Loiasis

Loiasis also known as African eye worm is an filarial infection caused by a parasitic roundworm (nematode) called Loa loa that is endemic in the forested areas of Central and western Africa and is transmitted by the bite of an infected Chrysops deer fly (Chrysops silacea or Chrysops dimidiata) ¹, ², ³, ⁴, ⁵, ⁶, ⁷, ⁸. Loiasis spreads to people through the repeated bites of deerflies that breed in rain forests in West and Central Africa which include 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. The highest prevalence of Loiasis was described for rural regions of Gabon, Equatorial Guinea and parts of Cameroon, the Central African Republic, the Democratic Republic of the Congo, and Republic of the Congo ⁹. It is estimated that between 3 and 13 million people are infected with Loa loa ¹⁰. Infection occurs most commonly among residents of endemic areas. It is unclear whether naturally acquired immunity develops after prolonged periods of exposure. Infection is asymptomatic 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 Loa loa infection increases with age and forest exposure ¹¹; the proportion of infected individuals varies depending on Chrysops vector abundance, which in turn is dependent on local ecology ³.

Most people infected with Loa loa parasitic roundworms do not develop symptoms (asymptomatic). But in those who do, symptoms can include ¹²:

• Itchy, non-painful body swelling that comes and goes, known as Calabar swelling. Calabar swelling can show up anywhere, although it’s more likely to happen near joints.
• Migration of the adult worm through the sclera or subconjunctival palpebral (under the eyelid) or bulbar tissue of the eye (the white part of the eyeball).
• Loa loa worms visibly crawling under your skin.

Less common symptoms include ¹²:

• Itching all over your body
• Muscle pain and joint pain
• Feeling weak and tired (fatigue)

In rare cases, people with loiasis may experience ¹²:

• Painful swellings of lymph glands
• Swollen scrotum, in men
• Inflammation of parts of the lungs
• Fluid collection around the lung
• Scarring of heart muscle
• Kidney damage, if infection continues for many years

If you traveled to or live in affected areas of Africa and you have Loiasis symptoms, your doctor may order a blood test. This test can show whether you have the Loa loa microfilariae in your blood. Your doctor may also perform a physical exam and look for signs of loiasis, such as itchy, swollen areas on your body.

Loa loa is usually diagnosed by the finding of microfilaria in peripheral blood smears or adults in the subconjunctiva. The blood films may be thick or thin and stained with Giemsa or hematoxylin-and-eosin (H&E). For increased sensitivity, concentration techniques can be used. These include centrifugation of the blood sample lysed in 2% formalin (Knott’s technique), or filtration through a Nucleopore® membrane. Microfilariae of Loa loa exhibit diurnal periodicity and a diagnosis is best made from blood collected during the midday (10 AM to 2 PM). The presence of Calabar swellings can aid in the diagnosis.

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.

Antiparasitic medications, like ivermectin and diethylcarbamazine (DEC), treat loiasis. Diethylcarbamazine is the treatment of choice and is known to be effective at eradicating both microfilariae and adult worms but must be used with caution ¹³. But people with high levels of Loa loa microfilariae in their blood (>8,000 microfilariae per ml) can have life-threatening reactions to these medications. Microfilarial loads are determined by calculating the number of microfilariae per milliliter using a measured quantity of blood ¹⁴. Your doctor may order a test to measure the number of microfilariae in your blood before giving you ivermectin or diethylcarbamazine (DEC).

If you have more than 8,000 microfilariae per milliliter of blood, ivermectin and diethylcarbamazine (DEC) may not be safe for you. Your doctor may recommend a medication called albendazole or a blood filtering procedure (apheresis) first. Albendazole and blood filtering (apheresis) lower the number of microfilariae in your blood. Then, ivermectin or diethylcarbamazine (DEC) may be safe for you to take.

Available data demonstrate that the risk of fatal encephalopathy in patients treated with diethylcarbamazine (DEC) with microfilarial loads <8,000 microfilariae per mL approaches zero. In those patients with microfilarial loads more than 8,000 microfilariae per mL (>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. Re-measurement of levels after albendazole treatment would be required prior to treatment with diethylcarbamazine (DEC).

Note that Diethylcarbamazine (DEC) is contraindicated in persons with onchocerciasis co-infection‎ because of the risk of blindness and/or severe exacerbation of skin disease.

Diethylcarbamazine (DEC) has been used worldwide for more than 50 years. Because Loiasis is rare in the United States, diethylcarbamazine (DEC) 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.

Because loiasis is rare in the U.S., your doctor may consult with an expert in tropical medicine to treat the infection. If you have a severe infection, you’ll need to see an experienced tropical medicine specialist.

Surgical removal of adult worms from the conjunctiva of the eye is indicated whenever the adult worm presents in the subconjunctival space, and is followed up with systemic medications, which prevent recurrence by reducing systemic micro- and macrofilarial loads.

