Tissue Nematodes, Trichinella, Dracuncula, Filaria

OVERVIEW: What every clinician needs to know

Parasite names and classification

Nematodes, or roundworms, are a category of helminths (worms). Two major groups of nematodes include Trichinella and filaria.

Trichinella are tissue nematodes that cause trichinellosis (aka trichinosis). Species that infect humans include: T. spiralis, T. pseudospiralis, T. nativa, T. nelsoni, T. bitovi, T. murelli, and T. papuae.

Filaria consist of a group of tissue nematodes, including Wuchereria bancrofti, Brugia malayi, and Brugia timori, which cause lymphatic filariasis, Onchocerca volvulus, which causes onchocerciasis (river blindness), and Loa loa, which causes loiasis.

What is the best treatment?

Trichinella: Most infections are mild and self-limited, only symptomatic treatment for fever and myalgia is needed. For severe infections, combinations of antiparasitic agents and prednisone are commonly used

albendazole 400mg orally twice daily for 10 to 14 days

PLUS

prednisone 30 to 60mg orally daily for 10 days

mebendazole 400mg orally three times daily for 10 days can be used in place of albendazole, but is not available in the United States

Loiasis: Treat with diethylcarbamazine as for lymphatic filariasis. The alternative is albendazole 200mg orally twice daily for 21 days. If concomitant loiasis and onchocerciasis are present, treat onchocerciasis first.

Onchocerciasis: Treat with ivermectin 150μg/kg orally, repeat every 3 to 4 months for several years.

Lymphatic filariasis: The best treatment is diethylcarbamazine (DEC) in a 14-day, gradually escalating oral dose to achieve a total of 72mg over the 14-day course. Note that DEC is only available in the United States from the Centers for Disease Control and Prevention Drug Service and should be provided after consultation with them and local infectious disease specialists. Also note that, if onchocerciasis is also present, treat that first with ivermectin, then treat with DEC, as otherwise DECtreatment alone mayprovoke severe encephalopathy or eye disease.

What are the clinical manifestations of infection with these organisms?

Trichinosis symptoms depend on the burden of parasites present and their stage of infection. The initial intestinal phase after ingestion is associated with nausea, abdominal pain, and diarrhea. The muscle encysting phase is associated with myalgias, muscle swelling, and weakness. Fever can be present throughout.
Point muscle tenderness, swelling, and periorbital edema are common physical findings. Rash, nail bed splinter hemorrhages or conjunctival hemorrhages, or hepatosplenomegaly can occur.
Lymphatic filariasis causes fever, swelling, redness, and pain in extremities and lymph nodes. Over time, hardening of the skin and soft tissues and elephantiasis of the extremities can result.
Some patients infected with these filaria develop tropical pulmonary eosinophilia, which can present with nocturnal, asthma-like attacks
Some of the hallmarks of onchocerciasis include marked pruritus, dermatitis, and pigmentation changes. Visual symptoms include photophobia, conjunctivitis, and eye pain secondary to uveitis or vision loss due to sclerosing keratitis or retinal destruction.
Patients with loiasis can have a broad range of presentations, from asymptomatic to intense pruritus and angioedema. A classic finding is Calabar swellings, which are caused by the migration of adult worms in the subcutaneous tissues. It is occasionally possible to see an adult worm traversing under the conjunctiva of the eye.

Do other diseases mimic the manifestations of these infections?

Trichinosis can be mistaken for other causes of severe myalgias, including infectious myositis and drug induced rhabdomyolysis. Severe cardiac manifestations must be distinguished from viral and autoimmune myocarditis. Neurotrichinosis can be mistaken for viral, fungal, or other parasitic causes of encephalitis.
For the major filarial diseases, filiarial lymphangitis, onchocerciasis, and loiasis, the main differential issue is to decide among these entities, since their geographic regions overlap and treatment differs.
Other causes of acute and chronic lymphangitis, including streptococcal and staphylococcal infection and malignancies, should also be considered.

What laboratory studies should you order and what should you expect to find?

Results consistent with the diagnosis:

In the muscle stage, trichinosis has a marked eosinophilia. There can also be leukocytosis, elevated creatine kinase (CK), and lactate dehydrogenase (LDH).
Eosinophilia and elevated IgE serum levels are seen with filarial lymphangitis, onchocerciasis, and loiasis and can vary from mild elevations to very high values, in loiasis especially.
In onchocerciasis, administering a small (50mg) dose of DEC to assess for the Mazzotti reaction (pruritus, rash, conjunctivitis, fever) is highly consistent with the diagnosis.

Results that confirm the diagnosis

Trichinosis: Muscle biopsy identifies larvae, giving a definitive diagnosis.

Polymerase chain reaction (PCR) can distinguish between species but is not commercially available.

