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Lymphatic filariasis: Treatment and prevention

Author: Amy D Klion, MD
Section Editor: Peter F Weller, MD, MACP
Deputy Editor: Elinor L Baron, MD, DTMH

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Nov 2022. | This topic last updated: Aug 24, 2022.

INTRODUCTION

Filariasis is caused by nematodes (roundworms) that inhabit the lymphatics and subcutaneous
tissues. Three species cause lymphatic filariasis: Wuchereria bancrofti, Brugia malayi, and Brugia
timori. Infection is transmitted by mosquito vectors; humans are definitive hosts. Lymphatic
filariasis is a major cause of disfigurement and disability in endemic areas, leading to significant
economic and psychosocial impact.

The treatment and prevention of lymphatic filariasis will be reviewed here. The epidemiology,
diagnosis, and clinical features of lymphatic filariasis and other filarial infections (including
onchocerciasis, loiasis, and mansonellosis) are discussed separately. (See "Lymphatic filariasis:
Epidemiology, clinical manifestations, and diagnosis" and "Onchocerciasis" and "Loiasis (Loa loa
infection)" and "Mansonella infections".)

TREATMENT

The approach to treatment of lymphatic filariasis requires an understanding of antimicrobial

agent mechanisms as well as attention to the possibility of coinfection. The clinical approach is
described below, followed by a discussion of data related to individual antimicrobial agents.

Clinical approach — The treatment of choice for lymphatic filariasis is diethylcarbamazine

(DEC); however, this agent is contraindicated in patients coinfected with onchocerciasis and
must be used with caution in patients with loiasis, since severe adverse events can occur in
individuals with high microfilarial loads ( table 1). In addition, variability in individual
responses to DEC have been described [1]. (See "Loiasis (Loa loa infection)", section on
'Treatment'.)

Doxycycline, which targets the intracellular endosymbiont, Wolbachia, is an alternative first-line

antifilarial therapy for nonpregnant adults and children >8 years of age with lymphatic filariasis.
Doxycycline has activity against adult worms and no effect on L. loa. Based on the available data
in the literature, we favor the clinical approach discussed in the following sections.

Individual treatment

Monoinfection — Patients with lymphatic filariasis (in the absence of onchocerciasis or

loiasis) should receive single-dose treatment with DEC (6 mg/kg), regardless of whether clinical
symptoms or microfilaremia are present [2-4]. Patients with tropical pulmonary eosinophilia
due to W. bancrofti infection are an exception; these patients should be treated with 14 to 21
days of DEC (6 mg/kg/day). Early lymphatic changes may be present before the onset of
symptoms, and reversal of early lymphatic dysfunction has been observed following DEC
treatment [5].

The addition of doxycycline (200 mg/day for four to six weeks) is also appropriate based on data
demonstrating that doxycycline has macrofilaricidal activity and reduces pathology in mild to
moderate disease [6-8]. Treatment is generally warranted even in the setting of advanced
disease to kill any remaining adult parasites, although clinical improvement may be limited.

For cases in which DEC is not available or contraindicated, doxycycline (200 mg/day for four to
six weeks) can also be used as an alternative first line therapy.

Concomitant infection — DEC is contraindicated in patients coinfected with

onchocerciasis and/or patients with loiasis who have high microfilarial loads due to the risk of
severe adverse events.

Onchocerciasis — DEC is contraindicated in patients with onchocerciasis, due to the

potential for severe adverse events related to killing of microfilariae in the eye and/or skin
(Mazzotti reaction) ( table 1). Therefore, treatment of onchocerciasis with ivermectin (150
mcg/kg single dose) should be administered to clear O. volvulus microfilariae in the skin and
eyes prior to standard treatment of lymphatic filariasis. (See 'Monoinfection' above.)

Based on kinetic studies of microfilarial clearance from the skin following ivermectin
administration, it seems prudent to wait approximately one month between administration of
ivermectin and initiation of DEC treatment [9,10]. In patients with ocular involvement, the
length of time needed to prevent exacerbation of eye disease with DEC is unknown.
Consequently, alternative therapy with doxycycline (200 mg orally once daily for four to six
weeks) followed by ivermectin (150 mcg/kg orally single dose) is reasonable for treatment of
both infections; however, the efficacy of this regimen compared with standard therapy for
treatment of lymphatic filariasis is not known. (See "Onchocerciasis", section on 'Treatment'.)

Loiasis — DEC is the treatment of choice for patients with L. loa coinfection and low or
undetectable levels of circulating microfilariae. However, as the microfilarial load increases, the
incidence of severe adverse effects (including fatal encephalopathy) related to the rapid killing
of microfilariae also increases ( table 1). For patients with lymphatic filariasis who are
coinfected with L. loa but have <2500 L. loa microfilariae/mL of blood, DEC therapy using the
standard regimen for loiasis (8 to 10 mg/kg/day for 21 days) should be administered. (See
"Loiasis (Loa loa infection)", section on 'Treatment'.)

