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emedicine.medscape.com

Filariasis
Updated: Jun 22, 2018
Author: Brian F Lich, MD; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD

Overview

Practice Essentials
Filariasis is a disease group caused by filariae that affects humans and animals (ie, nematode parasites of the family
Filariidae).[1] Of the hundreds of described filarial parasites, only 8 species cause natural infections in humans. The
World Health Organization (WHO) has identified lymphatic filariasis as a major cause of disability worldwide, with an
estimated 40 million individuals affected by the disfiguring features of the disease.[2]

In lymphatic filariasis, repeated episodes of inflammation and lymphedema lead to lymphatic damage, chronic
swelling, and elephantiasis of the legs (see the image below), arms, scrotum, vulva, and breasts.[3, 4, 5, 6, 7, 8]

Filariasis. Unilateral left lower leg elephantiasis secondary to Wuchereria bancrofti infection in a boy.

Signs and symptoms

Lymphatic filariasis

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Fever
Inguinal or axillary lymphadenopathy
Testicular and/or inguinal pain
Skin exfoliation
Limb or genital swelling - Repeated episodes of inflammation and lymphedema lead to lymphatic damage,
chronic swelling, and elephantiasis of the legs, arms, scrotum, vulva, and breasts

The following acute syndromes have been described in lymphatic filariasis:

Acute adenolymphangitis (ADL) - Sudden fever with lymphadenopathy

Filarial fever - Fever without associated adenitis
Tropical pulmonary eosinophilia (TPE) - Dry nocturnal cough

Onchocerciasis

The clinical triad of infection in onchocerciasis is as follows:

Dermatitis - Skin lesions include edema, pruritus, erythema, papules, scablike eruptions, altered pigmentation,
and lichenification
Skin nodules (ie, onchocercomas) - Tend to be common over bony prominences, with anatomic location
depending on geographic region of transmission
Ocular lesions - Usually related to the duration and severity of infection and are caused by an abnormal host
immune response to microfilariae; loss of visual acuity may occur

Loiasis

The diagnostic feature of loiasis is the Calabar swelling, ie, a large, transient area of localized, nonerythematous
subcutaneous edema resulting from a hypersensitivity reaction to the parasite. This is most common around the joints.
An additional manifestation of loiasis results from migration of the parasite across the conjunctiva, causing discomfort
and irritation of the eye.

Mansonelliasis

Mansonella infections are usually asymptomatic. If symptoms are present, they may include fever, pruritus, skin lumps,
lymphadenitis, and abdominal pain.

See Clinical Presentation for more detail.

Diagnosis
Microfilariae are detectable via examination of the following:

Blood - The microfilariae of all species that cause lymphatic filariasis and the microfilariae of Loa loa,
Mansonella ozzardi, and Mansonella perstans are detected in blood. [9] Wuchereria bancrofti can be detected
via by circulating filarial antigen (CFA) assays.
Urine - If lymphatic filariasis is suspected, urine should be examined macroscopically for chyluria and then
concentrated to examine for microfilariae.
Skin – Onchocerca volvulus and Mansonella streptocerca infections are diagnosed when microfilariae are
detected in multiple skin-snip specimens taken from different sites.
Eye - Microfilariae of O volvulus may be detected in the cornea or anterior chamber of the eye using slit-lamp
examination.

Useful imaging studies in the evaluation of filariasis include the following:

Chest radiography - Diffuse pulmonary infiltrates are visible in patients with TPE
Ultrasonography - Can be used to demonstrate and monitor lymphatic obstruction of the inguinal and scrotal
lymphatics; has also been used to demonstrate the presence of viable worms
Lymphoscintigraphy [10]

Histologic findings include the following:

Lymphatic filariasis - Affected lymph nodes demonstrate fibrosis and lymphatic obstruction with the creation of

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collateral channels
Elephantiasis - The skin is characterized by hyperkeratosis, acanthosis, lymph and fatty tissue, loss of elastin
fibers, and fibrosis
Onchocerciasis - Onchocercomas have a central stromal and granulomatous, inflammatory region where the
adult worms are found and a peripheral, fibrous section; microfilariae in the skin incite a low-grade inflammatory
reaction with loss of elasticity and fibrotic scarring

See Workup for more detail.

Management

Antimicrobials used in the treatment of filariasis include the following:

Diethylcarbamazine (DEC)
Ivermectin
Suramin
Mebendazole
Flubendazole
Albendazole
Doxycycline - Used to target Wolbachia, an endosymbiotic bacteria in multiple filarial species

Surgery

In lymphatic filariasis, large hydroceles and scrotal elephantiasis are manageable with surgical excision. Correcting
gross limb elephantiasis with surgery is less successful and may necessitate multiple procedures and skin grafting.

In onchocerciasis, nodulectomy with local anesthetic is a common treatment to reduce skin and eye complications.

See Treatment and Medication for more detail.

Background
Filariasis is a disease group affecting humans and animals, caused by filariae; ie, nematode parasites of the family
Filariidae.[1] Filarial parasites can be classified according to the habitat of the adult worms in the vertebral host, as
follows (see Pathophysiology, Etiology, and Workup):

Cutaneous group - Includes Loa loa, Onchocerca volvulus, and Mansonella streptocerca
Lymphatic group - Includes Wuchereria bancrofti, Brugia malayi, and Brugia timori
Body-cavity group - Includes M perstans and M ozzardi [11]

Of the hundreds of described filarial parasites, only 8 species cause natural infections in humans. The parasites of the
cutaneous and lymphatic groups are the most clinically significant. Other species of filariae may cause incomplete
infections because they are unable to reach adult maturity in human hosts and therefore cannot produce first-stage
larvae, known as microfilariae (eg, Dirofilaria immitis [dog heartworm], Dirofilaria [Nochtiella] repens, and Dirofilaria
tenuis [raccoon heartworm]). (See the image below.)

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Filariasis. This figure displays the life cycle of Wuchereria bancrofti in humans and mosquito vectors (ie, Aedes,
Anopheles, Culex, Mansonia species). Life cycles of other lymphatic nematodes (ie, Brugia malayi, Brugia timori) are
identical, while the life cycles for other filariae differ in the body location of adult worms, the microfilariae present, and
the arthropod intermediate hosts and vectors.