Table 1. Loiasis medications

Medication	Indication	Adult Dose	Children Dose
Diethylcarbamazine (DEC)	Symptomatic loiasis with <8,000 microfilariae/mL	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 <8,000 microfilariae/mL and failed 2 rounds diethylcarbamazine (DEC) OR Symptomatic loiasis, with ≥8,000 microfilariae/ml to reduce level to <8,000 microfilariae/ml prior to treatment with diethylcarbamazine (DEC)	200 mg orally twice daily for 21 days	200 mg orally twice daily for 21 days
Apheresis* followed by diethylcarbamazine (DEC)	Symptomatic loiasis, with ≥8,000 microfilariae/mL	N/A	N/A

Footnotes: * 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.

[Source ¹⁵ ]

Figure 1. Loa loa worm

Footnotes: Microfilaria of Loa loa in a thick blood smear, stained with Giemsa. Loa loa microfilariae (immature worms) are large (231 to 250 μm in length) on stained blood films with a short headspace and nuclei that extend irregularly to the tip of the tail. The microfilariae have a sheath that is not always visible, because it does not usually stain bright pink with Giemsa but can be visualized with hematoxylin stains. Of note is that sheaths may be shed if there is a delay in processing the blood specimen.

[Source ¹⁶ ]

Figure 2. Loa loa microfilariae (Loa loa immature worms)

Footnotes: Loa loa microfilariae (immature worms) purified after Percoll gradient cell separation (A) and May–Grünwald Giemsa staining (B and C). The sheath can be seen as an extended translucid structure along the end tail (arrows).

[Source ¹ ]

Figure 3. Loiasis signs and symptoms

Footnotes: (A) Illustration of typical signs, common but unspecific signs, and rare but clinically important complications of Loiasis. (B) Eye worm migration, Calabar swelling of the left hand, and dermal migration of adult worm.

[Source ¹⁷ ]

Figure 4. Loiasis

Footnotes: (A) Adult Loa loa subconjunctival worm in patient’s right eye. (B) Loa loa microfilaria (immature worm) in Giemsa-stained thick blood smear (original magnification, ×10). (C) Anterior end of microfilaria showing short headspace and nuclei that are coarse and densely packed throughout the length of the worm. A sheath is not present (original magnification, ×40). (D) Tapered tail with nuclei extending to the tip (original magnification, ×40).

[Source ¹⁸ ]

Figure 5. Chrysops silacea (deer fly)

Footnotes: View of Chrysops silacea deer fly with the typical two longitudinal stripes on the back that never extend beyond the third abdominal segment and may be so attenuated or interrupted as to be almost absent (A) and ventral side of the fly (B). The wing markings of the two species of Chrysops are similar. Chrysops silacea deer flies can carry more infective L3 Loa loa larvae along their proboscis and thorax. These serve as a source of natural infective-stage larvae of Loa loa. Only females take a blood meal, and, with rare exception, they feed during the daytime ¹⁹. Unlike numerous other groups of blood sucking flies, female deer flies do not enter structures and thus do not feed on humans indoors ¹⁹. Female deer flies typically feed on moving hosts and usually bite on the shoulders and head ¹⁹. They have a wide host range, attacking mammals of all sizes, including humans, and some species feed on birds and reptiles. Female deer flies are aggressive, persistent feeders that quickly return to bite again if they are interrupted before they take a complete blood meal ¹⁹.

[Source ¹ ]

Figure 6. Chrysops dimidiata (deer fly)

Footnotes: View of Chrysops dimidiata deer fly the abdominal stripes are broader and reach the fourth segment, where they usually become merged into the darker brown color of the terminal segments (A) and ventral side of the fly (B). The wing markings of the two species of Chrysops are similar. Chrysops dimidiata deer flies can carry more infective L3 Loa loa larvae along their proboscis and thorax. These serve as a source of natural infective-stage larvae of Loa loa. Only females take a blood meal, and, with rare exception, they feed during the daytime ¹⁹. Unlike numerous other groups of blood sucking flies, female deer flies do not enter structures and thus do not feed on humans indoors  ¹⁹. Female deer flies typically feed on moving hosts and usually bite on the shoulders and head ¹⁹. They have a wide host range, attacking mammals of all sizes, including humans, and some species feed on birds and reptiles. Female deer flies are aggressive, persistent feeders that quickly return to bite again if they are interrupted before they take a complete blood meal ¹⁹.

[Source ¹ ]

Figure 7. Loiasis geographic distribution

Footnotes: Zouré et al. ⁹ provided a comprehensive distribution of loiasis in Africa, which nearly corresponds to the distribution of Chrysops fly vectors ²⁰, ²¹ because the transmission of loiasis is correlated to the distribution of its vectors. According to these authors, two main zones of highly endemic loiasis can be distinguished: a western zone that comprises part of the Equatorial Guinea, Gabon, Cameroon, Republic of Congo, Central African Republic and Chad, Democratic Republic of Congo (DRC) and Angola; the second hyper‐endemic zone is mainly made up of the North‐Eastern part of the Democratic Republic of Congo (DRC) ⁹. Areas of low endemicity include most parts of Democratic Republic of Congo (DRC), north Cameroon and large sections of Angola, Nigeria, Chad and Sudan. Because some Chrysops flies are essentially zoophilic, the geographic distribution likely expands beyond the previously described area. For instance, Chrysops species have been described in Egypt ²² and in Rwanda ²¹, countries not mentioned in the previously described area of distribution.

[Source ⁹ ]

Can loiasis cause blindness?

