What is elephantiasis?

Causes and Symptoms

Elephantiasis is characterized by gross enlargement of a body part caused by the accumulation of fluid and connective tissue. It most frequently affects the legs but may also occur in the arms, breasts, scrotum, vulva, or any other body part. The disease starts with the slight enlargement of one leg or arm (or other body part). The limb increases in size with recurrent attacks of fever. Gradually, the affected part swells, and the swelling, which is soft at first, becomes hard following the growth of connective tissue in the area. In addition, the skin over the swollen area changes so that it becomes coarse and thickened, looking almost like elephant hide. The elephant-like skin, along with the enlarged body parts, gave the disease the name elephantiasis.

Elephantiasis is found worldwide, mostly in the tropics and subtropics. About 90 percent of cases of elephantiasis are a result of infection with a parasitic worm called Wuchereria bancrofti (W. bancrofti). W. bancrofti belongs to a group of
worms called filaria, or roundworms, and infection with a filarial worm is called filariasis. Filariasis caused by W. bancrofti is the most common and widespread type of human filarial infection and is often called Bancroft’s filariasis; filarial infections that can cause elephantiasis are known in general as lymphatic filariasis. Elephantiasis is the advanced, chronic stage of lymphatic filariasis, and only a small percentage of persons with the infection will develop elephantiasis. During Bancroft’s filariasis, adult forms of W. bancrofti live inside the human lymphatic system, and it is the person’s reaction to the presence of the worm that causes the symptoms of the disease. The worm’s life cycle is important in understanding how the disease is transmitted from one person to another, how the symptoms develop, and how to prevent and reduce the incidence of the disease.

The adult worms live in human lymphatic vessels and lymph nodes and measure about 4 centimeters in length for the male and 9 centimeters in length for the female. Both are threadlike and about 0.3 millimeters in diameter. After mating, the female releases large numbers of embryos or microfilariae (microscopic roundworms), which are more than one hundred times smaller in length and ten times thinner than their parents. They make their way from the lymphatic system into the bloodstream, where they can circulate for two years or longer. Interestingly, most strains of microfilariae exhibit a nocturnal periodicity, in which they appear in the peripheral blood system (the outer blood vessels, such as those in the arms, legs, and skin) only at night, mostly between the hours of 10 p.m. and 2 a.m., and spend the remainder of the time in the blood vessels of the lungs and other internal organs. This nighttime cycling into the peripheral blood is somehow related to the patient’s sleeping habits, and although it is unknown exactly how or why the microfilariae do this, it is necessary for the survival of the worms. The microfilariae must develop through at least three different stages (called the first, second, and third larval stages) before they are ready to mature into adults; these stages take place not within humans but within certain types of mosquitoes, which bite at night. Thus, the microfilariae appear in the peripheral blood just in time for the mosquitoes to bite an infected human and extract them so that they can continue their life cycle. It is important to note, therefore, that both humans and the proper type of mosquito are needed to keep a filariasis infection going in a particular area.

Female night-feeding
mosquitoes of the genera Culex, Aedes, and Anopheles serve as intermediate hosts for Wuchereria bancrofti. The mosquitoes bite an infected person and ingest microfilariae from the peripheral blood. The microfilariae pass into the intestines of the mosquito, invade the intestinal wall, and within a day find their way to the thoracic
muscles (the muscles in the middle part of the mosquito’s body). There they develop from first-stage to third-stage larvae in about two weeks, and the new third-stage larvae move from the thoracic muscles to the head and mouth of the mosquito. Only the third-stage larvae are able to infect humans successfully, and the third stage can mature only inside humans. When the mosquito takes a blood meal, infective larvae make their way through the proboscis (the tubular sucking organ with which a mosquito bites a person) and enter the skin through the
puncture wound. After they enter the skin, the larvae move by an unknown route to the lymphatic system, where they develop into adult worms. It takes about one year or longer for the larvae to grow into adults, mate, and produce more microfilariae.

A person contracts Bancroft’s filariasis by being bitten by an infected mosquito. Various forms of the disease can occur, depending on the person’s immune response and the number of times the person is bitten. The period of time from when a person is first infected with larvae to the time microfilariae appear in the blood can be between one and two years. Even after this time some persons, especially young people, show no symptoms at all, yet they may have numerous microfilariae in their blood. This period of being a carrier of microfilariae without showing any signs of disease may last several years, and such carriers act as reservoirs for infecting the mosquito population.