For patients with higher levels of L. loa microfilaremia (but less than 20,000 microfilariae/mL),
ivermectin pretreatment can be used to reduce the microfilarial load prior to administration of
DEC [11,12]. Patients with L. loa microfilarial loads greater than 20,000 microfilariae/mL should
be treated with doxycycline (200 mg orally once daily for four to six weeks), which has no effect
on L. loa. Albendazole (200 to 400 mg with fatty meal twice daily for 21 days) also has no direct
effect on L. loa microfilariae and is a reasonable alternative in patients who cannot take
doxycycline. Issues related to management of high-level Loa microfilaremia are discussed
further separately. (See "Loiasis (Loa loa infection)", section on 'Treatment'.)

Mass treatment — Mass drug administration reduces the bloodborne reservoir of

microfilariae to a level below that required for sustained transmission by local mosquito vectors
( figure 1 and figure 2). The period of microfilaremia has been estimated to be four to six
years, corresponding with the reproductive lifespan of the adult parasite. W. bancrofti has been
designated as a target for elimination since there are no animal hosts. Elimination of Brugian
filariasis is not feasible since this infection has a large domestic and wild animal reservoir. (See
"Lymphatic filariasis: Epidemiology, clinical manifestations, and diagnosis", section on
'Epidemiology'.)

Mass drug administration using various regimens of DEC (single dose and medicated salt),
ivermectin, and albendazole had been in place in some countries for more than 20 years prior
to 2000, when the Global Program for the Elimination of Lymphatic Filariasis was launched with
drug company donations of ivermectin and albendazole.

Since that time, mass drug administration programs have been implemented in more than 60
countries, with more than 5 billion doses of antifilarial therapy administered by 2014
( figure 3) [13,14]:
 ● In areas where lymphatic filariasis is endemic (in the absence of onchocerciasis or loiasis),
management consists of a three-drug combination regimen consisting of ivermectin,
diethylcarbamazine, and albendazole (single dose) or a two-drug combination regimen of
diethylcarbamazine plus albendazole (administered once yearly for three years) [15-17].

This approach is supported by a randomized trial including more than 180 adults in Papua
New Guinea with W. bancrofti microfilaremia treated with a single dose of the three-drug
regimen, a single dose of the two-drug regimen, or the two-drug regimen administered
once a year for three years [16]. Administration of the three-drug regimen was associated
with clearance of microfilaremia for three years in 98 percent of participants; it was
superior to the two-drug regimen administered once and noninferior to the two-drug
regimen administered once a year for three years. There were no serious adverse events.

● In areas where lymphatic filariasis and onchocerciasis are coendemic (in the absence of
loiasis), management consists of combination therapy with yearly ivermectin and
albendazole; presence of onchocerciasis precludes use of diethylcarbamazine [18,19].

● In areas where lymphatic filariasis and loiasis are coendemic, management consists of
albendazole monotherapy twice yearly [15,20]; unless onchocerciasis is hyperendemic, in
which case the benefits of ivermectin for onchocerciasis are felt to outweigh the risk of
serious adverse events from ivermectin treatment of loiasis, and combination therapy with
yearly ivermectin and albendazole is recommended.

Suppression of transmission to <1 percent (the predicted threshold for elimination) has been
achieved in several countries, including Egypt, Togo, and 12 Asian and Pacific Island countries. A
number of challenges remain; these include availability of funds for drug distribution and
monitoring, the persistence of hot spots of transmission [21], difficulties reaching populations
in remote areas and areas of conflict, and the occurrence of treatment-related encephalopathy
in areas endemic for loiasis [11,22]. Human immunodeficiency virus (HIV) coinfection does not
appear to affect response to mass therapy with ivermectin and albendazole [23].

Antimicrobial agents — Selection of therapy for treatment of lymphatic filariasis requires an

understanding of the microfilaricidal and macrofilaricidal activity of therapeutic agents. The
epidemiology of other filarial diseases is also important; in regions where loiasis and
onchocerciasis may coexist with lymphatic filariasis, additional consideration is important for
minimizing the likelihood of adverse effects.

Most of the studies regarding the efficacy of various regimens are derived from data from mass
chemotherapy programs. These data are helpful in determining the relative efficacy of the
drugs and combinations in terms of microfilaricidal and macrofilaricidal activity but do not
necessarily provide optimal data on management of infected individuals, particularly those who
live outside of endemic areas [24].

Diethylcarbamazine — DEC, a piperazine derivative, is a potent microfilaricidal and

macrofilaricidal agent with activity against W. bancrofti, B. malayi, and B. timori [25]. The
mechanism of action is uncertain; it is thought to alter microfilarial surface membranes or
inhibit filarial release of immunomodulatory eicosanoids, thereby enhancing destruction via
host immune responses [26,27]. DEC also has macrofilaricidal activity, likely via
hyperpolarization leading to immobilization of adult worms. Estimates suggest DEC kills
approximately 50 percent of adult worms, and its effect on adult worms in turn decreases the
microfilarial burden [28].

