Loa Loa
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''Loa loa'' is a filarial (
arthropod Arthropods ( ) are invertebrates in the phylum Arthropoda. They possess an arthropod exoskeleton, exoskeleton with a cuticle made of chitin, often Mineralization (biology), mineralised with calcium carbonate, a body with differentiated (Metam ...
-borne)
nematode The nematodes ( or ; ; ), roundworms or eelworms constitute the phylum Nematoda. Species in the phylum inhabit a broad range of environments. Most species are free-living, feeding on microorganisms, but many are parasitic. Parasitic worms (h ...
(roundworm) that causes ''Loa loa'' filariasis. ''Loa loa'' actually means "worm worm", but is commonly known as the "eye worm", as it localizes to the
conjunctiva In the anatomy of the eye, the conjunctiva (: conjunctivae) is a thin mucous membrane that lines the inside of the eyelids and covers the sclera (the white of the eye). It is composed of non-keratinized, stratified squamous epithelium with gobl ...
of the eye. ''Loa loa'' is commonly found in Africa.Schmidt, Gerald et al. "Foundations of Parasitology". 7th ed. McGraw Hill, New York, NY, 2005. It mainly inhabits rain forests in West Africa and has native origins in Ethiopia. The disease caused by ''Loa loa'' is called loiasis and is one of the
neglected tropical diseases Neglected tropical diseases (NTDs) are a diverse group of tropical infections that are common in low-income populations in developing regions of Africa, Asia, and the Americas. They are caused by a variety of pathogens, such as viruses, bacteri ...
. ''L. loa'' is one of three parasitic filarial nematodes that cause subcutaneous
filariasis Filariasis is a filarial infection caused by parasitic nematodes (roundworms) spread by different vectors. They are included in the list of neglected tropical diseases. The most common type is lymphatic filariasis caused by three species o ...
in humans. The other two are '' Mansonella streptocerca and Onchocerca volvulus'' (causes
river blindness Onchocerciasis, also known as river blindness, is a disease caused by infection with the parasitic worm ''Onchocerca volvulus''. Symptoms include severe itching, bumps under the skin, and blindness. It is the second-most common cause of blindne ...
). Maturing
larva A larva (; : larvae ) is a distinct juvenile form many animals undergo before metamorphosis into their next life stage. Animals with indirect development such as insects, some arachnids, amphibians, or cnidarians typically have a larval phase ...
e and adults of the "eye worm" occupy the subcutaneous layer of the skin – the fat layer – of humans, causing disease. The ''L. loa'' adult worm which travels under the skin can survive up to 10–15 years, causing inflammations known as Calabar swellings. The adult worm travels under the skin, where the female deposits the
microfilaria The microfilaria (plural microfilariae, sometimes abbreviated mf) is an early stage in the life cycle of certain parasitic nematodes in the family Onchocercidae. In these species, the adults live in a tissue or the circulatory system of vertebr ...
e which can develop in the host’s blood within 5 to 6 months and can survive up to 17 years. The young larvae, or microfilariae, develop in horseflies of the
genus Genus (; : genera ) is a taxonomic rank above species and below family (taxonomy), family as used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In bino ...
'' Chrysops'' (deer flies, yellow flies), including the species '' C. dimidiata'' and '' C. silacea'', which infect humans by biting them. After bites from these infected flies, the microfilariae are unique in that they travel in the peripheral blood during the day and migrate into the lungs at night.Turkington, C., & Ashby, B. (2007). Encyclopedia of Infectious Diseases. New York: Facts on File.


Morphology

''L. loa'' worms have a simple structure consisting of a head (which lacks lips), a body, and a blunt tail. The outer body of the worm is composed of a cuticle with three main layers made up of collagen and other compounds which aid in protecting the nematodes while they are inside the digestive system of their host. Juveniles have a similar appearance to adult worms, but are significantly smaller. Male adults range from 20 to 34 mm long and 350 to 430 μm wide. Female adults range from 20 to 70 mm long and can be about 425 μm wide. They vary in color.


Lifecycle

The human is the
definitive host In biology and medicine, a host is a larger organism that harbours a smaller organism; whether a parasitic, a mutualistic, or a commensalist ''guest'' (symbiont). The guest is typically provided with nourishment and shelter. Examples include ...
, in which the parasitic worms attain sexual maturity, mate, and produce microfilariae. The flies serve as intermediate hosts in which the microfilariae undergo part of their morphological development, and then are borne to the next definitive host. Two species of ''Chrysops'' deerflies, ''C. silacea'' and ''C. dimidiata'', are the main vectors for this filariasis. # A fly bearing third-stage filarial larvae in its proboscis infects the human host through the bite wound. # After entering the human host, the larvae mature into adults, commonly in subcutaneous tissue. Adult females measure about 40 to 70 mm in length and 0.5 mm in diameter. Males measure some 30 to 34 mm by 0.35 to 0.43 mm. # The adult female produces large numbers of microfilariae, about 250 to 300 μm in length and 6-8 μm in width. She continues to do so continuously for her lifetime, which typically spans several years. # Microfilariae tend to reside within spinal fluids, urine, and sputum; by day, they also circulate in the bloodstream. Apart from their presence in bodily fluids, however, microfilariae in the noncirculating phase also occur in the lungs. # The vector fly ingests microfilariae while feeding on the host's blood. # Once inside the vector, the microfilaria sheds its sheaths and escapes through the walls of the midgut into the fly’s haemocoel. # It then migrates through the hemolymph into the wing muscles in the fly's thorax. # In the thoracic muscles, the microfilaria develops successively into a first-stage larva, second-stage larva, and finally into the infectious third-stage larva. # The third-stage larva migrates to the fly’s proboscis. # Once the larva is established in the proboscis and the fly takes its next human blood meal, the cycle of infection continues.