In those patients showing symptoms from the infection, there are two stages of the disease: acute and chronic. In acute disease, the most common symptoms are a recurrent fever and lymphangitis or lymphadenitis in the arms, legs, or genitals. These symptoms are caused by an inflammatory response to the adult worms trapped inside the lymphatic system. Lymphangitis, an inflammation of the lymph vessels, is characterized by a hard, cordlike swelling or a red superficial streak that is tender and painful. Lymphadenitis is characterized by swollen and painful lymph nodes. The attacks of fever and lymphangitis or lymphadenitis recur at irregular intervals and may last from three weeks up to three months. The attacks usually become less frequent as the disease becomes more chronic. In the absence of reinfection, there is usually a steady improvement in the victim, each relapse being milder. Thus, without specific therapy, this condition is self-limiting and presumably will not become chronic in those acquiring the infection during a brief visit to an area where the disease is endemic.

The most obvious symptoms caused as a result of W. bancrofti infection, such as elephantiasis, are noted in the chronic stage. Chronic disease occurs only after years of repeated infection with the worms. It is seen only in areas where the disease is endemic and only occurs in a small percentage of the infected population. The symptoms are the result of an accumulation of damage caused by inflammatory reactions to the adult worms. The inflammation causes tissue death and a buildup of scar tissue that eventually results in the blockage of the lymphatic vessels in which the worms live. One of the functions of lymphatic vessels is to carry excess fluid away from tissues and bring it back to the blood, where it enters the circulation again as the fluid portion of the blood. If the lymphatic vessels are blocked, the excess fluid stays in the tissues, and swelling occurs. When this swelling is extensive, grotesque enlargement of that part of the body occurs.

Treatment and Therapy

One way in which doctors can tell whether a person has Bancroft’s filariasis is by taking a sample of peripheral blood at night and looking at the blood under a microscope to try to find microfilariae. Sometimes, the ability to find microfilariae is enhanced by filtering the blood to concentrate the possible microfilariae in a smaller volume of liquid. Many persons infected with W. bancrofti have no detectable microfilariae in their blood, so other methods are available. In the absence of microfilariae, a diagnosis can be made on the basis of a history of exposure, symptoms of the disease, positive antibody or skin tests, or the presence of worms in a sample of lymph tissue. It is important to note that in addition to W. bancrofti, a few other filarial worms and at least one bacteria can also cause elephantiasis; therefore, if symptoms of elephantiasis are observed, it is important to discover the correct cause so that the proper treatment can be given. Since chronic infection occurs after prolonged residence in areas where the disease occurs, patients with acute disease should be removed from those areas. They also should be reassured that elephantiasis is a rare complication that is limited to persons who have had constant exposure to infected mosquitoes for years. The best way to avoid contracting filariasis when traveling to an affected area is to avoid being bitten by mosquitoes. Insect repellent, mosquito netting, and other methods are helpful in this regard.

The World Health Organization (WHO) recommends treating lymphatic filariasis through mass drug administration to at-risk populations. The preferred regimen consists of a single dose of two combined drugs: albendazole and either ivermectin or diethylcarbamazine citrate (DEC). These drugs kill the parasites with the body. Generally, in the treatment of acute disease, excellent results are obtained when the proper dosages of the drugs are given. Side effects include nausea or vomiting, usually relatively mild, and fever and dizziness, the severity of which depends on the number of microfilariae a person has in his or her blood; the more microfilariae, the more severe the reaction. Other drugs have been used in the treatment of filariasis, including suramin, metrifonate, and levamisole, but they are generally less effective or more toxic than the WHO's recommended regimen. Additional treatment measures include bed rest and supportive measures, such as using hot and cold compresses to reduce swelling. The administration of antibiotics for patients with secondary bacterial infections and painkillers as well as anti-inflammatory agents during the painful, acute stage is helpful. Sometimes, swollen limbs can be wrapped in pressure bandages to force the lymph from them. If the distortion is not too great, this method is successful. It should also be noted that although drugs such as DEC, albendazole, and ivermectin might be effective in killing W. bancrofti, the chronic lesions resulting from the infection are mostly incurable. Signs of chronic filariasis, such as elephantiasis of the limbs or the scrotum, are usually unaffected or only incompletely cured by medication, and it sometimes becomes necessary to apply surgical or other symptomatic treatments to relieve the suffering of the patients. Chronic obstruction in less advanced stages is sometimes improved by surgery. The surgical removal of an elephantoid breast, vulva, or scrotum is sometimes necessary.