Filariasis has a significant economic and psychosocial impact in endemic areas, disfiguring and/or incapacitating more
than 40 million individuals.[2] With a strong association with mental illness, depression with filariasis is believed to
account for 5.09 million disability-adjusted life years (DALYs).[12] (See Epidemiology, Prognosis, Clinical Presentation,
and Treatment.)

Filariae have a specific geographic distribution. For example, W bancrofti is found in sub-Saharan Africa, Southeast
Asia, India, and the Pacific Islands. B malayi is found in similar locations but not in sub-Saharan Africa. B timori occurs
on Timor Island, in Indonesia. (See Epidemiology.)

In endemic areas, the prevalence of microfilaremia increases with age, as adult worms are gradually acquired over
years. Lymphatic filariasis is first contracted in childhood, and most individuals in endemic areas have been exposed
by the third or fourth decade of life. (See Pathophysiology and Etiology.)[13]

As with most helminths, adult filarial parasites replicate in a definitive host. The adult worm burden in an individual
cannot increase unless the host is exposed to additional microfilaria. Infected individuals cannot sustain higher levels
of parasitemia once they leave the endemic area.

Because the mosquito vector is inefficient, a relatively prolonged stay in an endemic area is usually required to acquire
the infection. Disorganized urbanization is adding to the vector population and hence to the increased incidence and
prevalence of such diseases in low-income countries.

Patient education
Patients should learn to protect against insect vectors and to refrain from self-treatment regimens, especially with
diethylcarbamazine (DEC), since this drug can lead to meningoencephalopathy. (See Treatment and Medication.)

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Pathophysiology
The filarial life cycle, like that of all nematodes, consists of 5 developmental (larval) stages in a vertebral host and an
arthropod intermediate host and vector. Adult female worms produce thousands of first-stage larvae, or microfilariae,
which are ingested by a feeding insect vector. Some microfilariae have a unique daily circadian periodicity in the
peripheral circulation. The arthropod vectors (mosquitoes and flies) also have a circadian rhythm in which they obtain
blood meals. The highest concentration of microfilariae usually occurs when the local vector is feeding most actively.
[14]

Microfilariae undergo two developmental changes in the insect. Third-stage larvae then are inoculated back into the
vertebral host during the act of feeding for the final two stages of development. These larvae travel through the dermis
and enter regional lymphatic vessels. During the next 9 months, the larvae develop into mature worms (20-100 mm in
length). An average parasite can survive for about 5 years.

The pre-patent period is defined as the interval between a vector bite and the appearance of microfilariae in blood,
with an estimated duration of about 12 months.

The following factors affect the pathogenesis of filariasis:

The quantity of accumulating adult worm antigen in the lymphatics [15, 16]
The duration and level of exposure to infective insect bites [17]
The number of secondary bacterial and fungal infections [15]
The degree of host immune response [18]

Filarial infection generates significant inflammatory immune responses that participate in the development of
symptomatic lymphatic obstruction. Increased levels of immunoglobulin E (IgE) and immunoglobulin G4 (IgG4)
secondary to antigenic (from dead worms) stimulation of Th2-type immune response have been demonstrated.[19]

Studies indicate that there is a familial tendency to lymphatic obstruction. This provides support for the hypothesis that
host genes influence lymphedema susceptibility.[20] Studies also suggest that microfilaremia may be increased in
individuals with low levels of mannose-binding lectin, suggesting a genetic predisposition.[8] Furthermore, a propensity
to develop chronic disease has been demonstrated in patients with polymorphisms of endothelin-1 and tumor necrosis
factor receptor II.[21]

Prenatal exposure seems to be an important determinant in conferring greater immune tolerance to parasite antigen.
[22] Thus, individuals from endemic areas are often asymptomatic until late in the disease when they have high worm
burden, whereas nonimmune expatriates tend to have brisk immune responses and more severe early clinical
symptoms, even in light infections.

Studies have shown that lymphatic filarial parasites contain rickettsia-like Wolbachia endosymbiotic bacteria.[23] This
association has been recognized as contributing to the inflammatory reaction seen in filariasis.

Etiology
Lymphatic filariasis
Mosquitoes of the genera Aedes, Anopheles, Culex, or Mansonia are the intermediate hosts and vectors of all species
that cause lymphatic filariasis.[24]

Acute lymphatic filariasis is related to larval molting and adult maturation to fifth-stage larvae. Adult worms are found in
lymph nodes and lymphatic vessels distal to the nodes. Females measure 80-100 mm in length and males are 40 mm.

The most commonly affected nodes are in the femoral and epitrochlear regions. Abscess formation may occur at the
nodes or anywhere along the distal vessel. Infection with B timori appears to result in more abscesses than infection
with B malayi or W bancrofti. (See the image below.)

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Filarial abscess scar on the left upper thigh in a young male who is positive for Wuchereria bancrofti microfilariae

Cellular invasion with plasma cells, eosinophils, and macrophages, together with hyperplasia of the lymphatic
endothelium, occurs with repeated inflammatory episodes. The consequence is lymphatic damage and chronic
leakage of protein-rich lymph in the tissues, thickening and verrucous changes of the skin, and chronic streptococcal
and fungal infections, which all contribute to the appearance of elephantiasis. (The skin of individuals with
elephantiasis is characterized by hyperkeratosis, acanthosis, lymph and fatty tissue, loss of elastin fibers, and fibrosis.)

B malayi elephantiasis is more likely to affect the upper and lower limbs, with genital pathology and chyluria being rare.
Secondary bacterial infection in elephantiasis can result in blindness.

Occult filariasis
Occult filariasis denotes filarial infection in which microfilariae are not observed in the blood but may be found in other
body fluids and/or tissues.