Seeing a worm in your eye can be unsettling and uncomfortable. But Loa loa worms, which are 1 to 3 inches long, don’t cause blindness and usually don’t damage your eyes ²³, ²⁴, ²⁵. The worm usually moves across your eye and back into your body. Your eye doctor can safely remove a visible worm with a minor procedure, but this will not cure the infection. You’ll need a followed up treatment with systemic medications, which prevent recurrence by reducing systemic micro- and macrofilarial loads.

Intraocular filariasis due to Loa loa is an uncommon occurrence, which presents with pain and foreign body sensation ²⁶. Unlike subconjunctival filariasis, intraocular filariasis is associated with significant risk of visual acuity loss with some patients ending up with complete blindness ²⁷). Your pre-operative presentation is strongly correlated with your postoperative outcome ²⁸, ²⁹, ³⁰, ³¹, ³². In general, patients with more advanced eye disease at presentation with more pronounced intraocular inflammation are more likely to suffer significant long-term vision loss, while patients whose intraocular filariae are removed prior to development of intraocular membranes may be able to return to their normal visual acuity  ³⁰.

What causes Loiasis

Loiasis also known as African eye worm is an filarial infection caused by a parasitic roundworm (nematode) called Loa loa that is endemic in the rain forests of Central and western Africa and is transmitted by the bite of an infected Chrysops deer fly (Chrysops silacea or Chrysops dimidiata) ¹, ², ³, ⁴, ⁵, ⁶, ⁷, ⁸. Loiasis spreads to people through the repeated bites of deerflies that breed in rain forests in West and Central Africa which include 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. The highest prevalence of Loiasis was described for rural regions of Gabon, Equatorial Guinea and parts of Cameroon, the Central African Republic, the Democratic Republic of the Congo, and Republic of the Congo ⁹. Only female Chrysops deer fly (Chrysops silacea or Chrysops dimidiata) take a blood meal, and, with rare exception, they feed during the daytime ¹⁹. Unlike numerous other groups of blood sucking flies, female deer flies do not enter structures and thus do not feed on humans indoors  ¹⁹. Female deer flies typically feed on moving hosts and usually bite on the shoulders and head ¹⁹. They have a wide host range, attacking mammals of all sizes, including humans, and some species feed on birds and reptiles. Female deer flies are aggressive, persistent feeders that quickly return to bite again if they are interrupted before they take a complete blood meal ¹⁹.

It is estimated that between 3 and 13 million people are infected with Loa loa ¹⁰. Infection occurs most commonly among residents of endemic areas. It is unclear whether naturally acquired immunity develops after prolonged periods of exposure. Infection is asymptomatic 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 Loa loa infection increases with age and forest exposure ¹¹; the proportion of infected individuals varies depending on Chrysops vector abundance, which in turn is dependent on local ecology ³.

When the Chrysops silacea or Chrysops dimidiata deer fly bite people with Loa loa infection, they pick up immature worms, or microfilariae, in that person’s blood ³³. The microfilairiae (immature worms) develop into infectious larvae (L3 larvae) in the fly and can then infect people ³³. When the deerfly bites a person’s skin to feed (take a bloodmeal), the infectious larvae (L3 larvae) enter the wound and begin moving through the person’s body (see Loa loa Life Cycle below).

It takes about five months for the third-stage infective L3 larvae to develop into adult worms. Larvae can only become adults inside the human body ³³. The adult worms live between layers of connective tissue (e.g., ligaments, tendons) under the skin and between the thin layers of tissue that cover muscles (fascia). Their microfilariae will spread into the lymph nodes and eventually the lungs ³³.

People who develop symptoms typically start seeing them about five months after they are infected. This is also when the microfilariae begin to enter the bloodstream. Adult worms can live in the body up to 17 years, reproducing most of this time ³³.

Loa loa Life Cycle

The vector for Loa loa filariasis are deer flies from two species of the genus Chrysops, Chrysops silacea and Chrysops dimidiata. During a blood meal, an infected Chrysops fly (day-biting flies) introduces third-stage infective L3 larvae onto the skin of the human host, where they penetrate into the bite wound (number 1). The larvae develop into adults that commonly reside in subcutaneous tissue (number 2). The female Loa loa worms measure 40 to 70 mm in length and 0.5 mm in diameter, while the males measure 30 to 34 mm in length and 0.35 to 0.43 mm in diameter. Adult Loa loa worms produce microfilariae measuring 250 to 300 µm by 6 to 8 μm, which are sheathed and have diurnal periodicity. Microfilariae have been recovered from spinal fluids, urine, and sputum. During the day they are found in peripheral blood, but during the noncirculation phase, they are found in the lungs (number 3). The Chrysops fly ingests microfilariae during a blood meal (number 4). After ingestion, the microfilariae lose their sheaths and migrate from the fly’s midgut through the hemocoel to the thoracic muscles of the arthropod (number 5). There the microfilariae develop into first-stage larvae (number 6) and subsequently into third-stage infective L3 larvae (number 7). The third-stage infective L3 larvae migrate to the fly’s proboscis (number 8) and can infect another human when the fly takes a blood meal (number 1).

