Lymphatic filariasis

Related Terms

Brugia malayi, Brugia timori, elephantiasis, infection, mosquito, nematode, parasite, parasitology, roundworm, Wuchereria bancrofti.

Background

Lymphatic filariasis, also known as elephantiasis, is a parasitic infestation of nematodes. Nematodes are worms, commonly known as roundworms because of their shape. The nematodes that invade the human body and damage internal structures are Brugia malayi, Brugia timori,and Wuchereria bancrofti.
The disease is transmitted from human to human by certain species of mosquitoes. Mosquito species that can transmit the disease are Culex quinquefasciatus mosquitoes and some Anopheles species; Brugia roundworms are primarily transmitted by Mansonia mosquitoes.
If a human is infected, he or she carries larvae, known as microfilariae, in the bloodstream. A larva is the transitional form of a worm between the egg and adult. If an infected person is bitten by a mosquito that is capable of carrying the microfilaria, these organisms then develop within the mosquito to an infective stage. The process takes one to three weeks before the larvae travel to the mosquito's biting mouth parts. When the mosquito bites another human, the larvae enter that person's bloodstream, thus completing the infectious cycle.
The microfilariae travel from the bloodstream into the lymphatic system, which is a network of vessels that maintain a delicate fluid balance between body's tissues and the bloodstream. They lodge in the lymphatic system where they mature into adult worms. These worms live for four to six years and produce millions of immature microfilariae that circulate in the blood.
The adult worms block the normal flow of lymphatic fluid, damaging the lymphatic system. This blockage produces tremendous enlargement of the arms, legs, or genitals, which may swell up to several times their normal size. The worms also lodge in the kidneys, causing damage to this organ.
More than 120 million people have lymphatic filariasis and more than 40 million of those individuals are seriously disfigured and incapacitated. Affected body parts include the arms, legs, genitals, and breasts. Tremendously swollen legs and genitals make walking difficult. Kidney damage caused by filariasis can cause serious health problems and even death. More than one billion people in developing countries are at risk of infection.
Of those currently infected, about one-third live in Africa, about one-third in India, and the rest in South Asia, the Americas, and Pacific Islands. In these regions, affected individuals usually live in poor, underdeveloped communities.

Signs and symptoms

Although lymphatic filariasis damages the lymphatic system, most individuals who are infected never develop symptoms. A small proportion of infected individuals will develop lymphedema, in which improper functioning of the lymph system causes fluid collection and swelling. This generally occurs in the legs but may also affect the breasts, arms, and genitalia. Lymphedema may not develop until several years after an individual has become infected. Men may develop swelling of the scrotum, called hydrocele.
Decreased functioning of the lymphatic system places individuals infected with lymphatic filariasis at increased risk for other infections. Frequent bacterial infections of the skin and lymph system causes the skin to harden and thicken, giving the skin the appearance of elephant skin.
Lymphatic filariasis can also lead to pulmonary tropical eosinophilia syndrome, which is characterized by cough, shortness of breath, and wheezing.

Diagnosis

In areas where lymphatic filariasis is commonplace, a person with tremendously swollen arms, legs, genitals, or breasts most likely has the disease. Until recently, diagnosis was very difficult because it required microscopic detection of the roundworms from a blood sample. In addition, the worms often exhibit a nocturnal periodicity, meaning that the microfilariae (larvae) are visible in the blood only during late night hours.
A simple "card test" is now available that detects antigens to the parasite. An antigen is a substance in the bloodstream that reacts to a foreign organism by a process known as an immune response. This test requires a finger prick to obtain a small blood sample but does not have to be done in a laboratory. This test markedly increases the ability to diagnose and treat the disease. This test can also identify individuals who carry the disease but have no symptoms and therefore can be used in a community screening program to detect how many people are infected. A more complex but highly accurate test that can be done in a genetics laboratory includes DNA sequencing for nematode-specific DNA in a blood sample.

Complications

The adult worms block the normal flow of lymphatic fluid, damaging the lymphatic system. This blockage produces tremendous enlargement of the arms, legs, or genitals, which may swell up to several times their normal size. The worms also lodge in the kidneys, causing damage and decreasing kidney function.
Lymphatic filariasis causes a severe social burden because infected individuals, both men and women, often are social outcasts and have physical limitations. Opportunities for employment and marriage are severely reduced.

