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Cutaneous filariasis 

Cutaneous filariasis
Chapter:
Cutaneous filariasis
Author(s):

Gilbert Burnham

DOI:
10.1093/med/9780199204854.003.070901_update_001

Update:

Treatment/prevention—impact of mass distribution of ivermectin.

Updated on 31 May 2012. The previous version of this content can be found here.
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Essentials

Filarial infections are transmitted by simulium flies, some of which bite humans almost exclusively, whereas others are to varying degrees zoophilic. They are found worldwide in humans and animals, the filariae which cause cutaneous infections being Onchocerca volvulus, Loa loa, and the mansonellas.

Onchocerciasis

Onchocerciasis (river blindness), caused by O. volvulus, infects perhaps 20 million people, mostly in Africa.

Clinical features—larvae introduced into the body when the vector takes a blood meal develop into male or female adult worms within palpable nodules, commonly located over bony prominences. Other important manifestations are: (1) Eye damage—microfilariae enter the cornea from the skin and conjunctiva; manifestations include sclerosing keratitis, iridocyclitis and (sometimes) choroidoretinal lesions; without treatment permanent visual impairment or blindness are common. (2) Skin disease—ranging from itching with a localized maculopapular rash, to intensely itching with a chronic generalised papular rash or lichenified hyperkeratotic lesions.

Diagnosis, treatment, and prevention—diagnosis is usually made by finding microfilariae in skin snips. Treatment is with ivermectin, often given as a single annual dose, which has dramatically reduced the eye and skin lesions that ravaged many communities in Africa and Latin America. Methods of prevention include adding insecticides to rivers to interrupt simulium breeding and mass distribution of ivermectin.

Loa loa

This filaria, for which humans are the only host, is transmitted by the chrysops fly in West and Central Africa. Clinical manifestations include transient localized inflammatory oedema (Calabar swellings), the appearance of a migrating worm under the skin or (most dramatically) crossing the eye, and (rarely) meningoencephalitis. Diagnosis is based on typical clinical findings, or traditionally by finding microfilariae in a daytime blood sample. Treatment is usually with diethylcarbamazine, although both ivermectin and albendazole are effective. All treatments risk serious adverse reactions in the heavily affected. The best prevention is avoiding chrysops fly bites.

Mansonellas

This group of filarial infections is transmitted by culicoides midges and is common to many countries, but of negligible clinical importance under most circumstances. Only Mansonella streptocerca produces clear-cut manifestations, most typically chronic papular skin lesions. Diagnosis is by finding characteristic microfilariae in the blood or skin. People who are asymptomatic do not require treatment, but M. streptocerca responds well to ivermectin.

Onchocerciasis

Onchocerciasis, or river blindness, occurs in 34 countries in Africa, Latin America, and the Arabian Peninsula (Fig. 7.9.1.1). Perhaps 18 million people are infected, and 125 million at risk of infection. The vast majority of these are in Africa. In 1995 it was estimated that infection with Onchocerca volvulus had caused blindness in 270 000 people, and left another 500 000 with severe visual impairment. Mass treatment with ivermectin has now greatly lessened the ocular burden of infection. Besides eye changes, onchocerciasis has chronic systemic effects, causing extensive and disfiguring skin changes, musculoskeletal complaints, weight loss, changes to the immune system, and perhaps also epilepsy and growth arrest. Skin lesions are the most common manifestation of onchocerciasis. Changes include acute and chronic itchy papular disease, and intensely pruritic lichenification. Lesions may be localized or widespread. In the later stages severe degenerative skin disease develops, with a loss of elastic tissue, and extensive pigmentary changes.

Fig. 7.9.1.1 Distribution of onchocerciasis in Africa, the Middle East, and Latin America.

Fig. 7.9.1.1
Distribution of onchocerciasis in Africa, the Middle East, and Latin America.

The disease, endemic to some of the world’s poorest areas, has a great impact on the economic and social fabric of communities. A complex human–parasite tolerance allows people who host millions of parasites to continue daily existence. Mass treatment with ivermectin has controlled the public health consequences of this disease in many heavily infected areas.

Epidemiology

The microfilariae of O. volvulus were first observed by O’Neill in Ghana in 1875 in an intensely pruritic chronic skin condition called ‘craw-craw’. Leuckart described the adult worm 20 years later, and in 1923 Blacklock in Sierra Leone showed the blackfly Simulium damnosum to be the vector. Hissette in the Congo and Robles in Guatemala linked blindness with onchocerciasis. Long before, Ghanaians along the Red Volta river had associated the biting flies with skin lesions and blindness.