Figure 8. Loa loa life cycle

[Source ³⁴ ]

Loiasis prevention

The best way to prevent Loiasis is to avoid Chrysops silacea or Chrysops dimidiata deer fly bites by limiting outdoor exposure during daytime and use of protective clothing are currently the only effective ways to prevent individuals from infectious bites ¹⁷. It is unclear whether classic insect repellents, including diethyltoluamide (DEET) and icaridin, confer protection against bites from Chrysops silacea or Chrysops dimidiata deer flies and consequent infection with Loa loa for travellers to or residents in endemic regions ¹⁷. Controlling deer flies (and horse flies) is nearly impossible ¹⁹. The use of insecticides to kill the fly larvae is not an option because the vast majority of species develop in natural habitats in which
insecticides cannot be applied due to environmental concerns ¹⁹. Even if they could be used, insecticides would be ineffective in controlling larvae because they are widely dispersed in a developmental site. The use of insecticides against adult
horse and deer flies is not a realistic option because they are relatively large to very large and unaffected by the rate of insecticide that can be applied according to product label ¹⁹. At best, an insecticide application aimed at adult flies might produce a minor and temporary reduction in biting. A number of trapping devices have been used to capture adults, but their value is limited to sampling. At best, trapping devices produce temporary, minor relief from female flies.

If you’re traveling to West or Central Africa and planning to stay for a long period of time, you can reduce your risk of loiasis infection by:

• Taking 300 milligrams (mg) of diethylcarbamazine (DEC) once a week.
• Wearing insect repellants with DEET (N,N-Diethyl-meta-toluamide or diethyltoluamide).
• Wearing long pants and long-sleeved shirts to keep flies off your skin.
• Applying an insecticide called permethrin to your clothes.

Historically, 60% dimethyl phthalate (DMP) solution conferred good protection against Chrysops bites ¹⁹, ⁴. However, due to the substantial potential for irritation of the eyes and the respiratory tract and its unclear carcinogenic potential, this hardly constitutes a practical control tool ³⁵, ³⁶.

Animal studies had indicated that diethylcarbamazine (DEC) might be used as a prophylactic (preventive) drug in the prevention of Loa loa infection ³⁷. A randomised controlled clinical trial evaluated weekly doses of 300 mg diethylcarbamazine (DEC) as a chemoprophylactic regimen for long-term travellers to Gabon, Cameroon, and Central African Republic ³⁸. In this study, weekly diethylcarbamazine (DEC) prophylaxis led to a complete protection from loiasis compared with a 30% attack rate in participants travelling to Gabon who had not taken the prophylaxis ³⁸. The safety profile of diethylcarbamazine (DEC) was good, although the tolerability analysis indicated increased frequency of nausea. Although diethylcarbamazine (DEC) prophylaxis might be used exceptionally on a case-by-case basis for people from non-endemic countries travelling for long-term visits to regions of highest transmission (eg, Peace-Corps volunteers, soldiers, or missionaries), this strategy is unsuitable for a group of people who are indigenous and native to a specific place, having originated from that location for a very long time with established Loa loa infections due to longterm safety concerns with the use of diethylcarbamazine (DEC) ³⁹.

Mass treatment of populations using mass drug administration (MDA) in endemic regions has proven extremely successful in controlling several neglected tropical diseases ⁴⁰. Ivermectin-based onchocerciasis control programmes simultaneously led to substantial reduction of Loa loa microfilaremia, indicating the usefulness of mass drug administration (MDA) for the future control of loiasis ⁴¹. However, to date no treatment regimen is safe and efficacious enough to be used routinely for loiasis control ¹⁷. Therefore, the clinical development of new drug regimens suitable for population-based mass drug administration (MDA) programmes is an important research priority ¹⁷. The roll-out of mass drug administration (MDA) programmes will allow the effective reduction of the infectious reservoir in the local population and will therefore reduce the number of newly infected individuals ¹⁷. The availability of such mass drug administration control programmes and the roll-out of effective diagnostic and treatment services for individual patient care will prove vital to reduce the intolerable morbidity and mortality that loiasis exerts today on affected communities ¹⁷.

Loiasis signs and symptoms

As with other diseases caused by parasitic worms, many people who are infected with Loa loa never develop symptoms (asymptomatic). But in those who do, the main symptoms are ¹²:

• Itchy, non-painful body swelling that comes and goes, known as Calabar swelling. Calabar swelling can show up anywhere, although it’s more likely to happen near joints.
• Migration of the adult worm through the sclera or subconjunctival palpebral (under the eyelid) or bulbar tissue of the eye (the white part of the eyeball).
• Loa loa worms visibly crawling under your skin.

Most patients with loiasis are asymptomatic. The classic clinical sign and symptom of loiasis is the formation of Calabar swellings, which are transient subcutaneous nodules created by migrating adult worms. Calabar swellings can occur anywhere on your body but are most common on the trunk and arms. Occasionally, adult worms will migrate to the eye and can be observed grossly in the conjunctiva ⁴².

Loa loa is referred to as “African Eye Worm” because the Loa loa worm can be observed migrating across the periorbital tissues and into the subconjunctiva. This observation is not associated with lasting damage to tissues. However, discomfort and foreign body sensation are commonly reported symptoms ⁶, ⁴³, ²³, ²⁴.