Adverse effects of DEC include fever, headache, anorexia, nausea, and arthralgias. These effects
are likely attributable to the host response following death of microfilariae (systemic reactions)
and damage to adult worms (local reactions). Dying microfilariae probably release
lipopolysaccharide-like proteins from endosymbiotic Wolbachia organisms within the filariae
[29,30]. Management consists of administration of antipyretic and/or anti-inflammatory agents.
Since post-DEC reactions are more severe in onchocerciasis and loiasis, evaluation for these
coinfections should be pursued prior to administering DEC. (See "Onchocerciasis" and "Loiasis
(Loa loa infection)".)

DEC should be avoided in pregnancy. Animal studies have not demonstrated teratogenicity. It is
not excreted in breast milk and is considered safe during lactation.

DEC is not commercially available in the United States but can be obtained from the United
States Centers for Disease Control and Prevention (CDC) under an Investigational New Drug
protocol (CDC Drug Service, Atlanta, GA 30333; telephone 404-718-4745) [31].

Doxycycline — A promising alternative approach to attacking the worm directly is to focus

treatment against Wolbachia, an intracellular bacterial symbiont of filarial parasites that is
present in microfilariae and adult worms of W. bancrofti and both Brugia species [32]. (See
"Lymphatic filariasis: Epidemiology, clinical manifestations, and diagnosis", section on
'Wolbachia'.)

Doxycycline has both microfilaricidal and macrofilaricidal activity and has demonstrated efficacy
in both W. bancrofti and B. malayi infections [33,34]:

● In a randomized trial including 72 Tanzanian patients with Bancroftian filariasis, patients

who received doxycycline (200 mg daily for eight weeks) had elimination of microfilaremia
and diminished detectability of adult worms compared with patients who received placebo
 (22 versus 88 percent, respectively) [35]. Subsequent trials have demonstrated the efficacy
of shorter regimens (four or six weeks may also be sufficient) [24,36,37] and that the
addition of albendazole may enhance microfilarial clearance by doxycycline [38].

● In a randomized trial including 161 Indonesian patients with Brugian filariasis, a six-week
course of doxycycline reduced the prevalence of microfilaremia compared with placebo
(77 versus 27 percent) [39].

There is also convincing evidence that doxycycline treatment, alone and in combination with
DEC, reduces clinical pathology, including lymph vessel dilation and hydrocele in affected
individuals [6,7]. A subsequent trial in 162 Ghanaian patients with lymphedema demonstrated
that doxycycline (200 mg/day for six weeks) was effective in reducing lymphedema regardless
of infection status as assessed by circulating antigen assay [8].

Tetracycline antibiotics may cause permanent tooth discoloration for children <8 years if used
repeatedly. However, doxycycline binds less readily to calcium than other tetracyclines and may
be used for ≤21 days in children of all ages [40].

Ivermectin — Ivermectin has microfilaricidal activity [41-43] but does not have significant
macrofilaricidal activity [44-47]. Therefore, the reduction in microfilaremia is not sustained
without repeat dosing. The clinical benefit of ivermectin is uncertain given the lack of activity
against adult worms, which play an important role in the pathogenesis of lymphangitis and
lymphedema. Ivermectin may have some effect in reducing the fertility of worms (in addition to
its microfilaricidal activity).

Ivermectin is at least as effective as DEC in reducing microfilaremia due to Bancroftian filariasis

[48,49]; a single dose has been shown to reduce microfilaremia by approximately 90 percent
even one year after treatment [41,42]. One study in South India demonstrated that a single
dose of ivermectin (150 microgram/kg) was approximately equivalent to a 12-day course of DEC
in suppressing microfilaremia for three to six months [50].

Ivermectin is the treatment of choice for onchocerciasis and should be used as part of the
regimen to treat patients with concomitant lymphatic filariasis and onchocerciasis but is
contraindicated in patients with loiasis and high levels of L. loa microfilariae in the blood due to
the risk of posttreatment encephalopathy. (See "Loiasis (Loa loa infection)", section on
'Ivermectin'.)

Albendazole — Albendazole has no direct effect on microfilariae but leads to a slow decline in

microfilaremia due to macrofilaricidal activity against the adult worms. Consequently, side
effects due to rapid killing of microfilariae are not seen, and albendazole can be used in
patients with concomitant loiasis or onchocerciasis.

In one study in the Democratic Republic of Congo, biannual administration of single-dose

albendazole (400 mg) led to microfilarial clearance in 37 percent of subjects at 12 months [51]
and a 94 percent reduction in the prevalence of microfilaremia after three years [52]. In
addition, results from two cohort studies of repeated albendazole administration in Central
Africa demonstrated a close relationship between adherence to therapy and clearance of
microfilariae, further supporting this approach [53].

Although most studies have demonstrated enhanced suppression of microfilaremia with

albendazole and ivermectin as compared with ivermectin alone, albendazole does not appear
to increase the microfilaricidal efficacy of DEC. In a small study that examined the effects of
albendazole and DEC on adult worm killing as assessed by scrotal ultrasound, combination
therapy was less effective than DEC alone [54].

Management of chronic pathology — The most common chronic complications of lymphatic

filariasis are recurrent lymphangitis or cellulitis, lymphedema, elephantiasis, and hydrocele.
Chyluria is relatively infrequent but does occur.