The occult syndromes are as follows:

Tropical pulmonary eosinophilia (TPE) - Symptoms result from allergic and inflammatory reactions elicited by
the microfilariae and parasite antigens of W bancrofti or B malayi that the lungs clear from the bloodstream
D immitis or D repens infection - Human infection with D immitis may result in pulmonary lesions of immature
Dirofilaria worms in the lung periphery; if D immitis larvae lodge in branches of the pulmonary arteries, they can
cause pulmonary infarcts
Filarial arthritis
Filarial breast abscess
Filarial-associated immune-complex glomerulonephritis

Onchocerciasis
O volvulus microfilariae from the skin are ingested by the Simulium species of blackflies. Chronic onchocerciasis
cases are hyper-responsive to parasite antigen, have increased eosinophilia, and result in the presence of high levels
of serum IgE. Patterns of onchocercal eye disease also are associated with parasite strain differences at the DNA
level.[25]

Loiasis
Mango flies or deerflies of Chrysops genus transmit loiasis. Response to L loa infection appears to differ between
residents and nonresidents in endemic areas. Nonresidents with infection appear to be more prone to symptoms than
residents despite lower levels of microfilaremia. Eosinophil, serum IgE, and antibody levels are also higher in
nonresidents with infection. (See the image below.)[26]

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Filariasis. Microfilariae of Loa loa detected in skin snips.

L loa meningoencephalopathy

Meningoencephalopathy is a severe and often fatal complication of infection. This syndrome is usually related to
diethylcarbamazine (DEC) administration in individuals with high-density microfilaremia but it may occur without drug
therapy.[27]

DEC causes a large influx of microfilariae into the cerebrospinal fluid, leading to capillary obstruction, cerebral edema,
hypoxia, and coma. Localized necrotizing granulomas are also present, in response to microfilariae. Endomyocardial
fibrosis, nephritic syndrome, and venous thrombosis may also be observed.

Epidemiology
Occurrence in the United States
No form of human filariasis is currently endemic to the United States. W bancrofti was once prevalent in Charleston,
South Carolina, because of the presence of suitable mosquito vectors. Immigrant populations and persons who have
traveled long-term to the tropics are potential reservoirs of infection.

Returning missionaries and overseas workers/volunteers are at particular risk for lymphatic filariasis and
onchocerciasis, because of the long pre-patent period and relatively high intensity of exposure required between
exposure to infective insect bites and the development of sexually mature adult worms.

Two cases of ocular onchocerciasis have been reported in the United States[28] as has a single case of a spinal mass
in a toddler due to Onchocerca lupi infection.[29]

Global occurrence
Lymphatic filariasis affects more than 120 million people worldwide and is found throughout the tropics and subtropics.
In 1997, the World Health Organization (WHO) initiated the Global Program to Eliminate Lymphatic Filariasis (GPELF)
with a goal to globally eliminate lymphatic filariasis as a public health problem by 2020.[2, 30] This initiative utilizes
mass drug administration (MDA) in 60 countries. The goal is to reduce prevalence levels to a point at which
transmission is no longer sustainable. This program has led to a prevalence reduction in 15 countries so far.[2]

At least 37 million people are infected with O volvulus globally. The vast majority of cases (99%) occur in sub-Saharan
Africa.[31] Onchocerciasis is the second leading infectious cause of blindness worldwide. Approximately half a million
people are affected.[32] In 2016, Abu-Hamed, Sudan, became the first region to eliminate the disease under a mass
treatment program with ivermectin.[33] Today, continued efforts to reduce disease prevalence are conducted via
guidance by the WHO and the Non-Governmental Development Organizations Coordination Group for Onchocerciasis

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Control.

Prevalence rates of L loa range from 3-13 million people worldwide.[34] Loiasis remains of particular interest when
initiating MDA programs for lymphatic filariasis because the drugs commonly used in these regimens (DEC) may have
adverse effects in patients with high-density Loa loa infection.

Sex- and age-related demographics

Both sexes are equally susceptible to filariasis. Because of different local and cultural practices, however, as well as
differences in exposure to insect vectors, one sex or the other may be exposed to infection more often.

Individuals of all ages are susceptible to infection and are potentially microfilaremic. Microfilaremia rates increase with
age through childhood and early adulthood, although clinical infection may not be apparent. The manifestation of acute
and chronic filariasis usually occurs only after years of repeated and intense exposure to infected vectors in endemic
areas.

Prognosis
The prognosis in filariasis is good if infection is recognized and treated early. Filarial diseases are rarely fatal, but the
consequences of infection can cause significant personal and socioeconomic hardship for those who are affected.

The morbidity of human filariasis results mainly from the host reaction to microfilariae or developing adult worms in
different areas of the body. Long-term disability may result from chronic lymphatic damage or blindness, depending on
the infectious filarial organism.

Presentation

History
Symptoms of filariasis are dependent on species and body type and can be acute or chronic in nature. Up to 70% of
infected individuals remain asymptomatic. Symptoms usually do not manifest until adolescence or adulthood, when
worm burden is usually the highest. Several symptomatic variations have been observed.[35]

Because cases of filariasis in North America and high-income countries are uncommon, physicians may initially miss
the diagnosis in these areas. To avoid this pitfall, physicians should obtain and document a thorough travel history
from patients with suspicious lesions.

Lymphatic filariasis
The clinical course of lymphatic filariasis is broadly divided into the following:

Asymptomatic microfilaremia - Patients with microfilaremia are generally asymptomatic, although those with
heavy microfilarial loads may develop acute and chronic inflammatory granulomas secondary to splenic
destruction. Passage of cloudy milklike urine may denote chyluria
Acute phases of adenolymphangitis (ADL)
Chronic, irreversible lymphedema

Lymphatic filariasis symptoms predominantly result from the presence of adult worms residing in the lymphatics. They
include the following:

Fever
Inguinal or axillary lymphadenopathy

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Testicular and/or inguinal pain

Skin exfoliation
Limb or genital swelling

The following acute syndromes have been described in filariasis:

Acute adenolymphangitis (ADL) - Sudden fever with lymphadenopathy

Filarial fever - Fever without associated adenitis
Tropical pulmonary eosinophilia (TPE) - Dry nocturnal cough

Acute ADL

This refers to the sudden onset of febrile, painful lymphadenopathy. Pathologically, the lymph node is characterized by
a retrograde lymphangitis, distinguishing it from bacterial lymphadenitis. Symptoms usually abate within 1 week, but
recurrences are possible.[36]

Signs and symptoms of ADL include episodic attacks of fever associated with inflammation of the inguinal lymph
nodes, testis, and spermatic cord, as well as with lymphedema. Skin exfoliation of the affected body part usually
occurs with resolution of an episode.

