Introduction

Filariasis is one of the most common causes of long-term disability and permanent damage, second only to leprosy.¹ Lymphatic filariasis is often called elephantiasis, which is transmitted by the filarial parasites carried by mosquitoes. Typically, infection occurs in childhood but eventually damages the lymphatic system. As the disease progresses, lymphoedema, elephantiasis, and painful symptoms like scrotal swelling occur, which might result in permanent disability. Currently, 882.5 million people around 44 countries are being treated for this condition and require proper chemotherapy to prevent the spread of the disease.² 

The main causative agents are the Nematodes belonging to the family Filariodidea. There are three varieties: Wuchereria bancrofti, Brugia malayi, and Brugia timori.² Wuchereria bancrofti is responsible for 90% of filarial cases.³ Worldwide, lymphatic filariasis is the most common cause of lymphoedema. Its catastrophic consequences are endemic to various tropical and subtropical regions.¹

Prognosis of filariasis

The prognosis of a disease refers to the probability or the expected development of the disease as it progresses. It is also the chance or the likelihood of recovery or recurrence.⁴ The prognosis usually depends upon the stage and the severity of the disease at the time of diagnosis. During the starting asymptomatic stage early after infection, the damage is usually less severe; this is followed by the acute phase, where symptoms like inflammation, adenolymphangitis (inflammation of the lymph nodes), fever, and swelling appear. If left untreated, the disease progresses into the chronic phase, leading to complications like lymphoedema, hydrocele (scrotal swelling), etc.⁵

The prognosis is good if detected early and treated promptly to avoid deformities. In the early stages, the disease can be treated with 5 annual doses of diethylcarbamazine, with or without ivermectin or albendazole. Symptoms correlated with growing worm burden appear. The most severe manifestation of the disease is elephantiasis, which is characterised by excessive swelling and thickening of skin tissues on the legs and the genitals.⁶

Acute phase outcomes

Acute phase outcomes can cause significant morbidity, and the lymphatic system is mainly affected. The outcomes include:

• Acute adenolymphangitis: This includes painful lymphadenopathy (swelling of lymph nodes) and retrograde lymphangitis (backwards movement of lymph fluid against lymphatic valves), which are specifically found in the lower extremities, inguinal nodes, genitalia, etc., leading to significant edema and elephantiasis. Secondary infections and skin breakdowns might result occasionally. Remissions can occur up to four times a year, lasting between 4 and 7 days, depending on the extent of lymphoedema.⁷ In particular, two conditions may occur: acute dermato-adeno-lymphangitis (ADLA) and acute filarial lymphagitis
• Acute fever: The fever might result without any additional signs of lymphadenopathy, and most of the time it is confused and misinterpreted for malaria or any other tropical disease⁷
• Swelling and inflammation: Due to the lymphatic blockage, certain areas in the body might become deformed, due to swelling and fluid accumulation. This is known as oedema, which can lead to inflammation

Chronic phase outcomes

Chronic phases occur after prolonged infection and repeated episodes of acute inflammation. Other characteristics are irreversible lymphatic damage and significant morbidity. If the acute phase is left untreated, lymphoedema, chyluria (presence of chyle, a milky bodily fluid, in urine), hydrocele, and elephantiasis usually result from the chronic phase 

As the lymphoedema progresses, the skin thickens in the affected area, followed by hypertrichosis (excessive hair growth), dark pigmentation, and nodules can also  develop. Other genital symptoms include funiculitis (spermatic cord inflammation),  chronic epididymitis, and lymphoedematous (thickened scrotal skin).

Long-term complications

1. Lymphatic filariasis disfigurement: Chronic swelling and enlargement of various body parts, resulting in disfigurement. The majority of chronic swelling occurs in the limbs, breasts, and genital areas
2. Chronic pain: As there is an accumulation of fluid in various areas due to oedema and inflammation, patients may experience persistent discomfort
3. Recurrent infections: Patients are vulnerable to secondary infections like cellulitis and lymphangitis due to the damaged and weakened lymphatic system
4. Occult (hidden) filariasis and tropical pulmonary eosinophilia: Under this condition, the microfilariae are typically found more in the tissues than in the blood.¹⁰ For tropical pulmonary eosinophilia, the eosinophil count is elevated as an obscure sign of B. malayi and W. bancrofti parasites in the lungs, resulting in symptoms like severe coughing and wheezing at night. An elevated eosinophil count up to  > 2500 cells/μl and IgE count may be observed⁸
5. Hydrocele: This is one of the most common manifestations of the chronic phase of filariasis, particularly in males. Accumulation of fluid occurs in the testicular sac (Tunica vaginalis), and gradually the scrotum and penis may enlarge to an extreme extent. Certain individuals might have swollen vesicles with lymph covering their scrotal skin^{8, 9}
6. Chyluria: This refers to the ejection of chyle, a lymphatic fluid enriched with lymphocytes, lipids, water, etc., in the urine. This occurs due to the blockage of the retroperitoneal lymph nodes beneath the cisterna chyli; this causes reflux and intestinal lymph to flow directly into renal lymphatics, which may burst and allow chyle to flow into the urinary system. This usually results in the formation of milky urine, and a large amount of essential nutrients are lost via this process, leading to weight loss⁸ 
7. Onchocerciasis: This is a skin and eye disease caused by mobile microfilariae, resulting in an elevated immune response causing eosinophilia and elevated IgE levels^{10, 11}
8. Loiasis: This is a parasite infection that results in the formation of itchy swelling in the body, which is often painless^{10, 12}
9. Psychosocial impact: Lymphatic filariasis can result in severe psychosocial suffering, social stigma, and social isolation
10. Lymphoedema: Lymphoedema of the extremities is very common, which can progress to elephantiasis^{9, 10}