Treatment

For effective control of the disease in a community, infected individuals must have the microfilariae completely removed (eradicated) from their blood. Until recently, a 12-day course of an antiparasitic drug called diethycarbamazine (DEC) was given to infected individuals. Following treatment, microfilariae are eradicated for a full year. Recent studies have shown that a single dose of DEC is equally effective for treatment.
The most effective treatment currently available is a single dose of two drugs administered at the same time. This two-drug treatment may include albendazole with either DEC or ivermectin and is 99% effective in removing microfilariae from the blood for one year.
Although these treatments remove the parasites and reduce swelling, additional measures to improve lymphatic fluid flow are used, such as elevating and massaging swollen limbs. Good hygiene of the affected limbs is necessary to further reduce swelling and prevent further infection with bacteria or fungi.
Current antiparisitic drug therapy is approaching 100% effectiveness. However, some drugs have unpleasant and sometimes serious side effects. Common side effects of albendazole, DEC, and ivermectin include chills, fever, and muscle pain (myalgia). The intensity of side effects is significantly higher with ivermectin than with DEC. Side effects usually are most severe 24 hours after taking the medicine. Serious side effects are rare and usually occur with prolonged usage. They include loss of vision, tunnel vision, and night blindness.

Integrative therapies

Note: Currently there is insufficient evidence available on the safety and effectiveness of integrative therapies for the prevention or treatment of lymphatic filariasis. The therapies below have been studied for their effect on infections in general, should be used only under the supervision of a qualified healthcare provider, and should not be used in replacement of other proven therapies.
Good scientific evidence:
Probiotics: Probiotics are beneficial bacteria (sometimes referred to as "friendly germs") that help to maintain the health of the intestinal tract and aid in digestion. Limited evidence with day care children suggests that supplementation with Lactobacillus GG may reduce the number of sick days, frequency of respiratory tract infections, and frequency of related antibiotic treatments. Fermented milk (with yogurt cultures and L. casei DN-114001) may reduce the duration of winter infections (gastrointestinal and respiratory), as well as average body temperature, in elderly people. Probiotics are generally considered safe and well-tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant.
Unclear or conflicting scientific evidence:
Oregano: Early study shows that taking oregano by mouth may help treat parasites. Further research is needed to confirm these results. Avoid in individuals with a known allergy or hypersensitivity to oregano. Based on historical use, it appears that oregano is well tolerated in recommended doses. However, reliable clinical trials demonstrating safety or efficacy of a particular dose or for a recommended treatment duration are currently lacking in the available literature. Oregano may lower blood sugar levels. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Serum glucose levels may need to be monitored by a healthcare provider, and medication adjustments may be necessary. Oregano is not recommended at doses above those normally found in food during pregnancy and lactation due to a lack of available scientific evidence.
Prayer: Prayer can be defined as a "reverent petition," the act of asking for something while aiming to connect with God or another object of worship. Prayer on behalf of the ill or dying has played a prominent role throughout history and across cultures. Prayer may help reduce the length of hospital stay as well as the duration of fever in patients with infections. However, early study is controversial and additional study is needed before a conclusion can be drawn. Prayer is not recommended as the sole treatment approach for potentially serious medical conditions, and should not delay the time it takes to consult with a healthcare professional or receive established therapies. Sometimes religious beliefs come into conflict with standard medical approaches, and require an open dialog between patients and caregivers. Based on one clinical study, patients certain that they were receiving intercessory prayer had a higher incidence of complications following cardiac bypass surgery than those who did not know they were being prayed for.
Propolis: Bees create propolis, a natural resin, to build their hives. Propolis is made from the buds of conifer and poplar trees, beeswax, and other bee secretions. Animal and laboratory studies suggest that propolis may help treat various types of infections. Initial human research reports possible benefits against bacteria in the mouth, genital herpes, urine bacteria, intestinal giardia infections, or H. pylori. Additional research is needed before a recommendation can be made. Avoid if allergic or hypersensitive to propolis, black poplar (Populas nigra), poplar bud, bee stings, bee products, honey, and Balsam of Peru. Severe allergic reactions have been reported. Use cautiously with asthma or gastrointestinal disorders. Avoid if pregnant or breastfeeding because of the high alcohol content in some propolis products.
Selenium: Selenium is a trace mineral found in soil, water, and some foods. It is an essential element in several metabolic pathways. Preliminary research reports that selenium can be beneficial in the prevention of several types of infection, including recurrence of erysipelas (bacterial skin infection associated with lymphedema), sepsis, or Mycoplasma pneumonia. Selenium may help prevent infection by stimulating immune function. Further research is needed to confirm these results before a clear recommendation can be made. Avoid if allergic or sensitive to products containing selenium. Avoid with history of nonmelanoma skin cancer. Selenium is generally regarded as safe for pregnant or breastfeeding women. However, animal research reports that large doses of selenium may lead to birth defects.

