Lymphatic Filariasis (Elephantiasis)

Lymphatic filariasis, also known as elephantiasis, is a chronic mosquito-borne infection caused by Wuchereria bancrofti, Brugia malayi, and B. timori. The majority of causes are due to W. bancrofti. Mosquitos are the vectors, and humans are the primary reservoir. Patients with acute infection can present with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, adenolymphangitis, dermatolymphangioadenitis, and tropical pulmonary eosinophilia. Patients with chronic infection present with lymphedema, which commonly affects the lower extremities (but can cause testicular swelling or hydrocele Hydrocele Accumulation of serous fluid between the layers of membrane (tunica vaginalis) covering the testis in the scrotum. Varicocele, Hydrocele, and Spermatocele). Long-term effects also include renal manifestations. Thick and thin peripheral blood smears are the mainstay of diagnosis. Lymphatic filariasis without co-infection is generally managed with diethylcarbamazine. Prognosis is good with early diagnosis and intervention. Elephantiasis, or late-stage lymphedema, is associated with significant disability and would require different methods (including surgery) to reduce swelling and complications.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Epidemiology and Etiology

Epidemiology

  • 120 million patients infected worldwide as of 2019
  • Geographic distribution:
    • Wuchereria bancrofti
      • Etiology for 90% of lymphatic filariasis
      • Most prevalent in sub-Saharan Africa, Southeast Asia, Indian subcontinent, Pacific islands, and Caribbean and South American tropical and subtropical climates
    • Brugia malayi: Southeast Asia, China, India, and Pacific islands
    • B. timori: Timor island of Indonesia
  • Most patients in endemic areas were exposed in their 30s or 40s.
  • Lymphatic filariasis has a 10:1 predilection for men over women.

Etiology

Lymphatic filariasis is caused by nematodes.

Causative species:

  • W. bancrofti
  • B. malayi
  • B. timori

General characteristics:

  • Nematode (roundworm)
  • Eukaryotic Eukaryotic Eukaryotes can be single-celled or multicellular organisms and include plants, animals, fungi, and protozoa. Eukaryotic cells contain a well-organized nucleus contained by a membrane, along with other membrane-bound organelles. Cell Types: Eukaryotic versus Prokaryotic
  • Thread-like, nuclei do not appear at the end of the tail
  • Anaerobic
  • Reproduce by sexual reproduction

Stages of life:

  • Microfilariae:
    • Found in the peripheral blood of the human host
    • Produced by adult nematodes
    • Ingested by a mosquito during a blood meal
  • Larvae:
    • Microfilariae that lose their sheaths
    • In the mosquito, microfilariae mature into larvae inside the mosquito: L1 (1st stage) larvae to L3 (3rd stage) larvae
    • L3 larvae travel to the mosquito’s proboscis, and human infection occurs during a blood meal.
    • In the infected human, larvae migrate to the bloodstream and lymphatics.
    • Maturity reached in 6–9 months
  • Adults:
    • Mature from L3 larvae in the regional lymphatics 
    • Adult female Wuchereria worms: 80–100 mm in length and 0.24–0.30 mm in diameter
    • Adult male Wuchereria worms: about 40 mm by 0.1 mm
    • Adult female Brugia worms: 43–55 mm in length
    • Adult male Brugia worms: 13–23 mm in length

Transmitted to mosquitoes:

  • W. bancrofti:
    • Aedes
    • Anopheles
    • Culex
    • Mansonia
    • Coquillettidia
  • Brugia: 
    • Aedes
    • Mansonia
Wuchereria bancrofti

Wuchereria bancrofti microfilariae

Image: “Neutrophil Alkaline Phosphatase stained peripheral smear” by Department of Hematology, All India Institute of Medical Sciences, New Delhi. License: CC BY 2.0

Pathophysiology

Transmission

  • The primary reservoir for filariasis is humans, and the vector is mosquitos. 
  • Transmission from human to human occurs via mosquito bites.

