/mL [24,58], subsequent data suggest that some patient groups (ie, males 31 to 40 years of age) may be at increased risk even with lower thresholds [59].

Use of albendazole is supported by a trial including 23 patients in Benin with microfilaremia (100 to 30,000/mL) who randomly assigned to receive albendazole (dosing above) or placebo [54]. Among those who received albendazole, microfilarial levels began to decrease at day 14 after treatment; by six months, levels fell to a geometric mean of 20 percent of pretreatment levels (versus 85 percent among those who received placebo). The gradual decline in blood microfilarial levels suggests that albendazole may have a preferential effect on adult worms; this may explain the lack of adverse effects associated with acute microfilarial clearance.

2500 to 20,000 microfilariae/mL — Patients with 2500 to 20,000 microfilariae/mL may warrant hospitalization when initiating treatment.

For these patients, microfilaremia may be reduced with ivermectin (150 mcg/kg single dose). Microfilarial counts should be checked two to four weeks later to ensure that the microfilarial load is <2500/mL prior to DEC therapy. If microfilarial levels remain ≥2500/mL, a repeat dose of ivermectin should be administered (algorithm 1).

Once microfilaremia levels are <2500/mL, diethylcarbamazine may be administered as outlined below. (See '<2500 microfilariae/mL' below.)

This approach is supported by a randomized trial including 95 patients with loiasis in Cameroon, those who received ivermectin standard dose (150 mcg/kg) had greater reduction in microfilaremia at 60 days than those who received a lower dose (25 mcg/kg single dose or two doses separated by two weeks; 61.5, 47.5, and 53.9 percent, respectively) [60].

For patients in whom ivermectin is contraindicated or ineffective, albendazole may be used as outlined above for patients with ≥20,000 microfilariae/mL. (See '≥20,000 microfilariae/mL' above.)

<2500 microfilariae/mL — DEC is the only agent that kills both worms and microfilariae, so it is needed to eradicate infection. However, DEC reduces microfilaremia rapidly which can be fatal in patients with high microfilarial loads; therefore DEC is given only once microfilaremia is reduced <2500/mL.

If DEC cannot be used or for patients who are refractory to DEC, albendazole is an alternative agent because it kills adult worms. Ivermectin does not kill adult worms so it cannot be used for definitive therapy.

●DEC as preferred regimen – For patients with <2500 microfilariae/mL, the preferred regimen for definitive treatment is DEC, a piperazine derivative with activity against both L. loa microfilariae and adult L. loa worms [61].

•Dosing of DEC – Treatment with DEC consists of a graded dosing schedule as follows:

-Day 1: 50 mg (1 mg/kg)

-Day 2: 50 mg (1 mg/kg) three times a day

-Day 3: 100 mg (1 to 2 mg/kg) three times a day

-Day 4 to 21: 9 mg/kg/day in three divided doses

DEC is not licensed for use in the United States; it can be obtained from the United States Centers for Disease Control and Prevention (CDC) for compassionate use (CDC Drug Service, Atlanta, GA 30333; telephone 404-639-2888).

•Adverse effects of DEC – Adverse events following treatment with DEC occur due to rapid killing of microfilariae and are most severe in patients with high levels of circulating microfilariae. Adverse effects can also occur among patients with no circulating microfilariae.

-Signs and symptoms – Symptoms include fever, headache, dizziness, myalgia/arthralgia, and transient exacerbation of Calabar swellings and urticaria. Serious reactions include encephalitis and/or shock; these are relatively uncommon [26].

DEC should be avoided in pregnancy.

-Management – Access to medical care should factor into the decision to treat with DEC. Most patients with low or undetectable microfilarial levels can be treated as outpatients; however, significant complications have been reported in such cases.

Tools for management of symptoms such as fever, urticaria, myalgia/arthralgia, urticaria, and Calabar swellings include oral antihistamines for mild symptoms and/or short course glucocorticoids (two to three days) for more severe symptoms. These may be administered prior to initiation of DEC, or to reduce the severity of symptoms once they develop. However, these tools are not effective for prevention of more serious reactions, including post-treatment encephalitis.

•Efficacy – A sustained decrease in microfilarial intensity occurs following treatment with DEC [62-64]. In one study, DEC (8 to 10 mg/kg per day for 21 days) reduced microfilaremia to 2 to 12 percent of the initial level for up to six months, killed 30 percent of adult worms, and eradicated infection in 50 percent of cases [65].

Given limited efficacy of DEC treatment, patients require follow-up. (See 'Follow up' below.)

There are no data available on shorter course therapy.

●Albendazole as alternative regimen – Albendazole is an alternative agent for treatment of loiasis. It has activity against adult L. loa worms but does not have significant microfilaricidal activity. Therefore, fewer adverse effects are observed with albendazole compared with DEC, since there is no antigen release associated with dying microfilariae [1].

Use of albendazole leads to a gradual decline in microfilariae levels over several months [54,66,67]. Cure rates following albendazole treatment of loiasis have not been studied directly.