The Onchocerciasis Control Programme controlled vector breeding in West Africa’s Volta basin between 1974 and 2002, and is thought to have prevented 600 000 cases of blindness. Today, the largest numbers of infected people live in Nigeria, Cameroon, Chad, Ethiopia, Uganda, Angola, and the Democratic Republic of the Congo. In the Americas, onchocerciasis was most common in the highland areas of Guatemala, but also present in Mexico, Venezuela, Colombia, Brazil, and Ecuador. An aggressive and efficient mass treatment of foci in these countries should eliminate onchocerciasis from the Americas by 2013.

In Africa, blindness was traditionally noted to be more common in savannah and woodland than rainforest areas, but people in forest areas had more depigmented skin disease. Different strains or forms of the parasite were shown to be present in savannah and woodland areas, particularly in West Africa. Environmental changes and migrations have now lessened these distinctions. Onchocercal skin disease reduces marital prospects (and dowry size), disrupts social relationships, and decreases the productivity of agricultural workers.

Parasitology

The larvae of O. volvulus enter the human during a blood meal taken by an infected female simulium fly. Within 1 to 3 months, larvae develop into male or female adult worms within palpable nodules commonly located over the bony prominences of the thorax, pelvic girdle, or knees (Fig. 7.9.1.2). Nodules may also be found on the head, particularly among children. These average 3 cm in diameter and are easily palpable, but some are deep, particularly around the pelvis.

Fig. 7.9.1.2 A 3-cm subcutaneous nodule.

Fig. 7.9.1.2
A 3-cm subcutaneous nodule.

A female worm may release 1300 to 1900 microfilariae per day for 9 to 11 years. From the nodules, these microfilariae find their way mainly to the skin and eyes. In the skin they are found predominantly in the subepidermal lymphatics. In the eye, most microfilariae are in the anterior chamber, but are also found in the retina and optic nerve. When an infected human is bitten, anticoagulants from the simulium fly create a pool of blood from which blood and microfilariae are ingested. Within the fly, those microfilariae that survive moult twice over the following 6 to 12 days to become infective larvae.

Microfilariae are about 250 to 300 µm in length and may live for up to 2 years. They move easily through the skin and connective tissue, ordinarily remaining within lymphatic vessels and provoking little reaction while alive. They have been seen in blood, urine, cerebrospinal fluid, and internal organs. Millions of microfilariae may be present in a heavily infected person. Although live microfilariae are tolerated by their human hosts, dead and dying microfilariae may evoke intense inflammatory reactions, which are responsible for the eye and skin damage.

Important Simulium spp. are complexes made up of sibling species, identifiable through the banding patterns of their larval chromosomes. In Africa, the main vectors are members of the S. damnosum complex or sensu lato (s.l.), which can fly long distances. The vectors in areas of Uganda, Tanzania, Ethiopia, and the Congo are members of the S. neavei complex. In the Americas, complexes of S. ochraceum, S. metallicum, and S. exiguum are the principal vectors; these cover shorter distances. Some simulium flies will bite humans almost exclusively, whereas other species are to varying degrees zoophilic.

Simulium develop in water courses varying in size from broad rivers to small streams, depending on the individual sibling species. Rapidly flowing water provides the oxygenation needed for the development of the immature stages. Most larvae and pupae develop on rocks or vegetation just below the water surface, but those of S. neavei develop on amphibious Potamonautes crabs. During this development period the larvae are susceptible to insecticides. These breeding patterns have made the larviciding of water sources an effective control approach. Unique relationships have developed between the simulium fly and local parasites, so that flies from one geographical area do not efficiently transmit parasites from other areas. Simulium flies of the Americas are in general less efficient at transmission than those of Africa, particularly those in savannah regions.

Clinical features

The manifestations of onchocerciasis are almost entirely caused by localized host inflammatory responses to dead or dying microfilariae. In a heavily infected person, 100 000 or more microfilariae die every day. The predominant immune response in onchocerciasis is antibody mediated, but with an important cellular component. Inflammatory responses may vary considerably between groups of people, depending on the length of exposure to antigens and the down-regulating activities of the host’s immune system.