Tropical pulmonary eosinophilia

TPE is a form of occult filariasis. Presenting symptoms include a dry, paroxysmal nocturnal cough; wheezing; dyspnea;
anorexia; malaise; and weight loss.

Symptoms of TPE are usually due to the inflammatory response to the infection. Characteristically, peripheral blood
eosinophilia and abnormal findings on chest radiography are observed. TPE is usually related to W bancrofti or B
malayi infection.

Onchocerciasis
Onchocerciasis is also known as “hanging groins, leopard skin, river blindness, or sowda.” Symptoms result from the
presence of microfilariae in the skin and eyes and include pruritus, subcutaneous nodules (onchocercomas),
lymphadenitis, and blindness.

Patients with onchocerciasis may report impaired visual acuity due to corneal fibrosis. Epilepsy has been associated
with onchocerciasis in some studies.[37]

Loiasis

The symptoms of L loa infection are usually confined to subcutaneous swellings on the extremities, localized pain,
pruritus, and urticaria. The lesions, known as Calabar swellings, result from a local hypersensitivity reaction to the
parasite and are named after the Nigerian city in which they were discovered.

Rare manifestations of infection include the following:

Arthritis
Breast calcification
Meningoencephalopathy
Endomyocardial fibrosis
Peripheral neuropathy
Pleural effusions
Retinopathy

M ozzardi, M perstans, and M streptocerca infection

Mansonella infections are usually asymptomatic. If symptoms are present, they may include fever, pruritus, skin lumps,
lymphadenitis, and abdominal pain.

Dirofilaria infection
The genus Dirofilaria is classified under the family of Filariidae and is commonly known as the parasitic cause of “heart

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worm” in dogs, cats, and other mammals. Clinical manifestations of the disease in humans are rare but may include
the following:

Symptoms of D immitis infection involve the respiratory system and include chest discomfort, cough, fever, and
hemoptysis.
Symptoms of D repens infection usually include a lump in the subcutaneous tissue, submucosa, or eyelid.

Physical Examination
Signs of filariasis present on examination are species-dependent and may be acute or chronic in nature.

Lymphatic filariasis

In lymphatic filariasis, repeated episodes of inflammation and lymphedema lead to lymphatic damage, chronic
swelling, and elephantiasis of the legs, arms, scrotum, vulva, and breasts. (See the images below.)[3, 4, 5, 6, 7, 8]

Lymphatic filariasis resulting from Wuchereria bancrofti infection may result in limb lymphedema, inguinal
lymphadenopathy, and hydrocele. Photograph taken by Professor Bruce McMillan and donated by John Walker, MD.

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Filariasis. Unilateral left lower leg elephantiasis secondary to Wuchereria bancrofti infection in a boy.

Filariasis. This is a close-up view of the unilateral lower leg elephantiasis shown in the previous image. Note the
lymphedema and typical skin appearance of depigmentation and verrucous “warts.”

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Filariasis. Lateral view of the right outer aspect of a leg affected by elephantiasis secondary to Wuchereria bancrofti
infection.

Filariasis. Inner aspect of the lower leg of the male patient in the previous image, showing gross elephantiasis
secondary to Wuchereria bancrofti infection.

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Filariasis. Unilateral left hydrocele and testicular enlargement secondary to Wuchereria bancrofti infection in a man
who also was positive for microfilariae.

Filariasis. Bilateral hydrocele, testicular enlargement, and inguinal lymphadenopathy secondary to Wuchereria
bancrofti infection.

The WHO grading system defines the severity of edema. The stages range from 1-7, and, as the stage increases, so
does the extent of edema and risk for secondary infection.[38]

Hydrocele is the most common manifestation of chronic W bancrofti infection in males in endemic areas but is rare
with B malayi and B timori infection.

Chyluria also may be present in chronically infected persons. Since large amounts of fat and protein are lost in the
urine, these conditions can lead to nutritional deficiencies.

Tropical pulmonary eosinophilia

Scattered wheezes and crackles occur in both lung fields. Lymphadenopathy and hepatomegaly may be present.

Onchocerciasis

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The clinical manifestations of infection include dermatitis, skin nodules, and ocular lesions, as follows:

Dermatitis - Skin lesions include edema, pruritus, erythema, papules, scablike eruptions, altered pigmentation,
and lichenification
Skin nodules (ie, onchocercomas) - Skin nodules tend to be common over bony prominences (see the image
below)

Filariasis. Onchocercomas of the forearm skin (sowda) in a Sudanese man.

Ocular lesions - Eye lesions are usually related to the duration and severity of infection and are caused by an
abnormal host immune response to microfilariae; loss of visual acuity may occur

Common eye findings in onchocerciasis include the following:

Punctate keratitis
Pannus formation
Corneal fibrosis
Iridocyclitis
Glaucoma
Choroiditis
Optic atrophy

Loiasis

The diagnostic feature of loiasis is the Calabar swelling, ie, a large, transient area of localized, nonerythematous
subcutaneous edema. This is most common observed around joints.

Peripheral nerve involvement in loiasis has also been described.[39] Microfilaremia tends to be asymptomatic.
Occasionally, the worm is observed migrating through subconjunctival or other tissues.

M ozzardi, M perstans, and M streptocerca infection

Subcutaneous or conjunctival nodules and lymphadenopathy may be detected in symptomatic persons.

