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 transient localized 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 — 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.

It is estimated that between 3 and 13 million people are infected [1]. 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].

Large-scale mapping of loiasis in Africa using a Rapid Assessment Procedure for Loiasis, based on community questionnaires documenting the prevalence of a history of eye worm, helped identify specific regions in ten African countries where loiasis is endemic, including many regions coendemic for onchocerciasis and lymphatic filariasis (figure 1) [4,5]. This is important given potential complications arising from ivermectin mass drug administration (MDA) programs for onchocerciasis and lymphatic filariasis in individuals with concomitant loiasis. In this regard, the pre-MDA maps of loiasis and onchocerciasis in 14 coendemic countries were reanalyzed using statistic and mathematic modelling to account for the impact of 30 years of MDA on microfilarial levels [6]. The results suggest that 31,000 coinfected people will remain at risk of severe adverse events in 2025 due to high L. loa microfilarial levels, most of whom live in areas hypoendemic for onchocerciasis.

Infection occurs most commonly in residents of endemic areas, but travelers to these regions can also be infected. In one series including 150 patients diagnosed with loiasis in Belgium, 58 percent were acquired by travelers to endemic regions [7]. Usually, prolonged exposure (months to years) is required for infection; however, cases have been reported after as little as four days of exposure [8-10]. It is unclear whether naturally acquired immunity develops after prolonged periods.

LIFE CYCLE — 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 (figure 2). 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. These larvae mature into adult worms over a period of three months. The 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.

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 larval microfilariae that are released into the bloodstream. Microfilariae can be detected on blood smears or Nuclepore-filtered blood. Microfilariae do not cause pathology in untreated loiasis but can contribute to complications following treatment. Microfilariae are responsible for transmission of infection since they are taken up during the blood meal of female flies. L. loa microfilariae exhibit greater numbers in the blood by day (diurnal periodicity) in accord with the daytime biting habits of the Chrysops vectors. The life cycle is completed following maturation of microfilariae into infective third-stage larvae within the fly, which occurs over a period of 10 to 12 days.

Adult worms can live for more than 20 years [10] but do not replicate within the human host. Therefore, once an individual is no longer exposed to infective larvae (ie, after leaving an endemic region), the microfilarial burden can increase (due to increased production by existing adult females), but the adult worm burden cannot increase.

CLINICAL MANIFESTATIONS — Many individuals with L. loa infection are asymptomatic; however, 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) [11]. The two cardinal clinical manifestations of loiasis are transient localized subcutaneous swellings (known as Calabar swellings) and migration of the adult worm across the subconjunctiva of the eye (picture 1).

Nonimmune individuals who travel to endemic regions and acquire L. loa infection are more prone to broader allergic-type symptoms than local residents; these include urticaria, pruritus, Calabar swellings, and occasionally asthma [12-14]. 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; however, microfilariae are rarely detectable in blood smears of these individuals. Similarly, an inverse relationship between the presence of detectable blood microfilariae and clinical symptoms has been described among individuals residing in endemic regions [15]. This is likely due to a combination of factors, including genetic factors, a low burden of infection, and a heightened immune response to the parasite [16]. (See 'Diagnosis' below.)

Calabar swellings — Transient localized subcutaneous swellings (known as Calabar swellings) are a form of angioedema potentially due to hypersensitivity reactions to migrating adult parasite and/or released microfilariae [1]. The swellings can occur anywhere on the body but are most frequently observed on the face and extremities; they are generally preceded by local pain or itching (picture 2). Typical Calabar swellings are nonerythematous and measure 5 to 20 cm in diameter. Swelling can extend into nearby joints or compress peripheral nerves. Calabar swellings usually resolve spontaneously after two to four days, but they occasionally last for several weeks. Recurrent episodes can develop at the same site or elsewhere.

Calabar swellings are most frequently observed in nonimmune visitors to endemic regions with extended exposure [12,16,17]. In one study, Calabar swellings were observed in 82 percent of those infected as visitors to endemic countries as compared with 50 percent of immigrants from endemic areas [16].

