Filarial Nematodes

Filariae are tissue-invasive nematodes that cause diseases such as elephantiasis, river blindness, and eye worm. The term “filaria” derives from the latin word “filum” that means “thread”, alluding to the thread-like appearance of these worms. Unlike intestinal nematodes, the adult forms live and reproduce in specific host tissues (NOT in the intestine) and produce larval forms called microfilariae. Filarial nematodes are transmitted through the bites of arthropods (mainly mosquitoes and flies).

Although we should not have bias, building the filariasis module was one of our favorites because these worms have very complex biology and unique features. We hope you enjoy learning it as much as we enjoyed making this lesson!

Lymphatic filariasis

Background & Epidemiology

The first group of filarial worms we will describe are Wuchereria bancrofti and Brugia malayi. Third stage larvae of these worms are transmitted to people by mosquito bites, and adult worms live in the lumen of the lymphatic vessels. The disease caused by these worms is called lymphatic filariasis (LF), which is characterized by lower extremity swelling. W. bancrofti is responsible for close to 90% of LF infections, whereas B. malayi causes about 10% [rarely, LF can be caused by other species such as Brugia timori, which will not be described in this lesson]. Infection with either requires repeated exposure (typically >3 months) to infected mosquitoes (rare in travelers).

Although both Wuchereria and Brugia share similar life cycles and pathogenesis, they have key differences that you should remember - summarized in the table below.

	W. bancrofti	B. malayi
Mammalian reservoir	Humans (Anthroponosis)	Felines and Monkeys (Zoonosis)
Vectors	Culex spp., Anopheles spp, Aedes spp.	Mansonia spp., Anopheles spp.
Distribution	Tropical regions of SubSaharan Africa, Egypt, Southeast Asia, Indian subcontinent, Brazil, Guyana, Dominican Republic, Haiti and Southwest Pacific Islands	Malaysia, Indonesia, Philippines

Figure 1. Age-standardized DALY rates for Lymphatic filariasis (taken from Global Health Metrics, Open Access)

Life Cycle

The life cycle of both Wuchereria and Brugia is very similar, explained in this video:

Figure 2. Life cycle of Wuchereria bancrofti

Pathogenesis & Clinical Presentation

What causes the disease in lymphatic filariasis?

In LF, disease is largely due to dysfunction of the lymphatic vessels. Much of the damage is caused by the host inflammatory response to the worms residing in the lymphatic vessels. Clinically, some patients experience recurrent episodes of lymphangitis with fevers and red streaks in the skin along the path of an inflamed lymphatic vessel. The worms themselves also directly contribute to impaired lymphatic flow by physically interfering with lymphatic valves and by releasing signals that cause irregular growth and dilation of lymphatic vessels. After months to years, lymphatic vessels can become chronically dilated, fibrotic, and calcified, and lose the ability to remove interstitial fluid, resulting in lymphedema.

NOTE: Notably, once lymphedema is present, individuals become susceptible to bacterial infections via breaks in the skin (which is less elastic due to lymphedema). Frequent bacterial infections then contribute to the clinical progression of LF by causing repeated inflammation and subsequent tissue remodeling of the skin and soft tissue. The combination of chronic lymphedema + recurrent remodeling can proceed to the point where the limb of a person resembles that of an elephant ("elephantiasis").

Does everyone develop symptoms?

What are the phases of lymphatic filariasis?

Acute lymphatic filariasis: the most prominent symptoms are episodic attacks of lymphangitis. Patients have local pain and erythema at the affected lymph node region. May be accompanied by systemic symptoms, such as fever, chills, or myalgias. Patients can also experience acute dermato-lymphangio-adenitis, which is a complicated name that means there is bacterial superinfection of the skin, underlying soft tissue, and lymphatic tissue. All of these events worsen the lymphatic damage.
Chronic lymphatic filariasis: results from repeated episodes of lymphangitis, causing lymphatic damage, as well as repeating inflammation of the skin and underlying soft tissues due to bacterial superinfection. During the chronic phase, there might not be any living adult worms, and thus patients may not be microfilaremic. The disease will depend on the location of the affected vessels.
1. 1. Lymphedema/Elephantiasis: most characteristic feature of LF. Extremities are deformed and skin becomes hardened.
  2. Genital disease: since many worms in bancroftian filariasis live in the lymphatics draining the genitals, it is common for male patients to experience hydrocele or chylocele.
  3. Chyluria: this may come up in your tests! Occurs when dilated retroperitoneal lymphatics rupture into the renal pelvis. Essentially, patients start peeing lymph, which can lead to malnutrition.

