Loa loa filariasis
Loa loa filariasis or 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 or mango fly, the vectors for Loa loa. The adult Loa loa filarial worm can reach from three to seven centimetres long and migrates throughout the subcutaneous tissues of humans, occasionally crossing into subconjunctival tissues of the eye where it can be easily observed. Loa loa does not normally affect vision but can be painful when moving about the eyeball or across the bridge of the nose. Loiasis can cause red itchy swellings below the skin called "Calabar swellings". The disease is treated with the drug diethylcarbamazine, and when appropriate, surgical methods may be employed to remove adult worms from the conjunctiva. Loiasis belongs to the group of neglected tropical diseases, and there is a call for it to be included in the high-priority listing.
Signs and symptoms
A filariasis such as loiasis most often consists of asymptomatic microfilaremia. Some patients can develop lymphatic dysfunction causing lymphedema. Episodic angioedema in the arms and legs, caused by immune reactions, are common. Calabar swellings are in surface area, sometimes erythematous, and not pitting. When chronic, they can form cyst-like enlargements of the connective tissue around the sheaths of muscle tendons, becoming very painful when moved. The swellings may last for one to three days and may be accompanied by localized urticaria and pruritus. They reappear at referent locations at irregular time intervals. Subconjunctival migration of an adult worm to the eyes can also occur frequently, and this is the reason Loa loa is also called the "African eye worm". The passage over the eyeball can be sensed, but it usually takes less than 15 minutes. Eyeworms affect men and women equally, but advanced age is a risk factor. Eosinophilia is often prominent in filarial infections. Dead worms may cause chronic abscesses, which may lead to the formation of granulomatous reactions and fibrosis.In the human host, Loa loa larvae migrate to the subcutaneous tissue, where they mature into adult worms in approximately one year, but sometimes up to four years. Adult worms migrate in the subcutaneous tissues at a speed of less than 1 cm/min, mating and producing more microfilariae. The adult worms can live up to 17 years in the human host.
Cause
Transmission
Loa loa infective larvae are transmitted to humans by the deer fly vectors of the tabanid genus Chrysops—''C. dimidiata and C. silacea. These carriers are blood-sucking and day-biting, and they are found in rainforest-like environments in western and central Africa. Infective larvae mature to adults in the subcutaneous tissues of the human host, after which the adult worms—assuming the presence of a male and female worm—mate and produce microfilariae. The cycle of infection continues when a non-infected mango or deer fly takes a blood meal from a microfilaremic human host, and this stage of the transmission is possible because of the combination of the diurnal periodicity of microfilariae and the day-biting tendencies of the Chrysops'' spp.Reservoir
Humans are the primary reservoir for Loa loa. Other minor potential reservoirs have been indicated in various fly-biting habit studies, such as hippopotamuses, wild ruminants, rodents, and lizards. A simian type of loiasis exists in monkeys and apes which is transmitted by the deer fly vector Chrysops langi. There is no crossover between the human and simian types of the disease.Vector
Loa loa is transmitted by several species of tabanid flies. The two most prominent vectors are from the tabanid genus Chrysops—''C. dimidiata and C. silacea. These species exist only in Africa and are popularly known as deer flies, mangrove flies or mango flies. Chrysops langi is also a competent vector species.Chrysops spp. are small with a large head and downward-pointing mouthparts. Their wings are clear or speckled brown. They are hematophagous and typically live in forested and muddy habitats like swamps, streams, reservoirs, and rotting vegetation. Female mango and deer flies require a blood meal for the production of a second batch of eggs. This batch is deposited near water, where the eggs hatch in 5–7 days. The larvae mature in water or soil, where they feed on organic material such as decaying animal and vegetable products. Fly larvae are long and take 1–3 years to mature from egg to adult. When fully mature, C. dimidiata and C. silacea assume the day-biting tendencies of all tabanids.
The bite of the mango fly can be very painful, possibly because of the laceration style employed; rather than puncturing the skin as a mosquito does, the mango fly makes a laceration in the skin and subsequently laps up the blood. Female flies require a fair amount of blood for their aforementioned reproductive purposes and thus may take multiple blood meals from the same host if disturbed during the first one.
