Background
Loiasis, commonly known as "African eye worm," is an infectious disease caused by the nematode Loa loa, which is transmitted to humans via the bite from one of two female Chrysops deerfly species: Chrysops silacea and Chrysops dimidiata. The risk of infection is highest in the rainforests of West and Central Africa and during the rainy season, when the deerfly (or mango fly or mangrove fly, as they are commonly known) are most prevalent. It is estimated that 3-13 million people have loiasis. [1] It is estimated that more than 10 million people have loiasis, with over 14 million people at risk for infection. [2]
The worm larvae that Chrysops flies deposit in human hosts mature into adults, which commonly reside in subcutaneous tissue. Most L loa infections are asymptomatic, although some progress to loiasis, which is characterized by localized painful subcutaneous joints (calabar swellings) and the migration of adult worms through the subconjuctiva of the eye.
Loiasis is commonly known as "African eye worm," since the adult form of the parasite can sometimes be found migrating across the conjunctiva of the eye. Repeated forest exposure involving repeated bites from infected flies increases the risk of infection and disease. [3]
L loa is endemic in eleven West and Central African countries, as follows (listed alphabetically):
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Angola
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Cameroon
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Central African Republic
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Chad
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Congo
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Democratic Republic of Congo
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Equatorial Guinea
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Ethiopia
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Gabon
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Nigeria
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Sudan
Ten of these countries have foci where the prevalence of infection exceeds 40%, a strong indicator of high-risk communities. [4] An estimated 14.4 million people live in these regions of high prevalence. [5] This range overlaps significantly with that of onchocerciasis and is of great epidemiological significance, since ivermectin, the major and most effective treatment for onchocerciasis, often leads to severe, and sometimes fatal, complications in individuals who are co-infected with L loa. [6]
Pathophysiology
L loa microfilariae mature into their infective third-stage larval forms in their Chrysops hosts, a process that typically takes 10-12 days to complete. These larvae make their way into humans when female flies take blood meals and migrate from the proboscis of an infected fly to the bite wound it creates.
Chrysops bites are typically quite painful, since, unlike mosquitoes, which use their probosces to puncture skin and suck blood out of their hosts, these flies use their probosces to create lacerations in the host’s skin and then lap up the blood from the wound that they create. When interrupted during a blood meal, Chrysops flies have been known to make new lacerations to continue to feed from the same host owing to the female's high blood demand for reproductive purposes. [7] In their human hosts, larvae migrate through the lymphatic system and mature into adults, residing in subcutaneous tissue for approximately 19 days.
Giemsa stained blood showing microfilaria of Loa loa with white blood cells present. Courtesy of Wikimedia Commons [Stefan Walkowski].
Inside the human host, larvae migrate to the subcutaneous tissue, where they mature into adult worms in approximately 1 year, although maturation can take up to 4 years. [7] Adult worms may live up to 17 years in subcutaneous tissue. [8] The migration of adult L loa worms through subcutaneous host tissue provokes the host’s immune response to this migration, causing many of the characteristic symptoms of loiasis, such as urticaria, pruritus, and calabar swelling (painful swelling in the joints). Occasionally, adult worms migrate through the subconjunctiva of the eye and are visible therein, giving rise to the disease's common name, "African eye worm."
Once fertilized, female worms release thousands of microfilariae per day (up to 22,000). These microfilariae accumulate in the pulmonary circulation, which serves as a reservoir from which they invade peripheral blood systems. Only a fraction of the microfilariae in the lungs exit into circulation, a process that may be mediated by their age. About 17 months pass between the introduction of L loa larvae into the host and the appearance of microfilariae in the blood. Microfilariae have lifespans of approximately 6-12 months, and the cycle of infection is continued when Chrysops flies feed on the blood of humans with microfilariae in their blood. [8]
L loa has diurnal periodicity, meaning that levels of microfilariae are higher in the blood during the daytime, typically highest between 10:00 am and 3:00 pm, which coincides with the maximum activity hours of the Chrysops vector. [8] However, microfilariae have also been found in blood samples collected at night. [9]
Etiology
Loiasis is caused by infection with L loa (tissue nematode) parasites transmitted by Chrysops flies (commonly known as the mango fly or mangrove fly). The adult L loa worm can migrate across the subconjunctiva of the human eye, giving rise to the worm's colloquial name, "African eye worm." Beyond this ocular pathology, loiasis also commonly manifests as skin findings (urticaria and pruritus), swelling (calabar swelling), and joint pain due to the immune reaction against the parasite. [10]
Epidemiology
Frequency
United States
Loiasis is not acquired in the United States. Some cases have been reported in travellers and immigrants from endemic areas. Months to years of exposure are typically required to establish infection, although some cases have been reported after as little as four days of exposure.
