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Onchocerciasis
Author: Michele E Murdoch, BSc, FRCP
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: May 2022. | This topic last updated: Oct 26, 2020.

INTRODUCTION

Onchocerciasis is caused by the filarial nematode Onchocerca volvulus. It is also known as "river
blindness" because the blackfly vector breeds near fast-flowing streams and rivers. The disease
affects rural communities and is a major cause of blindness, skin disease, and onchocerciasis-
associated epilepsy in endemic areas with serious socioeconomic consequences.

EPIDEMIOLOGY

In 2017, the global prevalence of infection with onchocerciasis was estimated at 20.9 million [1].
In 2017 to 2018, 205 million people were deemed at risk of onchocerciasis because they lived in
areas with potential for disease transmission [2]. More than 99 percent of cases occur in 31
African countries ( figure 1) whilst smaller foci of infection are found in Yemen and Central
and South America.

The first confirmed elimination of an onchocerciasis focus in Africa occurred in Abu Hamed,
Sudan, in 2016 [3]. Four countries in the Americas (Colombia, Ecuador, Mexico, and Guatemala)
have completed the World Health Organization verification process for elimination [4].
Transmission is ongoing in the Americas region in a single large transmission zone (the
"Yanomani area"), which extends across the border of Venezuela and Brazil ( figure 2). (See
'Mass treatment' below.)

Onchocerciasis is the second-leading infectious cause of blindness worldwide: approximately

500,000 people are blind due to onchocerciasis [5]. The epidemiologic patterns of infection

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differ between savanna and forest regions.

● In West African savanna areas, ocular onchocerciasis is common; it particularly affects the
anterior segment of the eye, though the posterior eye segment can also be affected. The
risks of visual impairment increase, in part, as the prevalence and intensity of infection in a
community rises [6]. The prevalence of infection can vary between villages and was
historically as high as 80 to 100 percent by the age of 20 years in some areas, with
blindness peaking at 40 to 50 years of age. Prior to control activities, hyperendemic
regions were frequently depopulated because of high rates of blindness.

● In African forest areas with a comparable intensity of onchocerciasis as savanna areas,

onchocercal skin disease predominates, with much less blindness. Furthermore, ocular
lesions, when present, usually involve the posterior eye segment. A multi-country study in
highly endemic forest communities found that itching affected 42 percent of the
population aged ≥20 years, and onchocercal skin lesions affected 28 percent of the
population aged ≥5 years. Strong associations were found between the prevalence of skin
lesions and troublesome itching and onchocercal endemicity [7]. The Global Burden of
Disease Study 2017 estimated 14.7 million people had skin disease due to onchocerciasis
[1].

The different savanna and forest epidemiologic patterns are thought to be due to the existence
of two strains of O. volvulus. The higher propensity for ocular disease with the savanna strain
has been correlated with higher quantities of Wolbachia DNA by polymerase chain reaction
(PCR); Wolbachia are endosymbiotic bacteria found in O. volvulus adults and microfilariae that
are essential for the filarial worm's fertility and survival [8]. Blindness from onchocerciasis is less
common in Latin America; this may be related to transmission intensity, strain differences,
genetic factors, or other causes.

Black flies are not efficient vectors of disease; a minimum stay of 12 months in endemic areas is
generally necessary to acquire infection. Thus, short-term travelers to endemic regions are
unlikely to become infected, though medical staff treating returned travelers should be aware
of this possibility [9].

LIFE CYCLE

Humans are the only definitive host for O. volvulus, although there are a number of other
onchocercal species that infect animals; a small number of human infections with Onchocerca
lupi (a parasite known to infect cats and dogs) have been described [10,11].

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Humans are infected with O. volvulus via the bite of a blackfly of the Simulium genus. The
blackfly deposits infective third-stage larvae into the human skin, which mature into adult
parasites (macrofilariae) over the next 6 to 12 months. The adult females measure 20 to 80 cm
in length; the adult males measure 3 to 5 cm. The females live in subcutaneous or deeper
intramuscular tissues and are surrounded by a fibrous capsule. The males migrate between
nodules to fertilize females. The number of female worms can range from 1 to 60 or more (
figure 3).

Approximately 10 to 12 months after initial infection (the prepatent period), the adult female
worms begin to produce microfilariae. Offspring microfilariae, which typically measure 220 to
300 micron in length, migrate through subcutaneous tissues. Adult parasites can survive for up
to 15 years, and each female can produce 1000 to 3000 microfilariae per day. The total
microfilarial load in highly infected subjects is more than 100 million [12].

When an infected human is bitten by another blackfly, the vector takes up microfilariae. Over a
period of one to three weeks, the filariae undergo maturation within the blackfly and develop
into infective third-stage larvae, thereby completing the life cycle.

PATHOGENESIS

The adult worms (macrofilariae) become encapsulated by fibrous tissue and form subcutaneous
nodules, often overlying bony prominences. The microfilariae move through subcutaneous,
dermal, and ocular tissues and the lymph system. They provoke a minimal immune response
while alive; when they die, they incite a clinical inflammatory response.

