Filariasis; Causes, Symptoms, Diagnosis, Treatment

Filariasis








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Filariasis is a parasitic disease caused by an infection with roundworms of the Filarioidea type.[rx] These are spread by blood-feeding Diptera as black flies and mosquitoes. This disease belongs to the group of diseases called helminthiases. Filarial Disease, or the general term “filariasis,” may also refer to a group of parasitic diseases caused by various species of filarial worms (nematodes). These include mumu, loiasis (Calabar swellings), dirofilariasis (human infection by dog heartworm), and onchocerciasis (river blindness)

Lymphatic filariasis (LF) is a vector-borne disease of the tropical and subtropical countries due to infection by filarial worms, which invade the lymphatics of humans initiating pathological changes leading to later filarial disease manifestations. As a result of its heritable nature, much more is known about the molecular basis of primary lymphoedema (LE) in comparison with what is known about the etiology and pathophysiology of secondary LE – caused by trauma, environmental factors (e.g. podoconiosis) or infection. The single largest source of secondary LE is lymphatic filariasis (LF), a disease caused by filarial nematodes [.

Another Name

  • Bancroftian Filariasis
  • Filarial Elephantiasis
  • Filariasis Malayi
  • Malayi Tropical Eosinphilia
  • Wuchereriasis

Lymphatic Filariasis

Caused by thread-like parasitic worms (Wuchereria bancroftiBrugia malayi and Brugia timori) that damage the human lymphatic system – transmitted by mosquitoes [rx]
One of the most disabling and disfiguring of diseases
80+ endemic countries [rx]
1+ billion people are at risk of infection
120 million people are infected. Of these…
43 million people have swelling of the limbs and breasts (known as lymphoedema) and genitals (known as hydrocoele), and their more chronic state – known as elephantiasis – in which the skin becomes enormously thickened, and is rough, hard, and fissured
It is a disease of poverty – affecting the “poorest of the poor” – preventing those afflicted from living a normal working and social life [rx]
Children acquire the disease early and are blighted for life

Types of Filariasis

Eight known filarial nematodes use humans as their definitive hosts. These are divided into three groups according to the niche they occupy in the body

  • Lymphatic filariasis – is caused by the worms Wuchereria bancroftiBrugia malayi, and Brugia timori. These worms occupy the lymphatic system, including the lymph nodes; in chronic cases, these worms lead to the syndrome of elephantiasis.
  • Subcutaneous filariasis – is caused by Loa loa (the eye worm), Mansonella streptocerca, and Onchocerca volvulus. These worms occupy the subcutaneous layer of the skin, in the fat layer. L. loa causes Loa loa filariasis, while O. volvulus causes river blindness.
  • Serous cavity filariasis – is caused by the worms Mansonella perstans and Mansonella ozzardi, which occupy the serous cavity of the abdomen. Dirofilaria immitis, the dog heartworm, rarely infects humans.

The adult worms, which usually stay in one tissue, release early larval forms known as microfilariae into the host’s bloodstream. These circulating microfilariae can be taken up with a blood meal by the arthropod vector; in the vector, they develop into infective larvae that can be transmitted to a new host.

The Transmission Cycle of Filariae

  • When a mosquito with infective stage larvae takes a blood meal, the parasites are deposited on the person’s skin from where they enter the body.
  • The larvae migrate to the lymphatic vessels where they develop into adult worms. This process may take 6–12 months, affecting the dilation and functioning of the lymphatic vessels.
  • The adult filariae live for several years in the human host, producing millions of microfilariae that circulate in the peripheral blood and are ingested by mosquitoes during blood-feeding.
  • The larval forms further develop inside the mosquito before becoming infectious to humans.
  • Thus, a cycle of transmission is established.

Life cycle of Filariae

Causes of Filariasis

Lymphatic filariasis is caused by infection with parasites classified as nematodes (roundworms) of the family Filariodidea. There are 3 types of these thread-like filarial worms:

  • Wuchereria bancrofti, which is responsible for 90% of the cases
  • Brugia malayi, which causes most of the remainder of the cases
  • Brugia timori, which also causes the disease
  • It starts when mosquitoes infected with the roundworm larvae bite you – The tiny larvae survive in your bloodstream and grow. They finish maturing in your lymph system. They can live there for years and cause a lot of damage to your lymph system. This is what causes the swelling.
  • Human filarial nematode worms have complicated life cycles – which primarily consists of five stages. After the male and female worms mate, the female gives birth to live microfilariae by the thousands. The microfilariae are taken up by the vector insect (intermediate host) during a blood meal. In the intermediate host, the microfilariae molt and develop into third-stage (infective) larvae. Upon taking another blood meal, the vector insect injects the infectious larvae into the dermis layer of the skin. After about one year, the larvae molt through two more stages, maturing into the adult worms.
  • Filariasis may cause chronic lymph node swelling (lymphadenopathy) – even in the absence of other symptoms. Longstanding obstruction of the lymphatic vessels may lead to several other conditions. These include accumulation of fluid in the scrotum (hydrocele), the presence of lymphatic fluid in the urine (chyluria), and/or abnormally enlarged lymphatic vessels (varices). Other symptoms may include progressive edema (elephantiasis) of the female external genitalia (vulva), breasts, and/or arms and legs. Chronic edema may result in skin that is abnormally thick and has a “warty” appearance.

Symptoms of Filariasis

  • The most spectacular symptom of lymphatic filariasis is elephantiasis – edema with thickening of the skin and underlying tissues—which was the first disease discovered to be transmitted by mosquito bites.[rx] Elephantiasis results when the parasites lodge in the lymphatic system.
  • Elephantiasis – affects mainly the lower extremities, while the ears, mucous membranes, and amputation stumps are affected less frequently. However, different species of filarial worms tend to affect different parts of the body; Wuchereria bancrofti can affect the legs, arms, vulva, breasts, and scrotum (causing hydrocele formation), while Brugia timori rarely affects the genitals. Those who develop the chronic stages of elephantiasis are usually free from microfilariae (microfilaraemia), and often have adverse immunological reactions to the microfilariae, as well as the adult worms.[rx]
  • People with lymphedema and elephantiasis – are unlikely to benefit from DEC treatment because most people with lymphedema are not actively infected with the filarial parasite.
  • When lymphatic filariasis develops into chronic conditions – it leads to lymphoedema (tissue swelling) or elephantiasis (skin/tissue thickening) of limbs and hydrocele (scrotal swelling). Involvement of breasts and genital organs is common. Such body deformities lead to social stigma, as well as financial hardship from loss of income and increased medical expenses. The socioeconomic burdens of isolation and poverty are immense.
  • The subcutaneous worms present with rashes – urticarial papules, and arthritis, as well as hyper- and hypopigmentation macules. Onchocerca volvulus manifests itself in the eyes, causing river blindness(onchocerciasis), one of the leading causes of blindness in the world.  Serous cavity filariasis presents with symptoms similar to subcutaneous filariasis, in addition to abdominal pain, because these worms are also deep-tissue dwellers.

Lymphatic filariasis can manifest itself in a variety of clinical and subclinical conditions. Traditionally, it has been accepted that people living in an endemic area can be classified into five groups

  • (1) uninfected but exposed
  • (2) clinically asymptomatic, infected
  • (3) those with the acute filarial disease with or without microfilaremia
  • (4) those with longstanding chronic infection associated with pathological conditions and
  • (5) those with tropical pulmonary eosinophilia (TPE).

Lymphedema and Elephantiasis

Lymphedema of extremities is a common chronic manifestation of LF, which on progression results in elephantiasis. Usually, the lower limbs are involved, either unilaterally or sometimes bilaterally in which case, the swelling tends to be asymmetrical. The upper limbs, male genitalia and rare breasts in the females may also be affected. The lymphedema of the limbs is commonly graded as follows []

  • Grade I – Pitting edema, reversible on the elevation of the affected limb.
  • Grade II – Pitting or non-pitting edema, which does not reverse on the elevation of the affected limb and there are no skin changes.
  • Grade III – Non-pitting edema that is not reversible, with thickening of the skin.
  • Grade IV – Non-pitting edema that is not reversible, with thickening of skin along with nodular or warty excrescences – the stage of elephantiasis.

In advanced stages of lymphedema, the skin is thickened and thrown into folds, often with hypertrichosis, black pigmentation, nodules, warty growth, intertrigo in the webs of toes or chronic non-healing ulcers []. The swelling may be so huge and grotesque that the patient is incapacitated requiring help even for personal needs. Fungal infections in the interdigital region and in deep folds are a common finding in advanced lymphedema.

