Lymphatic filariasis

Lymphatic filariasis also known as elephantiasis is caused by parasitic worms of the Filarioidea type. Many cases of the disease have no symptoms. Some however develop large amounts of swelling of the arms, legs, or genitals. The skin may also become thicker and pain may occur. The changes to the body can result in social and economic problems for the affected person.

The worms are spread by the bites of infected mosquito. Infections usually begin when people are children. There are three types of worms that cause the disease: Wuchereria bancrofti, Brugia malayi, and Brugia timori. Wuchereria bancrofti is the most common. The worms damage the lymphatic system. The disease is diagnosed by looking, under a microscope, at blood collected during the night. The blood should be in the form of a thick smear and stained with Giemsa. Testing the blood for antibodies against the disease may also be used.

Prevention is by treating entire groups in which the disease exists on a yearly basis in an effort to get rid of the disease entirely. This takes about six years. Medications used include albendazole with ivermectin or albendazole with diethylcarbamazine. The medications do not kill the adult worms but prevents further spread of the disease until the worms die on their own. Efforts to prevent mosquito bites are also recommended including reducing the number of mosquitoes and the use of bed nets.

More than 120 million people are infected with lymphatic filariasis. About 1.4 billion people are at risk of the disease in 73 countries. The areas where it is most common are Africa and Asia. The disease results in economic losses of many billions of dollars a year.

Signs and symptoms



The most spectacular symptom of lymphatic filariasis is "elephantiasis"â€"edema with thickening of the skin and underlying tissuesâ€"which was the first disease discovered to be transmitted by mosquito bites. Elephantiasis results when the parasites lodge in the lymphatic system.

The skin condition it causes is called elephantiasis tropica (also known as "Elephantiasis arabum").

Elephantiasis mainly affects 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 amicrofilaraemic, and often have adverse immunological reactions to the microfilariae, as well as the adult worms.

The subcutaneous worms present with skin 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.

Elephantiasis leads to marked swelling of the lower half of the body.

Causes



Elephantiasis occurs in the presence of microscopic, thread-like parasitic worms such as Wuchereria bancrofti, Brugia malayi, and B. timori, all of which are transmitted by mosquitoes. However, the disease itself is a result of a complex interplay between several factors: the worm, the symbiotic Wolbachia bacteria within the worm, the host’s immune response, and the numerous opportunistic infections and disorders that arise. Consequently, it is common in tropical regions and Africa. The adult worms only live in the human lymphatic system. The parasite infects the lymph nodes and blocks the flow of lymph throughout the body; this results in chronic edema, most often noted in the lower torso (typically in the legs and genitals).

Prevention



Studies have demonstrated transmission of the infection can be broken when a single dose of combined oral medicines is consistently maintained annually for approximately seven years. With consistent treatment, and since the disease needs a human host, the reduction of microfilariae means the disease will not be transmitted, the adult worms will die out, and the cycle will be broken.

The strategy for eliminating transmission of lymphatic filariasis is mass distribution of medicines that kill the microfilariae and stop transmission of the parasite by mosquitoes in endemic communities. In sub-Saharan Africa, albendazole (donated by GlaxoSmithKline) is being used with ivermectin (donated by Merck & Co.) to treat the disease, whereas elsewhere in the world, albendazole is used with diethylcarbamazine. Using a combination of treatments better reduces the number of microfilariae in blood. Avoiding mosquito bites, such as by using insecticide-treated mosquito bed nets, also reduces the transmission of lymphatic filariasis.

In 1993, the International Task Force for Disease Eradication declared lymphatic filariaisis to be one of six potentially eradicable diseases.

According to medical experts the worldwide efforts to eliminate lymphatic filariasis is on track to potentially be successful by 2020. An estimated 6.6 million children have been prevented from being infected, with another estimated 9.5 million in whom the progress of the disease has been stopped.

For podoconiosis, international awareness of the disease will have to rise before elimination is possible. In 2011, podoconiosis was added to the World Health Organization's Neglected Tropical Disease list, which was an important milestone in raising global awareness of the condition.

The efforts of the Global Programme to Eliminate LF are estimated to have prevented 6.6 million new filariasis cases from developing in children between 2000 and 2007, and to have stopped the progression of the disease in another 9.5 million people who had already contracted it. Dr. Mwele Malecela, who chairs the programme, said: "We are on track to accomplish our goal of elimination by 2020." In 2010, the WHO published a detailed progress report on the elimination campaign in which they assert that of the 81 countries with endemic LF, 53 have implemented mass drug administration, and 37 have completed five or more rounds in some areas, though urban areas remain problematic.

Treatment



Treatments for lymphatic filariasis differ depending on the geographic location of the endemic area. In sub-Saharan Africa, albendazole is being used with ivermectin to treat the disease, whereas elsewhere in the world, albendazole is used with diethylcarbamazine. Geo-targeting treatments is part of a larger strategy to eventually eliminate lymphatic filariasis by 2020.