In individuals with high levels of circulating microfilariae, treatment with ivermectin or albendazole may be useful for reduction of microfilaremia prior to treatment with DEC (see '≥20,000 microfilariae/mL' above). Albendazole has also been used as an alternative agent in individuals with L. loa infection that is refractory to multiple courses of DEC [54].

●Agents with no role – Agents with no role for definitive treatment of L. loa infection include:

•Ivermectin – Ivermectin has L. loa microfilaricidal activity but has no effect on adult worms so it is not curative for L. loa infection [68-71]. Therefore, ivermectin is not a preferred agent for treatment of loiasis.

Ivermectin can be used safely in patients with up to 20,000 microfilariae/mL of blood to reduce microfilarial levels prior to definitive treatment. In a systematic review and meta-analysis of the effect of ivermectin on L. loa microfilarial levels, a single dose of ivermectin reduced L. loa microfilarial density by 90 percent after one year [72]. There is some evidence to suggest that ivermectin alone can lead to symptomatic improvement in loiasis [73].

As with DEC, ivermectin can precipitate severe adverse events (encephalitis and/or shock), particularly in patients with high levels of circulating microfilariae [25,74]; the underlying pathophysiology of these appear to share a common pathophysiology [75].

•Doxycycline – Endosymbiotic Wolbachia have not been identified in L. loa by light or electron microscopy or by polymerase chain reaction (PCR) [76] (in contrast with other filariae such as W. bancrofti, Brugia malayi, and Onchocerca volvulus), precluding the use of doxycycline or other antibacterial agents for the treatment of loiasis [77].

•Imatinib – Despite preliminary data suggesting that imatinib (a tyrosine kinase inhibitor approved by the US Food and Drug Administration for treatment of chronic myelogenous leukemia and hypereosinophilic syndrome) has activity against L. loa microfilariae [78,79], results a clinical trial including 20 patients with microfilarial levels <2500/mL demonstrated no clear effect; furthermore, serious adverse events were reported among 4 of 15 patients who received drug and none of five patients who received placebo [80].

Follow up — Long-term follow-up is needed after therapy, and retreatment should be administered for patients with persistent microfilaremia. We perform repeat assessment for microfilaremia 6 and 12 months after completion of diethylcarbamazine [81].

Role of surgery — Surgical removal of worms from the eye or the skin can be performed for diagnostic purposes but is rarely necessary (see 'Adult worms' above). Surgical removal of worms is not practical for definitive cure, particularly in endemic areas where large worm burdens are common.

Subconjunctival worm migration does not result in ocular damage. Rare cases of intraocular worms have been described; in such cases, removal is indicated to prevent blindness [22].

TREATMENT OF COINFECTION

With onchocerciasis — Treatment of patients with loiasis-onchocerciasis coinfection warrants careful attention; diethylcarbamazine (DEC) is contraindicated in onchocerciasis since it can provoke severe inflammatory responses in the skin and eyes (Mazzotti reaction) (table 2).

The approach should be guided by microfilarial burden:

●L. loa microfilariae <20,000/mL – For these patients, treatment of onchocerciasis (with ivermectin 150 mcg/kg single dose) can be administered concomitantly with albendazole (200 mg twice daily for 21 days) for treatment of loiasis.

●L. loa microfilariae ≥20,000/mL – For these patients, the optimal approach is uncertain. The risks and benefits of ivermectin treatment for onchocerciasis must be weighed carefully; these include the clinical manifestations of onchocerciasis (ie, presence of eye involvement, extreme pruritus) and the L. loa microfilarial level.

Treatment options include:

•Preferred regimen – Ivermectin (150 mcg/kg single dose) for onchocerciasis (with close observation in an inpatient setting; adverse effects peak within 8 to 24 hours [75]), followed by albendazole (200 mg twice daily for 21 days) for loiasis (may be given as outpatient).

•Alternative regimens:

-Albendazole (200 mg daily for 21 days) for loiasis, followed by ivermectin (150 mcg/kg single dose) for onchocerciasis once reduction in L. loa microfilarial levels is documented. This regimen is not useful in patients with symptomatic onchocerciasis or eye involvement, since adequate microfilarial reduction can take 6 to 12 months.

-Doxycycline (200 mg daily for six weeks) for onchocerciasis, followed by albendazole (200 mg twice daily for 21 days) for loiasis. This is a regimen of last resort; doxycycline does not take effect very quickly and acts primarily against adult worms (which are not responsible for blindness or itching).

With lymphatic filariasis — The treatment of coinfection due to lymphatic filariasis and loiasis is the same as the treatment for loiasis monoinfection. (See 'Treatment of monoinfection' above.)

With onchocerciasis and lymphatic filariasis — The treatment of coinfection due to loiasis, onchocerciasis, and lymphatic filariasis is the same as the treatment for coinfection with loiasis and onchocerciasis. (See 'With onchocerciasis' above.)

PREVENTION — 

There is no vaccine against L. loa infection. Personal protection measures to avoid fly bites may have some utility in individual travelers. Large-scale vector control has not been shown to be feasible in endemic areas.

Prophylaxis is not necessary for most short-term travelers to endemic areas due to the low risk of infection.

