Lymphatic filariasis (LF), commonly known as elephantiasis, is a vector-borne neglected tropical disease (NTD) targeted for global elimination as a public health problem.
It is a painful and profoundly disfiguring disease, causing pain, severe disability, exclusion from work, increased medical expenses and social stigma.
LF is caused by infection with three species of thread-like nematode worms called nematodes of the family Filariodidea – Wuchereria bancrofti (responsible of 90% of the infections), Brugia malayi (most of the remainder of the cases) and Brugia timori. Male worms are about 3–4 centimetres in length, and female worms 8–10 centimetres. The male and female worms together form “nests” in the lymphatic vessels disrupting the normal function of the lymphatic system that maintain the delicate fluid balance between blood and body tissues and is essential for the body’s immune system. The worms can live for approximately 6–8 years and, during their life time, produce millions of microfilariae (immature larvae) that circulate in the blood.
Humans are the exclusive host of infection with W. bancrofti. Although certain strains of B. malayi can also infect some animal species (felines and monkeys), the life cycle in these animals is perceived as epidemiologically distinct from that in humans.
LF is transmitted by the bite of different types of mosquitoes: 1.-Culex mosquito, widespread across urban and semi-urban areas and the mayor vector of W. bancrofti, 2.-Anopheles mosquito, mainly found in rural areas, and 3.-Aedes mosquito mainly in endemic islands in the Pacific.
Mosquitoes are infected with microfilariae by ingesting blood when biting an infected host. Adult male and female worms lodge in the lymphatics. Fecund females release larvae (microfilaria) which periodically circulate in the blood. Microfilariae must mature into infective larvae within the mosquito. When infected mosquitoes bite people, mature parasite larvae are deposited on the skin from where they can enter the body. The larvae then migrate to the lymphatic vessels where they develop into adult worms, thus continuing a cycle of transmission.
Transmission in a community is influenced by the number of infected persons (prevalence), the density of microfilaria in the blood of infected persons, the density of vector mosquitoes, characteristics of the vector that affect development of infective larvae and frequency of human-vector contact.
The incubation period is completely variable, and can be as short as 4 weeks or as long as 8-16 months. It goes from the entrance of the infective larva into the human host and the presentation of clinical symptoms or observable signs.
Filarial infection can cause a variety of clinical manifestations. The vast majority of infected people are asymptomatic, showing no external signs of infection while contributing to transmission of the parasite. Virtually all of them have subclinical lymphatic damage and as many as 40% have kidney damage, with proteinuria and haematuria and alter the body immune system decreasing the ability of the body to fight against germs and infections.
The adult filarial worms cause inflammation of the lymphatic system, resulting in lymphangitis and lymphadenitis. These conditions lead to lymphatic vessel damage, even in asymptomatic people, and lymphatic dysfunction, which predispose the lower limbs in particular to recurrent bacterial infection. These secondary infections provoke adenolymphangitis (ADL), commonly called “acute attacks”, which are recurrent and the commonest symptom of lymphatic filariasis and play an important role in the progression of lymphoedema. It has been suggested that bacteria commonly gain access to damaged lymphatic vessels through “entry lesions”, often between the toes. ADL, which resembles erysipelas or cellulitis, is associated with local extreme pain and swelling and with fever and chills.
Lymphoedema and elephantiasis
Lymphoedema (tissue swelling) and its more advanced form, elephantiasis (skin/tissue thickening), occur primarily in the lower limbs and are commoner in women. Several factors have been implicated in the progression of lymphoedema, including repeated episodes of ADL. Although lymphoedema due to filariasis should be distinguished from conditions such as heart failure, malnutrition, venous disease, podoconiosis and HIV/AIDS-associated Kaposi sarcoma, there is no agreement on its classification. In its most advanced form, elephantiasis may prevent people from carrying out their normal daily activities.
Hydrocoele and chylocoele
Hydrocoele (scrotal swelling) is due to accumulation of fluid in the cavity of the tunica vaginalis. It has been suggested that true filarial hydrocoele occurs after the death of adult filarial worms, while a chylocoele is due to accumulation of fluid after the rupture of lymphatic vessels in the scrotal cavity.