Eye symptoms — The adult worm migrates to the eye and crawls beneath the conjunctiva, causing transient inflammation and edema. The adult worm usually measures 3 to 7 cm by 0.3 to 0.5 mm and typically migrates at the rate of 1 cm per minute. The worm may be visualized directly as it crosses the conjunctiva, which usually takes 10 to 20 minutes. Symptoms resolve spontaneously after the worm has left the eye, and usually there are no sequelae. Eye symptoms can occur in both endemic and nonimmune individuals. Rarely, adult worms invade the eye causing pain and intraocular inflammation [18,19].

Eye symptoms of loiasis should not be confused with intraocular microfilariae that characteristically develop with onchocerciasis. (See "Onchocerciasis".)

Other complications — Additional manifestations of loiasis in immune or nonimmune hosts include:

●Encephalitis – Encephalitis can occur in patients with loiasis, generally, but not always in the setting of treatment with diethylcarbamazine or ivermectin [20]. Symptoms can include headache, insomnia, or coma; death can result. Although most cases of encephalitis have been reported in patients with more than 30,000 microfilariae/mL of blood [21], neurologic symptoms can occur in patients with lower microfilarial levels [22]. The mechanism of post-treatment neurologic complications in L. loa infection is unknown; however, microfilariae have been described in the cerebrospinal fluid in a number of cases, suggesting that inflammation caused by dying microfilariae may play a role.

●Cardiomyopathy – Endomyocardial fibrosis leading to a secondary cardiomyopathy can develop in loiasis patients with a substantial eosinophilia.

●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 [12,23]. The exact mechanism of renal involvement is unclear; immune complexes are believed to play a role in some cases [8]. 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 also be observed [1]. Splenic nodules have also been described [24].

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 symptomatic 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 temporary residents of endemic areas (geometric mean absolute eosinophil count [AEC] 1532/microL) as compared with 64 percent of permanent residents of endemic areas (geometric mean AEC 670/microL) [16].

DIAGNOSIS — Loiasis should be suspected in an individual with an appropriate epidemiologic exposure, consistent clinical findings, and supportive laboratory findings. The definitive diagnosis is established by identifying the adult worm in the eye or subcutaneous tissue or microfilariae in the blood. Serology may also be useful.

Visualizing organisms — The diagnosis of loiasis can be definitively established by identifying a migrating adult worm in the subcutaneous tissue or conjunctiva (picture 1) or by detecting microfilariae in a blood smear (picture 3). Microscopy sensitivity is increased with a variety of concentration techniques, including Knott's concentration and Nuclepore filtration [25].

Adult worms range in length from 2.0 to 3.5 cm for males and 5 to 7 cm for females. Both are no more than 0.5 mm wide. 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).

L. loa typically has diurnal periodicity, meaning that the microfilariae are more abundant in the bloodstream during the daytime (between 10:00 AM and 2:00 PM) than at night. This coincides with the feeding pattern of the vector in most settings, thereby potentiating transmission of infection. It should be noted, however, that L. loa microfilariae have been demonstrated in blood smears collected at night in the Democratic Republic of Congo [26]. Periodicity testing conducted in the context of this study revealed atypical patterns. Consequently, although diurnal periodicity differentiates microfilariae in loiasis from the nocturnally periodic, large, sheathed microfilariae of Wuchereria bancrofti in most epidemiologic settings in Africa, species confirmation by other morphologic characteristics or polymerase chain reaction (PCR) may be necessary in some cases. Microfilariae of Mansonella perstans, another human filarial parasite that overlaps in geographic distribution with L. loa, are not periodic but can be distinguished from L. loa microfilariae on the basis of their small size and the absence of a sheath.

