# 136 - 240 Filarial and Related Infections

### 240 Filarial and Related Infections

with nonspecific abdominal pain and watery diarrhea. If untreated, 
repeated rounds of autoinfection can lead to protein-losing enter­
opathy, severe malabsorption, and ultimately death from cachexia, 
cardiac failure, or superinfection. The diagnosis is made by identify­
ing characteristic peanut-shaped (20 × 40 μm) eggs on microscopic 
examination of stool. Severely ill patients require hospitalization and 
supportive therapy in addition to prolonged anthelmintic treatment 
with albendazole (400 mg twice daily for 10 days) or mebendazole 
(500 mg daily for 20 days; Chap. 229).
■
■ABDOMINAL ANGIOSTRONGYLIASIS
Abdominal angiostrongyliasis is primarily a disease of children living 
in Latin America. The zoonotic parasite Angiostrongylus costaricensis 
causes eosinophilic ileocolitis after the ingestion of contaminated 
vegetation. A. costaricensis normally parasitizes the cotton rat and 
other rodents, with slugs and snails serving as intermediate hosts. 
Humans become infected by accidentally ingesting infective larvae 
in mollusk slime deposited on fruits and vegetables; children are at 
highest risk. The larvae penetrate the gut wall and migrate to mesen­
teric arterioles, where they develop into adult worms. Eggs deposited 
in the gut wall provoke an intense eosinophilic granulomatous reac­
tion, and adult worms may cause mesenteric arteritis, thrombosis, or 
frank bowel infarction. Symptoms may mimic those of appendicitis, 
including abdominal pain and tenderness, fever, vomiting, and a pal­
pable mass in the right iliac fossa. Leukocytosis and eosinophilia are 
prominent. CT with contrast typically shows inflamed bowel, often 
with concomitant obstruction, but a definitive diagnosis is usually 
made histologically after partial bowel resection. Pathologic exami­
nation reveals a thickened bowel wall with eosinophilic granulomas 
surrounding the Angiostrongylus eggs. In nonsurgical cases, the diag­
nosis rests solely on clinical grounds because larvae and eggs cannot 
be detected in the stool and serologic tests are not available. Medical 
therapy for abdominal angiostrongyliasis is of uncertain efficacy. 
Careful observation and surgical resection for severe symptoms are 
the mainstays of treatment.
Acknowledgment
The authors wish to acknowledge and thank Peter F. Weller, MD, author 
of prior editions of this chapter.
■
■FURTHER READING
Costa IN et al: Diagnosis of human strongyloidiasis: Application in 
clinical practice. Acta Trop 223:106081, 2021.
Else KJ et al: Whipworm and roundworm infections. Nat Rev Dis 
Primers 6:44, 2020.
Holland C et al: Global prevalence of Ascaris infection in humans 
(2010–2021): A systematic review and meta-analysis. Infect Dis Pov­
erty 11:113, 2022.
Krolewiecki A et al: Strongyloidiasis: A neglected tropical disease. 
Infect Dis Clin North Am 33:135, 2019.
Loukas A et al: Hookworm infection. Nat Rev Dis Primers 2:16088, 
2016.
Montressor A et al: The global progress of soil-transmitted helmin­
thiases control in 2020 and World Health Organization targets for 
2030. PLoS Negl Trop Dis 14:e0008505, 2020.
Moser W et al: Efficacy of recommended drugs against soil transmit­
ted helminths: Systematic review and network meta-analysis. BMJ 
358:j4307, 2017.
O’Connell EM et al: Ancylostoma ceylanicum hookworm in Myanmar 
refugees, Thailand, 2012-2015. Emerg Infect Dis 24:1472, 2018.
Shamsi S et al: A critical review of anisakidosis cases occurring globally. 
Parasitol Res 122:1733, 2023.