In rare cases, Loa loa has been noted to enter the anterior chamber of the eye, and live Loa loa worms have been reported in the vitreous. Such patients present with a grossly visible intraocular filarial worm on physical exam, usually with pain and photophobia. Associated vision loss at presentation has ranged from 6/24 to light perception. Slit lamp exam often reveals fibrinous membrane formation, cell/flare, and keratic precipitates. More prolonged cases may develop retinal detachments ²⁸, ²⁹, ³⁰, ³¹, ³².

Less common symptoms include ¹²:

• Itching all over your body
• Muscle pain and joint pain
• Feeling weak and tired (fatigue)

In rare cases, people with loiasis may experience ¹²:

• Painful swellings of lymph glands
• Swollen scrotum, in men
• Inflammation of parts of the lungs
• Fluid collection around the lung
• Scarring of heart muscle
• Kidney damage, if infection continues for many years

Loiasis diagnosis

If you traveled to or live in affected areas of Africa and you have Loiasis symptoms, your doctor may order a blood test. This test can show whether you have the Loa loa microfilariae in your blood. Your doctor may also perform a physical exam and look for signs of loiasis, such as itchy, swollen areas on your body.

Traditionally, the diagnosis of Loiasis requires demonstrating microfilariae in the peripheral blood or skin under microscopy. Loa loa is primarily diagnosed by the finding of microfilariae in thick and thin blood films stained with Giemsa, Wright, Wright-Giemsa, or hematoxylin stains. It is best performed using capillary or venous peripheral blood taken between 10AM and 4PM because peripheral microfilaremia peaks during the hot hours of the day ⁴⁴, ⁴⁵. Serpent-like moving microfilariae might be directly visualised in fresh blood or a more detailed morphological assessment is performed in stained blood smears ⁴⁶. The microfilariae measure 231 to 250 μm long on stained blood films and possess a sheath that usually does not stain with Giemsa. Also, the sheath may be shed and not visible if there is a delay in processing the blood. Loa loa microfilariae have a dense nuclear column with a short headspace and tail extending irregularly to the tip ⁴⁷. Loa loa may also be diagnosed by the gross examination of adult worms removed from the eye or in histopathologic examination of skin biopsy specimens. In both instances, the adults need to be differentiated from zoonotic filarids in the genus Dirofilaria ⁴⁷, ⁴⁸. The adults of both Loa loa and Dirofilaria worms are similar in size and macroscopic appearance. A distinguishing difference is that the adult Loa loa has small irregularly spaced bumps (bosses) on the surface of the cuticle, while the adult Dirofilaria has a thick cuticle with multiple longitudinal ridges ⁴⁸. Dirofilaria microfilariae are rarely seen in human blood and are unsheathed, and nuclei do not extend to the tip of the tail.

Staining is most commonly done with Giemsa stain, although the pathognomonic features including the presence of a sheath are better visualized by hematoxylin-based stains ⁴⁹. Rapid stains have been shown to be similarly accurate while substantially shortening the processing time ⁵⁰, ⁵¹. The sensitivity of microscopic assays relies most importantly on the total amount of blood being investigated. Concentration techniques with lysing solutions or filtration techniques improve sensitivity in individuals with low levels of microfilaremia ⁵², ⁵³, ⁵⁴. Over the past 5 years, an innovative approach for the time-efficient testing of large numbers of blood samples was established by a smartphone-based automated reader (the LoaScope) ⁵⁵. This diagnostic technique has been useful for ruling out Loa loa hypermicrofilaremia in onchocerciasis control programmes ⁵⁶, ⁵⁷, ⁵⁸. However, its diagnostic accuracy for individual case management has not yet been established and the device has an only limited availability.

Numerous approaches to improve Loa loa diagnostics have been initiated using biomarkers, such as immunoglobulin 4 (IgG4), polymerase chain reaction (PCR), reverse transcriptase PCR (RT-PCR), loop-mediated isothermal amplification, and lateral flow assays (LFAs) ⁵⁹, ⁶⁰, ⁶¹, ⁶². Absolute eosinophil counts and immunoglobulin E (IgE) levels, both are typically increased in patients with acute and chronic loiasis ⁶³. Although serology has high sensitivity, it often lacks specificity, particularly in co-infected residents of endemic regions. A rapid diagnostic test detecting Loa loa-specific antibodies seems particularly useful for large-scale mapping of Loa loa transmission in communities targeted for ivermectin mass drug administration (MDA) ⁵⁶, ⁶⁴, ⁶⁵. The test for Loa loa-specific antibodies has also shown reasonable diagnostic accuracy when used for patients of an Italian travel clinic ⁶². Whether the test has sufficiently high diagnostic accuracy for case management of permanent residents in high transmission regions is currently under investigation.

Direct detection of adult worms is desirable to prove infection in occult loiasis. The observation and potential extraction of an adult worm migrating through the eye, often documented by patients themselves via smartphone photography, has so far been the only certain detection method ⁶⁶, ⁶⁷. Several polymerase chain reaction (PCR) protocols have been advocated to detect occult loiasis. However, it remains unclear whether these assays truly detect migrating adult worms or rather submicroscopic microfilaremia. Independent validation in different settings is still absent, so no final conclusion can be drawn for their diagnostic accuracy in detecting occult loiasis ⁶⁸, ⁶⁹.