Eosinophils play an important role in the inflammatory response. Cellular proteins derived from eosinophils are deposited in connective tissues throughout the dermis, and bind to elastic fibres causing their destruction and, thereby, skin damage (see ‘Skin disease’ below).

An important discovery was that filarial parasites host endosymbiotic wolbachia bacteria. The inflammatory response to onchocerciasis seems largely attributable to the wolbachia rather than to the parasite itself. When the parasites were depleted of their wolbachia by doxycycline they did not induce corneal lesions. Further studies showed that inflammatory changes in the cornea in response to wolbachia were dependent on the expression of myeloid differentiation factor 88. Doxycycline may prove an alternative treatment for onchocerciasis in certain circumstances.

Exposure of the fetus to antigens associated with the parasite in utero and through breast milk may induce immune tolerance in residents of endemic areas. This could explain the difference in the disease patterns seen in people from nonendemic areas who become infected.

Among those coinfected with HIV there is a lessened reactivity to O. volvulus antigens, but no difference in adverse reactions following ivermectin treatment.

Eye damage

The risk of visual impairment increases as the prevalence and intensity of infection rises in a community. Microfilariae enter the cornea from the skin and conjunctiva. Punctate keratitis develops around dead microfilariae, and clears when inflammation settles. In those exposed to years of heavy infection, sclerosing keratitis and iridocyclitis are likely to develop, causing permanent visual impairment or blindness.

The first sign of sclerosing keratitis (Fig. 7.9.1.3a) is haziness at the medial and lateral margins of the cornea. This is followed by the migration of pigment onto the cornea, accompanied by a progressive ingrowth of vessels. Gradually the cornea becomes opacified. The central and superior areas are the last involved. Although eye lesions can be found wherever onchocerciasis occurs, blindness is most common in the West African savannah. Before control efforts began in Burkina Faso, 46% of men and 35% of women would eventually become blind.

Fig. 7.9.1.3 (a) Bilateral sclerosing keratitis in a man blinded by onchocerciasis in Nigeria and (b) onchocerciasis producing a Hissette–Ridley fundus and optic atrophy in a person with central keyhole vision remaining.

Fig. 7.9.1.3
(a) Bilateral sclerosing keratitis in a man blinded by onchocerciasis in Nigeria and (b) onchocerciasis producing a Hissette–Ridley fundus and optic atrophy in a person with central keyhole vision remaining.

(a, courtesy of Professor A D M Bryceson; b, courtesy of the Royal Tropical Institute, Amsterdam.)

Posterior segment lesions, which can coexist with anterior eye lesions, may be caused by inflammation around microfilariae entering the retina along the posterior ciliary vessels (Fig. 7.9.1.3b). Chorioretinal lesions are commonly seen at the outer side of the macula, or encircling the optic disc. Posterior segment changes are an important cause of loss of vision in Liberia. Optic atrophy has been reported in 1 to 4% of people with onchocerciasis in Cameroon, and 6 to 9% in northern Nigeria. Loss of peripheral vision is well recognized in onchocerciasis.

Skin disease

Of all the consequences of onchocerciasis, skin lesions are the most pervasive. Surveys of seven endemic sites in five African countries found that between 40 and 50% of adults had troublesome itching, which was so intense in some cases that the victims slept on their elbows and knees to minimize the symptom.

In its mildest form, onchocerciasis presents as itching with a localized maculopapular rash (Fig. 7.9.1.4). These reactive lesions and itching may be evanescent, clearing completely without treatment in a few months. In other instances, the papular lesions may become chronic, generalized, and accompanied by severe itching (Fig. 7.9.1.5). Oedema and excoriations can be associated, and lesions may heal with hyperpigmentation. Particularly distressing are lichenified hyperkeratotic lesions, which may be widespread and intensely itchy (Fig. 7.9.1.6). A localized form of chronic papular dermatitis, often confined to one extremity, is known as ‘sowda’, Arabic for dark. In this condition, first described from Yemen, there is an exceptionally strong IgG antibody response.

Fig. 7.9.1.4 Maculopapular rash.

Fig. 7.9.1.4
Maculopapular rash.

Courtesy of Mauricio Sauerbrey.

Fig. 7.9.1.5 Excoriated papular lesions of onchocerciasis with hyperpigmentation.

Fig. 7.9.1.5
Excoriated papular lesions of onchocerciasis with hyperpigmentation.

Fig. 7.9.1.6 Lichenified skin lesions with atrophy.

