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|A woman suffering from LF displays classic symptoms of the disease: swelling of her leg due to fluid build-up caused by blockage of her lymph system by worms.
Source: Andrea Peterson
Lymphatic filariasis (LF), a mosquito-borne disease, is caused by the parasitic filarial nematodes (roundworms) Wuchereria bancrofti (W. bancrofti), Brugia malayi (B. malayi), or Brugia timori (B. timori). Because the burden of the disease is determined by the intensity and the duration of the infection, the greatest impact of LF is on older age groups. People with the disease can suffer from disfigurement and permanent disabilities due to lymphedema (swelling from fluid build-up caused by improper functioning of the lymph system). Elephantiasis is a crippling condition in which limbs or other parts of the body are grotesquely swollen or enlarged. In addition, people with the disease suffer from hidden internal damage to the kidneys and lymphatic system caused by the filariae. Furthermore, the psychological and social stigma associated with the disease is significant and can adversely affect productivity and quality of life.
More than 120 million people are currently affected by the disease, with 40 million suffering from serious incapacitation and disfigurement. More than 90 percent of infections are due to W. bancrofti. Infection with B. malayi is limited to Asia (China, India, and Malaysia), where it may coexist with W. bancrofti. B. malayi is a zoonosis, with feline and primate reservoirs, affecting about 20 million people. B. timori infection is limited to the islands of southeastern Indonesia. No animal reservoir is known for B. timori or W. bancrofti.
Currently, one-third of the people infected with LF live in India; one-third are in Africa and one-third are in South Asia, the Pacific, and the Americas. However, over the past few decades, the prevalence of bancroftian filariasis has decreased significantly in Latin America. Still, endemic foci persist on several islands in the Caribbean (Haiti, Dominican Republic, and Trinidad and Tobago) and coastal areas of South America (Brazil, Guyana, and Suriname). Of greater concern are the more than 1 billion people who are at risk in more than 80 countries. In tropical and subtropical areas where LF is well established, the prevalence of infection continues to increase. In endemic communities, 10 to 50 percent of men and up to 10 percent of women can be affected.
Lymphatic filariasis results from parasitic worms that are transmitted by the bites of mosquitoes in tropical and subtropical regions of the world. Several species of mosquitoes can transmit the disease. In rural Africa, the Anopheles mosquito is the primary carrier of both LF and malaria. In many urban areas of the affected countries, including India, Culex species is the major vector of W. bancrofti and B. malayi. On some Pacific Islands, Aedes aegyptii and Mansonia are vectors of B. malayi. The efficiency of parasitic transmission to humans differs according to the genera of mosquito. For instance, Anopheles mosquitoes are generally less efficient vectors of W. bancrofti than Culex mosquitoes.
As an infected person ages, the number of microfilariae (baby worms) in the blood increases. There is a positive correlation between the intensity of transmission and the number of years of exposure to infective larvae and LF.
|Source: World Health Organization|
Life Cycle of W. bancrofti
Step 1: An infected mosquito deposits microscopic larvae while biting a person.
Step 2: The larvae migrate to the human lymphatic system.
Step 3: In the lymphatic system, the larvae mature into adult worms, where they mate and form nests. These nests cause blockages, resulting in fluid collection, swelling, and fever. Adult worms live for about 5 to 7 years.
Step 4: Female worms produce millions of microfilariae that swarm in the blood at night when mosquitoes bite.
Step 5: When a mosquito bites a person who has LF, it ingests the microfilariae and becomes infected.
Steps 6 and 7: While inside the mosquito, the microfilariae develop over a period of a week into infectious larvae, and the cycle continues.
While infections are contracted throughout life, most individuals can remain asymptomatic for years, with symptoms emerging during adolescence and adulthood.
Lympatic filariasis can cause a broad range of clinical manifestations, varying from people with no evident clinical disease to those with lymphedema and/or severe disfigurement of the extremities and genitalia. There is a huge potential of overlap in these symptom complexes, although an individual may also experience each at different times during his or her lifetime.
The majority of people infected by LF in endemic areas have few visible clinical manifestations despite the large number of circulating microfilariae in peripheral blood. Although almost all of those infected show no clinical manifestations, they have some degree of subclinical disease, which includes microscopic hematuria and/or proteinuria, dilated and tortuous lymphatic vessels, and scrotal lymphangiectasia in men.