O. volvulus adults and microfilariae harbor endosymbiotic Wolbachia bacteria, which are
essential for the filarial worm's fertility and survival. Release of Wolbachia-derived antigens from
dying parasites can activate innate immune responses and are thought to play an essential role
in the development of anterior segment onchocercal eye disease in an experimental murine
model [13]. Wolbachia bacteria mediate corneal pathology by activating Toll-like receptors on
mammalian cells, which in turn stimulate recruitment and activation of neutrophils and
macrophages [12,14-17].

The pathogenesis of posterior segment eye disease is less understood. Chorioretinal disease
continues to progress despite elimination of the parasite from the eye, suggesting the
involvement of an autoimmune phenomenon. Cross-reactivity has been found between O.
volvulus antigen Ov39 and the antigen hr44 found in the retinal pigment epithelium. Hr44,
however, is also found in the optic nerve and other ocular tissues. Transfer of Ov39-derived T

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cell lines, which proliferate in response to stimulation with hr44, have been shown to induce
inflammation of the limbus, iris, and choroid in naïve rats [18].

Corneal inflammation appears to occur in response to both Wolbachia and Onchocerca antigens,
while dermatologic manifestations appear to occur in response to Onchocerca antigens alone,
though the role of Wolbachia antigens has not been definitively excluded [19].

There is a spectrum of immune response to infection; some infected individuals have a minimal
immune response to parasite antigens, permitting proliferation of microfilariae in the absence
of clinical symptoms, while others have a relatively robust and symptomatic immune response
[12]. An immunogenetic basis for this clinical spectrum has been proposed [20], and differing
isotypic antibody responses may play a role [21]. A single nucleotide polymorphism in the
FcγRIIa gene affects the binding to the different immunoglobulin G (IgG) subclasses and may
influence the clinical outcome of onchocerciasis [22]. A genome-wide search for genetic
determinants of resistance to O. volvulus infection [23] detected linkage between microfilarial
load and chromosome 2p21-p14, though the decisive genetic variants have not been identified.

Cellular immune responses are stronger in individuals with severe onchodermatitis than those
with milder disease or uninfected individuals [24]. T-helper (Th) 2-type responses to O. volvulus
antigen, rather than Th1-type responses, were more prominent in a study of Ghanians exposed
to O. volvulus transmission and, in skin snip–positive individuals, the levels of interleukin (IL)-5
and IL-13 decreased with increasing microfilarial density [25]. Individuals with skin disease from
this same area had more pronounced Th 2-type responses compared with individuals without
skin lesions [19]. Subjects with a hyper-reactive form of skin disease (sowda) were significantly
associated with a variant of the IL-13 gene, which causes a brisk Th2-type immune response
with high IgE levels and a resultant low microfilarial burden [26].

A state of hyporesponsiveness or partial tolerance of cell-mediated responses exists in

asymptomatic persons with high microfilarial loads. Defects in T cell responses in human filarial
infections have been linked with expression of the T cell-inhibiting receptor, CTLA-4 [27].
Furthermore, a subset of CD4+ T cells, T regulatory-1 (Tr1) cells, which are known to suppress
immune responses, were demonstrated for the first time in a human infectious disease in
onchocerciasis [28]. Tr1 cells produce high levels of IL-10 and are thought to counteract Th2-
driven effector inflammatory responses in such individuals [29]. Elevated IgG4 also acts as
blocking antibody to inhibit IgE-mediated degranulation of effector cells and thus
downregulates pathogenetic responses, and Tr1 cells have been shown to induce B cells to
secrete IgG4 [30,31].

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Prostaglandin (PG)E2, which has an important role in innate and adaptive immune responses,
has been shown to be generated by O. volvulus parasites themselves [32]. In addition, PGE2 and
transforming growth factor (TGF)-beta have been demonstrated histochemically in infiltrating
host macrophages and plasma cells around O. volvulus in onchocercomas, and TGF-beta was
preferentially observed in the skin of infected individuals with "generalized" or hyporeactive
onchocerciasis and to a lesser degree in patients with the hyper-reactive form of onchocercal
skin disease [33,34].

Downregulation of host immunity may be induced by O. volvulus surface molecules and by

excretory-secretory products. The secretory omega-class glutathione transferase 3 from O.
volvulus (OvGST3) has a protective role against intracellular and environmental reactive oxygen
species. Significant IgG1 and IgG4 responses to recombinantly expressed OvGST3/5 were
detected in sera from onchocerciasis patients, indicating exposure of this secreted protein to
the host immune system [35].

Cho-Ngwa and colleagues used molecular techniques to identify and characterize O. volvulus
antigens that are possibly associated with the development of concomitant immunity. They
studied IgG subclass and IgE specific responses to an O. volvulus cysteine proteinase inhibitor,
onchocystatin (Ov-CPI-2), in putatively immune and infected individuals in a hyperendemic
region in Cameroon and found that both groups had similar IgG3 and IgE responses, but
infected persons had higher IgG1 and IgG4 responses. In the infected group, IgG3 levels
increased significantly with age, while IgG1 levels were high in infected individuals regardless of
age. They concluded that anti-Ov-CPI-2 IgG1 and/or IgG3 may be involved in protective
immunity in the putative immune and infected persons and proposed Ov-CPI-2 as a possible
target for an anti-L3 vaccine [36].