Dirofilaria infection
These infections are characterized as follows:

D repens infection - May result in painless subcutaneous, submucosal, or eyelid lumps

D immitis infection - Reduced localized air entry on chest auscultation may be detected

DDx

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Diagnostic Considerations
Differentials in the diagnosis of filariasis include the following:

Allergic bronchopulmonary aspergillosis

Systemic vasculitis
Chronic eosinophilic pneumonia
Idiopathic hypereosinophilic syndrome
Acute poststreptococcal glomerulonephritis

Lymphatic filariasis

Differential diagnoses of lymphatic filariasis include the following:[40]

Bacterial or fungal lymphadenitis - Sporotrichosis resulting from Sporothrix schenckii infection

Recurrent streptococcal lymphadenitis
Congenital or hereditary lymphedema - Milroy syndrome
Nonfilarial elephantiasis
Congenital hydrocele
Epididymal cysts
Carcinoma of the testis and/or scrotum
Lymphosarcoma

Occult filariasis

Differential diagnoses of occult filariasis include the following:

Asthma
Septic arthritis
Bacterial breast abscess
Idiopathic or poststreptococcal glomerulonephritis

Other

Other differential diagnoses of filariasis include the following:

Onchocerciasis - Vitiligo, trachoma, lepromatous leprosy

Loiasis - Hereditary and/or localized idiopathic angioedema

Differential Diagnoses
Angioedema

Asthma

Hodgkin Lymphoma

Hydrocele

Leprosy

Lymphedema

Non-Hodgkin Lymphoma

Scrotal Trauma

Testicular Trauma

Workup

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Workup

Approach Considerations
Traditionally, the diagnosis of filariasis requires demonstrating microfilariae in the peripheral blood or skin. However,
circulating filarial antigens (CFA) are now routinely used to diagnose W bancrofti infection. The microfilariae of all
species that cause lymphatic filariasis and the microfilariae of L loa, M ozzardi, and M perstans can be detected on a
blood smear.[9] Broadly, the diagnostic approach varies by group of filariasis.

Lymphatic filariasis

Microfilariae on blood smear examination: Draw blood at night, when levels of parasitemia are generally highest. The
three lymphatic filarial species can also be distinguished based on their morphologic characteristics on light
microscopy.

Circulating filarial antigen (CFA) detection: These assays are regularly available for only W bancrofti detection in
lymphatic filariasis.

Adult worms can be seen in the lymphatics.

Additional testing in lymphatic filariasis includes PCR and serology. PCR is not widely available and is mostly used in a
research setting. Serology testing for filarial antibodies cannot distinguish between past and present infection and are
not typically specific for filarial infections; however, specificity can be improved via assays based on certain
recombinant antigens, such as Wb123 in W bancrofti.[41]

Cutaneous filariasis

Definitive diagnosis of O volvulus and M streptocerca infections occurs when microfilariae are detected in multiple skin
snip specimens taken from different body sites. In addition, microfilariae of O volvulus may be detected in the cornea
or anterior chamber of the eye, using slit-lamp examination. O volvulus may also be detected with antigen testing,
although this is not regularly available.[42] Additional testing with serology and PCR have similar application in these
cases, as noted above. Of note, the Mazzoti test (detailed below) should not be routinely used in the diagnosis of
onchocerciasis owing to its risk of severe adverse reactions.

Loa loa infection can be definitively diagnosed by observing microfilariae on blood smear examination or by detecting
migrating adult worms in the subcutaneous tissue or conjunctiva. For travelers to endemic areas, serology can be
useful to detect exposure to Loa loa. Sensitivity and specificity of such testing varies depending on the assay used.

Body cavity filariasis

M ozzardi and M perstans infections can be definitively diagnosed by observing microfilariae on blood smear
examination. Additional testing with serology and PCR have similar application in these cases, as described above.

Detection of Microfilariae in Blood

The microfilariae of all species that cause lymphatic filariasis and the microfilariae of L loa, M ozzardi, and M perstans
are detected in blood. (See the image below.)

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Filariasis. Microfilariae of Mansonella perstans in peripheral blood.

Species that cause lymphatic filariasis have microfilarial levels that tend to peak at night, so it is recommended to
collect samples between 10:00 pm and 2:00 am. For loiasis, microfilariae levels peak between 10 am and 2 pm.
Capillary finger-prick or venous blood is used for thick blood films. Venous blood also can be concentrated or passed
through a Nuclepore filter before being examined microscopically to improve sensitivity.[43] The organism species can
be determined based on the microscopic appearance. W bancrofti and Brugia species have an acellular sheath. W
bancrofti has no nuclei in its tail, whereas B malayi has terminal and subterminal nuclei. (See the image below.)

Filariasis. Appearance of microfilariae after concentration of venous blood with a Nuclepore filter.

Filariasis. Microfilaria of Wuchereria bancrofti in a peripheral blood smear.

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Microfilariae may be absent in the following cases:

Patients with ADL or late chronic lymphatic disease

Typically, patients with loiasis, unless the infection has been present for many years

Detection of filarial antigen

The presence of circulating filarial antigens in the peripheral blood, with or without microfilariae, is diagnostic of filarial
infection and is useful in monitoring response to therapy. Commercial kits are available for W bancrofti to test venous
blood and can be quantitative (Og4C3 monoclonal antibody-based ELISA) or qualitative (immunochromatographic).
These assays have all demonstrated superior sensitivity over microscopy.[44]

Detection of filarial antibodies

The use of recombinant antigens for the diagnosis of certain filarial species has improved sensitivity and specificity of
these tests over the years. For W bancrofti, an IgG4 assay has been developed for the recombinant antigen Wb123
and demonstrates superior sensitivity and specificity in the diagnosis of bancroftian filariasis.[41] In addition, ICD card
tests for IgG4 antibodies against recombinant antigen Ov-16 in onchocerciasis have improved the sensitivity and
specificity of serologic testing in these cases.[45]

Serum immunoglobulin concentrations: Elevated serum IgE and IgG4 occur with active filarial disease. A multiplex
bead assay to monitor serial levels of serum antibody during treatment has been proposed.[46]

Complete blood cell count

Eosinophilia is marked in all forms of patent filarial infection.

Detection of Microfilariae in the Skin, Eye, and Urine

Skin

O volvulus and M streptocerca infections are diagnosed when microfilariae are detected in multiple skin snip
specimens from different body sites.

Preferred skin snip sites vary regionally. In suspected cases of African onchocerciasis, the recommended sites for skin
snips are the gluteal and thigh regions. For American onchocerciasis, the scapula and iliac crest areas are preferred.