Microfilaremia is observed more frequently among residents of endemic areas than in travelers [12,14,16,17]. In one study, microfilaremia was observed in only 22 percent of those infected as visitors to endemic countries as compared with 74 percent of immigrants from endemic areas [16]. One study demonstrating familial clustering of microfilarial density in an endemic area in Cameroon suggested that genetic predisposition is one factor that may contribute to high levels of microfilaremia in infected individuals [27].

Serology — Serologic tests are most useful for diagnosis of loiasis among travelers. In endemic populations, serology is generally not useful since antibodies remain positive for prolonged periods following infection and thus cannot distinguish between active or prior infections or quantitate microfilaremia. However, a negative result can exclude the possibility of L. loa infection.

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. Newer techniques, which measure specific IgG4 antibodies rather than total IgG, have been developed and are thought to be 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 [28]. 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 [29]. 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.

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 [30].

Other tests — Tests that detect circulating L. loa antigens are in development [31]. A real-time PCR assay has been developed at the Laboratory of Parasitic Diseases, National Institutes of Health that can detect and quantitate L. loa microfilaremia [32]. Subsequently, this assay has been adapted for loop-mediated isothermal amplification, a point-of-care molecular diagnostic tool that can be used in field settings [33,34].

Other novel point-of-care tools in development 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) [35,36]. 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 [36]. The tool is not designed for diagnosis of L. loa in individuals, as it is insensitive for detection of low levels of microfilaremia. (See "Onchocerciasis", section on 'Loa loa coinfection'.)

Assistance with serologic and other diagnostic tests is available from the Laboratory of Parasitic Diseases, National Institutes of Health (301-496-5398) and the United States Centers for Disease Control and Prevention.

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 endemicity overlap with those of loiasis, and coinfection can occur, which is important for decisions regarding treatment. The diagnosis 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 W. 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 [26,37,38]. The diagnosis 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 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 [18]. Geography may be helpful in some cases. For example, the natural host for B. procyonis is the raccoon, a species that 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 [39]. (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

Clinical approach — The treatment of choice for loiasis is diethylcarbamazine (DEC), which has activity against both L. loa microfilariae and macrofilariae (adult worms). Since the incidence and severity of treatment side effects increase with increasing blood microfilarial counts, quantification of blood microfilariae is essential before initiating treatment. This can be done by counting microfilariae on blood smears made from defined volumes of blood (eg, 50 microL) [5] or from larger volumes of blood (eg, 1 mL) concentrated through Nuclepore filters or using formalin (Knott's concentration) or saponin lysis. Quantification should be performed between 10:00 AM and 2:00 PM to capture the peak number of microfilariae circulating in the blood. In patients within two weeks of travel from a different time zone, the time of the blood draw should be adjusted accordingly.

Serious side effects of treatment are uncommon in patients with low numbers of microfilariae in the blood (2500 microfilariae/mL has been suggested as a threshold, although supporting data are lacking). In general, patients with any detectable microfilariae should be monitored closely during the first three days of treatment and hospitalization may be warranted for those with levels >2500 microfilariae/mL. Antihistamines and/or corticosteroids have been used to limit posttreatment reactions, including Calabar swellings and urticaria, but do not prevent serious side effects, including encephalopathy. In patients with high levels of microfilariae, the risks and benefits of treatment need to be considered. In general, treatment should be reserved for symptomatic patients, patients with marked elevations in the peripheral eosinophil count, and/or patients with concomitant onchocerciasis or lymphatic filariasis (who require therapy to prevent morbidity and mortality due to these infections).

An attempt should be made to lower blood microfilarial counts prior to DEC treatment. This can be accomplished using apheresis [40]; however, this is not feasible in most cases [41]. Treatment with albendazole, a benzimidazole with good oral bioavailability, has been shown to significantly decrease Loa microfilarial levels in a randomized trial (dosed 200 mg with fatty meal twice daily for three weeks) [42]. Adverse effects were not observed, even in individuals with >50,000 microfilariae/mL blood. Shorter higher dose regimens have not been effective. The gradual decrease in blood microfilarial levels over the course of several months suggests that albendazole may have preferential effects on adult parasites, explaining the lack of adverse effects associated with acute microfilarial clearance.