For individual travelers with longer-term exposures (such as Peace Corps personnel), we suggest prophylaxis with weekly diethylcarbamazine (DEC; 300 mg). This approach is supported by a randomized trials including 101 Peace Corps volunteers serving for two years in Gabon, Cameroon, and the Central African Republic [82]. In Gabon (where exposure to the parasite was heaviest), 6 of 20 volunteers (30 percent) in the placebo group had clinical disease, as compared with none of 16 (0 percent) in the DEC-treated group. Of those taking placebo, 50 percent became seropositive for antifilarial IgG antibody, as compared with 12 percent in the treatment group.

SUMMARY AND RECOMMENDATIONS

●Epidemiology – Loiasis, also known as African eye worm, is caused by the filarial nematode Loa loa. Loiasis is transmitted by the bite of the Chrysops fly; West and Central Africa are endemic regions. (See 'Epidemiology' above.)

●Clinical manifestations – Many individuals with L. loa infection are asymptomatic. The two cardinal clinical manifestations of loiasis are subcutaneous swellings (known as Calabar swellings) (picture 1) and migration of the adult worm across the subconjunctiva of the eye (known as eye worm) (picture 2). (See 'Signs and symptoms' above.)

Nonspecific but characteristic laboratory abnormalities include a high eosinophil count, hypergammaglobulinemia, and a high IgE level; these findings are more common in nonimmune individuals than in residents of endemic areas. (See 'Laboratory abnormalities' above.)

●Diagnosis – Loiasis should be suspected in an individual with relevant epidemiologic exposure, consistent clinical manifestations, and supportive laboratory findings. A definitive diagnosis of loiasis can be established by identifying a migrating adult worm in the subcutaneous tissue or conjunctiva or by detecting microfilariae in the blood (picture 3). Blood microfilaremia must be quantified prior to initiating treatment for loiasis.

●Treatment of monoinfection – We treat all patients with L. loa infection, given data demonstrating an association between microfilaremia and excess mortality. Drug dosing is summarized in the table (table 2). (See 'Rationale for universal treatment' above.)

•Patients with low microfilariae levels (<2500/mL) – For these patients, we suggest definitive treatment with diethylcarbamazine (DEC) (Grade 2C), given its activity against both L. loa microfilariae and adult L. loa worms. Albendazole is an alternative regimen. (See '<2500 microfilariae/mL' above.)

•Patients high microfilariae levels (≥2500/mL) – For these patients, we reduce microfilariae levels to <2500/mL prior to definitive treatment with DEC, given the risk of adverse events (encephalitis and/or shock) in patients with high levels of circulating microfilariae treated with DEC (algorithm 1).

-For patients with L. loa microfilariae 2500 to 20,000/mL, we suggest ivermectin for reduction of microfilaremia (Grade 2C), followed by definitive treatment with DEC. (See '2500 to 20,000 microfilariae/mL' above.)

-For patients with L. loa microfilariae >20,000/mL, we suggestion albendazole for reduction of microfilaremia (Grade 2C), followed by definitive treatment with DEC. Use of ivermectin in patients with high microfilarial load can provoke serious adverse effects. (See '≥20,000 microfilariae/mL' above.)

●Treatment of coinfection

•With onchocerciasis – Treatment of coinfection with loiasis and onchocerciasis warrants careful attention; use of DEC is contraindicated in onchocerciasis since it can provoke severe inflammatory responses in the skin and eyes (Mazzotti reaction). Drug dosing is summarized in the table (table 2). (See 'With onchocerciasis' above.)

-For patients with L. loa microfilariae <20,000/mL, treatment of onchocerciasis (with ivermectin) can be administered concomitantly with treatment of loiasis (with albendazole).

-For patients with L. loa microfilariae ≥20,000/mL, the optimal approach is uncertain. The risks and benefits of ivermectin treatment must be weighed carefully; these include evaluating the degree of onchocercal eye involvement and pruritus, as well as the L. loa microfilarial level. We suggest treatment with ivermectin (for onchocerciasis microfilarial reduction) followed by albendazole (for loiasis) (Grade 2C). Patients should be observed in an inpatient setting while receiving initial treatment with ivermectin.

•With lymphatic filariasis – The treatment of coinfection due to loiasis and lymphatic filariasis is the same as the treatment for loiasis monoinfection. (See 'With lymphatic filariasis' above.)

•With onchocerciasis and lymphatic filariasis – The treatment of coinfection due to loiasis, onchocerciasis, and lymphatic filariasis is the same as the treatment for coinfection with loiasis and onchocerciasis. (See 'With onchocerciasis and lymphatic filariasis' above.)

●Follow up – Following completion of treatment, we perform repeat assessment for microfilaremia 6 and 12 months later, with repeat treatment for patients with persistent microfilaremia. (See 'Follow up' above.)

●Prevention – For travelers with long-term exposure in endemic areas, we suggest prophylaxis with weekly DEC (Grade 2C). Prophylaxis is not necessary for most short-term travelers due to the low risk of infection.

Personal protection measures to avoid fly bites may have some utility in individual travelers, but large-scale vector control has not been shown to be feasible in endemic areas. There is no vaccine against L. loa infection. (See  above.)