Mazzotti test

Owing to the risk of severe adverse reactions, the Mazzotti test is not regularly used in the diagnosis of
onchocerciasis, especially in individuals with a high disease burden. In certain cases, the test may allow for a
presumptive diagnosis of cutaneous filariasis when skin snips are negative for microfilariae. To perform the test, a
single dose (50-100 mg) of DEC is given, and, if the patient is infected, he or she will experience an intense pruritic
rash with fever and edema. Steroids may be necessary to control this inflammatory reaction. Alternatively, a patch test
with 10% DEC solution can be placed on the skin, resulting in a more localized reaction.

Eye
Microfilariae of O volvulus may be detected in the cornea or anterior chamber of the eye using slit-lamp examination.

Urine examination and microscopy

Microfilariae may also be observed in chylous urine and hydrocele fluid. If lymphatic filariasis is suspected, urine
should be examined macroscopically for chyluria and then concentrated to examine for microfilariae.

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Imaging Studies
The following imaging studies can be used in the evaluation of filariasis:

Chest radiography - Diffuse pulmonary infiltrates are visible in patients with tropical pulmonary eosinophilia
(TPE)
Ultrasonography - Can be used to demonstrate and monitor lymphatic obstruction of the inguinal and scrotal
lymphatics
Lymphoscintigraphy [10]

Ultrasonography has also been used to demonstrate the presence of viable worms, which are seen to be in
continuous motion (ie, "filarial dance" sign). This imaging characteristic has been used to monitor the effectiveness of
treatment.[47] In addition, deep onchocercomas and vitreous changes in the eye can sometimes be detected with
ultrasonography.

Biopsy
Biopsy specimens should be obtained only in patients with cutaneous filariasis, as excising nodes may further impede
lymphatic drainage in patients with lymphatic filariasis. Adult worms of O volvulus and L loa are found in the nodules
and fibrotic tissue of the skin. L loa worms occasionally can be dissected from the conjunctiva of the eye or bridge of
the nose as they migrate through subcutaneous tissue.

Histologic Findings
Lymphatic filariasis

Affected lymph nodes demonstrate fibrosis and lymphatic obstruction with the creation of collateral channels. The skin
of individuals with elephantiasis is characterized by hyperkeratosis, acanthosis, lymph and fatty tissue, loss of elastin
fibers, and fibrosis. (See the image below.)

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Filariasis. Adult worms of Wuchereria bancrofti in cross section isolated from a testicular lump.

Onchocerciasis
Two areas are evident in onchocercomas: (1) a central stromal and granulomatous, inflammatory region where the
adult worms are found and (2) a peripheral, fibrous section. Microfilariae in the skin incite a low-grade inflammatory
reaction with loss of elasticity and fibrotic scarring. (See the image below.)

Filariasis. Adult Onchocerca volvulus contained within onchocercomas of the skin.

Treatment

Approach Considerations
Medical Management

The medical management of a filarial infection should be specific and based on the microfilariae isolated or
antigenemia detected. Specific attention should be paid to the presence of coinfection with multiple filarial organisms,
as this will alter the treatment regimen.

Mass drug administration (MDA) reduces the transmission of filarial infection and disease morbidity by decreasing the
burden of microfilaremia, resulting in suboptimal levels for transmission by disease vectors.[48, 49, 50, 51, 52, 53] The
effects of mass treatment on filariasis have reportedly been sustained for up to 6 years.[54, 55, 56, 57]

In 1997, the World Health Organization (WHO) initiated the Global Program to Eliminate Lymphatic Filariasis (GPELF)
with a goal to globally eliminate lymphatic filariasis as a public health problem by 2020.[2, 30] This initiative utilizes
mass drug administration (MDA) in 60 countries at risk to reduce prevalence levels to a point at which transmission is
no longer sustainable. The effort has led to a prevalence reduction in 15 countries thus far.[2] Overall, MDA strategies
have differed both in their drug regimen and frequency. Traditionally, annual mass treatment with albendazole plus
ivermectin or DEC has been used to interrupt the transmission of W bancrofti.

One study evaluated the effect of higher dose and increased frequency (twice yearly) of albendazole plus ivermectin
therapy for W bancrofti. It found that it resulted in complete microfilarial clearance, as well as a more sustained
clearance than that resulting from standard-dose albendazole-ivermectin treatment.[58] Another study demonstrated
that a 3-drug regimen (DEC, albendazole, ivermectin) resulted in better outcomes and fewer adverse events than
therapy with DEC and albendazole alone.[59]

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In 2016, Abu-Hamed, Sudan, became the first focus of onchocerciasis to eliminate the disease under a mass
treatment program with ivermectin.[33] Today, continued efforts to reduce disease prevalence are conducted via
guidance by the WHO and Nongovernmental Development Organizations Coordination Group for Onchocerciasis
Control.

Loiasis remains of particular interest when initiating MDA programs for lymphatic filariasis, because the drugs
commonly used in these regimens (DEC) may have adverse effects in patients with significant loiasis.

Although there have been efforts to develop an effective vaccine, none is currently available.[60]

Surgery

Lymphatic filariasis

Large hydroceles and scrotal elephantiasis can be managed with surgical excision. Correcting gross limb
elephantiasis with surgery is less successful and may necessitate multiple procedures and skin grafting.

Onchocerciasis

Nodulectomy with local anesthetic is a common treatment to reduce skin and eye complications.

Diet and activity

Fatty foods are restricted in individuals with proven chyluria that is associated with lymphatic filariasis. Because of
associated nutritional deficiencies, diets should be high in protein.

Individuals with chronic lymphatic filariasis are encouraged to mobilize (with compression bandage support and
regular exercise) the affected limb and to elevate it at night.

Prevention
Avoidance of bites from insect vectors is usually not feasible for residents of endemic areas, but visitors to these
regions should use insect repellent and mosquito nets. As noted above, mass drug administration programs are the
backbone of the goal to reduce prevalence rates to a point at which transmission is no longer sustainable.