Lymphatic pathology — Individuals with lymphedema should wash affected areas twice daily,
use antibacterial creams on small abrasions, keep nails clean, and wear shoes. The affected
limb should be exercised regularly to promote lymph flow and should be elevated at night.
Complex decongestive physiotherapy can also be effective in some cases. The National
Lymphedema Network provides a listing of certified lymphedema therapists in the United
States who have expertise in treating chronic lymphedema [55]. (See "Clinical staging and
conservative management of peripheral lymphedema".)

Secondary infections (especially bacterial) are contributing determinants of worsening

lymphedema and elephantiasis, particularly in individuals with late-stage disease. Aggressive
treatment of secondary infections and close attention to hygiene is critical. Antibiotic
prophylaxis should be considered in patients who experience recurrent infections despite
appropriate local care. (See "Acute cellulitis and erysipelas in adults: Treatment".)

Reconstructive surgery involving lymphatic-venous anastomoses have been attempted to

improve lymphatic drainage, but the long-term benefit is still unclear.

Hydrocele — The role of surgery depends upon the individual anatomy and local surgical
expertise. Drainage of hydroceles may give some immediate relief but is almost always followed
by reaccumulation of fluid. Hydrocelectomies can be helpful; among 301 patients with filariasis
in Nigeria, hydrocelectomy was performed safely even in a rural area [56].

Chyluria — Chyluria may be associated with secondary nutritional deficiency. In such cases,

low-fat, high-protein diets supplemented with medium-chain triglycerides can be helpful.

PREVENTION

The focus of disease control has been mass drug administration programs [25,57,58]. (See
'Mass treatment' above.)

Vector control with insecticide-treated bed nets is also a valuable tool for W. bancrofti
elimination in areas where anopheline mosquitoes transmit the parasite [59] along with other
personal protection measures against mosquitoes (eg, repellents). (See "Prevention of
arthropod and insect bites: Repellents and other measures".)

There is no vaccine available; attempts to develop effective vaccination are underway [60].

SUMMARY AND RECOMMENDATIONS

● Patients with lymphatic filariasis (in the absence of onchocerciasis or loiasis) should
receive treatment with diethylcarbamazine (DEC), regardless of whether clinical symptoms
or microfilaremia are present. The addition of doxycycline (200 mg/day for four to six
weeks) following DEC treatment is also appropriate based on data demonstrating that
doxycycline has macrofilaricidal activity and reduces pathology in mild to moderate
disease. Doxycycline (200 mg/day for four to six weeks) can also be used as an alternative
first line therapy in cases where DEC is not available or contraindicated. (See
'Monoinfection' above.)

● Patients with coinfection due to lymphatic filariasis and onchocerciasis (in the absence of
evidence for eye involvement) should undergo treatment of onchocerciasis first, with
ivermectin (150 mcg/kg single dose) alone, followed by standard treatment for lymphatic
filariasis ( table 1). In patients with eye involvement, doxycycline (200 mg orally once
daily for four to six weeks) followed by ivermectin (150 mcg/kg orally single dose) can be
used, although the relative efficacy of this regimen compared with the standard DEC-
containing regimen is not known. (See 'Onchocerciasis' above.)
 ● The approach to patients with concomitant infection due to lymphatic filariasis and loiasis
depends on the level of circulating L. loa microfilaremia ( table 1). For patients with
<2500 L. loa microfilariae/mL of blood, DEC therapy using the standard regimen for loiasis
(8 to 10 mg/kg/day for 21 days) should be administered. For patients with >2500 but
<20,000 L. loa microfilariae/mL of blood, ivermectin can be used to decrease the L. loa mf
load prior to DEC treatment. For patients with >20,000 L. loa microfilariae/mL of blood,
doxycycline (200 mg orally once daily for four to six weeks), which has no effect on L. loa, is
the treatment of choice for the lymphatic filariasis. Albendazole (200 to 400 mg with fatty
meal twice daily for 21 days) has no direct effect on L. loa microfilariae and is a reasonable
alternative in patients who cannot take doxycycline. Issues related to management of
high-level Loa microfilaremia are discussed further separately. (See 'Loiasis' above and
"Loiasis (Loa loa infection)".)

● Management of chronic complications of lymphatic filariasis is an important component of

therapy. Secondary (often bacterial) infections are contributing determinants of worsening
lymphedema and elephantiasis, particularly in individuals with late-stage disease.
Aggressive treatment of secondary infections and close attention to hygiene is critical.
Individuals with lymphedema should wash affected areas twice daily, use antibacterial
creams on small abrasions, keep nails clean, and wear shoes. The affected limb should be
exercised regularly to promote lymph flow and should be elevated at night. Prophylactic
antibiotics may be necessary in some cases. Hydrocelectomy can be useful in reducing
morbidity in affected patients. (See 'Management of chronic pathology' above.)

● Mass drug administration reduces the bloodborne reservoir of microfilariae to a level

below that required for sustained transmission by local mosquito vectors. Programs have
been initiated in more than 60 countries and use various combinations of albendazole,
ivermectin, and DEC. These programs have led to suppression of transmission to <1
percent (the predicted threshold for elimination) in several countries; many challenges
remain. (See 'Mass treatment' above.)