Serology, including enzyme linked immunoassay (EIA), can also help make the diagnosis, but there may be some cross-reactivity with other helminths.
In filarial lymphangitis, diagnosis is made by identifying microfilariae in the blood. The highest numbers of circulating W. bancrofti microfilariae are found at night (the exception is W. bancrofti from the South Pacific which do not demonstrated this nighttime surge), so large volume blood samples are taken at midnight, filtered, and then examined under the microscope. Blood can also be drawn after a small 2mg/kg dose of DEC to provoke microfilaremia. Caution must be taken to rule out concomitant onchocerciasis.

Testing for microfilariae antigen can also make the diagnosis, and serology is also available.

Scrotal ultrasonography can reveal adult worms in the lymphatic vessels in males.
Onchocerciasis: The diagnosis is made by counting the microfilariae that emerge from a skin snip biopsy soaked in saline.

Serology is available and can help make the diagnosis of onchocerciasis.

In loiasis, the diagnosis is made by isolating adult worms from the subcutaneous or subconjunctival tissues, finding microfilariae in filtered blood samples, or obtaining positive L. loa serology.

What imaging studies will be helpful in making or excluding the diagnosis of these diseases?

In trichinosis, plain x-rays may show calcified cysts ($). Brain CT ($$) or MRI ($$$) may also show multiple lesions in the parenchyma.($ = 60–125, $$ 125–500, $$$ 500–1,000, $$$$ >1,000)
For filiarial lymphagitis, onchocerciasis, and loiasis, imaging is generally not helpful.

What complications can be associated with these parasitic infections, and are there additional treatments that can help to alleviate these complications?

Complications of Trichinella infections include myocarditis, pneumonia, encephalitis, and nephritis. For these severe manifestations, antiparasitic treatment with albendazole, as well as corticosteroids to decrease the immune response, should be used.

Complications of filiarial lymphangitis are disfigurement and loss of limb function with chronic disease, as well as pulmonary disease in those patients who develop tropical pulmonary eosinophilia.

The primary complication of onchcocerciasis is blindness.

Loiasis can be complicated by severe reactions to DEC treatment, including fatal encephalopathy. Albendazole and steroid pretreatment may decrease the occurrence.

What is the life cycle of these parasites, and how do the life cycles explain infections in humans?

Life cycle

Trichinella

Infection is acquired when undercooked meat with encysted larvae is ingested. The larvae then mature in the small bowel into adult worms—the females release larvae that then penetrate the intestines and migrate to striated muscle, where they form cysts.

Unlike other nematodes, there is no arthropod vector for Trichinella species.

A good diagram of the life cycle of Trichinella can be found on the Centers for Disease Control and Prevention (CDC) website. (Centers for Disease Control and Prevention. Parasites – Trichinellosis (also known as Trichinosis). Available at: http://www.cdc.gov/parasites/trichinellosis/biology.html. Accessed 17 July 2012.)

The larvae can be found in the muscles of many types of animals including rodents, bears, pigs, and moose. Humans most often get the infection from eating infected swine.

There is no real seasonal variation.

The infection is perpetuated in carnivorous or omnivorous animals that eat the meat of other infected animals.

The CDC estimates that 10,000 cases are reported worldwide each year. The highest rates are in China and Eastern Europe. There are between 10 to 20 cases in the United States annually.

People that eat undercooked pork or hunt and eat bear, cougars, boars, and other wild game are at risk for trichinosis.

The number of cases associated with livestock have decreased with more careful animal husbandry practices (i.e., not feeding raw pork to other animals), and educating people about the dangers of consuming undercooked meat.

Lymphatic filariasis (W. bancrofti, B. malayi, B. timori)

Mosquitoes are the host for all three and introduce the filarial by biting both infected humans and susceptible humans. The major mosquito species vary by location and include species of Culex, Aedes, Anopheles, and Mansonia.

W. bancrofti infect only humans, whereas B. malayi and B. timori can also infect domestic animals.

The life cycle of W. bancrofti can be found at the CDC website. (Centers for Disease Control and Prevention. Parasites – Lymphatic Filarisis. Available at: http://www.cdc.gov/parasites/lymphaticfilariasis/biology_w_bancrofti.html. Accessed 17 July 2012.)

There are seasonal differences in infection rates relating to the prevalence of the mosquito vector.

Standing water that provides breeding sites for the mosquito vector is a major contributor to transmission.

One hundred and twenty million people worldwide are estimated to be infected with filariae, the majority of which have W. bancrofti. Infections occur in Africa, Latin America, Southeast Asia, and the Indian Subcontinent. Two-thirds of all global infections are in Asia.

Both rural and urban populations are susceptible. The transmission from the mosquito vector is not highly efficient, so infection largely occurs in residents of endemic areas, rather than in visitors.

Onchocerciasis

O. volvulus is transmitted between humans by the bite of the blackfly (genus Simulium). There are no animal hosts for O. volvulus. The life cycle is available for review on the CDC website. (Centers for Disease Control and Prevention. Parasites – Onchocerciasis (also known as River Blindness). Available at: http://www.cdc.gov/parasites/onchocerciasis/biology.html. Accessed 17 July 2012.)

The key vector is the blackfly, which breeds in fast moving streams and rivers.