Consultations

To prevent inappropriate treatment, consult an infectious disease specialist in all cases of suspected filariasis outside
of endemic nations. Other possible consultations include:

Urologist
Ophthalmologist
General surgeon
Plastic surgeon

Pharmacologic Therapy
Lymphatic filariasis
Diethylcarbamazine (DEC) is the treatment of choice for lymphatic filariasis. However, when co-infection with other
filarial organisms exists or in the context of mass drug administration, the treatment course must be adjusted
accordingly.

Treatment for lymphatic filariasis monoinfection consists of DEC 6 mg/kg for 12 days. Alternatively, doxycycline (200
mg/d) may be added to the regimen for a 6-week course. Studies indicate reduced severity of lymphedema in certain
cases.[61] Other regimens, including doxycycline for 23 days followed by doxycycline plus albendazole for 7 days,
have also been shown to be safe and effective.[62] As stated above, in the context of MDA to reduce microfilaremia in

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endemic areas, annual (or semi-annual) multidrug regimens of albendazole plus ivermectin or DEC are used.

Patients with asymptomatic microfilaremia can be treated on an outpatient basis. Supervision of oral DEC therapy and
post-administration observation are recommended for patient compliance with therapy and for the management of
febrile reactions in heavily infected patients.

Inpatient care may initially be required for adenolymphangitis (ADL) and chronic filariasis. Such care includes the use
of antihistamines, steroids, pain relief, and intravenous antibiotics for secondary infections.

Lymphedema

Steroids can be used to soften and reduce the swelling of lymphedematous tissues. As noted above, mild to moderate
filarial lymphedema has been shown to improve with a 6-week course of doxycycline, independent of ongoing
infection.[61]

Bed rest, limb elevation, and compression bandages traditionally have been used for the management of chronic
lymphedema.

Chronic filariasis

Treatment of chronic filariasis does not change the prognosis, as irreversible fibrosis usually destroys lymphatic tissue.
However, asymptomatic patients, hoping to diminish progression of the disease, still typically undergo treatment,
although the benefit of this is unclear.[63]

Chyluria

In the treatment of chyluria, a special low-fat, high-protein diet supplemented with medium-chain triglycerides may
prove beneficial.

Secondary infection

Supportive care should include the prevention of secondary infection, especially in patients with advanced disease.
Individuals with chronic infections should wash the affected area frequently, apply antiseptic creams to abrasions, wear
comfortable footwear, and exercise the affected limb to aid lymphatic flow.

Concomitant infections

The treatment regimen must be adjusted in patients who are co-infected with onchocerciasis and/or loiasis to avoid a
severe adverse reaction to DEC.

For concomitant infection with onchocerciasis, DEC cannot be used as primary treatment owing to the risk of
complications resulting from dying microfilariae in the eye or skin. To avoid this, co-infected patients can be treated
first with ivermectin followed by DEC treatment one month later. However, when there is ocular involvement, this
timing mechanism remains unclear.[64] Alternatively, doxycycline 200 mg/d for 6 weeks may be given first, followed by
a single dose of ivermectin 150 mcg/kg; however, these studies were solely evaluated in onchocerciasis and did not
focus on individuals co-infected with lymphatic filariasis.[65]

For concomitant infection with loiasis, treatment variation depends on the level of Loa loa microfilariae in the blood. In
general, if microfilarial levels of Loa loa are low (< 2500/mL), DEC can be safely administered with low risk for serious
adverse reactions. One study indicated that ivermectin could safely be used until Loa loa levels reached 8000
microfilariae/mL, at which point the threshold for a severe reaction to ivermectin significantly increased.[66] If levels
exceed 8000 microfilariae/mL, pretreatment with albendazole 200 mg bid for 3 weeks has shown potential benefit in its
ability to decrease microfilarial levels in loiasis.[67]

Onchocerciasis
The primary treatment of onchocerciasis depends on the prevalence and transmission of the disease in the area. In
areas with high transmission rates, ivermectin is administered at a dose of 150 mcg/kg once every 3 months until
symptoms resolve.[68] . In nonendemic areas, the same treatment regimen as above with ivermectin may be used;
however, some regimens that include doxycycline 200 mg/d for 4-6 weeks followed by ivermectin have been
investigated.[69]

Moxidectin is an antiparasitic drug that was approved by the FDA in June 2018 to treat onchocerciasis in patients aged

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12 years or older. The WHO initiated clinical trials for use in onchocerciasis in 2009.[70] Moxidectin is closely related
to ivermectin but yields a more sustained reduction in microfilarial levels. FDA approval was based on a double-blind,
parallel group, superiority trial (n=1472) that compared moxidectin (8 mg PO once) with ivermectin (150 mcg/kg PO
once). The trial took place in Ghana, Liberia, and the Democratic Republic of the Congo. Results showed skin
microfilarial loads (ie, parasite transmission reservoir) were lower from month 1 to month 18 after moxidectin treatment
than after ivermectin treatment, with an 86% difference at month 12. Moxidectin would therefore be expected to reduce
parasite transmission between treatment rounds more than ivermectin could, thus accelerating progress toward
elimination.[71]

Loiasis
In general, DEC is used as the primary treatment for loiasis; however, owing to the risk of severe encephalopathy in
patients with significant microfilaremia, the regimen is adjusted accordingly. Thus, before starting therapy, an accurate
microfilarial count must be obtained.

If a patient has a low level of microfilariae in the blood (< 2500/mL), he or she can be safely treated with DEC 8-10
mg/kg/d for 21 days. If microfilarial levels are higher, patients should be treated only if they are symptomatic. In these
cases of high microfilarial levels and symptoms, patients can be pretreated with albendazole 200 mg bid for 3 weeks
prior to definitive treatment with DEC.[67] When available, apheresis lowers microfilarial counts prior to treatment with
DEC.[72]

Mansonella infection

Treatment strategies for M perstans infection vary based on regional strain differences. Several treatment courses
may be needed to achieve cure. Wolbachia, an endosymbiont found in many filarial species, will predict whether
doxycycline is necessary to clear microfilaremia.[73] For strains that do not contain Wolbachia, treatment with DEC
and mebendazole or mebendazole alone may be effective, although rates of microfilarial clearance are low.