Pretreatment with albendazole may provide an alternative to apheresis in patients with high-level microfilaremia, although in many cases microfilarial levels remain above a safe threshold for DEC treatment and should be checked prior to initiation of DEC. Multiple courses may be necessary [20]. Ivermectin has L. loa microfilaricidal activity and, similar to DEC, can precipitate adverse events in patients with high levels of circulating microfilariae. Unlike DEC, however, ivermectin has no effect on adult worms and is not curative in L. loa infection. A study comparing post-treatment reactions in 12 patients with loiasis following single-dose ivermectin or DEC suggested that the underlying pathophysiology of post-treatment reactions following DEC and ivermectin share a common pathophysiology [43].

Endosymbiotic Wolbachia have not been identified in L. loa by light or electron microscopy or by polymerase chain reaction [44] (in contrast with other filariae that infect humans such as W. bancrofti, Brugia malayi, and Onchocerca volvulus), precluding the use of doxycycline or other antibacterial agents for the treatment of loiasis [45]. 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 [46,47], 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 5 patients who received placebo [48].

Diethylcarbamazine — The treatment of choice for loiasis is diethylcarbamazine, a piperazine derivative. DEC has activity against both L. loa microfilariae and adult worms, so a sustained decrease in microfilarial intensity occurs following treatment [49-52]. In one study, DEC (8 to 10 mg/kg per day for 21 days) lowered 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 [53]. However, a single course of treatment is curative in only 40 to 50 percent of patients. Relapsed infection can also occur.

Adverse events following treatment with DEC are due to rapid killing of the microfilariae and are most severe in patients with high levels of circulating microfilariae, although adverse effects can occur even in amicrofilaremic patients. Reactions are common, though serious reactions (encephalitis and/or shock) are relatively uncommon [22]. Therefore, asymptomatic patients with high levels of circulating microfilariae should not receive treatment. Apheresis (if available) or pretreatment with albendazole should be considered prior to DEC treatment of symptomatic patients with high levels of circulating microfilariae. (See 'Clinical approach' above.)

Treatment for patients without evidence of microfilaremia consists of DEC 9 mg/kg/day orally in three divided doses for 21 days [54]. Treatment for patients with microfilaremia consists of a graded dosing schedule for DEC 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

A single 21-day course of DEC is curative in approximately 50 percent of patients. There are no data available on shorter course therapy. Long-term follow-up is needed after therapy, and retreatment should be considered if symptoms recur [55]. DEC should be avoided in pregnancy.

DEC is not licensed for use in the United States, but 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).

Albendazole — Albendazole is an alternative agent for treatment of loiasis. Albendazole has macrofilaricidal activity, causing sterilization or death of adult L. loa worms. Unlike DEC, albendazole does not have significant microfilaricidal activity. Consequently, fewer adverse effects are observed with albendazole compared with DEC, since there is no massive antigen release associated with dying microfilariae [1].

Use of albendazole against the adult worm leads to a gradual decline in microfilariae levels over several months [42,56,57]. Although cure rates following albendazole treatment of loiasis have not been studied directly, the fact that microfilariae are not completely eliminated in most patients suggests that albendazole is less effective than DEC as initial therapy.

In individuals with high levels of circulating microfilariae loads, treatment with albendazole may be useful for reduction of microfilaremia prior to treatment with DEC. Albendazole has also been used as an alternative agent in individuals with L. loa infection that is refractory to multiple courses of DEC [42]. A dose of 200 mg twice daily for three weeks has been used.

Ivermectin — Ivermectin is not a preferred therapeutic agent for treatment of loiasis. It has microfilaricidal activity against L. loa but is not active against adult worms [58-61]. As with DEC, the rapid microfilaricidal effect of ivermectin can result in severe adverse events (encephalitis and/or shock), particularly in individuals with high-level microfilaremic infections [21,62]. Ivermectin pretreatment is indicated in patients with concomitant onchocerciasis and loiasis.