Philip J. Budge, Thomas B. Nutman

Filarial and Related 

Infections
Filarial worms are nematodes that dwell in the subcutaneous tissues 
and the lymphatics. Eight filarial species infect humans (Table 240-1); of 
these, four—Wuchereria bancrofti, Brugia malayi, Onchocerca volvulus, 
and Loa loa—are responsible for most symptomatic filarial infec­
tions. Filarial parasites, which infect an estimated 170 million persons 
worldwide, are transmitted by specific species of mosquitoes or other 
arthropods and have a complex life cycle, including insect-borne 
infective larval stages and adult worms that reside in either lymphatic 
or subcutaneous tissues of humans. The offspring of adults are micro­
filariae, which, depending on their species, are 200–250 μm long 
and 5–7 μm wide, may or may not be enveloped in a loose sheath, and 
either circulate in the blood or migrate through the skin (Table 240-1). 
To complete the life cycle, microfilariae are ingested by the arthropod 
vector and develop over 1–2 weeks into new infective larvae. Adult 
worms live for many years, whereas microfilariae survive for 3–36 months. 
The intracellular bacterial endosymbiont Wolbachia has been found in 
all stages of Brugia, Wuchereria, Mansonella, and Onchocerca species 
and has become a target for antifilarial chemotherapy.
Usually, infection is established only with repeated, prolonged 
exposures to infective larvae. Since the clinical manifestations of 
filarial diseases develop relatively slowly, these infections should be 
considered chronic, with possible long-term debilitating effects. The 
nature, severity, and timing of clinical manifestations in patients with 
filarial infections who are native to endemic areas and have lifelong 
exposure may differ significantly from those who are travelers or who 
have recently moved to these areas. Characteristically, filarial disease is 
more acute and intense in newly exposed individuals than in natives 
of endemic areas.
CHAPTER 240
Filarial and Related Infections 
LYMPHATIC FILARIASIS
Lymphatic filariasis is caused by W. bancrofti, B. malayi, or Brugia timori. 
The threadlike adult parasites reside in afferent lymphatics or lymph 
nodes, where they may remain viable for more than two decades.
■
■EPIDEMIOLOGY
W. bancrofti, the most widely distributed filarial parasite of humans, 
affects an estimated 51 million people and is found throughout the 
tropics and subtropics, including Asia and the Pacific Islands, Africa, 
areas of South America, and the Caribbean basin. Humans are the 
only definitive host for the parasite. Generally, the subperiodic form 
is found only in the Pacific Islands; elsewhere, W. bancrofti is noctur­
nally periodic. Nocturnally periodic forms of microfilariae are scarce 
in peripheral blood by day and increase at night, whereas subperiodic 
forms are present in peripheral blood at all times and reach maximal 
levels in the afternoon. Natural vectors for W. bancrofti are Culex 
mosquitoes in urban settings and Anopheles or Aedes mosquitoes in 
rural areas.
Brugian filariasis due to B. malayi occurs primarily in eastern India, 
Indonesia, Malaysia, and the Philippines. B. malayi also has two forms 
distinguished by the periodicity of microfilaremia. The more common 
nocturnal form is transmitted in areas of coastal rice fields, while the 
subperiodic form is found in forests. B. malayi naturally infects cats as 
well as humans. The distribution of B. timori is limited to the islands of 
southeastern Indonesia.
■
■PATHOLOGY
The principal pathologic changes of lymphatic filariasis result from 
inflammatory damage to the lymphatics, which is typically caused by 
adult worms and not by microfilariae. Adult worms live in afferent 
lymphatics or sinuses of lymph nodes and cause lymphatic dilation 
and thickening of the vessel walls. The infiltration of plasma cells,

TABLE 240-1  Characteristics of the Filariae
ORGANISM
PERIODICITY
DISTRIBUTION
VECTOR
LOCATION OF ADULT
Wuchereria bancrofti
Nocturnal
Cosmopolitan areas worldwide, 
including South America, Africa, 
southern Asia, Papua New Guinea, 
China, Indonesia
 
Subperiodic
Eastern Pacific
Aedes (mosquitoes)
Lymphatic tissue
Blood
+
Brugia malayi
Nocturnal
Southeast Asia, Indonesia, India
Mansonia, Anopheles (mosquitoes)
Lymphatic tissue
Blood
+
 
Subperiodic
Indonesia, Southeast Asia
Coquillettidia, Mansonia (mosquitoes)
Lymphatic tissue
Blood
+
Brugia timori
Nocturnal
Indonesia
Anopheles (mosquitoes)
Lymphatic tissue
Blood
+
Loa loa
Diurnal
West and Central Africa
Chrysops (deerflies)
Subcutaneous tissue
Blood
+
Onchocerca volvulus
None
South and Central America, Africa
Simulium (blackflies)
Subcutaneous tissue
Skin, eye
–
Mansonella ozzardi
None
South and Central America
Culicoides (midges)
Undetermined site
Blood
–
 
None
Caribbean
Simulium (blackflies)
Undetermined site
Blood
–
Mansonella perstans
None
South and Central America, Africa
Culicoides (midges)
Body cavities, 
mesentery, perirenal 
tissue
Mansonella 
streptocerca
None
West and Central Africa
Culicoides (midges)
Subcutaneous tissue
Skin
–
eosinophils, and macrophages in and around the infected vessels, along 
with endothelial and connective tissue proliferation, leads to tortuosity 
of the lymphatics and damaged or incompetent lymph valves. Lymph­
edema and chronic stasis changes with hard or brawny edema develop in 
the overlying skin. These consequences of filarial infection are due both 
to the direct effects of the worms and to the host’s inflammatory response 
to the parasite. Inflammatory responses are believed to cause the 
granulomatous and proliferative processes that precede total lymphatic 
obstruction. It is thought that the lymphatic vessel remains patent as 
long as the worm remains viable, and that the death of the worm leads to 
enhanced granulomatous reactions and fibrosis. Lymphatic obstruction 
results, and despite collateralization, lymphatic function is compromised.
PART 5
Infectious Diseases
■
■CLINICAL FEATURES
The most common presentations of the lymphatic filariases are asymp­
tomatic (or subclinical) microfilaremia, hydrocele (Fig. 240-1), acute 
adenolymphangitis (ADL), and chronic lymphatic disease. In areas 
FIGURE 240-1  Hydrocele associated with Wuchereria bancrofti infection.