Loiasis treatment

There are several drugs with known activity against the adult or larval developmental stages of Loa loa, which are of varying clinical usefulness. Antiparasitic medications, like ivermectin and diethylcarbamazine (DEC), treat loiasis. But people with high levels of Loa loa microfilariae in their blood (> 8,000 microfilaria/mL) can have life-threatening reactions to these medications ⁷⁰. Your doctor may order a test to measure the number of microfilariae in your blood before giving you ivermectin or diethylcarbamazine (DEC). Diethylcarbamazine (DEC) is contraindicated in persons with onchocerciasis co-infection‎ because of the risk of blindness and/or severe exacerbation of skin disease. 

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 diethylcarbamazine (DEC). Some will require additional courses of diethylcarbamazine (DEC) or a trial of albendazole. Diethylcarbamazine (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 diethylcarbamazine (DEC) (300 mg once a week) can be used to prevent infection in long-term travelers to endemic areas.

Diethylcarbamazine (DEC) has been used worldwide for more than 50 years. Because Loiasis is rare in the United States, diethylcarbamazine (DEC) 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.

There is some evidence that albendazole given twice daily for 21 days may be an effective treatment for loiasis that is refractory to diethylcarbamazine (DEC) treatment. It also may be used to reduce microfilarial load prior to initiation of diethylcarbamazine (DEC) treatment. The response to albendazole is slow so close, frequent monitoring would be needed to determine when it is safe to treat with diethylcarbamazine (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 reduced with the concomitant use of antihistamines or corticosteroids during the first seven days of treatment. There is also the risk of fatal encephalopathy with diethylcarbamazine (DEC) treatment; this risk has not been shown to be eliminated by corticosteroid treatment.

If you have more than 8,000 microfilariae per milliliter of blood, ivermectin and diethylcarbamazine (DEC) may not be safe for you. Your doctor may recommend a medication called albendazole or a blood filtering procedure first. Albendazole is a broad-spectrum antihelmintic and antiprotozoal agent of the benzimidazole type that is FDA-approved for the treatment of a variety of parasitic worm infections ⁷¹, ⁷². Albendazole is thought not to directly kill Loa loa microfilariae but rather to suppress embryogenesis and release of microfilariae. This leads to a relatively slow and gradual but also safe reduction of microfilaremia over a period of about 3 weeks ⁴³. It has been postulated that longer treatment courses of albendazole alone or in combination with ivermectin also exert adulticidal activity, although further evidence is needed ⁷³. Due to these pharmacodynamic features, albendazole therapy is advocated for the safe and gradual reduction of microfilaremia before administration of diethylcarbamazine (DEC) for curative therapy.

Albendazole and blood filtering lower the number of microfilariae in your blood or reduce the parasitic load before introducing a curative treatment such as ivermectin or diethylcarbamazine (DEC). Then, ivermectin or diethylcarbamazine (DEC) may be safe for you to take.

The main limitation of albendazole-based regimens is the necessity for prolonged treatment courses leading to problems in treatment adherence, the requirement for biological follow-up to rule out liver toxicity, and possible intolerance due to allergic reactions ⁷⁴. Development of encephalitis on initiation of albendazole therapy has been reported occasionally but is considered rare ⁷⁵, ⁷⁶. Albendazole may induce worm migration from the blood to other compartments such as the central nervous system (brain and spinal cord). The encephalopathy may result from the death of the microfilaria in the central nervous system (brain and spinal cord) and the ensuing inflammation ⁷⁰. The rapid release of antigens can also lead to severe immune-mediated reactions ⁷⁶.

Diethylcarbamazine (DEC) is the gold standard for curative treatment of loiasis and is the oldest of the commonly used antifilarial drugs and the only drug that has specifically been developed to treat filarial infections. The mode of action of diethylcarbamazine (DEC) is incompletely understood but its action is thought to be mediated indirectly by rendering the filarial pathogens susceptible to the host’s immune system ⁷⁷. Diethylcarbamazine (DEC) induces a paralysis and rapid destruction of microfilariae in the liver and a fast clearance of microfilariae from peripheral blood ⁷⁸, ⁷⁹. Diethylcarbamazine (DEC) also exerts substantial adulticidal activity against Loa loa, leading to complete cure in around 40% to 80% of patients per 3-week treatment cycle ⁸⁰, ⁸¹. Due to diethylcarbamazine (DEC) rapid onset of action, a large proportion of patients with high microfilarial loads have moderate to severe adverse drug reactions, particularly at the onset of treatment. Severe and life-threatening reactions, including encephalopathy, are often associated with retinal hemorrhages and have been ascribed to embolisms of microfilariae rapidly killed by diethylcarbamazine (DEC) ⁸², ⁸³, ⁸⁴, ⁸⁵. Other complications, such as kidney insufficiency, pleural effusion, or laryngeal edema have been reported ⁸², ⁸⁶.