Doxycycline treatment typically kills or sterilizes the filarial nematode. In an open-label, randomized trial, Coulibaly et
al recruited patients with M perstans infection from four African villages in Mali. Patients were randomly assigned to
receive 200 mg of doxycycline orally every day for 6 weeks or no treatment. At 12 months, 97% of patients who
received doxycycline had no detectable blood levels of M perstans, compared with 16% of patients in the group who
did not receive treatment. At 36 months, M perstans remained suppressed in 75% of patients who had received
doxycycline.[74]

M ozzardi may be treated with ivermectin while DEC is commonly used for M streptocerca. Ivermectin has been used
to treat these infections and those strains of M ozzardi that contain Wolbachia may respond to doxycycline. M ozzardi
strains do not respond to DEC treatment.

Long-Term Monitoring
Patient monitoring includes posttreatment follow-up for 12 months, with examination of peripheral blood and skin snips
for microfilariae.

Observe and monitor oral therapeutic plans with DEC because compliance with therapy is poor and usually
incomplete.

Patients with filariasis are, by default, at risk for other parasitic infections, because areas endemic for bancroftian
filariasis are also endemic for other parasites. After treatment, patients should be monitored for symptoms that are
characteristic of parasitic infections.

Albendazole
Albendazole is a broad-spectrum anthelmintic. It decreases adenosine triphosphate (ATP) production in worms,
causing energy depletion, immobilization, and, finally, death.

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Doxycycline (Doxy 100, Vibramycin, Doryx, Monodox, Alodox)

Doxycycline is a broad-spectrum, synthetically derived, bacteriostatic antibiotic in the tetracycline class. In filariasis, it
is primarily used to target Wolbachia, an endosymbiotic bacterium in onchocerciasis and lymphatic filariasis.
Doxycycline is almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically
active metabolite in high concentrations.

Doxycycline inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal
subunits of susceptible bacteria. It may block dissociation of peptidyl transfer RNA (t-RNA) from ribosomes, causing
RNA-dependent protein synthesis to arrest.

Contributor Information and Disclosures

Author

Brian F Lich, MD Assistant Professor of Medicine, Department of Medicine, University of Oklahoma College of
Medicine

Brian F Lich, MD is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Coauthor(s)

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf
Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master
of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of
Physicians, London

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of
Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of
America, Oklahoma State Medical Association, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Rhett L Jackson, MD, FACP David Ross Boyd Professor and Chief, Section of General Internal Medicine,
Department of Medicine, University of Oklahoma College of Medicine; Assistant Chief, Medicine Service, Oklahoma
City Veterans Affairs Hospital

Rhett L Jackson, MD, FACP is a member of the following medical societies: American College of Physicians-American
Society of Internal Medicine, American Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Pranatharthi Haran Chandrasekar, MBBS, MD Professor, Chief of Infectious Disease, Department of Internal
Medicine, Wayne State University School of Medicine

Pranatharthi Haran Chandrasekar, MBBS, MD is a member of the following medical societies: American College of
Physicians, American Society for Microbiology, International Immunocompromised Host Society, Infectious Diseases
Society of America

Disclosure: Nothing to disclose.

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Additional Contributors

Siddharth Wayangankar, MD, MPH Resident Physician, Department of Internal Medicine, Oklahoma University
Health Sciences Center

Siddharth Wayangankar, MD, MPH is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Rhett L Jackson, MD, FACP David Ross Boyd Professor and Chief, Section of General Internal Medicine,
Department of Medicine, University of Oklahoma College of Medicine; Assistant Chief, Medicine Service, Oklahoma
City Veterans Affairs Hospital

Rhett L Jackson, MD, FACP is a member of the following medical societies: American College of Physicians-American
Society of Internal Medicine, American Medical Association

Disclosure: Nothing to disclose.

Acknowledgements

Rosemary Johann-Liang, MD Medical Officer, Infectious Diseases and Pediatrics, Division of Special Pathogens and
Immunological Drug Products, Center for Drug Evaluation and Research, Food and Drug Administration

Rosemary Johann-Liang, MD is a member of the following medical societies: American Academy of Pediatrics,
American Medical Association, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Thomas M Kerkering, MD Chief of Infectious Diseases, Virginia Tech Carilion School of Medicine

Thomas M Kerkering, MD is a member of the following medical societies: Alpha Omega Alpha, American College of
Physicians, American Public Health Association, American Society for Microbiology, American Society of Tropical
Medicine and Hygiene, Infectious Diseases Society of America, Medical Society of Virginia, and Wilderness Medical
Society

Disclosure: Nothing to disclose.

Charles S Levy, MD Associate Professor, Department of Medicine, Section of Infectious Disease, George Washington
University School of Medicine

Charles S Levy, MD is a member of the following medical societies: American College of Physicians, Infectious
Diseases Society of America, and Medical Society of the District of Columbia

Disclosure: Nothing to disclose.

Michael D Nissen, MBBS, FRACP, FRCPA Associate Professor in Biomolecular, Biomedical Science & Health, Griffith
University; Director of Infectious Diseases and Unit Head of Queensland Paediatric Infectious Laboratory, Sir Albert
Sakzewski Viral Research Centre, Royal Children's Hospital

Disclosure: Nothing to disclose.

Russell W Steele, MD Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical
Professor, Department of Pediatrics, Tulane University School of Medicine

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American
Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases
Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric
Research, and Southern Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of
Pharmacy; Editor-in-Chief, Medscape Drug Reference

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Disclosure: Medscape Salary Employment

Robert W Tolan Jr, MD Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at
Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine

Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American
Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene,
Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for
Social Responsibility

Disclosure: Novartis Honoraria Speaking and teaching

John Charles Walker, MSc, PhD Head, Department of Parasitology, Center for Infectious Diseases and Microbiology,
Westmead Hospital, Westmead, Australia; Senior Lecturer, Department of Medicine, University of Sydney, Australia

Disclosure: Nothing to disclose.

Martin Weisse, MD Program Director, Associate Professor, Department of Pediatrics, West Virginia University

Martin Weisse, MD is a member of the following medical societies: Ambulatory Pediatric Association, American
Academy of Pediatrics, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy;
Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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