Figure 3. Elephantiasis in a patient with lymphatic filariasis

Figure 4. Elephantiasis in a patient with lymphatic filariasis

Figure 5. Chyluria

Are microfilariae involved in the pathology of LF?

Yes, they can. Rarely, individuals develop a pulmonary hypersensitivity response to microfilariae called tropical pulmonary eosinophilia (TPE). Individuals can experience fever and/or nocturnal asthma (remember microfilaremia occurs at night). Patients have high IgE levels and eosinophilia. Chest radiography may show interstitial infiltrates. If untreated, it can progress to restrictive lung disease. TPE occurs in <1% of patients with LF.

What about Wolbachia spp.?

You probably have heard of Wolbachia. This is an intracellular, endosymbiont gram negative bacteria (related to Rickettsia spp.) that is crucial for the fertility and development of some filarial worms, including W. bancrofti and B. malayi. It’s important to know of it because treating Wolbachia ultimately results in the death of the adult worms. Since it’s related to Rickettsia, Wolbachia can be treated with doxycycline (this may help you remember!).

Diagnosis

As with all diseases, diagnosis starts with clinical suspicion in the right epidemiological context (ask yourself what is the presentation? And who is the host?). Definitive diagnosis can be supported through different modalities based on the disease stage:

Acute filariasis

During acute disease, individuals are microfilaremic, and may experience episodic lymphangitis as a result of the dying adult worms. In addition to clinical recognition of past or present episodes of lymphangitis, diagnosis can be aided through the following:

Microscopy and blood smear (stained with Giemsa): definitive diagnosis has traditionally depended upon microscopically observing the microfilariae in the blood. Ideally needs to be collected between 22:00-02:00 hours [remember nocturnal periodicity]. Concentration techniques (e.g., Knott’s technique or membrane filtration) are preferred.
Antigen test, also known as circulating filarial antigen (CFA): more sensitive than microscopy. Can be used for daytime testing and can give a quantitative result correlating with adult worm burden. These are available in the form of ELISA or an immunochromatographic (“rapid”) card. Important test tip: current CFA tests only work for W. brancrofti and thus are not effective for diagnosing B. malayi.
Serology: particularly useful when individuals have no microfilariae in the blood. Does not differentiate between present or past infection.
Ultrasound: can detect the presence of motile adult worms in lymphatic vessels (“filarial dance sign”). Filarial worms can be seen in the intrascrotal lymphatics in infected men. Adult worm death following treatment with DEC can be subsequently followed.

Chronic filariasis

During the chronic stage, individuals no longer may have microfilariae in the blood, so smear/antigen testing can be negative. In addition to clinical recognition of lymphedema, diagnosis is fundamentally done via:

Serology: particularly useful when individuals have no microfilariae in the blood. Does not differentiate between present or past infection.
Ultrasound

Figure 6. Microfilaria of W. bancrofti

Figure 7. Microfilaria of B. malayi

Treatment

Treatment of filarial nematodes is COMPLICATED. Many physicians are unfamiliar with these drugs, and they need careful management and monitoring. You will NOT treat this alone.

As a general concept please know the following:

The drug of choice for lymphatic filariasis (W. bancrofti, B. malayi) is called diethylcarbamazine (DEC), which kills microfilariae AND adult worms.
Before starting DEC, one MUST rule out co-infection with Onchocerca volvulus and Loa Loa! Why? Because DEC can rapidly kill these worms and causes blindness, encephalopathy and other side effects you don’t want to run into.
There are other alternative regimens that include the use of albendazole, ivermectin or doxycycline - phone a friend first!
In addition to antiparasitics, individuals will need care for some of the complications. For example, they may need surgery for the hydrocele, wound care for lymphedema, compression bandages and garments, among others.

Prevention

Mass drug administration (MDA) campaigns to interrupt transmission in endemic areas. Regimens vary per region, but include single doses or combinations of albendazole, ivermectin, and DEC.
Mosquito control and mosquito prevention

Onchocerciasis

Background & Epidemiology

Let’s move to the next filarial worm in this lesson, Onchocerca volvulus, the cause of onchocerciasis (also known as “river blindness”). These adult worms live in the subcutaneous tissues and are transmitted by blackflies of the genus Simulium. Blackflies live and breed in fast-flowing rivers and streams. Consequently, infections most commonly occur in areas close to fast-flowing rivers and streams (unlike LF which is more widespread). Most of the infections occur in Africa (>95%), with some smaller pockets of endemicity in Yemen and in the Venezuela-Brazil border.