Manifestations can be protean and classified as

Acute

  • Fever with chills and rigors
  • Lymphedema with pain
  • Lymphadenopathy (cervical, axillary, inguinal and generalized Acute Filarial Lymphangitis/Acute Dermatolymphangioadenitis)
  • Chyluria
  • Hematuria
  • Inflammatory granuloma or abscesses
  • Pain in testes
  • Funiculitis
  • Epididymoorchitis

Chronic

Occult

  • Pulmonary eosinophilia, mono, and polyarthritis
  • Tenosynovitis
  • Glomerulonephropathy
  • Retroperitoneal lymphangitis (acute abdomen)
  • Central serous retinopathy
  • Iridocyclitis, recurrent scleritis and macular edema
  • Endomyocardial fibrosis
  • Urticarial
  • Recurrent upper respiratory infections
  • Asthmatic bronchitis
  • Any lymph node or any body part can be affected but commonly genital lymphatics are involved in males.

Asymptomatic

  • Endemic normal negative for Mf but positive for antigens (pre-patency) and asymptomatic microfilaremia – is characterized by the presence of microfilaria in peripheral blood during the night but without any overt clinical manifestations of filariasis with or without antigens – also known as Mf carrier

Diagnosis of Filariasis

The diagnosis of filariasis requires examination of a blood smear for the presence of the larval roundworm W. bancrofti or B. malayi. Since the number of parasites (parasitemia) in the blood is higher during the night, blood samples are best obtained at night. When parasites are not found in the blood, the adult worms may occasionally be found in a lymph node sample from an infected individual.

  • Microfilariae on Giemsa stained – thin and thick blood film smears, using the “gold standard” known as the finger prick test. The finger prick test draws blood from the capillaries of the fingertip; larger veins can be used for blood extraction, but strict windows of the time of day must be observed. Blood must be drawn at appropriate times, which reflect the feeding activities of the vector insect
  • Serologic techniques – provide an alternative to microscopic detection of microfilariae for the diagnosis of lymphatic filariasis. Patients with active filarial infection typically have elevated levels of antifilarial IgG4 in the blood and these can be detected using routine assays.

Concentration Methods

Various concentration methods are applied: membrane filter, Knott’s concentration method, and sedimentation technique.

  • Polymerase chain reaction (PCR) Test – and antigenic assays, which detect circulating filarial antigens, are also available for making the diagnosis. The latter are particularly useful in microfilaraemia cases. Spot tests for antigen[rx] are far more sensitive, and allow the test to be done anytime, rather in the late hours.
  • Lymph node aspirate and chylous fluid Test  – may also yield microfilariae. Medical imaging, such as CT or MRI, may reveal “filarial dance sign” in the chylous fluid; X-ray tests can show calcified adult worms in lymphatics. The DEC provocation test is performed to obtain satisfying numbers of parasites in daytime samples. Xenodiagnosis is now obsolete, and eosinophilia is a nonspecific primary sign.
  • Immuno-chromatographic-card Test (ICT) – card test for filarial antigenemia and ultrasonography for locating the adult worms are usually negative once lymphedema is established []. Rarely ultrasonography may be used to assess thickening of the tissues in the swollen limbs. Lymphoscintigraphy helps to assess the structural and functional changes in the lymphatics. Lymphatic dilatation, dermal backflow or obstruction to lymph flow in the edematous limbs can be demonstrated by this method.

Specific Tests

  • Direct detection of microfilaria on blood smears
  • Serologic tests
  • DNA PCR and radiology
  • Eosinophilia (>3000/microliter)
  • Microscopic hematuria
  • Microscopic proteinuria

Blood Smears

  • Samples are drawn ideally between 10 pm and 2am due to peak biting time of mosquito vectors
  • 20 microliters of blood can detect microfilariae, but a 1 mL blood sample may be required to make a diagnosis
  • >10,000 microfilariae per 1 mL of blood can be found in endemic regions
  • Samples are stained and centrifuged
  • Microfilariae species can be differentiated by morphological characteristics

Antibody Test

  • Serologic testing for filarial antibodies can detect elevated levels of IgG and IgE
  • Poor specificity
  • Cannot distinguish between filarial types
  • Cannot differentiate between past and present infections
  • Newer tests are being developed that look at specific anti-filarial IgG4 antibodies for showing active infections[13]

Antigen Test

  • Detect the presence of adult worms
  • Circulating Filarial Antigen (CFA) tests are considered the gold standard for diagnosing Wuchereria bancrofti infections
  • No antigen testing currently available for Brugian malayi filariasis

Nonspecific tests

  • Eosinophilia
  • High IgE levels and lymphoscintigraphy (that reveal dilated lymph channels or backflow even in the early stage of infection)