ACKNOWLEDGMENT

The UpToDate editorial staff acknowledges Dr. Karin Leder, who contributed to earlier versions
of this topic review.

Use of UpToDate is subject to the Terms of Use.

REFERENCES

1. Sankari T, Subramanian S, Hoti SL, et al. Heterogeneous response of Wuchereria bancrofti-

infected persons to diethylcarbamazine (DEC) and its implications for the Global
Programme to Eliminate Lymphatic Filariasis (GPELF). Parasitol Res 2021; 120:311.
2. United States Centers for Disease Control and Prevention. Parasites - Lymphatic Filariasis. h
ttp://www.cdc.gov/parasites/lymphaticfilariasis/treatment.html (Accessed on July 01, 2013).
3. Cartel JL, Celerier P, Spiegel A, et al. A single diethylcarbamazine dose for treatment of
Wuchereria bancrofti carriers in French Polynesia: efficacy and side effects. Southeast Asian
J Trop Med Public Health 1990; 21:465.
4. Andrade LD, Medeiros Z, Pires ML, et al. Comparative efficacy of three different
diethylcarbamazine regimens in lymphatic filariasis. Trans R Soc Trop Med Hyg 1995;
89:319.
5. Moore TA, Reynolds JC, Kenney RT, et al. Diethylcarbamazine-induced reversal of early
lymphatic dysfunction in a patient with bancroftian filariasis: assessment with use of
lymphoscintigraphy. Clin Infect Dis 1996; 23:1007.
6. Debrah AY, Mand S, Marfo-Debrekyei Y, et al. Reduction in levels of plasma vascular
endothelial growth factor-A and improvement in hydrocele patients by targeting
endosymbiotic Wolbachia sp. in Wuchereria bancrofti with doxycycline. Am J Trop Med Hyg
2009; 80:956.
7. Mand S, Pfarr K, Sahoo PK, et al. Macrofilaricidal activity and amelioration of lymphatic
pathology in bancroftian filariasis after 3 weeks of doxycycline followed by single-dose
diethylcarbamazine. Am J Trop Med Hyg 2009; 81:702.
8. Mand S, Debrah AY, Klarmann U, et al. Doxycycline improves filarial lymphedema
independent of active filarial infection: a randomized controlled trial. Clin Infect Dis 2012;
55:621.
9. Greene BM, Taylor HR, Cupp EW, et al. Comparison of ivermectin and diethylcarbamazine in
the treatment of onchocerciasis. N Engl J Med 1985; 313:133.

10. Lariviere M, Vingtain P, Aziz M, et al. Double-blind study of ivermectin and

diethylcarbamazine in African onchocerciasis patients with ocular involvement. Lancet
1985; 2:174.
11. Gardon J, Gardon-Wendel N, Demanga-Ngangue, et al. Serious reactions after mass
treatment of onchocerciasis with ivermectin in an area endemic for Loa loa infection.
Lancet 1997; 350:18.
12. Kamgno J, Pion SD, Chesnais CB, et al. A Test-and-Not-Treat Strategy for Onchocerciasis in
Loa loa-Endemic Areas. N Engl J Med 2017; 377:2044.
13. Hopkins DR. Disease eradication. N Engl J Med 2013; 368:54.

14. 489 Global programme to eliminate lymphatic filariasis: progress report, 2014. Wkly
Epidemiol Rec 2015; 90:489.
15. World Health Organization. Guideline for alternative mass drug administration regimens to
eliminate lyphatic filariasis, 2017. http://www.who.int/lymphatic_filariasis/resources/97892
41550161/en/ (Accessed on November 20, 2017).
16. King CL, Suamani J, Sanuku N, et al. A Trial of a Triple-Drug Treatment for Lymphatic
Filariasis. N Engl J Med 2018; 379:1801.
17. Hast MA, Tufa A, Brant TA, et al. Notes from the Field: Impact of a Mass Drug
Administration Campaign Using a Novel Three-Drug Regimen on Lymphatic Filariasis
Antigenemia - American Samoa, 2019. MMWR Morb Mortal Wkly Rep 2020; 69:656.

18. Thomsen EK, Sanuku N, Baea M, et al. Efficacy, Safety, and Pharmacokinetics of
Coadministered Diethylcarbamazine, Albendazole, and Ivermectin for Treatment of
Bancroftian Filariasis. Clin Infect Dis 2016; 62:334.
19. Fischer PU, King CL, Jacobson JA, Weil GJ. Potential Value of Triple Drug Therapy with
Ivermectin, Diethylcarbamazine, and Albendazole (IDA) to Accelerate Elimination of
Lymphatic Filariasis and Onchocerciasis in Africa. PLoS Negl Trop Dis 2017; 11:e0005163.
20. Ouattara AF, Bjerum CM, Aboulaye M, et al. Semiannual Treatment of Albendazole Alone is
Efficacious for Treatment of Lymphatic Filariasis: A Randomized Open-label Trial in Cote
d'Ivoire. Clin Infect Dis 2022; 74:2200.
21. Rao RU, Samarasekera SD, Nagodavithana KC, et al. Comprehensive Assessment of a
Hotspot with Persistent Bancroftian Filariasis in Coastal Sri Lanka. Am J Trop Med Hyg 2018;
99:735.
22. Twum-Danso NA. Loa loa encephalopathy temporally related to ivermectin administration
reported from onchocerciasis mass treatment programs from 1989 to 2001: implications
for the future. Filaria J 2003; 2 Suppl 1:S7.
23. Kroidl I, Saathof E, Maganga L, et al. Prevalence of Lymphatic Filariasis and Treatment
Effectiveness of Albendazole/ Ivermectin in Individuals with HIV Co-infection in Southwest-
Tanzania. PLoS Negl Trop Dis 2016; 10:e0004618.