MICROFILARIAL 
LOCATION
SHEATH
Culex, Anopheles (mosquitoes)
Lymphatic tissue
Blood
+
Blood
–
where W. bancrofti or B. malayi is endemic, most infected individuals 
have few overt clinical manifestations of filarial infection despite the 
presence of circulating microfilariae in the peripheral blood. Although 
they may be clinically asymptomatic, virtually all persons with 

W. bancrofti or B. malayi microfilaremia have some degree of subclini­
cal disease that includes microscopic hematuria and/or proteinuria, 
dilated (and tortuous) lymphatics (visualized by imaging), and—in 
men with W. bancrofti infection—scrotal lymphangiectasia (detect­
able by ultrasound). Despite these findings, most individuals appear 
to remain clinically asymptomatic for years; in relatively few does the 
infection progress to either acute or chronic disease.
ADL is characterized by high fever, lymphatic inflammation (lym­
phangitis and lymphadenitis), and transient local edema. The lym­
phangitis is retrograde, extending peripherally from the lymph node 
draining the area where the adult parasites reside. Regional lymph 
nodes are often enlarged, and the entire lymphatic channel can become 
indurated and inflamed. Concomitant local thrombophlebitis can 
occur as well. In brugian filariasis, a single local abscess may form 
along the involved lymphatic tract and subsequently rupture to the sur­
face. The lymphadenitis and lymphangitis can involve both the upper 
and lower extremities in both bancroftian and brugian filariasis, but 
involvement of the genital lymphatics occurs almost exclusively with 
W. bancrofti infection. This genital involvement can be manifested by 
funiculitis, epididymitis, and scrotal pain and tenderness. In endemic 
areas, another type of acute disease—dermatolymphangioadenitis 
(DLA)—is recognized as a syndrome that includes high fever, chills, 
myalgias, and headache. Edematous inflammatory plaques clearly 
demarcated from normal skin are seen. Vesicles, ulcers, and hyperpig­
mentation also may be noted. There is often a history of trauma, burns, 
irradiation, insect bites, punctiform lesions, or chemical injury. Entry 
lesions, especially in the interdigital area, are common. DLA is often 
diagnosed as cellulitis.
If lymphatic damage progresses, transient lymphedema can develop 
into lymphatic obstruction and the permanent changes associated with 
elephantiasis (Fig. 240-2). Brawny edema follows early pitting edema, 
the subcutaneous tissues thicken, and hyperkeratosis occurs. Fissur­
ing of the skin develops, as do hyperplastic changes. Superinfection of 
these poorly vascularized tissues becomes a problem. In bancroftian 
filariasis, in which genital involvement is common, hydroceles may 
develop (Fig. 240-1); in advanced stages, this condition may evolve into 
scrotal lymphedema and scrotal elephantiasis. Furthermore, if there 
is obstruction of the retroperitoneal lymphatics, increased renal lym­
phatic pressure leads to rupture of the renal lymphatics and the devel­
opment of chyluria, which is usually intermittent and most prominent 
in the morning.

FIGURE 240-2  Elephantiasis of the lower extremity associated with Wuchereria 
bancrofti infection.
The clinical manifestations of filarial infections in travelers or trans­
migrants who have recently entered an endemic region are distinctive. 
Given a sufficient number of bites by infected vectors, usually over a 
3- to 6-month period, recently exposed patients can develop acute lym­
phatic or scrotal inflammation with or without urticaria and localized 
angioedema. Lymphadenitis of epitrochlear, axillary, femoral, or ingui­
nal lymph nodes is often followed by evolving retrograde lymphangi­
tis. Acute attacks are short-lived and are not usually accompanied by 
fever. With prolonged exposure to infected mosquitoes, these attacks, 
if untreated, become more severe and lead to permanent lymphatic 
inflammation and obstruction.
■
■DIAGNOSIS
A definitive diagnosis can be made only by detection of the para­
sites and hence can be difficult. Adult worms localized in lymphatic 
vessels or nodes are largely inaccessible. Microfilariae can be found 
in blood, in hydrocele fluid, or (occasionally) in other body fluids. 
Such fluids can be examined microscopically, either directly or—for 
greater sensitivity—after concentration of the parasites by the pas­
sage of fluid through a polycarbonate cylindrical-pore filter (pore 
size, 3 μm) or by the centrifugation of fluid fixed in 2% formalin 
(Knott’s concentration technique). The timing of blood collection is 
critical and should be based on the periodicity of the microfilariae in 
the endemic region involved. Many infected individuals do not have 
microfilaremia, and definitive diagnosis in such cases can be difficult. 
Assays for circulating antigens of W. bancrofti permit the diagnosis 
of microfilaremic and cryptic (amicrofilaremic) infection. Two tests 
are commercially available: an enzyme-linked immunosorbent assay 
(ELISA) and a rapid-format lateral flow assay. Both assays have sen­
sitivities of 93–100% and specificities approaching 100%, although 
false positives can occur in individuals infected with Loa loa (see 
“Loiasis” below). There are currently no tests for circulating antigens 
in brugian filariasis.
Polymerase chain reaction (PCR)–based assays for DNA of W. ban­
crofti and B. malayi in blood have been developed. A number of studies 
indicate that the sensitivity of this diagnostic method is equivalent to or 
greater than that of parasitologic methods.