Theoretically, it should be possible first to control and eventually to eliminate Bancroft’s filariasis. Conditions that are highly favorable for continued propagation of the infection include a pool of microfilariae carriers in the human population and the right species of mosquitoes breeding near human habitations. Thus, control can be effected by treating all microfilariae carriers in an affected area and eliminating the necessary mosquitoes. It is important to note that eliminating the mosquitoes alone will not control the disease, especially in tropical areas, since the breeding period and season in which the disease can be transmitted is so extensive. In some temperate areas, where Bancroft’s filariasis used to be endemic, measures that removed the mosquitoes alone aided in the elimination of the disease from that area, since in temperate areas the breeding period and thus the season for transmission is so short. In tropical areas, both drug therapy and mosquito control must be applied in order to control the disease.

The mosquito population can be controlled in four ways. First, general sanitation measures such as draining swamps can be carried out in order to reduce the areas where the mosquitoes are breeding. Second, insecticides can be used to kill the adult mosquitoes. Third, larvacides can be applied to sources of water where mosquitoes breed in order to kill the mosquito larvae. Finally, natural mosquito predators, such as certain species of fish, can be introduced into waters where mosquitoes breed to eat the mosquito larvae. Numerous problems stand in the way of eradication, such as poor sanitation, persons who do not cooperate with medical intervention, mosquitoes that become resistant to all known insecticides, increasing technology that yields increasing water supplies and therefore places for mosquitoes to breed, large populations, ignorance of the cause of the disease, and lack of medicine and distribution channels.

Perspective and Prospects

Dramatic symptoms of elephantiasis, especially the enormous swelling of legs or the scrotum, were recorded in much of the ancient medical literature of India, Persia, and the Far East. The embryonic form of microfilariae was first discovered and described in Paris in 1863. The organism was named for O. Wucherer, who also discovered microfilariae in 1866, and Joseph Bancroft, who discovered the adult worm in 1876. Two important facts about W. bancrofti—namely, its development in mosquitoes and the nocturnal periodicity of the microfilariae—were discovered by Patrick Manson between 1877 and 1879. This was the first example of a disease being transmitted by a mosquito, and its discovery earned for Manson the title of founder of tropical medicine. These and most of the other essential facts of the disease were discovered before the end of the nineteenth century. Progress in the epidemiology and control of filariasis came after World War II. In 1947, DEC was shown to kill filariae in animals, and this result was followed by the successful use of DEC in the treatment of humans. The first promising results in the control of Bancroft’s filariasis by mass administration of DEC were reported in 1957 on a small island in the South Pacific. Through subsequent studies, it has become clear that effective control of the infection can be achieved if sufficient dosages of DEC and related drugs are administered to infected populations.

Filariasis is a serious health hazard and public health problem in many tropical countries. Infection with W. bancrofti has been recorded in nearly all countries or territories in the tropical and subtropical zones of the world. The infection occurs primarily in coastal areas and islands that experience long periods of high humidity and heat. Infections have also been noted in some temperate zone districts, such as mainland Japan, central China, and some European countries. In early 2013, the WHO estimated that more than 120 million people worldwide were infected and more than 1.4 billion were at risk.

Bibliography

Beaver, Paul C., and Rodney C. Jung. Animal Agents and Vectors of Human Disease. 5th ed. Philadelphia: Lea & Febiger, 1985.

Biddle, Wayne. A Field Guide to Germs. 2d ed. New York: Anchor Books, 2002.

Frank, Steven A. Immunology and Evolution of Infectious Disease. Princeton, N.J.: Princeton University Press, 2002.

Global Health, Division of Parasitic Diseases and Malaria. "Lymphatic Filariasis." Centers for Disease Control and Prevention, February 1, 2012.

Joklik, Wolfgang K., et al. Zinsser Microbiology. 20th ed. Norwalk, Conn.: Appleton and Lange, 1997.

MedlinePlus. "Lymphatic Diseases." MedlinePlus, April 23, 2013.

Ransford, Oliver. “Bid the Sickness Cease.” London: John Murray, 1983.

Roberts, Larry S., and John Janovy, Jr., eds. Gerald D. Schmidt and Larry S. Roberts’ Foundations of Parasitology. 7th ed. Boston: McGraw-Hill Higher Education, 2005..

Salyers, Abigail A., and Dixie D. Whitt. Bacterial Pathogenesis: A Molecular Approach. 2d ed. Washington, D.C.: ASM Press, 2002.

World Health Organization. "Lymphatic Filariasis." World Health Organization, March 2013.