Disease


Signs and symptoms

Usually, about five months are needed for larvae (transferred from a fly) to mature into adult worms, which they can only do inside the human body. The most common display of infection is the localized allergic inflammations called
Calabar Calabar (also referred to as Callabar, Calabari, Calbari, Cali and Kalabar) is the capital city of Cross River State, Nigeria. It was originally named Akwa Akpa, in the Efik language, as the Efik people dominate this area. The city is adjac ...
or Cameroon swellings that signify the migration of the adult worm in the tissues away from the injection site by the vector. The migration does not cause significant damage to the host and is referred to as benign. However, these swellings can be painful, as they are mostly found near the joints. Although most infections with ''L. loa'' are asymptomatic, symptoms generally do not appear until years, or even more than a decade, after the bite from an infected fly. However, symptoms can appear as early as four months after a bite. These parasites have a diurnal periodicity in which they circulate in the peripheral blood during the daytime, but migrate to vascular parts of the lungs during the night, where they are considered non circulatory. Therefore, the appearing and disappearing characteristics of this parasite can cause recurrent swelling that can cause painful enlargements of
cyst A cyst is a closed sac, having a distinct envelope and division compared with the nearby tissue. Hence, it is a cluster of cells that have grouped together to form a sac (like the manner in which water molecules group together to form a bubb ...
s in the connective tissue surrounding tendons. Additionally, chronic abscesses can be caused by the dying worms. The most visual sign of an adult worm infections is when the worm crosses the sclera of the eye, which causes significant pain to the host and is usually associated with inflammation and less likely, blindness. Eye worms typically cause little eye damage and last a few hours to a week. Other tissues in which this worm can be found includes: the penis, testes, nipples, bridge of the nose, kidneys, and heart. The worms in these locations are not always externally visible.


Risk factors

People at the highest risk for acquiring
loiasis ''Loa loa'' filariasis, (Loiasis) is a skin and eye disease caused by the nematode worm ''Loa loa''. Humans contract this disease through the bite of a deer fly (''Chrysops'' spp.) or mango fly, the Vector (epidemiology), vectors for ''Loa loa' ...
are those who live in the rainforests of West or Central Africa. Furthermore, the probability of getting bitten by a deerfly increases during the day and during rainy seasons. The flies are also attracted to smoke from wood fires. These flies do not commonly enter houses, but they are attracted to the houses that are well lit, so will congregate outside. Travelers can be infected in less than 30 days after arriving in an affected area, although they are more likely to be infected whilst being bitten by multiple deerflies over the course of many months. Men are more susceptible than women due to their increased exposure to the vectors during activities such as farming, hunting, and fishing.Zierhut, M., Pavesio, C., Ohno, S., Oréfice, F., Rao, N. A. (2014). Intraocular Inflammation. Springer Dordrecht Heidelberg London New York.


Diagnosis

The main methods of diagnosis include the presence of microfilariae in the blood, the presence of a worm in the eye, and the presence of skin swellings. However, in cases where none of those is the case, a blood count can be done. Patients with infections have a higher number of blood cells, namely eosinophils, as well as high IgE levels that indicate an active infection with helminth parasites. Due to the migration of microfilariae during the day, the accuracy of a blood test can be increased when samples are taken between 10 am and 2 pm. A Giemsa stain is the most commonly used diagnostic test that uses a thick blood smear to count the microfilariae. Other than blood, microfilariae can also be observed in urine and saliva samples.