Fig. 7.9.1.6
Lichenified skin lesions with atrophy.

Light-skinned expatriates infected while visiting an endemic area may present 1 year or more later with intensely itchy and red macular or maculopapular lesions. These may be confined to one area of the body or be more generalized, and may be associated with fever, muscle and joint pain, and sometimes oedema. Rash may sometimes persist for several months following ivermectin treatment.

In endemic areas, degenerative skin changes may develop in some people with long-standing infection. Elastic fibres are destroyed, leaving the skin thinned with a wrinkled cigarette-paper appearance. The atrophied skin begins to sag, the most extreme state being ‘hanging groin’ with its apron-like skin folds (Fig. 7.9.1.7). Depigmentation of the pretibial areas, or ‘leopard skin’, is a characteristic finding in older people living in endemic areas (Fig. 7.9.1.8).

Fig. 7.9.1.7 ‘Hanging groins’.

Fig. 7.9.1.7
‘Hanging groins’.

(Courtesy of the late Dr B O L Duke.)

Fig. 7.9.1.8 Depigmented ‘leopard skin’.

Fig. 7.9.1.8
Depigmented ‘leopard skin’.

Other conditions associated with onchocerciasis

Both men and women with onchocerciasis weigh less than uninfected people and report more musculoskeletal pains. Evidence, first from Uganda and more recently from other African countries, has suggested a possible association between epilepsy and onchocerciasis. There is also evidence for an association between increasing microfilarial load and excess mortality.

A peculiar pattern of growth arrest beginning around the age of 6 to 10 years was reported from a Ugandan onchocerciasis focus near Jinja in 1951. This Nakalanga syndrome now seems to have disappeared from the area following the elimination of onchocerciasis, but has been noted in western Uganda, and may be present in Burundi. A condition of children in South Sudan, known as ‘nodding disease’, occurs in areas of onchocerciasis endemicity, though its pathogenesis is unknown. ‘Nodding disease’ has also affected small areas of Uganda and Tanzania. Clinical features include head nodding, mental retardation, stunted growth, blindness, body stiffness, endless running nose and saliva, and faecal and urinary incontinence. Onchocerciasis and neurocysticercosisare unlikely to be the cause and attention is turning to possible toxic contamination of food.

Diagnosis

Finding microfilariae in skin snips has been the time-honoured method of diagnosis. Microfilariae lie close to the surface, and are most plentiful in the iliac crest area, except in Latin America, where they are more common in the shoulder and scapular areas. Using either a scalpel blade or a sclerocorneal punch, four to six snips (about 5 mg each) are taken under sterile conditions and immersed in normal saline. Microfilariae swimming free of the skin fragments can be counted easily with a dissecting microscope within 24 h. The examination of excised onchocercal nodules shows sections of adult worms. Enzyme immunoassay and polymerase chain reaction (PCR) diagnostic methods have a high degree of sensitivity and specificity. Eosinophilia is common in onchocerciasis.

The Mazzotti test, in which people with onchocerciasis react with itching and a skin rash to 50 mg of oral diethylcarbamazine, is seldom needed for diagnosis, and can be dangerous in heavy infections.

For community assessment, the prevalence of nodules in 30 to 50 men over the age of 20 years, multiplied by 1.5, gives the approximate community prevalence of onchocerciasis. Where the prevalence of nodules is more than 40% the risk of blinding disease is high.

Treatment

The introduction of ivermectin for onchocerciasis in 1987 was one of the milestones of tropical disease treatment. The symptoms of onchocerciasis can be effectively controlled by the treatment of individuals attending clinics, or through the mass treatment of endemic communities.

Ivermectin is derived from Streptomyces avermitilis. A single dose of 150–200 µg/kg clears microfilariae from the skin for several months. Annual treatment controls microfilarial counts, and prevents the progression of clinical findings, although in some locations it is given twice yearly, with the intention of interrupting transmission. Treatment can be repeated if itching returns before the next dose is due. In the absence of reinfection, individual treatment should probably be continued anually for 10 years or more, or until microfilariae are no longer detectable. In Nigeria, after 8 years of treatment, gross visual impairment decreased from 16% to 1%, nodule prevalence fell from 59% to 18%, and papular skin dermatitis reduced from 15% to 2%. Treatment in pregnancy and under the age of 5 years is not recommended, although there has been no clear evidence of harm (increased risk of malformations or abortions) where treatment has been given inadvertently.