In cases of suspected lymphatic filariasis, examination of the scro­
tum, the lymph nodes, or (in female patients) the breast by means of 
high-frequency ultrasound in conjunction with Doppler techniques 
may result in the identification of motile adult worms within dilated 
lymphatics (Video 240-1). Worms may be visualized in the lymphatics 
of the spermatic cord in up to 80% of men infected with W. bancrofti. 
Live adult worms have a distinctive pattern of movement within 
the lymphatic vessels (termed the filarial dance sign). Radionuclide 
lymphoscintigraphic imaging of the limbs reliably demonstrates wide­
spread lymphatic abnormalities in both subclinical microfilaremic 
persons and those with clinical manifestations of lymphatic pathology. 
Although of potential utility in the delineation of anatomic changes 
associated with infection, lymphoscintigraphy is unlikely to assume 
primacy in the diagnostic evaluation of individuals with suspected 
infection; it is principally a research tool, although it has been used 
more widely for assessment of lymphedema of any cause. Eosinophilia 
and elevated serum concentrations of IgE and antifilarial antibody 
support the diagnosis of lymphatic filariasis. There is, however, exten­
sive cross-reactivity between filarial antigens and antigens of other 
helminths. Of note, W. bancrofti– and B. malayi–specific antigens have 
been identified and are now available for use in rapid diagnostic tests 
with specificities of >98%. However, seropositivity cannot be equated 
with active infection: residents of endemic areas can become sensitized 
to filarial antigens through exposure to infective mosquitoes without 
having patent filarial infections.

The ADL associated with lymphatic filariasis must be distinguished 
from thrombophlebitis, infection, and trauma. Retrograde evolution 
is a characteristic feature that helps distinguish filarial lymphangitis 
from ascending bacterial lymphangitis. Chronic filarial lymphedema 
must also be distinguished from the lymphedema of malignancy, post­
operative scarring, trauma, chronic edematous states, and congenital 
lymphatic system abnormalities.
CHAPTER 240
Filarial and Related Infections 
TREATMENT
Lymphatic Filariasis
With newer definitions of clinical syndromes in lymphatic filariasis 
and new tools to assess clinical status (e.g., ultrasound, lymphos­
cintigraphy, circulating filarial antigen assays, PCR), approaches to 
treatment based on infection status can be considered.
Orally administered diethylcarbamazine (DEC; 6 mg/kg daily for 
12 days), which has both macro- and microfilaricidal properties, 
remains the drug of choice for the treatment of active lymphatic fila­
riasis (defined by microfilaremia, antigen positivity, or adult worms 
on ultrasound), although albendazole (400 mg twice daily by mouth 
for 21 days) also has demonstrated macrofilaricidal efficacy. A 4- to 
6-week course of oral doxycycline (targeting the intracellular Wol­
bachia) also has significant macrofilaricidal activity, as does DEC/
albendazole used daily for 7 days. The addition of DEC to a 3-week 
course of doxycycline is also efficacious in lymphatic filariasis.
Regimens that combine single doses of albendazole (400 mg) 
with either DEC (6 mg/kg) or ivermectin (200 μg/kg) all have a 
sustained microfilaricidal effect and are the mainstay of programs 
for the eradication of lymphatic filariasis in Africa (albendazole/
ivermectin) and elsewhere (albendazole/DEC) (see “Prevention 
and Control,” below). More recently, a regimen using single doses 
of the three major antifilarial drugs (albendazole/DEC/ivermectin) 

has been shown to sustain microfilarial clearance out to at least 
2 years.
As already mentioned, a growing body of evidence indicates 
that, although they may be asymptomatic, virtually all persons with 
W. bancrofti or B. malayi microfilaremia have some degree of sub­
clinical disease (hematuria, proteinuria, abnormalities on lympho­
scintigraphy). Thus, early treatment of asymptomatic persons who 
have microfilaremia is recommended to prevent further lymphatic 
damage. For ADL, supportive treatment (including the administra­
tion of antipyretics and analgesics) is recommended, as is antibiotic 
therapy if secondary bacterial infection is likely. Similarly, because

lymphatic disease is associated with the presence of adult worms, 
treatment with DEC is recommended for microfilaria-negative car­
riers of adult worms.