Circulating microfilariae can be detected by examining thick smears (20–60 μl) of finger-prick blood under the microscope. Blood must be collected at a specific time – either at night or during the day – depending on the periodicity of the microfilariae. The method is inexpensive and feasible at individual and community levels for mapping the endemicity of lymphatic filariasis and monitoring mass drug administration (MDA).
The Alere Filariasis Test Strip (FTS) is a rapid diagnostic test recommended for mapping, monitoring and transmission assessment surveys (TAS) for the qualitative detection of Wuchereria bancrofti antigen in human blood samples. The Brugia Rapid point-of-care cassette test (BRT) is recommended for use during TAS to detect IgG4 antibody against Brugia spp. in human blood samples.
The primary goal of treating affected communities is to eliminate microfilariae from the blood of infected individuals in order to interrupt transmission of infection by mosquitoes. Studies have shown that > 5 years of mass drug administration (MDA) with preventive chemotherapy reduces microfilariae from the bloodstream and prevents the spread of microfilariae to mosquitoes. Preventive chemotherapy involves a combined dose of two medicines given annually to an entire at-risk population as follows: albendazole (400 mg) plus ivermectin (150–200 μg/kg) or diethylcarbamazine citrate (DEC) (6 mg/kg). MDA with albendazole (400 mg) alone should be given preferably twice per year to stop the spread of LF in areas where Loa loa is present.
All people with filariasis who have microfilaraemia or a positive antigen test should receive antifilarial drug treatment to eliminate microfilariae. Unfortunately, the medicines available have limited effect on adult worms. Infected patients can be treated with one of the following regimens:
- a single dose of a combination of albendazole (400 mg) with ivermectin (150–200 μg/kg) in areas where onchocerciasis is co-endemic; in areas where onchocerciasis is non co-endemic, either
- a single dose of a combination albendazole (400 mg) plus diethylcarbamazine (6 mg/kg), or
- DEC (6 mg/kg) alone for 12 days.
Avoidance of mosquito bites through personal protection measures or community-level vector control and participation in MDA is the best option to prevent lymphatic filariasis.
Managing morbidity and preventing disability
Management of morbidity and disability prevention (MMDP) in lymphatic filariasis require a broad strategy involving both secondary and tertiary prevention. Secondary prevention includes simple hygiene measures, such as basic skin care and exercise, to prevent ADL and progression of lymphoedema to elephantiasis. For management of hydrocoele, surgery may be appropriate. Tertiary prevention includes psychological and socioeconomic support for people with disabling conditions to ensure that they have equal access to rehabilitation services and opportunities for health, education and income.
Activities beyond medical care and rehabilitation include promoting positive attitudes towards people with disabilities, preventing the causes of disabilities, providing education and training, supporting local initiatives, and supporting micro- and macro-income-generating schemes. The activities can also include education of families and communities to help patients with lymphatic filariasis to fulfil their roles in society. Thus, vocational training and appropriate psychological support may be necessary to overcome the depression and economic loss associated with the disease. MMDP must be continued in endemic communities after MDA has stopped and after validation, as chronically affected patients are likely to remain in these communities.
The prevalence of filarial infection in children has become better understood in recent years. In communities where filariasis is transmitted, all ages are affected. Whereas the disease was once thought to affect only adults, it now appears that most infections are acquired in childhood. Initial infection is followed by a long period of subclinical disease, which progresses in later life to clinically manifest disease.
An estimated 120 million people in tropical and subtropical areas of the world are infected with LF; of these, almost 25 million men have genital disease (most commonly hydrocoele) and almost 15 million, mostly women, have lymphoedema or elephantiasis of the leg. Of the total population requiring preventative chemotherapy, 57% live in the South-East Asia Region (9 countries) and 37% live in the African Region (35 countries).
Of the 1.23 billion people that are at risk, 80% live in the following countries: Bangladesh, Côte d’Ivoire, Democratic Republic of Congo, India, Indonesia, Myanmar, Nigeria, Nepal, Philippines and the United Republic of Tanzania.