Direct Methods

  • Visualization of microfilaria (or the adult worm) – is made by microscopic examination of a thick film of blood collected between 10:00 PM and 2:00 AM, with or without DEC provocation, stained by Giemsa or hematoxylin-eosin for the presence of microfilaria. The adult worm may be found in fluids drawn from swollen areas or serious collections.
  • X-ray tests – can show calcified adult worms in lymphatics.
  • Ultrasonography – can show the ’filarial dance’.1, 2, 7 Lymph node aspirate and chylous fluid may also yield microfilaria or worm.
  • Direct diagnosis – though definitive, is difficult, because of timing inconvenience of blood collection, long pre-patency, low patency (<60%) and inadequate sensitivity.

Treatment of Filariasis

Non-Pharmacological 

The following treatment modalities offer relief and help to prevent further progression of the swelling:

  • Using an elasto-crepe bandage or tailor-made stockings while ambulant
  • Keeping the limb elevated at night, after removing the bandage
  • Regular exercising of the affected limb
  • Regular light massage of the limb especially in early edema, to stimulate the lymphatics and to promote the flow of lymph towards larger patent vessels
  • Intermittent pneumatic compression of the affected limb using single or multicell jackets
  • Heat therapy using either wet heat or hot ovens
  • Gently washing the swollen and damaged skin every day with soap and water
  • Moisturizing the skin
  • Elevating swollen limbs to improve the flow of fluid and lymph
  • Disinfecting wounds to prevent secondary infections
  • Exercising regularly to support the lymphatic system, as directed by a doctor
  • Wrapping the limbs to prevent further swelling, as instructed by a doctor

Medications

Topical Benzopyrones and Flavonoids

  • Topical benzopyrones and flavonoids are advocated for the treatment of lymphedema. These drugs are supposed to reduce high protein edema by stimulating macrophages to remove the proteins from the tissues when administered for long periods []. Further controlled trials are needed to substantiate this claim.
  • The recommended treatment for people outside the United States is albendazole combined with ivermectin.[rx][rx] A combination of diethylcarbamazine and albendazole is also effective.[rx][rx] Side effects of the drugs include nausea, vomiting, and headaches.[rx] All of these treatments are microfilaricides; they have no effect on the adult worms. While the drugs are critical for the treatment of the individual, proper hygiene is also required.[rx]

Antibiotic doxycycline

  • It was suggested for treating elephantiasis.[rx] Filarial parasites have symbiotic bacteria in the genus Wolbachia, which live inside the worm and seem to play a major role in both its reproduction and the development of the disease. This drug has shown signs of inhibiting the reproduction of the bacteria, further inducing sterility.[rx]Clinical trials in June 2005 by the Liverpool School of Tropical Medicine reported an eight-week course almost completely eliminated microfilaraemia.[rx] [rx]
  • Some studies have shown adult worm killing with treatment with doxycycline (200mg/day for 4–6 weeks).


Diethylcarbamazine (DEC)

  • DEC has been used worldwide for more than 50 years. Because this infection is rare in the U.S., the drug is no longer approved by the Food and Drug Administration (FDA) and cannot be sold in the U.S. Physicians can obtain the medication from CDC after confirmed positive lab results. CDC gives the physicians the choice between 1 or 12-day treatment of DEC (6 mg/kg/day).
  • One day treatment is generally as effective as the 12-day regimen. DEC is generally well tolerated. Side effects are in general limited and depend on the number of microfilariae in the blood. The most common side effects are dizziness, nausea, fever, headache, or pain in muscles or joints.
  • These preventive chemotherapy medicines have a limited effect on adult parasites but effectively clear microfilariae from the bloodstream and prevent the spread of parasites to mosquitoes. Large-scale treatment conducted annually for 4-6 years, treating all persons living in areas where the infection is present can interrupt the transmission cycle.
Streamlined Dose
Age in Years Dose of DEC Number of Tablets
< 2 Nil Nil
2–5 100 mg 1 tablet of 100 mg
6–14 200 mg 2 tablets of 100 mg each
15 & above 300 mg 3 tablets of 100 mg each

WHO Recommends the Following MDA Regimens

  • Albendazole (400 mg) alone twice per year for areas co-endemic with loiasis
  • Ivermectin (200 mcg/kg) with albendazole (400 mg) in countries with onchocerciasis
  • Diethylcarbamazine citrate (DEC) (6 mg/kg) and albendazole (400 mg) in countries without onchocerciasis

Recent evidence indicates that the combination of all three medicines can safely clear almost all microfilariae from the blood of infected people within a few weeks, as opposed to years using the routine two-medicine combination.