In persons with chronic manifestations of lymphatic filariasis, 
treatment regimens that emphasize hygiene, prevention of sec­
ondary bacterial infections, and physiotherapy have gained wide 
acceptance for morbidity control. These regimens are similar to 
those recommended for lymphedema of most nonfilarial causes 
and are known by a variety of names, including complex deconges­
tive physiotherapy and complex lymphedema therapy. Hydroceles 
(Fig. 240-1) can be managed surgically. With chronic manifesta­
tions of lymphatic filariasis, drug treatment should be reserved 
for individuals who have evidence of active infection; however, 
in some settings, a 6-week course of doxycycline has been shown 
to provide improvement in filarial lymphedema irrespective of 
disease activity.
Side effects of DEC treatment in infected individuals may 
include fever, chills, arthralgias, headaches, nausea, and vomit­
ing. Both the development and the severity of these reactions are 
directly related to the number of microfilariae circulating in the 
bloodstream. The adverse reactions may represent either an acute 
hypersensitivity reaction to the antigens being released by dead 
and dying parasites or an inflammatory reaction induced by the 
intracellular Wolbachia endosymbionts freed from their intracel­
lular niche.
Ivermectin has a side effect profile similar to that of DEC when 
used in lymphatic filariasis. In patients infected with L. loa who 
have high levels of microfilaremia, DEC—like ivermectin (see 
“Loiasis,” below)—can elicit severe encephalopathic complications. 
When used in single-dose regimens for the treatment of lymphatic 
filariasis, albendazole is associated with relatively few side effects.
PART 5
Infectious Diseases
■
■PREVENTION AND CONTROL
To protect themselves against filarial infection, individuals must 
avoid contact with infected mosquitoes by using personal protective 
measures, including bed nets, particularly those impregnated with 
insecticides such as permethrin. Mass drug administration (MDA) 
is the current approach to elimination of lymphatic filariasis as a 
public health problem. The underlying tenet of this approach is that 
mass annual distribution of antifilarial chemotherapy—albendazole 
with either DEC (for all areas except those where onchocerciasis is 
co-endemic; see section on onchocerciasis treatment, below) or iver­
mectin or with both ivermectin and DEC (triple-drug therapy)—will 
profoundly suppress microfilaremia. If the suppression is sustained, 
then transmission can be interrupted.
Created by the World Health Organization in 1997, the Global 
Programme to Eliminate Lymphatic Filariasis is based on mass 
administration of single annual doses of DEC plus albendazole in nonAfrican regions and of albendazole plus ivermectin in Africa. Available 
information from late 2022 indicated that >935 million persons in 68 
countries had thus far participated. Not only has lymphatic filariasis 
been eliminated in some defined areas, but collateral benefits—avoidance 
of disability and treatment of intestinal helminths and other condi­
tions (e.g., scabies and louse infestation)—also have been noted. The 
strategy of the global program is being refined, and attempts are being 
made to integrate this effort with other mass-treatment strategies (e.g., 
deworming programs, malaria control, and trachoma control) in an 
integrated control strategy.
TROPICAL PULMONARY EOSINOPHILIA
Tropical pulmonary eosinophilia (TPE) is a distinct syndrome that 
develops in some individuals infected with the lymphatic-dwelling 
filarial species. Most cases have been reported from India, Pakistan, 
Sri Lanka, Brazil, Guyana, and Southeast Asia; the decreasing inci­
dence of TPE in the past decade probably reflects global MDA efforts.
■
■CLINICAL FEATURES
The main features include a history of residence in filaria-endemic 
regions, paroxysmal cough and wheezing (usually nocturnal and 

