Life cycle

The life cycle, in common with all nematodes, has 5 developmental or larval stages in a vertebral host and an arthropod intermediate host and vector.

• Adult female worms produce thousands of first-stage larvae or microfilariae that are ingested by a feeding insect vector.
• The arthropod vectors are mosquitoes or flies. They may have a circadian rhythm in which they feed and this correlates with a circadian rhythm of the microfilariae in the circulation.
• The highest concentration of microfilariae usually occurs at the time of day when the local vector is most active in feeding.
• Microfilariae undergo 2 stages of development in the insect.
• Larvae at the third stage are then inoculated back into the vertebral host during feeding and the final 2 stages of development follow.

Epidemiology

• More than 120 million people in the world are estimated to be affected by lymphatic filariasis, with 40 million seriously affected according to the World Health Organisation.^[1]
• It is found throughout the tropics and subtropics.
• In 1997, the World Health Organisation started a programme to eradicate lymphatic filariasis from the world.^[1]

Both sexes are affected equally. The rate of infection increases throughout childhood and adolescence although it may be many years before the clinical features are seen.

Lymphatic filariasis is caused by Wuchereria bancrofti, Brugia malayi, and Brugia timori. It is spread by mosquitoes of the genera Aedes, Anopheles, Culex, and Mansonia. 90% of lymphatic filariasis is caused by W. bancrofti and the rest is mostly caused by B. malayi. B. malayi does not affect genitalia lymphatics.

Presentation

The symptoms are predominantly the result of adult worms in the lymphatics. There are three broad types of clinical scenarios:

• Asymptomatic infection
• Acute infection
• Chronic infection

Asymptomatic infection

• This is seen commonly in areas where the disease is endemic.
• Patients have no symptoms but microfilaria can be detected in peripheral blood smears.
• These patients will already have irreversible lymphatic changes highlighting the importance of their detection and treatment.

Acute infection

This includes acute adeno-lymphangitis (ADL) and acute filarial lymphangitis (AFL)

Acute adeno-lymphangitis

This is the commonest acute presentation.
It is characterised by:

• Fever and painful lymphadenopathy in the groin and axillae.
• Affected areas are painful, tender, red and swollen - usually result of superimposed bacterial infection.
• Occur several times in a year and more so in rainy seasons. The reason for this is that in the rainy season the moisture between toes increases leading to fungal infections which damage the skin allowing worms to invade.
• This is why each episode of ADL enhances the development of lymphoedema.

Acute filarial lymphangitis

• Rare compared with ADL
• Caused by dying adult worms (either spontaneously or with treatment)
• Characterised by small tender nodules at the site of worms dying which may either be along the involved lymphatic or in the scrotum
• Tender and enlarged lymphatics may be seen
• There is no fever or secondary infections

Chronic infection

• This is manifested by lymphoedema, elephantiasis and lesions of the genito-urinary system.
• Lymphoedema is the commonest and may progress to elephantiasis.
• The lower limbs are most commonly involved - but the upper limbs, genitalia and breast in females may also be involved.
• Frequent episodes of ADL lead to the progression of lymphoedema.
• Hydrocele is commonly seen in chronic infection.
• Chylocoele, chyluria and chylous ascites occur rarely.

Tropical pulmonary eosinophilia

This is a form of occult filariasis. Presenting symptoms include:

• Paroxysmal dry cough
• Scattered wheezes and crackles are heard in both lungs
• Dyspnoea
• Anorexia
• Malaise
• Weight loss
• Lymphadenopathy and hepatomegaly may be found

Investigations

Blood

The usual means of detecting the parasite is by examination of peripheral blood. Most species, and all those that produce lymphatic involvement, may be detected by this method. It may be necessary to take the blood at a time when the circadian rhythm gives a high count. Another technique is to give a small dose of the drug DEC to precipitate them into the circulation.

Immunological tests

Circulating filarial antigen may be detected using commercially available kits to test venous blood. This can be used in diagnosis and to monitor treatment. Antibody tests are also available. Eosinophilia is marked in all forms of filarial infection. Serum IgE and IgG4 is elevated with active disease. Polymerase chain reaction tests are also available which have a high specificity and sensitivity.

Urinalysis

If lymphatic filariasis is suspected, urine should be examined macroscopically for chyluria and then concentrated to examine microscopically for microfilariae. Chyluria results from obstruction of lymphatic drainage.

Imaging

Obstruction of the inguinal and scrotal lymphatics can be demonstrated and monitored by ultrasound. More recently ultrasonography has been used to detect adult worms in male scrotal lymphatics and lymphoscintigraphy has been used to detect lymphatic changes.^[2]

It is important to appreciate that some of the newer and more sophisticated investigation methods may not be available in areas where the disease is endemic. Thus use of peripheral blood smears and immunological tests is the predominant detection method used.

Management

Control of the disease appears to be aimed at treatment of individuals and treatment of populations rather than vector control.^[3]

General measures

• Bed rest, limb elevation, and compression bandages are the traditional management of lymphoedema.
• Once infection has occurred a "foot care programme" is paramount to break the cycle of infection and worsening lymphoedema. This involves washing of the affected area (including webs of the toes and deep folds), wiping area dry, clipping and cleaning nails, avoiding injuries or infections and applying antifungal substances.^[2]
• Prevention of repeated ADLs is also important and may require long term antibiotic therapy eg oral penicillin or long acting parenteral penicillin. Unfortunately, a lot of these simple measures are not achievable in areas where the disease is endemic due to economic and other political factors.

Drugs

• The most commonly used drug to treat the condition is diethyl-carbamazine, usually abbreviated to DEC. It will kill both adult worms and microfilariae.^[2] It is not licensed for use in the UK but can be used on a named patient basis.
• Rapid destruction of worms can be associated with the development of fever, headache, myalgia, sore throat lasting 1-2 days. Thus lower doses may be used initially in heavy infection and steroid cover may be given for this reason.
• DEC should be given for a longer duration in Tropical Eosinophilia Syndrome (treatment for 1 month is usual).
• Other drugs may be used alone or in combination with DEC.
• Ivermectin may be used for W. bancrofti alone or in combination with DEC. It is highly effective but adverse reactions need supervision.^[4]
• Mebendazole and its analogue flubendazole may be used. Albendazole is another possibility. A single-dose ivermectin with or without albendazole appears to be effective to treat W. bancrofti infection.^[5][6] The global filariasis elimination programme advises this combination. There is a serious risk of adverse effects, so patients should be observed for a while after initiating treatment.

Community treatment

• The elimination of lymphatic filariasis from a community requires delivery of annual drug treatments to at least 80% of the eligible members of endemic populations for at least 5 years. For various reasons, this is not being achieved in much of sub-Saharan Africa.^[7]

Complications and prognosis

• Filarial diseases are rarely fatal, but those affected tend to suffer poor health, they have more time off work and are less productive.^[8]
• The WHO has identified lymphatic filariasis as the second leading cause of permanent and long-term disability in the world after leprosy.
• The morbidity of human filariasis mainly results from the host reaction to microfilariae or developing adult worms in different areas of the body.

Prevention

This is based on avoidance of bites by vectors when in endemic areas. The article on Malaria discusses avoidance of mosquito bites.