Life cycle

  1. Mosquitos deposit L3 larvae into a human’s skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin, which burrow through the bite wound to the bloodstream.
  2. L3 larvae migrate to the lymph nodes and regional lymphatics and mature into adults, which have a predilection for inguinal lymph nodes.
  3. Adult worms undergo sexual reproduction, with females birthing microfilariae that migrate actively through lymph and blood.
  4. A mosquito ingests the microfilariae during a blood meal. 
  5. After ingestion, the microfilariae work their way through the wall of the mosquito’s midgut and reach the thoracic muscles. 
  6. Within the mosquito, the microfilariae develop into L1 larvae.
  7. L1 larvae subsequently develop into L2 then L3 infective larvae.
  8. The L3 larvae migrate to the mosquito’s proboscis, where they can infect a human during the mosquito’s next blood meal.
Filarial life cycle

Schematic of the filarial life cycle of Wuchereria bancrofti:

(1) During a blood meal, an infected mosquito introduces L3 larvae into the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin of the human host.
(2) These larvae develop into adults that commonly reside in the lymphatics.
(3) Adults produce microfilariae that migrate actively through lymph and blood.
(4) A mosquito ingests the microfilariae during a blood meal.
(5) After ingestion, the microfilariae work their way through the wall of the mosquito’s midgut and reach the thoracic muscles.
(6) In the thoracic muscles, the microfilariae develop into L1 larvae.
(7) The L1 larvae subsequently develop into L3 infective larvae.
(8) The L3 larvae migrate to the mosquito’s proboscis.
(9) The L3 larvae can infect another human when the mosquito takes another blood meal.

Image by Lecturio.

Disease process

  • After mating, the adult female lays thousands of microfilariae daily:
    • In most areas, W. bancrofti microfilariae are in circulation (found in the bloodstream) during nocturnal hours.
    • In the South Pacific, the microfilariae are found in the circulation all day.
  • Acute infection:
    • Filarial antigens trigger increased cytokines and immunoglobulins Immunoglobulins Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins (IgE and IgG4).
    • Molting, dying, or dead adult worms produce pathologic changes:
      • Dilatation of lymphatics
      • Hyperplasia of vascular endothelium
      • Lymphangitis (infiltration of eosinophils, lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes in the lymphatics, and thrombi formation)
  • Chronic and repeated infections lead to:
    • Granuloma formation
    • Fibrosis of lymphatic vessels and the surrounding connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue
  • Effects:
    • Contractile dysfunction and lymphatic occlusion, causing lymphedema and prohibiting lymphatic drainage
    • Susceptibility of the human host to bacterial and fungal infections, which further contribute to tissue damage
  • Adult filaria can survive inside humans for up to 9 years. 
  • Adult worms also carry Wolbachia (endosymbiotic bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview) in their gut, which appear to benefit the worms.

Clinical Presentation

Symptoms may take 9 months up to 1 year to manifest after the initial infection. Children or individuals in endemic areas often remain asymptomatic (subclinical infection), while others show acute and/or chronic signs and symptoms.

Acute manifestations

  • Filarial fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever:
    • Typically low-grade fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, self-limiting
    • May have myalgias
    • +/– Lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy
  • Acute adenolymphangitis (ADL):
    • Fever and lymphadenopathy
    • Lymphangitis ( inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation spread distally to the lymph node), with lymphatic vessels in the leg Leg The lower leg, or just "leg" in anatomical terms, is the part of the lower limb between the knee and the ankle joint. The bony structure is composed of the tibia and fibula bones, and the muscles of the leg are grouped into the anterior, lateral, and posterior compartments by extensions of fascia. Leg(s) becoming warm, enlarged, red, and tender
    • Commonly seen in inguinal lymph nodes but can also affect the genitalia ( epididymitis Epididymitis Epididymitis and orchitis are characterized by acute inflammation of the epididymis and the testicle, respectively, due to viral or bacterial infections. Patients typically present with gradually worsening testicular pain and scrotal swelling along with systemic symptoms such as fever, depending on severity. Epididymitis and Orchitis in males)
    • Lasts a few days then resolves, but recurs periodically
  • Acute dermatolymphangioadenitis (DLA):
    • Fever, chills
    • Edematous plaques (commonly interdigital) that are believed to be entry lesions and caused by bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview
    • Lymphedema (worsens with recurrent episodes)
    • Seen in endemic areas
  • Tropical pulmonary eosinophilia (TPE):
    • Immune reaction to microfilariae trapped in the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs
    • Restrictive lung disease, which can progress to interstitial pulmonary fibrosis Pulmonary Fibrosis Idiopathic pulmonary fibrosis is a specific entity of the major idiopathic interstitial pneumonia classification of interstitial lung diseases. As implied by the name, the exact causes are poorly understood. Patients often present in the moderate to advanced stage with progressive dyspnea and nonproductive cough. Pulmonary Fibrosis
    • Wheezing Wheezing Wheezing is an abnormal breath sound characterized by a whistling noise that can be relatively high-pitched and shrill (more common) or coarse. Wheezing is produced by the movement of air through narrowed or compressed small (intrathoracic) airways. Wheezing
    • Shortness of breath
    • Bloody sputum
    • Eosinophilia