Figure 8. Age-standardized DALY rates for Onchocerciasis (taken from Global Health Metrics, Open Access)

Figure 9. Blackfly

Life Cycle

Figure 10. Life cycle of Onchocerca volvulus

Pathogenesis & Clinical Presentation

The clinical presentation of onchocerciasis is highly variable and depends on specific transmission dynamics of each endemic focus. Most individuals require repeated exposure to the parasite in order to become infected (less common in travelers). The incubation period is usually in the order of months - typically 12-18 months. While many infections remain asymptomatic, symptomatic cases may involve skin disease, eye disease or both.

Skin disease

Lesions caused by adult worms: adults reside inside of fibrous capsules within the subcutaneous tissues and form painless, mobile nodules called onchocercomas. These are typically found over bony areas like the iliac crests, shoulder girdle, the head or the hips. Onchocercomas may not be clinically evident in soft tissues, but can become palpable over bony prominences (here, ultrasound can be helpful!). Of note, nodule distribution patterns vary by transmission area.
Figure 11. Onchocerca nodule
Lesions caused by microfilariae (“onchodermatitis”): long-standing exposure to the microfilariae in the skin drives most of the clinical disease seen in onchocerciasis. Initially, individuals experience generalized pruritus, which is considered one of the earliest manifestations of onchocerciasis and can be confused with scabies! Chronic pruritus and microfilariae-induced inflammation lead to papular dermatitis, dry skin and lichenification. The dermatitis is seen mainly on the buttocks and the shoulders. Late in the disease, the skin can become atrophied (simulating early aging), hyperpigmented (“leopard skin”) or hypopigmented.

Note: All of the clinical manifestations of onchocerciasis are caused by microfilariae, EXCEPT the subcutaneous nodules

Eye disease

Ocular manifestations are induced by the microfilariae. Initial corneal lesions include punctate keratitis (seen as “snowflake” opacities), which can later progress to sclerosing keratitis. This irreversible transition can take up to 20-30 years. Microfilariae can be found in all ocular tissues, except the lens, and can induce anterior uveitis, choroido-retinitis, and ultimately can lead to optic atrophy. If untreated, individuals can become blind! (hence the term “river blindness”)

Note: All of the clinical manifestations of onchocerciasis are caused by microfilariae, EXCEPT the subcutaneous nodules

Complications

Does Onchocerca volvulus carry Wolbachia?

Answer

YESSSS. Just like Lymphatic filariasis O. volvulus DOES CARRY Wolbachia - an endosymbiotic intracellular gram negative bacteria. Doxycycline can be used as treatment for onchocerciasis in certain settings.

Diagnosis

Suspect onchocerciasis in an individual with a compatible clinical syndrome who lived in an endemic area (rare in short-term travelers). Diagnosis can be further supported with:

Skin snip - this is the MOST COMMON method to diagnose onchocerciasis. Essentially, a tiny piece of superficial skin is taken with a razor, punch or needle, then placed in saline. After a few hours, any microfilariae present will emerge and can be seen under the microscope. The CDC, has an excellent description on how to do one in the “Testing and diagnosis” section, click here.
Nodulectomy - a surgical removal of the nodule allows for visualization of the adult worms.
Slit lamp examination - after asking the patients to place his/her head between his/her own knees for up to 5-10 minutes, the provider can potentially see microfilariae in the cornea or anterior chamber of the eye.
Serology - there are Ab tests that can aid in the diagnosis.

Figure 12. Onchocerca volvulus smear after skin snip

Treatment

As a general concept, this is what you should remember:

The drug of choice for O. volvulus is ivermectin, which ONLY kills the microfilariae. Treatment must be given at least every 3-6 months for many years (usually ~15-20 years) until adults naturally die.
Before starting ivermectin, one MUST rule out co-infection with Loa loa!!! Ivermectin can precipitate encephalopathy in those co-infected with Loa loa and a high microfilarial load.

Prevention

Mass drug administration (MDA) campaigns to interrupt transmission in endemic areas. Regimens vary per region, but usually include ivermectin every 3-6 months.
Simulium control and prevention.

Loiasis

Background & Epidemiology

Loiasis is the last filarial infection we will review, which is caused by nematodes of the genus Loa loa. Adult worms live and migrate across the subcutaneous tissues and occasionally through the sub-conjunctiva. Loa loa is endemic to the rainforests of central and west Africa and it is transmitted by flies of the genus Chrysops.