Limiting the numbers of microfilariae through annual ivermectin treatment improves early and advanced anterior segment eye lesions, halts the development of optic nerve disease, and improves severe onchocercal skin lesions. Adverse reactions to ivermectin commonly consist of increased itching, swelling of the face or extremities, and headache and body pains. Hypotension has been reported rarely after treatment in heavily infected people. Bullae have been seen occasionally. The most pronounced adverse reactions occur after the first ivermectin treatment, decreasing after subsequent treatment cycles. Ivermectin has no adverse effects in uninfected people. Although ivermectin temporarily reduces the release of microfilariae by adult worms, it does not destroy the adults. Those coinfected with Loa loa, are at risk of developing potentially fatal central nervous system events after treatment with ivermectin. Although most severe reactions occur with L. loa counts more than 30 000 microfilariae/ml, caution should be observed when treating anyone with counts greater than 8000 microfilariae/ml. It has been suggested that treatment with ivermectin in coinfected people be preceded by a 3-week course of albendazole to bring the L. loa count to less than 8000 microfilariae/ml.

Ivermectin appears to have several separate actions against the parasite. In microfilariae it acts primarily on parasite neurotransmitters, producing paralysis. This action appears to be mediated by the potentiation or direct opening of glutamate-gated chloride channels. The prolonged disappearance of microfilariae after a single treatment is the result of the drug’s effect on embryogenesis in the adult female worm. There is also a poorly understood direct effect on the adult worm, which may be greatest against male worms. Treatment with ivermectin does not prevent the development of new infections by additional larvae introduced by bites of infected flies.

Resistance to ivermectin has been reported where veterinary parasites have been exposed to high and prolonged selection pressures. In 2007, in an area in Ghana under treatment for many years, the ivermectin effect of reducing embryogenesis was noted to have lessened, although ivermectin still retained its microfilaricidal effects. Further study found that people in this area of Ghana had received irregular treatment, with low coverage levels achieved. This has not been seen elsewhere. As ivermectin is the only agent currently available for the control of onchocerciasis, the development of widespread parasite resistance would be of very serious consequence.

Prevention and control

Methods have included insecticides added to rivers to interrupt simulium breeding, mass distribution of ivermectin, and nodulectomy in an attempt to prevent blindness.

Vector control

Killing simulium larvae by adding the insecticide dichlorodiphenyltrichloroethane (DDT) to rivers eliminated onchocerciasis in Kenya and the Mabari forest of Uganda. In 1974, the Onchocerciasis Control Programme was formed to control simulium by larviciding rivers in the Volta basin of West Africa using ecologically suitable compounds. This highly successful vector control programme, later supplemented with ivermectin distribution, has now permitted tens of millions of people to live free of disease. Mass distribution of ivermectin is now the principal method for onchocerciasis control, although vector control may still be appropriate in a few locations, especially where transmission is with S. naevi.

Ivermectin mass distribution

After the effectiveness of ivermectin had been shown, its manufacturer Merck & Co. established the Mectizan Donation Program to provide the drug free ‘for as long as necessary to as many as necessary’. Between 1988 and 2011, 900 million ivermectin treatments had been approved for endemic countries by the Mectizan Donation Program which oversees drug approvals.

The goal of a control programme in Latin America has been the elimination of disease through twice yearly treatment. This has effectively interrupted transmission in 7 of 13 foci with as few as 11 six-monthly treatments. It is anticipated that by 2012 transmission of onchocerciasis will be interrupted and treatment may be stopped, though with post-treatment surveillance in place. In Africa follow-up of three foci in Mali and Senegal where treatment was stopped after 15 to 17 years have shown that only a few cases of onchocerciasis remain, and that any black fly transmission is below the level necessary to sustain disease in the community. This has raised interest in elimination of onchocerciasis in Africa, previously thought not to be possible. Based on data from the Americas, twice or even four times yearly ivermectin treatment could greatly shorten the time needed to reach a point where transmission of onchocerciasis cannot be sustained in a community. Other models are not quite as optimistic. Treatment programs in Africa have focused on meso- and hyperendemic areas of disease, originally with a goal of reducing blindness. Elimination programmes would have to greatly expand treatment to include very large areas where onchocerciasis is hypoendemic. Because of the need to treat 85% or more of the eligible population for 15 to 20 years, initial efforts would be to focus on ‘shrinking the map’, with wide-scale elimination a more distant goal for Africa. However, the use of community-based distributors in Africa has proved a highly efficient and cost-effective approach which could take treatment to many new areas with treatment for other conditions included as well. The areas of Angola and northern Democratic Republic of Congo, which are heavily coinfected with Loa loa, present a great challenge to mass treatment.