probably related to the nocturnal periodicity of microfilariae), weight 
loss, low-grade fever, lymphadenopathy, and pronounced blood eosin­
ophilia (>3000 eosinophils/μL). Chest x-rays or computed tomography 
(CT) scans may be normal but generally show increased bronchovascu­
lar markings. Diffuse miliary lesions or mottled opacities may be pres­
ent in the middle and lower lung fields. Tests of pulmonary function 
show restrictive abnormalities in most cases and obstructive defects 
in half. Characteristically, total serum IgE levels (4–40 KIU/mL) and 
antifilarial antibody levels are markedly elevated.
■
■PATHOLOGY
In TPE, microfilariae and parasite antigens are rapidly cleared from 
the bloodstream by the lungs. The clinical symptoms result from 
allergic and inflammatory reactions elicited by the cleared parasites. 
In some patients, trapping of microfilariae in other reticuloendothelial 
organs can cause hepatomegaly, splenomegaly, or lymphadenopathy. A 
prominent, eosinophil-enriched, intra-alveolar infiltrate is common, 
and with it comes the release of cytotoxic proinflammatory eosinophil 
granule proteins that may mediate some of the pathology seen in TPE. 
In the absence of successful treatment, interstitial fibrosis can lead to 
progressive pulmonary damage.
■
■DIFFERENTIAL DIAGNOSIS
TPE must be distinguished from asthma, Löffler’s syndrome, allergic 
bronchopulmonary aspergillosis, allergic granulomatosis with polyan­
giitis (eosinophilic granulomatosis with polyangiitis or Churg-Strauss 
syndrome), other systemic vasculitides (most notably, periarteritis 
nodosa), chronic eosinophilic pneumonia, and the hypereosinophilic 
syndromes (HESs).
TREATMENT
Tropical Pulmonary Eosinophilia
DEC is used at a daily dosage of 4–6 mg/kg for 14 days. Symptoms 
usually resolve within 3–7 days after the initiation of therapy. 
Relapse, which occurs in ~12–25% of cases (sometimes after an 
interval of several years), requires re-treatment.
ONCHOCERCIASIS
■
■EPIDEMIOLOGY
Onchocerciasis (“river blindness”) is caused by the filarial nematode 
O. volvulus, which infects an estimated 37 million individuals in 
31 countries worldwide. The majority of individuals infected with 
O. volvulus live in the equatorial region of Africa extending from the 
Atlantic coast to the Red Sea. In the Americas, the only remaining 
countries with isolated foci are Venezuela and Brazil. The infection is 
also found in Yemen.
■
■ETIOLOGY
Infection in humans begins with the deposition of infective larvae on the 
skin by the bite of an infected blackfly. The larvae develop into adults, 
which are typically found in subcutaneous nodules. About 7 months 
to 3 years after infection, the gravid female releases microfilariae that 
migrate out of the nodule and throughout the tissues, concentrating in 
the dermis. Infection is transmitted to other persons when a female fly 
ingests microfilariae from the host’s skin and these microfilariae then 
develop into infective larvae. Adult O. volvulus females and males are 
~40–60 cm and ~3–6 cm in length, respectively. The life span of adults 
can be as long as 18 years, with an average of ~9 years. Because the 
blackfly vector breeds along free-flowing rivers and streams (particu­
larly in rapids) and generally restricts its flight to an area within several 
kilometers of these breeding sites, both biting and disease transmission 
are most intense in these locations.
■
■PATHOLOGY
Onchocerciasis primarily affects the skin, eyes, and lymph nodes. 
In contrast to the pathology in lymphatic filariasis, the damage in

onchocerciasis is elicited by microfilariae and not by adult parasites. 
In the skin, there are mild but chronic inflammatory changes that can 
result in loss of elastic fibers, atrophy, and fibrosis. The subcutaneous 
nodules (onchocercomata) consist primarily of fibrous tissues sur­
rounding the adult worm, often with a peripheral ring of inflammatory 
cells surrounded by an endothelial layer (characterized as lymphatic in 
origin). In the eye, neovascularization and corneal scarring lead to cor­
neal opacities and blindness. Inflammation in the anterior and poste­
rior chambers frequently results in anterior uveitis, chorioretinitis, and 
optic atrophy. Although punctate opacities are due to an inflammatory 
reaction surrounding dead or dying microfilariae, the pathogenesis of 
most manifestations of onchocerciasis is still unclear.
■
■CLINICAL FEATURES
Skin 
Pruritus and rash are the most common manifestations of 
onchocerciasis. The pruritus can be incapacitating; the rash is typically 
a papular eruption (Fig. 240-3) that is generalized rather than localized 
to a particular region of the body. Long-term infection results in exag­
gerated and premature wrinkling of the skin, loss of elastic fibers, and 
epidermal atrophy that can lead to loose, redundant skin and hypo- or 
hyperpigmentation. Localized eczematoid dermatitis can cause hyper­
keratosis, scaling, and pigmentary changes. In an immunologically 
hyperreactive form of onchodermatitis (commonly termed sowdah or 
localized onchodermatitis), the affected skin darkens as a consequence 
of the profound inflammation that occurs as microfilariae in the skin 
are cleared.
Onchocercomata 
These subcutaneous nodules, which can be pal­
pable and/or visible, contain the adult worm. They are most common 
over the coccyx and sacrum, the trochanter of the femur, the lateral 
anterior crest, and other bony prominences. Nodules vary in size and 
characteristically are firm and not tender. It has been estimated that, for 
every palpable nodule, there are four deeper nonpalpable ones.
Ocular Tissue 
Visual impairment is the most serious complication 
of onchocerciasis and usually affects only those persons with moder­
ate or heavy infections. Lesions may develop in all parts of the eye. 
The most common early finding is conjunctivitis with photophobia. 
Punctate keratitis—acute inflammatory reactions surrounding dying 
microfilariae and manifested as “snowflake” opacities—is common 
among younger patients and resolves without apparent complications. 
Sclerosing keratitis occurs in 1–5% of infected persons and is the lead­
ing cause of onchocercal blindness. Anterior uveitis and iridocyclitis 
FIGURE 240-3  Papular eruption as a consequence of onchocerciasis.

develop in ~5% of infected persons. Characteristic chorioretinal lesions 
develop as a result of atrophy and hyperpigmentation of the retinal 
pigment epithelium. Constriction of the visual fields and overt optic 
atrophy may occur.