Communities within a few kilometers of rivers or streams in endemic areas are at highest risk. In Africa, there are epidemiologic differences also noted between infections obtained in open, savannah areas compared to forests. Anterior eye disease and resultant blindness are much more common in the savannah, whereas skin manifestations without blindness predominate in the forest-acquired cases.

It is estimated that 35 million people are infected with O. volvulus. Ninety-nine percent of cases are in sub-Saharan Africa; other areas include Mexico, Guatemala, Ecuador, Yemen, and Brazil.

The incidence is decreasing, with concerted control efforts in the Americas and in Africa and as collaborations among governments, nongovernmental organizations, and private companies increase. Merck, the manufacturer of ivermectin, has pledged to donate free drugs to the eradication effort.

Loiasis

L. loa exist as microfilariae in the blood of infected humans and also as adult worms in subcutaneous tissue. The life cycle can be found on the CDC website. (Centers for Disease Control and Prevention. Parasites – Loiasis. Available at: http://www.cdc.gov/parasites/loiasis/biology.html. Accessed 17 July 2012.)

Deer flies (horseflies) of the genus Chrysops are daytime feeders and the vector for transmission between humans. There are no animal hosts. To match the fly’s feeding pattern, the levels of microfilariae in humans is highest in the daytime.

The deer fly lives in the forest canopy and lays eggs in swampy ground. The prevalence of infection varies with the vector and can be affected by seasonal rains and other weather conditions.

It is estimated that there are 3 to 15 million people infected worldwide. Most of the infections are asymptomatic; therefore, it is difficult to ascertain the true prevalence. Most cases are from West and Central Africa.

Those who are most at risk are residents of endemic regions, not short-term travelers, although rare cases have been reported in individuals who have been in high transmission areas for as little as 2 weeks.

Prevention

Trichinella

There is no prophylaxis or vaccine available.

The best prevention is to avoid eating undercooked pork or any meat from a predator (i.e., cougar, bear, wild hog).

Thoroughly cooking meet to a temperature of 77°C or freezing at -15°C for 3 weeks usually kills the larvae (although T. nativa, which is found in the Arctic, can withstand cold).

Lymphatic filariasis

Mass treatment in endemic areas with ivermectin plus albendazole one to two times per year has been implemented as part of a global eradication strategy for W. bancrofti, which has no animal reservoir.

There is no current effective vaccine against these filariae.

Avoidance of mosquito bites via use of repellant, protective clothing, and bed nets is recommended for prevention.

Onchocerciasis

Mass treatment is given with single dose ivermectin to residents of endemic areas. This is repeated every 6 to 12 months for several years. There are some data that treating with doxycycline in addition to ivermectin may be more effective in clearing infection by eliminating the symbiotic bacteria of the genus Wolbachia that may be necessary for O. volvulus replication.

There is no effective vaccine for onchocerciasis.

Avoidance of mosquito bites via use of repellant, protective clothing, and bed nets is recommended for prevention.

Attempts at blackfly control have worked in the short term but are less effective than mass treatment and personal protection measures for ongoing interruption of transmission.

Loiasis

Mass treatment can be helpful to decrease infections in endemic areas; however, these efforts are not directed at L. loa specifically, but at filariasis or onchocerciasis. When providing mass treatment with DEC, L. loa co-infection may result in severe inflammatory reactions, so caution is needed as noted in the treatment section above.

There is no effective vaccine.

Avoidance of mosquito bites via use of repellant, protective clothing, and bed nets is recommended for prevention.

Attempts to control the deer fly vector have not been successful.

How do these organisms cause disease?

All helminths cause disease by either direct effects or by stimulating an immune response that subsequently can damage host tissues. The worms have also developed multiple methods to evade the host immune system, including encapsulation in cysts and attenuating the host’s immune response. Eosinophilia is a key characteristic of human infection by helminthes.

WHAT’S THE EVIDENCE for specific management and treatment recommendations?

Gottstein, B, Pozio, E, Nöckler, K. “Epidemiology, diagnosis, treatment, and control of trichinellosis”. Clin Microbiol Rev. vol. 22. 2009 Jan. pp. 127-45. (This is a general overview of the clinical and epidemiologic issues of human disease with Trichinella.)

Hoerauf, A, Pfarr, K, Mand, S, Debrah, AY, Specht, S. “Filariasis in Africa—treatment challenges and prospects”. Clin. vol. 17. Microbiol Infect 2011 Jul. pp. 977-85. (This is a good overview of clinic and prevention aspects of both lymphatic filariasis and onchocerciasis in Africa.)

Mackenzie, CD, Homeida, MM, Hopkins, AD, Lawrence, JC. “Elimination of onchocerciasis from Africa: possible”. Trends Parasitol. vol. 28. 2012 Jan. pp. 16-22. (This source reviews the progress made toward global elimination of onchocerciasis.)

Padgett, JJ, Jacobsen, KH. “Loiasis: African eye worm”. Trans R Soc Trop Med Hyg. vol. 102. 2008 Oct. pp. 983-9. (This is a review of the features of human Loa loa infection.)

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