24. Hoerauf A. Filariasis: new drugs and new opportunities for lymphatic filariasis and
onchocerciasis. Curr Opin Infect Dis 2008; 21:673.
25. Tisch DJ, Michael E, Kazura JW. Mass chemotherapy options to control lymphatic filariasis: a
systematic review. Lancet Infect Dis 2005; 5:514.
26. Frayha GJ, Smyth JD, Gobert JG, Savel J. The mechanisms of action of antiprotozoal and
anthelmintic drugs in man. Gen Pharmacol 1997; 28:273.
27. Maizels RM, Bundy DA, Selkirk ME, et al. Immunological modulation and evasion by
helminth parasites in human populations. Nature 1993; 365:797.
28. Klion AD, Ottesen EA, Nutman TB. Effectiveness of diethylcarbamazine in treating loiasis
acquired by expatriate visitors to endemic regions: long-term follow-up. J Infect Dis 1994;
169:604.

29. Hise AG, Gillette-Ferguson I, Pearlman E. The role of endosymbiotic Wolbachia bacteria in
filarial disease. Cell Microbiol 2004; 6:97.
30. Taylor MJ, Cross HF, Bilo K. Inflammatory responses induced by the filarial nematode
Brugia malayi are mediated by lipopolysaccharide-like activity from endosymbiotic
Wolbachia bacteria. J Exp Med 2000; 191:1429.
31. Centers for Disease Control and Prevention - Parasites. www.cdc.gov/ncidod/dpd/professio
nal/drgsrv_drug_table.htm (Accessed on December 11, 2009).
32. Stolk WA, de Vlas SJ, Habbema JD. Anti-Wolbachia treatment for lymphatic filariasis. Lancet
2005; 365:2067.
33. Hoerauf A, Volkmann L, Hamelmann C, et al. Endosymbiotic bacteria in worms as targets
for a novel chemotherapy in filariasis. Lancet 2000; 355:1242.

34. Taylor MJ. Wolbachia bacteria of filarial nematodes in the pathogenesis of disease and as a
target for control. Trans R Soc Trop Med Hyg 2000; 94:596.
35. Taylor MJ, Makunde WH, McGarry HF, et al. Macrofilaricidal activity after doxycycline
treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial.
Lancet 2005; 365:2116.
36. Debrah AY, Mand S, Specht S, et al. Doxycycline reduces plasma VEGF-C/sVEGFR-3 and
improves pathology in lymphatic filariasis. PLoS Pathog 2006; 2:e92.
37. Debrah AY, Mand S, Marfo-Debrekyei Y, et al. Macrofilaricidal effect of 4 weeks of treatment
with doxycycline on Wuchereria bancrofti. Trop Med Int Health 2007; 12:1433.
38. Gayen P, Nayak A, Saini P, et al. A double-blind controlled field trial of doxycycline and
albendazole in combination for the treatment of bancroftian filariasis in India. Acta Trop
2013; 125:150.

39. Supali T, Djuardi Y, Pfarr KM, et al. Doxycycline treatment of Brugia malayi-infected persons
reduces microfilaremia and adverse reactions after diethylcarbamazine and albendazole
 treatment. Clin Infect Dis 2008; 46:1385.
40. American Academy of Pediatrics. Red Book: 2021-2024 Report of the Committee on Infectio
us Diseases, 32 ed, Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH (Eds), American Acade
my of Pediatrics, Itasca, IL 2021.

41. Cao WC, Van der Ploeg CP, Plaisier AP, et al. Ivermectin for the chemotherapy of bancroftian
filariasis: a meta-analysis of the effect of single treatment. Trop Med Int Health 1997; 2:393.
42. Addiss DG, Beach MJ, Streit TG, et al. Randomised placebo-controlled comparison of
ivermectin and albendazole alone and in combination for Wuchereria bancrofti
microfilaraemia in Haitian children. Lancet 1997; 350:480.
43. Shenoy RK, Kumaraswami V, Rajan K, et al. Ivermectin for the treatment of periodic
malayan filariasis: a study of efficacy and side effects following a single oral dose and
retreatment at six months. Ann Trop Med Parasitol 1992; 86:271.
44. Nicolas L, Plichart C, Nguyen LN, Moulia-Pelat JP. Reduction of Wuchereria bancrofti adult
worm circulating antigen after annual treatments of diethylcarbamazine combined with
ivermectin in French Polynesia. J Infect Dis 1997; 175:489.
45. Weil GJ, Lammie PJ, Richards FO Jr, Eberhard ML. Changes in circulating parasite antigen
levels after treatment of bancroftian filariasis with diethylcarbamazine and ivermectin. J
Infect Dis 1991; 164:814.
46. Dreyer G, Noroes J, Amaral F, et al. Direct assessment of the adulticidal efficacy of a single
dose of ivermectin in bancroftian filariasis. Trans R Soc Trop Med Hyg 1995; 89:441.