Nodulectomy

A third form of onchocerciasis control has been the nodulectomy programmes of Mexico and Guatemala. For many years, health workers have moved from village to village removing nodules, especially around the head. The evidence for this preventing blindness is not strong.

Eliminating infections

Although ivermectin brings great relief to the individual, and has a clear impact on the disease in mass distribution programmes for affected populations, it does not kill adult worms. While symptoms and risks are controlled through annual treatment, the disease itself is not eliminated, and the potential for the development of drug resistance remains. A number of macrofilaricidal drugs capable of eliminating the disease through the killing of adult worms have been tested, but none has so far proved suitable for either individual or mass treatment. However, the search continues. It is the availability of a safe, inexpensive macrofilaricidal drug that is most likely to make the elimination of onchocerciasis possible.

Loiasis

Loa loa is a filaria transmitted by Chrysops spp. flies in West and Central Africa. The adult worm migrates beneath the skin, and sometimes across the eye, moving at about 1 cm per minute. Periodically, the infection causes sudden but transient localized inflammatory oedema known as Calabar swellings.

Parasitology

The larvae of L. loa burrow into human skin during feeding of the chrysops or mangrove fly (C. silacea or C. dimidiata). In humans, the parasites mature and live in the fascial layers. After 1 year or more, microfilariae are produced. Microfilariae are most heavily present in the blood in the daytime, between 10.00 and 15.00, when the chrysops fly bites. Once taken up by the fly, microfilariae go through developmental stages in the fly’s thoracic muscles. After 10 days the fly is able to infect a human, and can do so for another 5 days.

Epidemiology

Infection is most common around the Gulf of Guinea, particularly in Nigeria and Cameroon, but extends through Central Africa into Chad, Sudan, and Uganda, and south to the Congo and Angola (Fig. 7.9.1.9). Humans are the only host, although a similar parasite is found in monkeys in the same areas. The fly lives in the rainforest canopy, and descends to bite humans, attracted perhaps by movement. Transmission may be most intense during the rainy season, when flies are breeding on the muddy banks of forest streams.

Fig. 7.9.1.9 Map of the approximate distribution of Loa loa.

Fig. 7.9.1.9
Map of the approximate distribution of Loa loa.

Clinical features

The first clinical symptoms of loiasis may appear as soon as 5 months after infection, or as late as 13 years. Calabar swellings appear suddenly, most commonly on the forearms or wrists, and sometimes following heavy exercise or exposure to heat. These oedematous lesions are red and itchy, and may be associated with fever and irritability, but are generally nontender. After several days the affected part returns to normal. However, recurrence is common at irregular intervals. Swellings are not confined to the arms, but may be present in the face, breasts or legs. Calabar swellings are a hypersensitivity reaction to worm antigens, which may be released in the process of migration or perhaps during the maturation of the worm. A high proportion of eosinophils are seen in peripheral blood smears, often exceeding 70%.

A second common feature is the appearance of a migrating worm (Fig. 7.9.1.10). This may be under the skin in any location, but is most dramatic when it crosses the eye (‘eye worm’; Fig. 7.9.1.11). Other than local irritation of the conjunctiva while the worm is passing, and the obvious concern of the host, there are no serious consequences. The time of passage may last from 30 min to more than 1 day.

Fig. 7.9.1.11 Loa loa crossing the bulbar conjunctiva.

Fig. 7.9.1.11
Loa loa crossing the bulbar conjunctiva.

Rare but potentially serious consequences of L. loa are meningoencephalitis, renal disease, and endomyocardial fibrosis. Arthralgias have also been noted. The meningoencephalitis may occur spontaneously, although usually after treatment with diethylcarbamazine or ivermectin. Fatalities have been reported following treatment. The renal and endocardial complications of loiasis may have an immune origin.

Laboratory diagnosis

Diagnosis has traditionally been by the finding of microfilariae in a daytime blood sample, or by a history or typical clinical findings. The use of more sensitive PCR methods has shown that many, even perhaps most, of those infected do not have microfilariae in their peripheral blood.