Which of the cross-cutting issues are relevant
WASH, integrated skin and wound management, management of disease complications, prevention of disability, physical rehabilitation, inclusion, stigma and mental wellbeing, and preventive chemotherapy.
Water, sanitation and hygiene (WASH) are critical in the prevention and care for many NTDs, including Lymphatic filariasis. Provision of safe water, sanitation and hygiene is one of the five key interventions within the global NTD roadmap.
In order to prevent infection, improved sanitation and water management can reduce breeding sites of vectors which transmit the microscope disease-causing worms. People with chronic LF disabilities need to maintain rigorous personal hygiene using water and soap to prevent secondary infection. Clean water and hygiene at health facilities and homes are essential for wound management.
People with LF are often subject to stigma, leading to social exclusion including reduced education and work opportunities, and further challenges to accessing WASH. The prejudice, stigmatization and discrimination that people experience can be more limiting than the condition itself. It may have social, psychological and health-related consequences.
Relevant tools and/or interventions
Global Programme to Eliminate Lymphatic Filariasis (GPELF)
The GPELF launched by the WHO in 2000, aims to eliminate lymphatic filariasis as a public health problem.The elimination strategy has two components: (1) to stop the spread of infection (interrupting transmission); and (2) to alleviate the suffering of affected populations (controlling morbidity).
Stop the spread of infection:
In order to interrupt transmission, endemic areas must be mapped and a strategy of preventive chemotherapy called mass drug administration (MDA) to treat the entire at-risk population. Successful MDA will prevent new infections and no new cases of clinical disease. Most of these community programmes are based on once-yearly administration of single doses of two drugs given together for at least 5 years with a coverage of at least 65% of the total at-risk population.
Adult worms can remain viable for years. Therefore it is necessary to deliver several rounds of MDA. At least five rounds are recommended to reduce infections in the community to levels below a threshold at which mosquitoes are unable to continue spreading the parasites from person to person and new infections are prevented.
Vector control is supplemental to the core strategy of MDA and can enhance elimination efforts by reducing the mosquito density and preventing human-mosquito contact. Malaria control interventions such as residual spraying and sleeping under long-lasting insecticidal nets have collateral benefits in reducing transmission of LF.
In order to control the morbidity, a core strategy of morbidity management and disability prevention (MMDP) is needed. Suffering caused by the disease can be alleviated through a minimum recommended package of care to manage lymphedema and hydrocele. These services should be available within primary health care systems in all areas of known patients.
Alleviating the suffering of affected persons is targeted by health education for communities. Here the focus is on intensive local hygiene practices and the prevention of debilitating and painful episodes of inflammation.
Other diseases related to Lymphatic filariasis
Podoconiosis, also known as non-filarial elephantiasis, is a type of tropical lymphoedema clinically distinguished from lymphatic filariasis (LF) through being ascending (unlike LF, rarely involves the groin) and commonly bilateral but asymmetric. Evidence suggests that podoconiosis is the result of a genetically determined abnormal inflammatory reaction among barefoot population (or persons with prolonged contact with soil) to mineral particles in irritant red clay soils derived from volcanic deposits.
It is mostly found in highland areas of tropical Africa, Central America and North-West India (more than 1000 meters above sea level). It is a non-parasitic disease and, like LF, results in impairments due to lymphoedema. As is the case for LF, a basic package of care can alleviate suffering and prevent further progression of disease and disability.
Stigmatization of people with podoconiosis is pronounced; patients being excluded from school, local meetings, churches and mosques, and barred from marriage with unaffected individuals.
Men and women are equally affected in most communities. All of the major community-based studies have shown onset of symptoms in the first or second decade and a progressive increase in podoconiosis prevalence up to the sixth decade.
Primary prevention consists of avoiding or minimizing exposure to irritant soils by wearing shoes or boots and by covering floor surfaces inside traditional huts. Secondary and tertiary prevention is similar to that used in management of LF.