47. Kazura JW. Ivermectin and human lymphatic filariasis. Microb Pathog 1993; 14:337.
48. Ottesen EA, Campbell WC. Ivermectin in human medicine. J Antimicrob Chemother 1994;
34:195.
49. Chodakewitz J. Ivermectin and Lymphatic Filariasis: A Clinical Update. Parasitol Today 1995;
11:233.
50. Ottesen EA, Vijayasekaran V, Kumaraswami V, et al. A controlled trial of ivermectin and
diethylcarbamazine in lymphatic filariasis. N Engl J Med 1990; 322:1113.
51. Pion SD, Chesnais CB, Bopda J, et al. The impact of two semiannual treatments with
albendazole alone on lymphatic filariasis and soil-transmitted helminth infections: a
community-based study in the Republic of Congo. Am J Trop Med Hyg 2015; 92:959.
52. Pion SDS, Chesnais CB, Weil GJ, et al. Effect of 3 years of biannual mass drug administration
with albendazole on lymphatic filariasis and soil-transmitted helminth infections: a
community-based study in Republic of the Congo. Lancet Infect Dis 2017; 17:763.
 53. Campillo JT, Awaca-Uvon NP, Missamou F, et al. Results From 2 Cohort Studies in Central
Africa Show That Clearance of Wuchereria bancrofti Infection After Repeated Rounds of
Mass Drug Administration With Albendazole Alone Is Closely Linked to Individual
Adherence. Clin Infect Dis 2021; 73:e176.
54. Dreyer G, Addiss D, Williamson J, Norões J. Efficacy of co-administered diethylcarbamazine
and albendazole against adult Wuchereria bancrofti. Trans R Soc Trop Med Hyg 2006;
100:1118.

55. National Lymphedema Network. http://www.lymphnet.org (Accessed on January 28, 2013).

56. Thomas G, Richards FO Jr, Eigege A, et al. A pilot program of mass surgery weeks for
treatment of hydrocele due to lymphatic filariasis in central Nigeria. Am J Trop Med Hyg
2009; 80:447.
57. Ottesen EA. Major progress toward eliminating lymphatic filariasis. N Engl J Med 2002;
347:1885.
58. Global Programme to Eliminate Lymphatic Filariasis. Wkly Epidemiol Rec 2006; 81:221.
59. Reimer LJ, Thomsen EK, Tisch DJ, et al. Insecticidal bed nets and filariasis transmission in
Papua New Guinea. N Engl J Med 2013; 369:745.
60. Grieve RB, Wisnewski N, Frank GR, Tripp CA. Vaccine research and development for the
prevention of filarial nematode infections. Pharm Biotechnol 1995; 6:737.
Topic 5680 Version 32.0
GRAPHICS

Approach to treatment of a patient with lymphatic filariasis, onchocerciasis,

and/or loiasis

Lymphatic Treatment of Alternative

Onchocerciasis Loiasis Comment
filariasis choice treatments

+ - - DEC (6 mg/kg for 1. IVM (200  

12 days)* mcg/kg)
+ ALB
(400 mg)
2. IVM (200
mcg/kg)
+ DEC (6
mg/kg)
3. ALB (200
mg twice
daily for
21 days)
4. DOXY
(200 mg
daily for
six
weeks)

- + - IVM (150 mcg/kg IVM (150 DEC can cause sev

every 6 to 12 mcg/kg) + post-treatment
months) DOXY (200 mg reactions and
daily for six exacerbate ocular
weeks) disease

- - + Low microfilariae: ALB (200 DEC and IVM can

DEC (8 mg/kg/day mg twice provoke serious s
for 21 days) daily for 21 effects in patients
days) ¶ high microfilariae
High microfilariae:
counts
Apheresis or ALB
(200 mg twice
daily for 21 days)
to
lower microfilariae
count prior to DEC

+ + - IVM (150 mcg/kg) 1. IVM (200 Pretreatment with

followed by DEC (6 mcg/kg) to clear
 mg/kg for 12 + ALB Onchocerca microf
days) (400 mg) is necessary prior
2. IVM + administration of
ALB (200 for LF
mg twice
daily for
21 days)
3. IVM +
DOXY
(200 mg
daily for
six
weeks)

+ - + Same as Loa alone Same as Loa Same as Loa alone

alone

- + + Low microfilariae: IVM (150 Due to the slow ef

IVM (150 mcg/kg) mcg/kg) + ALB of ALB on Loa
followed by DEC (8 (200 mg twice microfilariae, ALB
mg/kg for 21 daily for 21 should only be us
days) days) an alternative to
apheresis to lowe
High microfilariae:
Loa microfilariae i
Apheresis to
is no evidence of
lower microfilariae
onchocercal eye
prior to IVM
involvement
followed by DEC
(as for low
microfilariae)

+ + + Same as Same as Same as Onchocer

Onchocerca + Loa Onchocerca + Loa
Loa

DEC: diethylcarbamazine; IVM: ivermectin; ALB: albendazole; DOXY: doxycycline.