Acute adenolymphangitis (ADL), characterized by sudden onset of high fever, painful lymph node, lymphatic inflammation, and transient local edema, is usually the first manifestation of LF, which usually occurs during adolescence. The retrograde nature of the lymphangitis distinguishes filarial-induced illness from bacterial-induced lymphangitis. Involvement of the genital lymphatics appears exclusively with W. bancrofti infection. Asymptomatic persons may have an ADL episode that lasted 4 to 7 days, with approximately one to three recurrences per year. However, in persons with pre-existing lymphatic disease of the affected extremities, episodes of ADL tend to be more severe and of longer duration. Filarial fever may occur as an episode of acute fever in the absence of inflammation of the lymphatics. In endemic areas, filarial fever may be confused with other febrile manifestations, especially malaria. Epidemiological context and laboratory findings often are supportive of the diagnostic.
Tropical pulmonary eosinophilia (TPE) is a syndrome that develops in some persons in their 30s who are infected with either W. bancrofti or B. malayi. TPE affects more males than females (4-to-1 ratio), and the majority of cases have been reported in Southeast Asia, Pakistan, India, Sri Lanka, Brazil, and Guyana. Administration of diethylcarbamazine (DEC) leads to significant improvement in symptoms and an important decrease of eosinophilia as well as IgE. If not treated, TPE may progress to restrictive lung disease with interstitial fibrosis.
Lymphedema of the limbs, genitalia, and breasts are common manifestations of lymphatic filarial infection. The World Health Organization (WHO) has developed a grading system to quantify the severity of lymphedema of the legs.
Lymphedema of the genitalia usually involves swelling of the scrotum and/or thickening of scrotal or penile skin. Affected adult females living in endemic areas may experience unilateral or bilateral swelling of the breast.
Disease involving the male’s genitourinary system is the most common manifestation of LF due to W. bancrofti. Genitalia involvement is not common in Brugia infection. The prevalence of disease of the female genitalia is not yet known. Chronic disease of the male genitalia mostly produces hydroceles, the diameter of which may vary from 5 cm to more than 30 cm. Parasites are generally not found in the fluid.
Chyluria is a condition that is caused by obstruction or physiological impairment of the renal lymphatics, along with the passage of lymph into the genitourinary track. Patients may occasionally pass urine with a milky appearance. Chyluria may have serious nutritional consequences because large quantities of fat and protein are lost in the urine.
Diagnosis of LF is achieved through a combination of sound epidemiological history, clinical findings, and laboratory tests.
In endemic areas, lymphedema of the limbs or disease of the male genitalia in an individual more than 15 years of age is likely due to a filarial infection in the absence of other obvious causes, such as congestive heart failure or trauma to the lymphatic system.
A definitive diagnosis can be difficult because it is made only by detection of the worm; however, adult parasites localized in lymphatic vessels or nodes are mostly inaccessible. High frequency ultrasound coupled with Doppler techniques may identify motile adult worms in the scrotum (up to 80 percent of infected men) and in the female breast. This technique of diagnosis is very expensive and not suitable for mass or routine diagnostics in developing countries.
Microfilariae can be found through laboratory examination of nocturnal blood. However, many infected individuals do not have microfilaremia, and definitive diagnosis may be difficult.
Assays for circulating antigens of W. bancrofti allow the diagnosis of microfilaremic and cryptic infection. Two tests are currently available: the enzyme-linked immunosorbent assay test and the immunochromatographic card test. The two tests have sensitivity that range from 96 to 100 percent and a specificity of 99 percent.
An antibody-based assay (dipstick test) for diagnosing Brugian filarial infection has been developed for use in Brugian filariasis-endemic areas.
Because disease may persist in individuals with burned-out infections, it is impossible to exclude a diagnosis of filarial-induced disease in the absence of circulating antigens or parasites. This situation may occur in persons with multiple courses of treatment or who have left the endemic areas.
Prevention, Control, and Elimination
Studies have demonstrated that transmission of the infection can be broken when a single dose of combined oral medicines is consistently maintained annually for approximately 7 years. Currently, available drugs for preventive chemotherapy to eliminate LF include DEC, albendazole (donated by GlaxoSmithKline), and ivermectine (donated by Merck & Co., Inc.).
The current strategy of the Global Programme to Eliminate Lymphatic Filariasis is based on mass treatment with a single annual dose of DEC plus albendazole or albendazole plus ivermectine for areas where onchocerciasis is also endemic (DEC not recommended because of possible reduction in visual acuity in onchocerciasis-infected persons); the treatment is administered for about 7 years. To date, tremendous results have been achieved in many countries in the interruption of disease transmission.
The strategy of the Global Programme to Eliminate Lymphatic Filariasis is being refined and guided by ongoing research to understand the ecology and transmission efficiency of diverse mosquito vector species and efficacy of various drug regimens combined with insecticide-impregnated nets used in malaria control programs.