WHO now recommends the following MDA regimen in countries without onchocerciasis:

  • ivermectin (200 mcg/kg) together with diethylcarbamazine citrate (DEC) (6 mg/kg) and albendazole (400 mg) in certain settings

Surgical Procedures

  • There are various surgical options available to offer relief of lymphedema, like lymph node-venous shunts, mentoplasty and excision with skin grafting []. Even after surgery, the local care of the limb should be continued for life, so that ADLA attacks and recurrence of the swelling are prevented [].
  • Surgery may be used to treat some people with filariasis who develop an abnormal accumulation of fluid in the scrotum (hydrocele). Surgery may also be performed to remove the remains of adult worms and calcifications developing around them. Treatment of elephantiasis of the legs usually consists of elevation and support from elastic stockings.

Physical Therapy 

  • Clinical manifestations of filariasis such as lymphedema and elephantiasis are caused by prolonged exposure to filariae and the mosquitos that transmit them in endemic regions. These affected individuals are usually not actively infected; rather, they are suffering from the effects of years of exposure to one of the three nematodes. Medical management is not appropriate for these individuals.
  • Physical therapy management of the disease primarily consists of treatment from a lymphedema therapist, along with education of proper skincare and hygiene. Appropriate exercise prescription and wound care management are also indicated. There is no physical therapy intervention indicated for hydrocele; those infected usually do not respond well to DEC, and surgery is required in some cases.

Lymphatic Filariasis as a unique and successful program

Two drugs (largely donated or inexpensive) once per year for the time-limited duration
DEC + albendazole in areas where onchocerciasis is not endemic
Albendazole + Mectizan® where onchocerciasis is co-endemic with lymphatic filariasis
Two major pharmaceutical companies involved
A global disease (80 endemic countries; 1+ billion at risk) but regionalized programmatically
Many synergistic/integration opportunities in the program ​[rx]
Major successes already demonstrated
Disability alleviation and prevention component to increase coverage and compliance via household and community self-help
Mass drug distribution – an overtly pro-poor intervention
The intervention provides an entry point to both rural and urban health settings
Different drug distribution systems dependent on country decisions
Separation of programmatic and GAELF responsibilities
A free non-restrictive alliance with diverse partners
The strong involvement of academic institutions and research funders
The wide use of IT for dissemination and communication

 

Prevention

  • Avoiding mosquito bites is the best form of prevention – The mosquitoes that carry the microscopic worms usually bite between the hours of dusk and dawn. Living in Fiji, there are many good reasons to avoid mosquito bites, such as other serious diseases as Dengue Fever. You should protect yourself by;
  • Mosquito control – is a supplemental strategy supported by WHO. It is used to reduce transmission of lymphatic filariasis and other mosquito-borne infections. Depending on the parasite-vector species, measures such as insecticide-treated nets, indoor residual spraying or personal protection measures may help protect people from infection.
  • The use of insecticide-treated nets – in areas where Anopheles is the primary vector for filariasis enhances the impact on the transmission during and after MDA. Historically, vector control has in select settings contributed to the elimination of lymphatic filariasis in the absence of large-scale preventive chemotherapy.

To prevent lymphedema from getting worse, patients should ask their physician for a referral to a lymphedema therapist so they can be informed about some basic principles of care such as hygiene, elevation, exercises, skin and wound care, and wearing appropriate shoes.

  • Sleep under a mosquito net.
  • Wear long sleeves and trousers.
  • Use mosquito repellent on exposed skin between dusk and dawn.
  • Stay indoors
  • Wear insect repellent when outdoors
  • Use mosquito nets when sleeping
  • Install flywire on your windows and doors
  • Wear long sleeves and trousers if working outdoors for long periods

You should also take the time to destroy mosquito breeding habitats in your home and community by following these steps, especially in the lead up to and during the summer wet season;

  • Clear leaves and other rubbish from roof gutters and from around the house
  • Remove old tires
  • Don’t leave empty tins, bottle, buckets or drums around, turn upside down to prevent stagnant water forming
  • Cover stored water drums securely
  • Cut long grass
  • Work with your village or neighborhood to remove common breeding habitats from shared areas
  • Remove potential indoor breeding habitats including vases, water try under the fridge, empty bottles and cans, stored water
  • Remove coconut shells and husks as they accumulate water for mosquitoes to breed in.

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