* A longer course (14 to 21 days) is recommended for tropical pulmonary eosinophilia.

¶ This regimen has only been demonstrated to be effective in DEC-refractory disease.

Graphic 86736 Version 2.0

Wuchereria life cycle

Different species of the following genera of mosquitoes are vectors of W. bancrofti

filariasis depending on geographical distribution. Among them are: Culex (C.
annulirostris, C. bitaeniorhynchus, C. quinquefasciatus, and C. pipiens); Anopheles (A.
arabinensis, A. bancroftii, A. farauti, A. funestus, A. gambiae, A. koliensis, A. melas, A.
merus, A. punctulatus, and A. wellcomei); Aedes (A. aegypti, A. aquasalis, A. bellator, A.
cooki, A. darlingi, A. kochi, A. polynesiensis, A. pseudoscutellaris, A. rotumae, A. scapularis,
and A. vigilax); Mansonia (M. pseudotitillans, M. uniformis); Coquillettidia (C.
juxtamansonia). During a blood meal, an infected mosquito introduces third-stage
filarial larvae onto the skin of the human host, where they penetrate into the bite
wound (1). They develop in adults that commonly reside in the lymphatics (2). The
female worms measure 80 to 100 mm in length and 0.24 to 0.30 mm in diameter,
while the males measure about 40 mm by 0.1 mm. Adults produce microfilariae
measuring 244 to 296 mcm by 7.5 to 10 mcm, which are sheathed and have nocturnal
periodicity, except the South Pacific microfilariae, which have the absence of marked
periodicity. The microfilariae migrate into lymph and blood channels moving actively
through lymph and blood (3). A mosquito ingests the microfilariae during a blood
meal (4). After ingestion, the microfilariae lose their sheaths and some of them work
their way through the wall of the proventriculus and cardiac portion of the mosquito's
midgut and reach the thoracic muscles (5). There, the microfilariae develop into first-
stage larvae (6) and subsequently into third-stage infective larvae (7). The third-stage
infective larvae migrate through the hemocoel to the mosquito's proboscis (8) and
can infect another human when the mosquito takes a blood meal (1).

Reproduced from: Centers for Disease Control and Prevention. DPDx: Lymphatic filariasis. Available at:
http://www.cdc.gov/dpdx/lymphaticFilariasis/index.html.

Graphic 74534 Version 7.0

Brugia life cycle

The typical vectors for Brugia malayi filariasis are mosquito species from the genera
Mansonia and Aedes. During a blood meal, an infected mosquito introduces third-stage
filarial larvae onto the skin of the human host, where they penetrate into the bite
wound (1). They develop into adults that commonly reside in the lymphatics (2). The
adult worms resemble those of Wuchereria bancrofti but are smaller. Female worms
measure 43 to 55 mm in length by 130 to 170 mcm in width, and males measure 13 to
23 mm in length by 70 to 80 mcm in width. Adults produce microfilariae, measuring 177
to 230 mcm in length and 5 to 7 mcm in width, which are sheathed and have nocturnal
periodicity. The microfilariae migrate into lymph and enter the blood stream, reaching
the peripheral blood (3). A mosquito ingests the microfilariae during a blood meal (4).
After ingestion, the microfilariae lose their sheaths and work their way through the wall
of the proventriculus and cardiac portion of the midgut to reach the thoracic muscles
(5). There, the microfilariae develop into first-stage larvae (6) and subsequently into
third-stage larvae (7). The third-stage larvae migrate through the hemocoel to the
mosquito's proboscis (8) and can infect another human when the mosquito takes a
blood meal (1).

Reproduced from: Centers for Disease Control and Prevention. DPDx: Lymphatic filariasis. Available at:
http://www.cdc.gov/dpdx/lymphaticFilariasis/index.html.
Graphic 52000 Version 6.0
Distribution of lymphatic filariasis and status of preventive chemotherapy (PC)

The boundaries and names shown and the designations used on this map do not imply the expression of an
the World Health Organization concerning the legal status of any country, territory, city, or area or of its aut
delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for whi
agreement.

Reprinted from WHO Preventive Chemotherapy Joint Reporting Form. Annual country reports, 2016, World Health Organization, Copy
http://apps.who.int/gho/cabinet/pc.jsp (Accessed on July 29, 2019).

Graphic 81417 Version 4.0

Contributor Disclosures
Amy D Klion, MD No relevant financial relationship(s) with ineligible companies to disclose. Peter F
Weller, MD, MACP Consultant/Advisory Boards: GlaxoSmithKline [Eosinophilic diseases]. Other Financial
Interest: AstraZeneca [Hypereosinophilic syndrome]. All of the relevant financial relationships listed have
been mitigated. Elinor L Baron, MD, DTMH No relevant financial relationship(s) with ineligible companies
to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
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