Lymph Nodes 
Mild to moderate lymphadenopathy is common, 
particularly in the inguinal and femoral areas, where the enlarged 
nodes may hang down in response to gravity (“hanging groin”), some­
times predisposing to inguinal and femoral hernias.
Other Manifestations 
Some heavily infected individuals develop 
cachexia with loss of adipose tissue and muscle mass. A form of dwarf­
ism, Nakalanga dwarfism, has been attributed to pituitary involvement 
in this infection. An association between onchocerciasis and epilepsy 
(including an epidemic form termed nodding syndrome) has gained 
attention recently. Among adults who become blind, there is a three- to 
fourfold increase in mortality rate.
■
■DIAGNOSIS
Definitive diagnosis depends on the detection of an adult worm in 
an excised nodule or, more commonly, of microfilariae in a skin snip. 
Skin snips are obtained with a corneal-scleral punch or by lifting of 
the skin with the tip of a needle and excision of a small (1- to 3-mm) 
piece with a sterile scalpel blade. Both methods collect a blood-free 
skin biopsy sample extending to just below the epidermis. The biopsy 
tissue can be incubated in tissue culture medium or in saline on a 
glass slide or flat-bottomed microtiter plate. After incubation for 2–4 h 
(or occasionally overnight in light infections), microfilariae emer­
gent from the skin can be seen by low-power microscopy or can be 
detected by PCR.
CHAPTER 240
Eosinophilia and elevated serum IgE levels are common, but, because 
these features are seen in many parasitic infections, are not diagnostic 
in themselves. Immunoassays to detect antibodies to Onchocercaspecific antigens are being used both in specialized laboratories and at 
the point of contact in rapid-diagnostic formats.
Filarial and Related Infections 
TREATMENT
Onchocerciasis
The main goals of therapy are to prevent the development of irre­
versible lesions and to alleviate symptoms. Chemotherapy is the 
mainstay of management. Ivermectin, a semisynthetic macrocyclic 
lactone active against microfilariae, is the first-line agent for the 
treatment of onchocerciasis. It is given orally in a single dose of 
150 μg/kg, either yearly or semiannually. More frequent ivermectin 
administration (every 3 months) has been suggested to ameliorate 
pruritus and skin disease.
After treatment, most individuals have few or no reactions. Pruri­
tus, cutaneous edema, and/or maculopapular rash occur in ~1–10% 
of treated individuals. In areas of Africa co-endemic for O. volvulus 
and L. loa, however, ivermectin is contraindicated (as it is for preg­
nant or breast-feeding women) because of severe posttreatment 
encephalopathy, especially in patients who are heavily microfilaremic 
for L. loa (>30,000 microfilariae/mL). Although ivermectin treatment 
results in a marked drop in microfilarial density, its effect can be 
short-lived (<3 months in some cases). Thus, it is occasionally nec­
essary to give ivermectin more frequently for persistent symptoms. 
Another macrocyclic lactone, moxidectin, has a more prolonged 
microfilaricidal effect but is not yet commercially available.
A 6-week course of doxycycline is macrofilaristatic, rendering 
female adult worms sterile for long periods.
■
■PREVENTION
Vector control has been beneficial in highly endemic areas in which 
breeding sites are vulnerable to insecticide spraying, but most areas 
endemic for onchocerciasis are not suited to this type of control. 
Community-based administration of ivermectin every 6–12 months is 
being used to interrupt transmission in endemic areas. This measure, 
in conjunction with vector control, has already helped eliminate the

FIGURE 240-4  Adult Loa loa worm being surgically removed after its subconjunctival 
migration.
infection in most of Latin America and has reduced the prevalence of 
disease in many endemic foci in Africa. No drug has proved useful for 
prophylaxis of O. volvulus infection.
LOIASIS
■
■ETIOLOGY AND EPIDEMIOLOGY
Loiasis is caused by L. loa (the African eye worm), which is present in 
the rainforests of West and Central Africa. Adult parasites (females, 
50–70 mm long and 0.5 mm wide; males, 25–35 mm long and 0.25 mm 
wide) live in subcutaneous tissues. Microfilariae circulate in the 
blood with a diurnal periodicity that peaks between 10:00 a.m. and 
2:00 p.m.
PART 5
Infectious Diseases
■
■CLINICAL FEATURES
Manifestations of loiasis in natives of endemic areas may differ from 
those in temporary residents or visitors. Among the indigenous popu­
lation, loiasis is often an asymptomatic infection with microfilaremia. 
Infection may be recognized only after subconjunctival migration 
of an adult worm (Fig. 240-4) or may be manifested by episodic 
Calabar swellings—evanescent localized areas of angioedema and 
erythema developing on the extremities and less frequently at other 
sites. Nephropathy, encephalopathy, and cardiomyopathy can occur 
but are infrequently diagnosed. Although historically considered 
relatively benign in endemic populations, recent studies show loiasis is 
associated with chronic morbidity and increased mortality in endemic 
populations. In patients who are not residents of endemic areas, aller­
gic symptoms predominate, episodes of Calabar swelling tend to be 
more frequent, microfilaremia is less common, and eosinophilia and 
increased levels of antifilarial antibodies are characteristic.
■
■PATHOLOGY
The pathogenesis of the manifestations of loiasis is poorly understood. 
Calabar swellings are thought to result from a hypersensitivity reaction 
to adult worm antigens.
■
■DIAGNOSIS
Definitive diagnosis of loiasis requires the detection of microfilariae in 
the peripheral blood or the isolation of the adult worm from the eye 
(Fig. 240-4) or from a subcutaneous biopsy specimen collected from 
a site of swelling developing after treatment. PCR-based assays for the 
detection of L. loa DNA in blood are available in specialized laboratories 
and are highly sensitive and specific, as are some newer recombinant 
antigen–based serologic techniques. In practice, the diagnosis must 
often be based on a characteristic history and clinical presentation, 
blood eosinophilia, and elevated levels of antifilarial antibodies, particu­
larly in travelers to an endemic region, who are often amicrofilaremic.