Although Chrysops dimidiata and C. silacea are attracted to canopied rainforests, they do not do their bite there. Instead, they leave the forest and take most blood meals in open areas. The flies are attracted to smoke from wood fires and they use visual cues and sensation of carbon dioxide plumes to find their preferred host, humans.
A study of Chrysops spp. biting habits showed that C. dimidiata and C. silacea'' take human blood meals approximately 90% of the time, with hippopotamus, wild ruminant, rodent, and lizard blood meals making up the other 10%.
Morphology
Adult Loa worms are sexually dimorphic, with males considerably smaller than females at 30–34 mm long and 0.35–0.42 mm wide compared to 40–70 mm long and 0.5 mm wide. Adults live in the subcutaneous tissues of humans, where they mate and produce wormlike eggs called microfilariae. These microfilariae are 250–300 μm long, 6–8 μm wide, and can be distinguished morphologically from other filariae, as they are sheathed and contain body nuclei that extend to the tip of the tail.Lifecycle
During a blood meal, an infected Chrysops fly introduces third-stage filarial larvae onto the skin of the human host, where they penetrate the bite wound. The larvae develop into adults that commonly reside in subcutaneous tissue. The female 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. Adults 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. The fly ingests microfilariae during a blood meal. After ingestion, the microfilariae lose their sheaths and migrate from the fly's midgut through the hemocoel to the thoracic muscles of the arthropod. There the microfilariae develop into first-stage larvae and subsequently into third-stage infective larvae. The third-stage infective larvae migrate to the fly's proboscis and can infect another human when the fly takes a blood meal.Diagnosis
examination of microfilariae is a practical diagnostic procedure to find Loa loa. It is important to time the blood collection with the known periodicity of the microfilariae. The blood sample can be a thick smear, stained with Giemsa or haematoxylin and eosin. For increased sensitivity, concentration techniques can be used. These include centrifugation of the blood sample lyzed in 2% formalin, or filtration through a nucleopore membrane.Antigen detection using an immunoassay for circulating filarial antigens constitutes a useful diagnostic approach because microfilaremia can be low and variable. Though the Institute for Tropical Medicine reports that no serologic diagnostics are available, tests that are highly specific to Loa loa have been developed in recent years. This is even though many recently developed methods of antibody detection are of limited value because substantial antigenic cross-reactivity exists between filaria and other parasitic worms, and a positive serologic test does not necessarily distinguish among infections. The new tests have not reached the point-of-care level yet, but show promise for highlighting high-risk areas and individuals with co-endemic loiasis and onchocerciasis. Specifically, Thomas Nutman and colleagues at the National Institutes of Health have described the a luciferase immunoprecipitation assay and the related QLIPS. Whereas a previously described LISXP-1 ELISA test had poor sensitivity, the QLIPS test is practical, as it requires only a 15-minute incubation, while delivering high sensitivity and specificity. No report on the distribution status of LIPS or QLIPS testing is available, but these tests would help to limit complications derived from mass ivermectin treatment for onchocerciasis or dangerous strong doses of diethylcarbamazine for loiasis alone.
Calabar swellings are the primary tool for visual diagnosis. Identification of adult worms is possible from tissue samples collected during subcutaneous biopsies. Adult worms migrating across the eye are another potential diagnostic, but the short timeframe for the worm's passage through the conjunctiva makes this observation less common.
In the past, healthcare providers used a provocative injection of Dirofilaria immitis as a skin-test antigen for filariasis diagnosis. If the patient was infected, the extract would cause an artificial allergic reaction and associated Calabar swelling similar to that caused, in theory, by metabolic products of the worm or dead worms.
Blood tests to reveal microfilaremia are useful in many, but not all cases, as one-third of loiasis patients are amicrofilaremic. By contrast, eosinophilia is almost guaranteed in cases of loiasis, and blood testing for eosinophil fraction may be useful.