Life Cycle

Figure 13. Life cycle of Loa loa

Pathogenesis & Clinical Presentation

Most infections are asymptomatic; however, when clinical manifestations do happen, they include:

Subcutaneous localized angioedema (“calabar swelling”)

Eye disease

Does Loa loa carry Wolbachia?

Answer

NO. Unlike Lymphatic filariasis and Onchocerciasis, Loa loa DOES NOT, and I repeat, DOES NOT carry Wolbachia - the endosymbiont intracellular gram negative bacteria. Doxycycline plays NO role in treating loiasis.

Diagnosis

Suspect loiasis in an individual with a compatible clinical syndrome, traveling from or living in an endemic area. Eosinophilia can be present. Diagnosis can be further supported with:

Microscopy and blood smear (stained with Giemsa): definitive diagnosis has traditionally depended upon microscopically observing the microfilariae in the blood. Because microfilariae exhibit peak levels in the blood during the daytime, blood should ideally be collected between 10:00-14:00 hours. Concentration techniques (e.g., Knott’s technique or membrane filtration) are preferred.
Serology: does not differentiate present or past infection. It is more useful for non-immune travelers.
Direct visualization: can see the adult worm in the subconjunctiva.

Figure 14. Loa loa microfilaria

Treatment

As a general concept, this is what you should remember about treating Loa loa:

The drug of choice for Loa loa is diethylcarbamazine (DEC), which kills microfilariae AND adult worms. Sometimes steroids are given concomitantly.
Before starting DEC, one MUST rule out co-infection with Onchocerca volvulus and Lymphatic filariasis! Hopefully you remember by now that before treating any of these filarial worms, you need to rule out the others, or complications can be BAAAD.
Before starting DEC, one must also quantify the levels of L. loa microfilariae in the blood. DEC should not be given to individuals with high circulating microfilaria levels (>2,500 microfilariae/mL) due to risk of severe post-treatment inflammatory reactions (including encephalopathy and death).
Surgical removal of an adult L. loa worm can be conducted when a worm is migrating through the sub-conjunctival space, as seen in this video. This can be helpful for diagnosis and for symptomatic relief, though it is not typically necessary to achieve cure.

	Lymphatic filariasis	Onchocerciasis	Loiasis
Continents affected	Africa The Americas Asia	Africa The Americas	Africa
Periodicity of microfilariae	Nocturnal	Nocturnal	Diurnal
Presence of Wolbachia	Yes	Yes	No
Stage causing most disease	Adults	Microfilariae > Adults	Adults
Definitive habitat	Lymphatic vessels	Subcutaneous tissues	Subcutaneous tissues, Eye
Diagnosis	Blood smear Antigen Serology US	Skin snips Nodulectomy Slit lamp exam Serology	Blood smear Serology
Drug of choice	DEC	Ivermectin	DEC

Table 2. General concepts/summary of medically important filariasis

Other Media Resources (Optional)

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References

View All References

Despommier, D.D. et al. (2019) Parasitic Diseases. Seventh Edition. Parasites Without Borders, Inc. NY.
Reyes Romero, H., Navarro Rojas, P. and Reyes Barrios, H. (2013) Medicina tropical y enfermedades del viajero Vol Tomo II. Caracas: Consejo de Desarrollo Científico y Humanístico Universidad Central de Venezuela.
Beeching, N. and Gill, G. (2014) Lecture notes tropical medicine, 7th edition. John Wiley & Sons.
CDC Yellow Book 2024: Health Information for International Travel. Oxford University Press
Blumberg, L. et al. (2021) Oxford Handbook of Tropical Medicine. Oxford: Oxford
Hunter’s Tropical Medicine and Emerging Infectious Diseases. (2020). In Elsevier eBooks.
Hotez, P. J. (2013). The filarial infections: Lymphatic filariasis (elephantiasis) and Dracunculiasis (Guinea worm). Forgotten People Forgotten Diseases, 57–75. https://doi.org/10.1128/9781555818753.ch4
Cross JH. Filarial Nematodes. In: Baron S, editor. Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Chapter 92. Available from: https://www.ncbi.nlm.nih.gov/books/NBK7844/
Babu, S., & Nutman, T. B. (2010). Lymphatic filariasis. Topley & Wilson’s Microbiology and Microbial Infections. https://doi.org/10.1002/9780470688618.taw0203
Nutman, T. B. (2009). Filarial infections. Tropical Diseases in Travelers, 243–253. https://doi.org/10.1002/9781444316841.ch25

This lesson was last updated September 25 2025

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