Diethylcarbamazine (DEC) is also contraindicated in patients with co-infection with Onchocerca volvulus due to the risk for highly inflammatory skin and eye reactions leading to non-reversible complications ⁸⁷, ⁸⁸, ⁸⁹. Therefore, diethylcarbamazine (DEC) should be used with great caution and experts recommend its use only in individuals with microfilaremia below 2000 microfilariae per mL (<2000 microfilariae/mL). Slow titration of diethylcarbamazine (DEC) doses over the first days of treatment and concomitant use of corticosteroids and antihistamines are advocated to dampen a potential over-reactive immunological response ⁸⁴, ⁹⁰. Often, more than one cycle of diethylcarbamazine (DEC) therapy is necessary for complete cure. Due to the potential safety issues associated with diethylcarbamazine treatment, it is most commonly used in non-endemic settings and is rarely employed in endemic regions for the treatment of loiasis.

Single-dose ivermectin therapy at 150–200 mcg/kg has a profound and rapid microfilaricidal effect, leading to an approximately 80% reduction of Loa loa microfilaremia. Ivermectin acts on the glutamate-gated chlorine channels of filarial pathogens but might also inhibit the worm’s immunomodulatory activity ⁹¹. Ivermectin leads to sustained suppression of microfilaremia, which is exerted over a period that by far exceeds the interval of pharmacokinetically relevant drug concentrations ⁹², ⁹³, ⁹⁴. This long-term sterilizing effect would be uniquely well suited for use in mass drug administration (MDA) programmes as a single-dose treatment regimen targeting the infectious stages of Loa loa. However, ivermectin used in mass drug administration (MDA) programmes to control onchocerciasis has been shown to be associated with treatment-emergent encephalopathy, a risk that is closely linked to the peripheral microfilarial load of Loa loa ⁹⁵, ⁹⁶, ⁹⁷, ⁹⁸, ⁹⁹. Conjunctival hemorrhages, delirium, and movement disorders are typical clinical signs for ivermectin-associated encephalopathy, which, in the absence of an established specific therapy, might result in death or long-term complications. Similar to the assumed pathophysiology of encephalopathy, kidney changes linked to capillary embolisms of decaying microfilariae were reported after ivermectin treatment of loiasis ¹⁰⁰. On the basis of ivermectin’s stage-specific action, preferentially targeting microfilariae while not being active against the adult developmental stages, it might be hypothesized that ivermectin exerts no direct effect on the signs and symptoms of loiasis caused by the migrating adult worms. However, it remains unclear whether ivermectin truly lacks any adulticidal activity and limited evidence suggests some benefit on subjective signs and symptoms ¹⁰¹.

On the basis of the current understanding of ivermectin’s safety in the treatment of loiasis, most experts would discourage its use in patients with microfilaraemia above 8000 microfilariae per mL (8000 microfilariae/mL) without previous medical or mechanical reduction of microfilaremia below this threshold. Given its unclear usefulness in alleviating clinical signs and symptoms caused by adult stages of Loa loa, ivermectin’s indication for individual treatment approaches is limited. Ivermectin might be of therapeutic value as a sequential drug following albendazole therapy, as this combination was highly efficacious in patients treated in a non-endemic region ¹⁰², ⁷³. However, this high cure rate was not confirmed when ivermectin was used in a region of high transmission and therefore requires further evidence ¹⁰³.

Table 2. Loiasis medications

Antiparasitic medications	Dosage and instruction
Occult loiasis
Diethylcarbamazine (first-line treatment)	9 mg/kg in three divided doses daily for 21 days; more than one treatment cycle of 21 days might be necessary as cure rate is between 40% and 80% per cycle; contraindication in patients co-infected with onchocerciasis
Albendazole (alternative treatment option)	400 mg* twice daily for 4-week treatment cycle; cure rate is unclear
Albendazole–ivermectin (alternative treatment option)	Albendazole (as described above) followed sequentially by single-dose 150–200 μg (microgram)/kg ivermectin; conflicting reports on overall cure rate
Microfilaremia, 1 to 2000 microfilariae per mL
Diethylcarbamazine (first-line treatment)	Slow titration starting with 50 mg single dose on day 1, 50 mg three times on day 2, 100 mg three times on day 3, and subsequent 9 mg/kg divided in three daily doses until day 21; each 21-day treatment cycle leads to a 40–80% cure rate; more than one cycle might be needed; contraindication in patients co-infected with onchocerciasis
Albendazole (alternative treatment option)	400 mg* twice daily for 4-week treatment cycle leads to relatively safe reduction of microfilaraemia; cure rate is unclear
Albendazole–ivermectin† (alternative treatment option)	Albendazole (as described above) followed sequentially by single-dose 150–200 μg/kg ivermectin leads to relatively safe reduction of microfilaraemia; conflicting reports on overall cure rate
Microfilaremia, 2000 to 8000 microfilariae per mL
Albendazole (first-line treatment)	400 mg* twice daily for 4-week treatment cycle as stand-alone treatment or as preparatory treatment to lower microfilaria load to less than 2000 microfilariae per mL for sequential treatment with diethylcarbamazine (see above)
Ivermectin (first-line treatment)	150–200 μg (microgram)/kg single dose as preparatory treatment to lower microfilaria load to less than 2000 microfilariae per mL for sequential treatment with diethylcarbamazine (see above)
Albendazole–ivermectin† (alternative treatment option)	Albendazole (as described above) followed sequentially by single dose 150–200 μg (microgram)/kg ivermectin as stand-alone treatment or as preparatory treatment to lower microfilaria load to less than 2000 microfilariae per mL for sequential treatment with diethylcarbamazine (see above)
Microfilaremia, 8,000 to 30,000 microfilariae per mL
Albendazole (first-line treatment)	400 mg* twice daily for 4-week treatment cycle as stand-alone treatment or as preparatory treatment to lower microfilaria load to less than 8000 microfilariae per mL for sequential treatment with ivermectin† as stand-alone treatment or as preparatory treatment to lower microfilaria to less than 2000 microfilariae per mL for sequential treatment with diethylcarbamazine (see above)
Microfilaremia, more than 30,000 microfilariae per mL
Apheresis (first-line treatment)	Mechanical reduction of microfilaria load by several cycles of apheresis safely reduces microfilaria load before treatments as indicated above
Albendazole (alternative treatment option)	Rare reports on encephalopathy associated with albendazole therapy indicates that this treatment approach is not without risk; gradual reduction of microfilariae is the treatment objective before treatment as indicated above for loiasis with microfilaria less than 30,000 microfilariae per mL
Adjunct treatments	Antihistamines and corticosteroids might be used for the first few days of treatment to reduce the severity of adverse drug reactions; however, adjunct treatments have no influence on the occurrence or severity of potentially life-threatening serious adverse events including encephalopathy