Chronic manifestations

  • Lymphedema:
    • Chronic swelling of the limb from chronic inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the lymphatic vessels
    • Graded based on the extent and progression of the symptoms:
      • Grade 0: subclinical
      • Grade I: pitting edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema of the extremities, reversible (↓ with limb elevation)
      • Grade II: pitting or nonpitting edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema of the extremities, nonreversible
      • Grade III: nonpitting edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema with skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin thickening and overgrowths, nonreversible  (elephantiasis)
  • Hydrocele:
    • Lymphatic disease involving the scrotum
    • Unilateral or bilateral
  • Renal involvement:
    • Chyluria (milky urine): 
      • Normally, lymphatic vessels have no communication with the urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract.
      • In filariasis, fluid with intestinal lymph and chylomicrons leak into the urine intermittently.
      • Leads to protein loss
    • Hematuria and proteinuria also seen (but with unclear mechanism)
Elephantiasis

Filariasis:
A patient with chronic lymphedema of the right lower extremity manifesting as elephantiasis

Image: “Elephantiasis” by Humpress Harrington et al. License: CC BY 2.0

Diagnosis

Laboratory tests

  • Peripheral blood smear:
    • Thick and thin smears
    • Venipuncture or finger/heel stick
    • Taken between 10 pm and 2 am (microfilaria have nocturnal periodicity)
    • Giemsa or Wright stains
  • Circulating filarial antigen (W. bancrofti): 
    • Detects antigens of adult filarial worms
    • May be positive even in those without microfilariae
  • Antifilarial antibody tests:
    • Elevated levels of antifilarial IgG4 in the blood 
    • Used mostly for travelers (who are not from endemic areas)
  • PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) for antigen detection
    • Used in research
    • Assay not approved for commercial use
  • Biopsy: tissue from cutaneous lesions
  • Additional laboratory tests:
    • In areas endemic for onchocerciasis (Onchocerca volvulus Volvulus A volvulus is the twisting or axial rotation of a portion of the bowel around its mesentery. The most common site of volvulus in adults is the colon; most frequently the sigmoid volvulus. Patients typically present with symptoms of bowel obstruction such as abdominal pain, distension, vomiting, and constipation/obstipation. Volvulus) or loiasis (Loa loa), co-infection has to be determined, as management will differ.
    • CBC showing eosinophilia and elevated IgE noted in TPE

Imaging

  • Ultrasonography:
    • Reveals adult worms moving in lymphatic vessels
    • The “filarial dance sign”—an irregular worm movement pattern—may be detected on Doppler.
  • Lymphoscintigraphy:
    • Assess lymphatic drainage
    • Can detect preclinical lymphedema
  • Chest X-ray:
    • To evaluate for TPE
    • Diffuse interstitial lesions and pronounced bronchoalveolar markings

Management

Treatment

Filariasis without co-infection:

  • Diethylcarbamazine (DEC): 
    • 1st-line therapy
    • Single dose
    • 2–3 weeks of treatment for TPE due to W. bancrofti
  • Doxycycline: 
    • In addition to DEC or an alternative therapy
    • For nonpregnant adults and children > 8 years of age
    • Effective against Wolbachia

Filariasis with loiasis:

  • DEC intake increases the risk of life-threatening encephalopathy in co-infection as microfilarial load increases.
  • Medication will vary depending on the load:
    • < 2500 L. loa microfilariae/mL: DEC
    • > 2500–8000 microfilariae/mL: ivermectin to decrease the microfilarial load, then DEC
    • > 8000 microfilariae/mL: doxycycline for 4–6 weeks

Filariasis with onchocerciasis:

  • DEC intake worsens eye disease (↑ risk of blindness).
  • Treatment options:
    • Treat onchocerciasis 1st with ivermectin, followed by DEC. 
    • For those with eye disease, give doxycycline followed by ivermectin.

Surgical treatment:

  • Skin debulking and lymphovenous anastomosis for drainage improvement
  • Surgical excision of hydrocele Hydrocele Accumulation of serous fluid between the layers of membrane (tunica vaginalis) covering the testis in the scrotum. Varicocele, Hydrocele, and Spermatocele

Long-term management to reduce lymphedema progression:

  • Skin hygiene
  • Wearing comfortable shoes
  • Compressive bandages
  • Limb elevation
  • Cold and heat therapy
  • Antibiotic and antifungals to prevent flares

Prevention

  • Avoid mosquito bites:
    • Sleep Sleep Sleep is a reversible phase of diminished responsiveness, motor activity, and metabolism. This process is a complex and dynamic phenomenon, occurring in 4-5 cycles a night, and generally divided into non-rapid eye movement (NREM) sleep and REM sleep stages. Physiology of Sleep in an air-conditioned room or under mosquito nets.
    • Use mosquito repellent.
    • Wear long sleeves and trousers.
  • Mosquito control with insecticide spraying
  • Global Program for the Elimination of Lymphatic Filariasis:
    • Launched to eliminate spread and reduce morbidity
    • Consists of an annual mass drug administration (for at least 5 years) implemented using various regimens with:
      • DEC
      • Ivermectin
      • Albendazole

Complications and prognosis

Occult filariasis is a filarial infection that extends into tissues, without any evidence in the blood. This leads to chronic complications, such as:

  • TPE
  • Filarial arthritis
  • Filaria-associated immune complex glomerulonephritis
  • Filarial breast abscesses

Prognosis:

  • When diseases is diagnosed and treated early, the prognosis is good. 
  • As symptoms may present later in adulthood, lymphedema and, subsequently, elephantiasis are associated with disability and morbidity.

Differential Diagnosis

  • Onchocerciasis: infection caused by the filarial nematode Onchocerca volvulus Volvulus A volvulus is the twisting or axial rotation of a portion of the bowel around its mesentery. The most common site of volvulus in adults is the colon; most frequently the sigmoid volvulus. Patients typically present with symptoms of bowel obstruction such as abdominal pain, distension, vomiting, and constipation/obstipation. Volvulus. also called river blindness: The vector for O. volvulus Volvulus A volvulus is the twisting or axial rotation of a portion of the bowel around its mesentery. The most common site of volvulus in adults is the colon; most frequently the sigmoid volvulus. Patients typically present with symptoms of bowel obstruction such as abdominal pain, distension, vomiting, and constipation/obstipation. Volvulus is the black fly from the Simulium genus. Manifestations involve the eye (keratitis, uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea, chorioretinitis Chorioretinitis Chorioretinitis is the inflammation of the posterior segment of the eye, including the choroid and the retina. The condition is usually caused by infections, the most common of which is toxoplasmosis. Some of these infections can affect the fetus in utero and present as congenital abnormalities. Chorioretinitis, optic atrophy), skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin (subcutaneous nodules, dermatitis), and nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System ( seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures). Diagnosis is by skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin snip biopsy. Treatment is with ivermectin.
  • Loiasis: infection caused by the filarial nematode Loa loa. Loiasis is also known as the African eye worm. Transmission is via a bite of the Chrysops fly. Infected individuals can be asymptomatic, but the disease can manifest with subcutaneous swellings (Calabar swelling) and the subconjunctival migration of the adult worm. Diagnosis is through peripheral blood smear (microfilariae seen) or identification of a migrating worm in the eye or subcutaneous tissue. Treatment is with DEC if microfilarial load is low. With elevated levels of microfilariae, reduction of the load is required before treatment with DEC.
  • Other testicular conditions: Other testicular infections may include varicocele Varicocele A condition characterized by the dilated tortuous veins of the spermatic cord with a marked left-sided predominance. Adverse effect on male fertility occurs when varicocele leads to an increased scrotal (and testicular) temperature and reduced testicular volume. Varicocele, Hydrocele, and Spermatocele or dilatation of the pampiniform venous plexus, which is connected to the internal spermatic or gonadal vein. Varicoceles present with a painless “bag of worms” appearance upon exam. Hydrocele or extra fluid in the tunica vaginalis leading to a swollen scrotum can be congenital or can be from trauma. Spermatocele Spermatocele A cystic dilation of the epididymis, usually in the head portion (caput epididymis). The cyst fluid contains dead spermatozoa and can be easily differentiated from testicular hydrocele and other testicular lesions. Varicocele, Hydrocele, and Spermatocele, or epididymal cyst, commonly arises from the head of the epididymis and usually presents as a painless, incidental scrotal mass on exam.
  • Other etiology of lymphedema: abnormal interstitial fluid accumulation from lymphatic obstruction. Primary lymphedema is from impaired lymphatic function or anomalous development due to genetic disorder(s). Secondary lymphedema has an underlying disease or treatment that led to the swelling. Causes include malignancy (and treatment), infection, trauma, or inflammatory conditions. The diagnostic approach involves a thorough history and examination, with workup dependent on clinical suspicion.