Treatment

Adult worms found in the eye can be surgically removed with forceps after being paralyzed with a topical anesthesia. The worm is not paralyzed completely, so if it is not extracted quickly, it can vanish upon attempting extraction.
Ivermectin Ivermectin is an antiparasitic drug. After its discovery in 1975, its first uses were in veterinary medicine to prevent and treat heartworm and acariasis. Approved for human use in 1987, it is used to treat infestations including head lice ...
has become the most common antiparasitic agent used worldwide, but can lead to residual microfilarial load when given in the management of loiasis. Treatment with ivermectin has shown to produce severe adverse neurological consequences in some cases. These treatment complications can be increased in individuals co-infected with
onchocerciasis Onchocerciasis, also known as river blindness, is a disease caused by infection with the parasitic worm ''Onchocerca volvulus''. Symptoms include severe itching, bumps under the skin, and blindness. It is the second-most common cause of blindne ...
. Some of these patients experienced cases of coma and resultant
encephalopathy Encephalopathy (; ) means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of overall brain dysfunction; this syndrome ...
, parkinsonism, and death. After about 12 hours, the first signs start to appear and include fatigue, pain in joints,
mutism In human development, muteness or mutism is defined as an absence of speech, with or without an ability to hear the speech of others. Mutism is typically understood as a person's inability to speak, and commonly observed by their family members, c ...
, and incontinence. Severe disorders of the consciousness start to develop after about a day. Although Ivermectin is a common treatment for loiasis, the
Centers for Disease Control The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency under the Department of Health and Human Services (HHS), and is headquartered in Atlanta, ...
(CDC) recommends treatment with diethylcarbamazine (DEC). Symptoms may be resolved with as little as 1–2 courses of DEC. DEC is chosen over Ivermectin because evidence supports its ability to kill both the adult worms and the microfilariae, which are the main cause of the severe neurological problems mentioned above. In some cases, albendazole may also be an effective treatment used to reduce the microfilariae prior to treatment with DEC. The body's response to albendazole is slow, so the patient being treated must be monitored closely and frequently to ensure it is effective.


Prevention

Currently, no control programs or vaccines for loiasis are available. However, diethylcarbamazine treatment is suggested to the reduce risk of infection. Avoiding areas where the vectors, deerflies, are found also reduces risk. This includes swamps, bogs, and shaded areas near rivers or near wood fires. Fly bites can be reduced by using insect repellents such as
DEET ''N'',''N''-Diethyl-''meta''-toluamide, also called diethyltoluamide or DEET (, from DET, the initials of di- + ethyl + toluamide), is the oldest, one of the most effective, and most common active ingredients in commercial insect repellents. ...
and wearing long sleeves and pants during the daytime.
Permethrin Permethrin is a medication and an insecticide. As a medication, it is used to treat scabies and lice. It is applied to the skin as a cream or lotion. As an insecticide, it can be sprayed onto outer clothing or mosquito nets to kill the insects ...
treatment on clothes is an additional repellent that could be used. Also, using malaria nets can reduce the number of fly bites acquired.


Epidemiology

Reports of microfilaremia have been made in Angola, Benin, Cameroon, Central African Republic, Congo, the Democratic Republic of Congo, Equatorial Guinea, Gabon, Nigeria, and Sudan, and possibly rare cases in Chad, Ghana, Guinea, Liberia, Uganda, and Zambia. Of the 10 countries that have high rates of infection, about 40% of the people who live in the area have reported being infected with the worm in the past. The population in high-risk areas is about 14.4 million; in addition, 15.2 million people live in areas where around 20–40% of people admitted to having the worm in the past.Centers for Disease Control and Prevention (CDC). (2015 January 20). Parasites – Loiasis. Global Health – Division of Parasitic Diseases. Retrieved from: https://www.cdc.gov/parasites/loiasis/ Epidemiological studies have been emphasized in the western part of Africa. In this area, the disease is considered endemic. A study conducted by the Research Foundation in Tropical Diseases and Environment in 2002 had a sample of 1458 persons, spanning 16 different villages, and found'' Loa loa'' presence in these villages ranging from 2.22 to 19.23% of the population. The disease was found to be slightly more prevalent in men. In a different country in western Africa, a cross-sectional community survey was conducted in Gabon, Africa. The study was performed by the department of Tsamba-Magotsi from August 2008 to February 2009. The study of 1,180 subjects evaluated the presence of microfilaria using microscopy. The carriage rate of ''L. loa'' in the subjects tested was 5%. This rate falls within the range of the study listed above. In the western part of Africa, an increase in prevalence has been associated with the distribution of ivermectin, which is used to prevent the infection of onchocerciasis, which is also very prevalent in the same region. Patients with ''L. loa'' who are treated with ivermectin have extreme adverse effects, including death. Therefore, a prevalence mapping system was created called REMO. REMO is used to determine which areas to distribute the ivermectin based on lower levels of ''L. loa'' prevalence. The area discovered to be the most overlapping was where Cameroon and the Democratic Republic of Congo overlap. A study performed to review reported cases of ''L. loa'' in nonendemic countries in the past 25 years reviewed 102 cases of imported loiasis, 61 of them from Europe and 31 from the US. Three-quarters of the infestations were acquired in three countries considered endemic: Cameroon, Nigeria, and Gabon. In the subjects viewed, peripheral blood microfilariae were detected 61.4% of the time, eye worm migration 53.5% of the time, and Calabar swellings 41.6% of the time. A trend appeared in the symptoms of the patients where Calabar swellings and eosinophilia were more common among travelers. African immigrants tended to have microfilaremia. Eye worm migration was observed in a similar proportion between the two groups. Only 35 of the patients underwent clinical follow-up. The researchers concluded that ''L. loa'' would end up migrating to Europe and the United States, due to increased travel to already endemic regions.


See also

* List of short species names


References


Taxonomy Browser: Loa Loa.
National Center for Biotechnology Information (NCBI). {{DEFAULTSORT:Loa Loa Parasitic diseases Parasitic nematodes of humans Nematodes described in 1864 Spirurida Taxa named by Thomas Spencer Cobbold