Prevention

Providing the necessary education, vaccination, and treatment of infected individuals in large undeveloped areas of the world is a difficult task.
Infection with lymphatic filariasis can be prevented by avoiding mosquito bites, especially during the hours from dusk to dawn, when infected mosquitoes are more likely to bite. In addition, sleeping under a mosquito net and wearing a long-sleeve shirt and long pants can help prevent infection.
Infected individuals can prevent elephantiasis by keeping the skin clean and free of harmful bacteria.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Bagavan A, Rahuman AA, Kamaraj C, et al. Larvicidal activity of saponin from Achyranthes aspera against Aedes aegypti and Culex quinquefasciatus (Diptera: Culicidae). Parasitol Res. 2008 Apr 6.
Frances SP, Baade LM, Kubofcik J, et al. Seroconversion to filarial antigens in Australian defence force personnel in Timor-Leste. Am J Trop Med Hyg. 2008 Apr;78(4):560-3.
Natural Standard: The Authority on Integrative Medicine. .
Hewitson JP, Harcus YM, Curwen RS, et al. The secretome of the filarial parasite, Brugia malayi: proteomic profile of adult excretory-secretory products. Mol Biochem Parasitol. 2008 Jul;160(1):8-21.
Rathaur S, Yadav M, Gupta S, et al. Filarial glutathione-S-transferase: A potential vaccine candidate against lymphatic filariasis. Vaccine. 2008 Apr 25.
Subramanyam Reddy G, Vengatesvarlou N, Das PK, et al. Tolerability and efficacy of single-dose diethyl carbamazine (DEC) or ivermectin in the clearance of Wuchereria bancrofti microfilaraemia in Pondicherry, south India. Trop Med Int Health. 2000 Nov;5(11):779-85.
Supali T, Djuardi Y, Pfarr KM, et al. Doxycycline treatment of Brugia malayi-infected persons reduces microfilaremia and adverse reactions after diethylcarbamazine and albendazole treatment. Clin Infect Dis. 2008 May 1;46(9):1385-93.
World Health Organization (WHO). .

Causes

Lymphatic filariasis is a parasitic infestation of nematodes, a type of worm. The nematodes that invade the human body and damage internal structures are Brugia malayi, Brugia timori,and Wuchereria bancrofti. The disease is transmitted from human to human by certain species of mosquitoes. Lymphatic filariasis cannot be spread to humans if the mosquitoes carrying the disease are not present in the area. A mosquito that transmits an infection is known as a vector.
If a human is infected, he or she carries larvae, known as microfilariae, in the bloodstream. If an infected person is bitten by a mosquito that is capable of carrying the microfilaria, these organisms then develop within the mosquito to an infective stage. The process takes one to three weeks before the larvae travel to the mosquito's biting mouth parts. When the mosquito bites another human, the larvae enter that person's bloodstream, thus completing the infectious cycle.
The microfilariae travel from the bloodstream into the lymphatic system, where they lodge and mature. Adult worms live for four to six years and produce millions of immature microfilariae that circulate in the blood.

Risk factors

More than 120 million people have lymphatic filariasis. Of those currently infected, about one-third live in Africa, about one-third in India, and the rest in South Asia, the Americas, and Pacific Islands. In these regions, affected individuals usually live in poor, underdeveloped communities.
In order to contract lymphatic filariasis, repeated bites from infected mosquitoes are required over the course of several months. Individuals who live in tropical or sub-tropical areas are at greatest risk for the disease. Individuals who live or work there for a short time or tourists visiting such areas are at fairly low risk.

Research

Current research is focused on vaccines to prevent the disease, different drug combinations that better treat the infection, and pesticides to kill the mosquitoes that carry the worms. Filarial glutathione-S-transferase is currently under investigation as a possible vaccine. This substance is an enzyme that has been shown to inactivate and kill the microfilariae and adult female worms.
The nematode Brugia malayi is of particular interest for current research because of evidence that infection with the organism results in marked reduction (down-modulation) of the infected human's or host's immune response. This is accomplished by secretions from the parasites, which are essentially an expression of its genome. Analyzing this genome should provide important new understanding of the parasite's biology.
Doxycycline is under investigation as a supplementary agent to use with albendazole, DEC, or ivermectin therapy. Doxycycline is an antibiotic effective against a large variety of bacteria. It appears to boost the effect of antiparasitic drugs used to treat lymphatic filariasis and malaria.
The leaf extracts of Acalypha indica are under investigation as a potential pesticide that kills mosquito larvae.

Future research

Future research is focused on the same areas as current research: vaccines to prevent the infection, more effective treatment for infected individuals, and pesticides to kill the mosquitoes that transmit the nematodes from person to person.
A major focus of future research will be in the area of genomics. As knowledge increases, effective treatment of the condition should follow.