References

  1. Bjerum, C.M., Ouattara, A.F., Aboulaye, M., Kouadio, O., Marius, V.K., Andersen, B.J., Weil, G.J., Koudou, B.G., King, C.L. (2020). Efficacy and safety of a single dose of ivermectin, diethylcarbamazine, and albendazole for treatment of lymphatic filariasis in Côte d’Ivoire: an open-label randomized controlled trial. Clin Infect Dis 71:e68–e75.
  2. Centers for Disease Control and Prevention. (2019). Lymphatic filariasis. Retrieved May 10, 2021, from http://www.cdc.gov/parasites/lymphaticfilariasis/ 
  3. Chandy, A., Thakur, A.S., Singh, M.P., Manigauha, A. (2011). A review of neglected tropical diseases: filariasis. Asian Pac J Trop Med 4:581–586. 
  4. Kalyanasundaram, R., Khatri, V., Chauhan, N. (2020). Advances in vaccine development for human lymphatic filariasis. Trends Parasitol 36:195–205. 
  5. Klion, A.D. (2021). Lymphatic filariasis: epidemiology, clinical manifestations, and diagnosis. UpToDate. Retrieved April 27, 2021, from: https://www.uptodate.com/contents/lymphatic-filariasis-epidemiology-clinical-manifestations-and-diagnosis
  6. Klion, A.D. (2021). Lymphatic filariasis: treatment and prevention. UpToDate. Retrieved May 10, 2021, from https://www.uptodate.com/contents/lymphatic-filariasis-treatment-and-prevention
  7. Lich, B. (2018). Filariasis. Medscape. Retrieved May 10, 2021, from https://emedicine.medscape.com/article/217776-overview
  8. Mehrara, B. (2021) Clinical staging and conservative management of peripheral lymphedema. UpToDate. Retrieved May 10, 2021, from https://www.uptodate.com/contents/clinical-staging-and-conservative-management-of-peripheral-lymphedema
  9. Newman, T.E., Juergens, A.L. (2020). Filariasis. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK556012/ 
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  11. Ryan K.J. (Ed.), (2017). Tissue nematodes. Chapter 55 of Sherris Medical Microbiology, 7th ed. McGraw-Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=2268&sectionid=176089905
  12. Shenoy, R.K. (2008). Clinical and pathological aspects of filarial lymphedema and its management. Korean J Parasitol 46(3):119–125.
  13. Shukla, S.K., Kusum, A., Sharma, S., Kandari, D. (2019). Filariasis presenting as a solitary testicular mass. Trop Parasitol 9(2):124–126.

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