Treatment

The standard treatment has been diethylcarbamazine, which kills microfilariae and many adult worms. The treatment is commonly given in doses of 5-mg/kg divided into 3 daily doses for 21 days. Fever, arthralgia, and itching can occur during treatment. Ivermectin at 200 µg/kg dramatically decreases the number of microfilariae and some of the loiasis symptoms, but has little macrofilaricidal effect. Two courses of treatment may be required. As with diethylcarbamazine, there is a risk of potentially fatal meningoencephalitis in those with high microfilarial counts. It is prudent not to treat those with concomitant onchocerciasis until L. loa counts have been reduced below 8000 microfilariae/ml with albendazole. Treatment with small doses of invermectin does not offer any advantages.

Since many people with loiasis also have onchocerciasis, careful monitoring for severe eye and skin inflammation is important when giving diethylcarbamazine. Blood films for microfilariae or PCR tests should be followed to indicate the need for retreatment. Ivermectin is very active against microfilariae, but like diethylcarbamazine, poses the risk of a serious meningoencephalitis. As L. loa does not harbour wolbachia, treatment with doxycycline is ineffective.

Prevention

The best prevention is avoiding chrysops fly bites. Having window screens on dwellings, wearing clothing to protect the legs and forearms, and avoiding areas where biting is frequent can reduce the risk. Chemoprophylaxis with diethylcarbamazine has been suggested, using either 5 mg/kg on three consecutive days in a month, or a weekly dose of 300 mg while living in an area of transmission.

Mansonellosis

Mansonella spp. are a group of filarial species common to many countries, but are of negligible clinical importance under most circumstances. Infection is transmitted by Culicoides spp. midges.

Epidemiology

Mansonella (formerly Dipetalonema) perstans is found in much of tropical Africa, as well as Trinidad and several parts of South America. The adult worms live free in the abdominal cavity, and microfilariae are found in the blood and skin. Mansonella ozzardi is found in the West Indies and Central and South America. In addition to culicoides, simulium flies have been reported to transmit M. ozzardi in the Amazon basin. Mansonella streptocerca is a common infection in West and Central Africa, extending into western Uganda. Both microfilariae and adult worms are found in the skin, but without the nodules seen in onchocerciasis. Unless M. streptocerca microfilariae are differentiated parasitologically from those of O. volvulus, inappropriate mass onchocerciasis treatment programmes could be implemented.

Clinical manifestations

Of the mansonellas, only M. streptocerca produces clear-cut symptoms, although even these can be confused with those of O. volvulus, which may be a coinfection. Chronic papular lesions are commonly present, often associated with postinflammatory hyperpigmentation. Lichenification may occur less commonly. Hypopigmentation has been noted in areas of skin overlying the location of adult worms in the skin. In general, these findings are not easily distinguishable from those of onchocerciasis. Eosinophilia is common.

M. perstans has been reported to produce Calabar-like swellings, pruritus, fever, and headache. M. ozzardi infections are generally asymptomatic, although fever, arthralgia, headache, and itching have been associated with infection in the Amazon area.

Diagnosis

Diagnosis is by finding characteristic microfilariae in the blood or skin. The tails of the microfilariae have a distinctive walking-stick shape, and contain four prominent nuclei, distinguishing them from microfilariae of O. volvulus. A PCR assay as been described for M. streptocerca, and both quantitative buffy coat fluorescent staining and enzyme immunoassay methods for M. perstans. Eosinophilia is a characteristic finding.

Treatment

In asymptomatic people no treatment is required. M. streptocerca responds well to ivermectin, producing prolonged suppression of circulating microfilariae. Mild reactions similar to those in onchocerciasis may be seen. The treatment of M. perstans with doxycycline is effective, consistent with the effect of the drug on wolbachia. A combination of both diethylcarbamazine and mebendazole is highly effective against M. perstans, while ivermectin has little effect.

Further reading

Boussinesq M (2006). Loiasis. Ann Trop Med Parasitol, 100, 715–31.Find this resource:

Bregani ER, et al. (2006). Comparison of different anthelminthic drug regimens against Mansonella perstans filariasis. Trans R Soc Trop Med Hyg, 100, 458–63.Find this resource:

Brieger WR, et al. (1998). The effects of ivermectin on onchocercal skin disease and severe itching: results of a multicentre trial. Trop Med Int Health, 3, 951–61.Find this resource:

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