Another form of effective treatment involves rigorous cleaning of the affected areas of the body. Several studies have shown that these daily cleaning routines can be an effective way to limit the symptoms of lymphatic filariasis. The efficacy of these treatments suggests that many of the symptoms of elephantiasis are not directly a result of the lymphatic filariasis but rather the effect of secondary skin infections.

In addition, surgical treatment may be helpful for issues related to scrotal elephantiasis and hydrocele. However, surgery is generally ineffective at correcting elephantiasis of the limbs.

A vaccine is not yet available but is likely to be developed in the near future.

Treatment for podoconiosis consists of consistent shoe-wearing (to avoid contact with the irritant soil) and hygiene - daily soaking in water with an antiseptic (such as bleach) added, washing the feet and legs with soap and water, application of ointment, and in some cases, wearing elastic bandages. Antibiotics are used in cases of infection.

Antibiotics

In 2003 it was suggested that the common antibiotic doxycycline might be effective in treating lymphatic filariasis. The parasites responsible for elephantiasis have a population of symbiotic bacteria, Wolbachia, that live inside the worm. When the symbiotic bacteria are killed by the antibiotic, the adults may either be outright killed or rendered permanently infertile due to reproductive abnormalities that occur in the absence of the bacteria, and the larvae may either die or fail to develop properly.

Clinical trials by the Liverpool School of Tropical Medicine in June 2005 reported that an 8 week course almost completely eliminated microfilariaemia.

Prognosis



About 40 million disfigured and incapacitated by the disease. Elephantiasis caused by lymphatic filariasis is one of the most common causes of disability in the world. In endemic communities, approximately 10 percent of women can be affected with swollen limbs and 50 percent of men can have from mutilating genital disease. In areas endemic for podoconiosis, prevalence can be 5% or higher.

Epidemiology



Lymphatic filariasis affects 120 million people and one billion people at risk for infection. It is considered endemic in tropical and subtropical regions of Asia, Africa, Central and South America, and Pacific Island nations.

In communities where lymphatic filariasis is endemic, as many as 10% of women can be afflicted with swollen limbs, and 50% of men can suffer from mutilating genital symptoms.

Filariasis is considered endemic in 73 countries; 37 of these are in Africa.

In the Americas, it is present in Brazil, Costa Rica, the Dominican Republic, Guyana, Haiti, Suriname, and Trinidad and Tobago.

In the Middle East, it is present only in Yemen.

In Asia, it is present in Bangladesh, Cambodia, India, Indonesia, Laos, Malaysia, Maldives, the Philippines, Sri Lanka, Thailand, Timor-Leste and Vietnam.

In the Pacific region, it is endemic in American Samoa, the Cook Islands, Fiji, French Polynesia, Micronesia, Niue, Samoa, Tonga, Tuvalu, Papua New Guinea, and Vanuatu.

In many of these countries, considerable progress has been made towards elimination of filariasis. Elimination of the disease may have been achieved in several countries, but awaits official confirmation by the WHO.

History



Lymphatic filariasis is thought to have affected humans since about 4000 years ago. Artifacts from ancient Egypt (2000 BC) and the Nok civilization in West Africa (500 BC) show possible elephantiasis symptoms. The first clear reference to the disease occurs in ancient Greek literature, where scholars differentiated the often similar symptoms of lymphatic filariasis from those of leprosy.

The first documentation of symptoms occurred in the 16th century, when Jan Huyghen van Linschoten wrote about the disease during the exploration of Goa. Similar symptoms were reported by subsequent explorers in areas of Asia and Africa, though an understanding of the disease did not begin to develop until centuries later.

In 1866, Timothy Lewis, building on the work of Jean-Nicolas Demarquay and Otto Henry Wucherer, made the connection between microfilariae and elephantiasis, establishing the course of research that would ultimately explain the disease. In 1876, Joseph Bancroft discovered the adult form of the worm. In 1877, the lifecycle involving an arthropod vector was theorized by Patrick Manson, who proceeded to demonstrate the presence of the worms in mosquitoes. Manson incorrectly hypothesized that the disease was transmitted through skin contact with water in which the mosquitoes had laid eggs. In 1900, George Carmichael Low determined the actual transmission method by discovering the presence of the worm in the proboscis of the mosquito vector.

Research directions



University of Illinois at Chicago (UIC) inventors have developed a novel vaccine for the prevention of lymphatic filariasis. This vaccine has been shown to elicit strong, protective immune responses in mouse models of lymphatic filariasis infection.The immune response elicited by this vaccine has been demonstrated to be protective against both W. bancrofti and B. malayi infection.

On September 20, 2007, geneticists mapped the genome (genetic content) of Brugia malayi, the roundworm which causes elephantiasis (lymphatic filariasis). Determining the content of the genes might lead to development of new drugs and vaccines.

References





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