International
L loa is endemic in eleven West and Central African countries, as follows (listed alphabetically):
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Angola
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Cameroon
-
Central African Republic
-
Chad
-
Congo
-
Democratic Republic of Congo
-
Equatorial Guinea
-
Ethiopia
-
Gabon
-
Nigeria
-
Sudan
Map of the estimated prevalence of eye worm history in Africa. Courtesy of PLoS Neglected Tropical Diseases.
Ten of these countries have foci where the prevalence of infection exceeds 40%. An estimated 14.4 million people live in these regions of high prevalence. [5] In these regions, the vast majority of infections are asymptomatic, so the range and endemicity of loiasis in many regions have not yet been determined.
The range of loiasis overlaps significantly with that of onchocerciasis and is of great epidemiological significance, since ivermectin, the major and most effective treatment for onchocerciasis, often leads to severe, and sometimes fatal, complications when administered to individuals infected with L loa. [6, 11] Furthermore, L loa infection may be misdiagnosed as onchocerciasis based on skin snip, potentially underestimating the prevalence of loiasis in co-endemic areas. [12]
The probability of infection has been found to increase with age and depends on vector abundance, which, in turn, depends on local ecology. Disease and vector infection rates are significantly higher in forested areas, the natural habitats of the Chrysops vectors, than in other ecological settings such as grassland savannas, sunlit riverbanks, forest clearings, and villages. [13]
The Chrysops vectors that carry L loa typically bite during the daytime and are most prevalent during the rainy season. They preferentially take blood meals from humans, although some nonhuman hosts have been identified (rodents and large wild animals such as buffalo and hippopotamuses). [14] They are attracted to signs of human activity, such as movement and smoke from wood fires. [7]
Morbidity/Mortality
Although L loa infections are typically described as benign and the vast majority of cases are asymptomatic, a 2017 retrospective review of 28 Cameroonian villages found heightened mortality rates (4.1%) in individuals with over 30,000 microfilariae per mL of blood, as well as significantly earlier deaths among individuals older than 25 years with over 30,000 microfilariae per mL of blood, compared to amicrofilaremic individuals, suggesting an increased mortality rate associated with high-grade L loa infection. [15]
Beyond these findings, many complications due to L loa infection have been described, albeit in a minority of cases. Worm migration through the subconjunctiva may progress to invasion of the eye itself by adult worms, causing pain, intraocular inflammation, and even blindness. [16]
In addition, encephalitis is known to occur in individuals with L loa infection, often due to administration of diethylcarbamazine (DEC) or ivermectin, drugs used in the treatment of other nematode infections, such as onchocerciasis (river blindness). This encephalitis may lead to events such as coma and may be fatal. [17]
Endomyocardial fibrosis has also been observed in cases of chronic loiasis and may progress to cardiomyopathy and, sometimes, death. [18, 19]
Renal involvement has also been reported in loiasis. Kidney failure due to loiasis-related nephropathy is uncommon but has been documented. [19]
Sex
Loiasis may be more common in males than in females, [11, 20] potentially owing to differences in outdoor exposure and occupations. [7]
Age
The prevalence of loiasis in a population increases with age, [11, 2]
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Giemsa stained blood showing microfilaria of Loa loa with white blood cells present. Courtesy of Wikimedia Commons [Stefan Walkowski].
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A fly of the Chrysops genus. Courtesy of Flickr [Judy Gallagher].
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Map of the estimated prevalence of eye worm history in Africa. Courtesy of PLoS Neglected Tropical Diseases.
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Live adult Loa loa worm in the anterior chamber of the eye. Courtesy of PLoS Neglected Tropical Diseases.