TREATMENT
Loiasis
DEC (8–10 mg/kg per day administered orally for 21 days) is effec­
tive against both the adult and the microfilarial forms of L. loa, but 
multiple courses are frequently necessary before loiasis resolves 
completely. In cases of heavy microfilaremia, allergic or other 
inflammatory reactions can take place during treatment, including 
central nervous system involvement with coma and encephalitis. 
Heavy infections can be treated initially with apheresis to remove 
the microfilariae and with glucocorticoids (40–60 mg of predni­
sone per day) followed by low doses of DEC (0.5 mg/kg per day). 
If antifilarial treatment has no adverse effects, the prednisone dose 
can be tapered rapidly and the dose of DEC gradually increased to 
8–10 mg/kg per day.
Albendazole or ivermectin is effective in reducing microfilarial 
loads, although neither is approved for this purpose by the U.S. 
Food and Drug Administration. Moreover, ivermectin is contra­
indicated in patients with >30,000 microfilariae/mL because this 
drug has been associated with severe adverse events (including 
encephalopathy and death) in heavily infected patients with loiasis 
in West and Central Africa. DEC (300 mg weekly) is an effective 
prophylactic regimen for loiasis.
STREPTOCERCIASIS
Mansonella streptocerca, found mainly in the tropical forest belt of 
Africa from Ghana to the Democratic Republic of the Congo, is trans­
mitted by biting midges. The major clinical manifestations involve the 
skin and include pruritus, papular rashes, and pigmentation changes. 
Many infected individuals have inguinal adenopathy, although most 
are asymptomatic. The diagnosis is made by detection of the charac­
teristic microfilariae in skin snips. Ivermectin at a single dose of 150 
μg/kg leads to sustained suppression of microfilariae in the skin and is 
probably the treatment of choice for streptocerciasis.
MANSONELLA PERSTANS INFECTION
M. perstans, distributed across the center of Africa and in northeastern 
South America, is transmitted by midges. Adult worms reside in 
serous cavities—pericardial, pleural, and peritoneal—as well as in the 
mesentery and the perirenal and retroperitoneal tissues. Microfilariae 
circulate in the blood without periodicity. The clinical and pathologic 
features of the infection are poorly defined. Most patients appear to be 
asymptomatic, but manifestations may include transient angioedema 
and pruritus of the arms, face, or other parts of the body (analogous 
to the Calabar swellings of loiasis); fever; headache; arthralgias; and 
right-upper-quadrant pain. Occasionally, pericarditis and hepatitis 
occur. The diagnosis is based on the demonstration of microfilariae in 
blood or serosal effusions. Perstans filariasis is often associated with 
peripheral-blood eosinophilia and antifilarial antibody elevations.
With the identification of a Wolbachia endosymbiont in M. perstans, 
doxycycline (200 mg twice a day) for 6 weeks has been established as 
the first effective treatment for this infection.
MANSONELLA OZZARDI INFECTION
The distribution of M. ozzardi is restricted to Central and South America 
and certain Caribbean islands. Adult worms are rarely recovered from 
humans. Microfilariae circulate in the blood without periodicity. 
Although this organism has often been considered nonpathogenic, 
headache, articular pain, fever, pulmonary symptoms, adenopathy, 
hepatomegaly, pruritus, and eosinophilia have been ascribed to M. ozzardi 
infection. The diagnosis is made by detection of microfilariae in 
peripheral blood. Ivermectin is effective in treating this infection.
ZOONOTIC FILARIAL INFECTIONS
Dirofilariae that affect primarily dogs, cats, and raccoons occasionally 
infect humans incidentally, as do Brugia and Onchocerca parasites that 
affect small mammals. Because humans are an abnormal host, the