Footnotes: Proposed treatment algorithm for individual case management of occult and microfilaraemic loiasis.

* 200 mg administered twice daily has also been shown to exert a substantial effect on microfilarial load. Given albendazole’s overall limited bioavailability with important interindividual and intraindividual variability and the good safety profile of albendazole at a daily dose of 800 mg, a dose regimen of 400 mg twice daily is suggested in this proposed treatment algorithm.

† Ivermectin is administered after 28 days of albendazole therapy and confirmation of microfilaraemia below 8000 microfilariae per mL.

[Source ¹⁷ ]

Apheresis and host-directed therapies

Apheresis is a medical procedure that involves separating one or more components from a patient’s blood and returning the remaining blood to the body. A non-drug intervention successfully used for patients with hypermicrofilaraemic loiasis is apheresis. Here, mechanical reduction of microfilaraemia in several cycles safely reduces microfilarial loads and thus prepares the patient for safe follow-on treatment with antifilarial drugs for complete cure ¹⁰⁴, ¹⁰⁵, ¹⁰⁶, ¹⁰⁷, ¹⁰⁸, ¹⁰⁹.

Another therapeutic approach for excessive hypermicrofilaraemia is the use of host-directed therapies. These include corticosteroid therapy to dampen potential hyper-reaction of the immune system on the release of decaying microfilariae as well as novel therapeutic approaches using monoclonal antibodies targeting the eosinophilic immune reaction ⁹⁰, ¹¹⁰, ¹¹¹, ¹¹², ¹¹³. Although the use of corticosteroids is included in several treatment recommendations, there is no clear evidence for its usefulness to avoid serious adverse drug reactions. This knowledge gap and the evaluation of host-directed therapies remain research priorities.

Surgery

The mechanical extraction of adult worms is technically relatively straightforward when the migration path becomes visible in the subconjunctival tissue, as well as during its infrequent and transient intradermal passage ¹¹⁴. Although the physical extraction of an adult worm constitutes a causative treatment approach, it might arguably only be of value in individuals with infection with a single or few worms, which is almost exclusively the case in temporary travellers after return from transmission regions. This procedure is of only limited therapeutic value for permanent residents in transmission zones due to the multiplicity of infections and high risk for re-infection ¹⁷.

Subconjunctival filariasis

Procedure: Given that a worm in the subconjunctival space may quickly migrate out of sight, the worm should first be grasped externally with forceps to prevent migration. Subsequent subconjunctival injection of 2% lidocaine with epinephrine 1:100,000 can then be used to simultaneously numb the region and paralyze the worm. A peritomy generally ≤ 5 mm allows access to the paralyzed worm, which can then be removed with a second set of forceps ²⁴.

Postoperative Care: Systemic diethylcarbamazine or albendazole with topical steroids and antibiotics

Intraocular filariasis

Intraocular filariasis due to Loa loa is an uncommon occurrence, which presents with pain and foreign body sensation ²⁶. Unlike subconjunctival filariasis, intraocular filariasis is associated with significant risk of visual acuity loss and blindness.

Anterior chamber filariasis

Procedure: Intracameral filarial worms may be removed with an anterior chamber washout, followed by a subconjuctival injection of steroids and antibiotics ³⁰. In patients with more prolonged disease and more intense intraocular inflammation, excision of intracameral fibrinous membranes may be indicated ²⁹.

Postoperative Care: Case reports suggest that patients often require high doses and prolonged courses of topical steroids, as well as topical antibiotics and sometimes mydriatics.

Vitreous chamber filariasis

One case report of Loa loa in the vitreous was effectively treated with vitrectomy with steroid cover ¹¹⁵.

Loiasis prognosis

Many people who have loiasis don’t know they have it (asymptomatic), and may not have serious health problems from it. If you have symptoms or suspect you have loiasis, see an experienced tropical medicine specialist. Medications can treat the infection and prevent possible complications.

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