Onchocerciasis coinfection — Coinfection with loiasis and onchocerciasis warrants special attention, since DEC is contraindicated in onchocerciasis and can provoke severe inflammatory responses in the skin and eyes (Mazzotti reaction) (table 2). If the burden of L. loa microfilariae is low, pretreatment with ivermectin can be administered prior to DEC. The optimal length of time between ivermectin and DEC treatment is uncertain; 6 to 12 months may be reasonable. If the burden of L. loa microfilariae is high, the risks and benefits of treatment need to be weighed as discussed above, and apheresis or albendazole should be considered prior to sequential treatment with ivermectin and DEC. (See 'Clinical approach' above.)

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 [63]. In an earlier randomized study including 59 patients with Onchocerca volvulus and eye involvement, a single dose of ivermectin was associated with slow elimination of microfilariae over the course of six months with minimal inflammatory reaction [64].

Surgery — Surgical removal of worms from the eye or the skin can be performed for diagnostic purposes. This is generally not a practical method for cure of infection, however, particularly in endemic areas where large worm burdens are common. Surgical removal of subconjunctival worms is not required for therapeutic management since migration of the worm does not result in ocular damage. Rare cases of intraocular worms have been described; in such cases, removal is indicated to prevent blindness [18].

PREVENTION — There is no vaccine against L. loa 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.

A weekly 300 mg dose of DEC can be given for prophylaxis against loiasis for individual travelers [54]. This should be considered for workers with longer-term exposures (eg, Peace Corps personnel) but is not necessary for most short-term travelers to endemic areas [65].

SUMMARY AND RECOMMENDATIONS

●Loiasis, also known as African eye worm, is caused by the filarial nematode Loa loa. Loiasis is transmitted by the bite of Chrysops flies (figure 2); west and central Africa are endemic regions for infection. Infection is occult in a large proportion of patients; therefore, in many areas, the epidemiology of loiasis has not been clearly defined. Infection occurs most commonly in residents of endemic areas, but travelers to these regions can also be infected. (See 'Epidemiology' above.)

●Most individuals with L. loa infection are asymptomatic. The clinical manifestations include transient localized subcutaneous swellings (known as Calabar swellings) and migration of the adult worm across the subconjunctiva of the eye (picture 1). Nonimmune individuals who travel to endemic regions and acquire L. loa infection are generally more prone to hypersensitivity reactions to microfilariae and/or migrating adult worms than local residents. Eosinophilia (>3000/microL) is more common in nonimmune individuals. (See 'Clinical manifestations' above.)

●The diagnosis of loiasis can be definitively established by identifying a migrating adult worm in the subcutaneous tissue or conjunctiva (picture 1) or by detecting microfilariae in a blood smear (picture 3). Serologic tests have been developed and are most useful for diagnosis of loiasis among travelers. New polymerase chain reaction techniques are sensitive and quantitative assays of infection and levels of microfilaremia. (See 'Diagnosis' above.)

●We suggest diethylcarbamazine (DEC) for treatment of patients with loiasis and <2500 microfilariae per mL of blood (Grade 2C). Use of DEC can lead to adverse events (encephalitis and/or shock) in patients with high levels of circulating microfilariae due to rapid microfilariae killing. Therefore, reduction of microfilariae with apheresis (if available) or albendazole should be pursued prior to DEC treatment in the management of patients with symptomatic loiasis and >2500 microfilariae per mL of blood. Patients with concomitant loiasis and onchocerciasis should receive ivermectin treatment prior to definitive therapy with DEC or a regimen that does not contain DEC. (See 'Treatment' above.)

●There is no vaccine against L. loa 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 are no mass community chemotherapy programs in place for loiasis. (See 'Prevention' above.)