Management of chronic filariasis

Diethylcarbamazine continues to be the most effective drug for care. According to the Centers for Disease Control and Prevention (CDC), 6 mg/kg/day of DEC for a day or a 12 day course is recommended.¹³ Patients suffering from loiasis or onchocerciasis should be treated with doxycycline with ivermectin or albendazole.⁷

In cases of scrotal elephantiasis or massive hydroceles, surgical excision may be required.⁶ Surgical debulking of fibrous tissue may be carried out for cases with severe elephantiasis. Lymphovenous anastomosis is a surgical procedure that aims to improve lymphatic oedema and reduce lymphoedema.⁶

Lymphoedema patients should be treated by a therapist who understands the importance of fundamental care concepts including hygiene, oedema reduction, exercise, and wound care. ⁷ A nutritional diet is always advisable for patients with chyluria who are malnourished due to the loss of effective nutrients.

Prevention of long-term complications

To prevent long-term complications, supportive care, lifestyle modification, and off-cause medical management are crucial. The following preventive techniques may be employed: 

• Early detection and management: The goal is to halt the disease progression through early detection and intervention. There are certain drugs effective in reducing long-term consequences¹⁴ 
• WHO has started a preventive chemotherapy strategy, Mass Drug Administration (MDA). As a part of MDA, all the patients at risk receive an annual dose of medication that lowers the burden (number) of the microfilariae population in the bloodstream and prevents the transfer of the parasite to the mosquitoes. However, their impact is limited on adult parasites²

The success of the MDA program depends upon the effectiveness of the regimen and the percentage of the population that receives the medication.

• Management of morbidity: To ensure continuity of care, the healthcare system should provide fundamental services such as morbidity management and disability prevention. With basic skin care practices, physical activity, and elevating limbs, one can minimise and prevent the severity of disease and progression²
• Vector management: It is employed to minimise the spread of other illnesses carried by the mosquitoes. Measures like mosquito nets, indoor residual spraying, or personal protective equipment help protect people from the infection and prevent parasite transmission. In the past, vector control helped lymphatic filariasis eradication in certain regions where the treatment was unavailable² 
• Adherence to the treatment plan can reduce symptoms and improve the patient’s quality of life.²
• Health education and awareness: Raising community awareness regarding how filariasis is transmitted and the importance of early treatment can help improve adherence to policies and measures⁶ 
• Monitoring and evaluation: Ongoing evaluation of treatment results and community health programs can help identify the care gaps and enhance filariasis management tactics¹⁵

Research and future directions

The field of filarial research is experiencing an explosion in interesting advancements, spanning from the discovery of innovative antifilarial medications and diagnostic tools to the decoding of fundamental disease mechanisms.¹⁶ More research on the effectiveness of herbal medicine against filariasis is yet to be carried out. Also, research in the advancements of therapy to eliminate adult parasites is yet to be done, which is the best way to reduce disease burden.

Summary

Wuchereria bancrofti, Brugia malayi, and Brugia timori are the nematodes responsible for causing lymphatic filariasis in humans. Adult worms infect the lymphatic system and mature there, releasing microfilariae into the bloodstream, which are then spread through mosquito vectors. Due to a dysfunctional lymphatic system, major ramifications like elephantiasis, hydrocele, lymphopenia, lymphangitis, etc., may arise. The prognosis is good if detected early and treated promptly to avoid deformities. In the early stages, it can be treated with a 5 annual dose-regimen. Acute phase outcomes can cause significant morbidity, and the lymphatic system is mainly affected. Chronic phases occur after a prolonged infection and repeated episodes of acute inflammation. The chronic phase is characterised by irreversible lymphatic damage and significant morbidity. The primary chronic phase outcomes are lymphoedema, ejection of chyle in the urine that leads to impaired renal system, hydrocele, and elephantiasis. Medication adherence might prove useful to reduce further complications. There is currently no vaccine for filariasis, and more research is being carried out to eradicate filariasis in the coming future.