CLINICAL MANIFESTATIONS

The main clinical manifestations of onchocerciasis are ocular changes, pruritus, subcutaneous
nodules, and onchocercal skin disease, in addition to some systemic features.

Ocular onchocerciasis — The first ocular sign of infection is the presence of microfilariae in the
eye in the absence of any other pathology detected by slit-lamp examination. Presence of
microfilariae in the anterior chamber is associated with the subsequent development of
anterior segment lesions and also progression of posterior eye lesions [37]. Additional
manifestations include:

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● Punctate keratitis – Punctate keratitis is a relatively common acute, transient finding.

White cell infiltrates form around dead microfilariae in the cornea, causing "snowflake
opacities," especially at the three and nine o'clock positions ( picture 1). Punctate
keratitis is reversible.

● Sclerosing keratitis – Sclerosing keratitis is chronic full-thickness fibrovascular change of

the cornea and occurs in the setting of longstanding infection, particularly in savanna
regions. These changes start typically at the three and nine o'clock positions and can
extend across the entire cornea ( picture 2).

● Uveitis – Uveitis in the setting of onchocerciasis typically presents with flare in the absence
of an accompanying cell infiltrate.

● Optic atrophy – Optic atrophy is a relatively chronic finding; optic disc pallor can occur
following an episode of optic neuritis.

● Onchochorioretinitis – Onchochorioretinitis is a common chronic finding. The first layer

damaged is the retinal pigment epithelium, and this is most frequently found just
temporal to the macula. Subsequently, more extensive loss of the retinal pigment
epithelium occurs with retinal death and atrophy and loss of the underlying choroid. The
end-stage Hissette-Ridley fundus appearance is named after the authors who made the
first descriptions ( picture 3) [38,39]. Fluorescein angiography will detail chorioretinal
lesions.

Subcutaneous nodules — Subcutaneous nodules ("onchocercomata") are typically 0.5 to 3.0

cm in diameter; they usually contain one or two adult male and two or three adult female
worms. The majority of nodules are deep (not palpable), and they do not usually cause
significant symptoms. They typically appear over bony prominences and have an apparent
predisposition for different anatomic sites depending upon the geographic area, reflecting the
different vector biting habits in different regions. Infections acquired in Africa tend to cause
nodules over the iliac crests and around the pelvic girdle; infections acquired in Latin America
are more commonly associated with nodules on the head, neck, and upper extremities. It is
often helpful to ask the patient if they know where any nodules are located, then stand behind
the patient to palpate, following a set routine checking all preferred sites (eg, head and
shoulder girdle first, then ribs, iliac crests, ischial tuberosities, sacrococcygeal region,
trochanters, knees, and ankles).

Ultrasonography can be useful for detection of deeper, nonpalpable nodules. (See

'Ultrasonography' below.)

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Onchocercal skin disease — Generalized itching is often the first manifestation of infection,
and onchocerciasis should be considered as a possible diagnosis whenever a patient from an
endemic area presents with itching or has an itchy rash. Early dermatologic signs due to
onchocerciasis include intensely pruritic inflammatory papules, nodules, and plaques.
Subsequent lymphadenopathy can develop, most commonly in the inguinal region. After
prolonged enlargement and inflammation, the lymph nodes may become fibrotic, resulting in
lymphatic obstruction and sometimes genital elephantiasis.

Onchocercal skin disease may be classified as follows [40]:

● Acute papular onchodermatitis – Acute papular onchodermatitis manifests as small (1 to 3

mm diameter) scattered pruritic papules, vesicles, or pustules often across the shoulders
or buttocks. It is common in children and young adults.

● Chronic papular onchodermatitis – Chronic papular onchodermatitis comprises larger

(approximately 3 to 9 mm diameter), flat-topped pruritic papules, often symmetrically
distributed over buttocks, waist, and shoulders. It is seen in children and adults and
postinflammatory hyperpigmentation is common.

● Lichenified onchodermatitis (sowda) – Lichenified onchodermatitis is a regular feature of

onchocerciasis in some regions, particularly Yemen and Sudan, although it is seen less
commonly elsewhere. Teenagers and young adult males typically manifest with
hyperpigmented pruritic papules and plaques limited to one limb with associated edema
and soft enlargement of the draining lymph nodes. It is also known as "sowda" (Arabic for
black or dark).

● Skin atrophy – Skin atrophy manifests with loss of skin elasticity and excessive wrinkling of
the skin around the buttocks, waist, and upper thighs in adults; the resulting skin has the
appearance of tissue paper. In order to avoid confusion with senile atrophy of the skin, the
term onchocercal atrophy is reserved for individuals aged less than 50 years old.

● Hanging groin – Hanging groin is atrophy affecting the skin of the groin and anterior
thigh. Inguinal lymph nodes enlarge in a sling of atrophic skin on the medial thigh, then,
as the nodes shrink and become fibrotic, they leave redundant folds of loose skin.

● Depigmentation – Depigmentation (leopard skin) typically occurs on the anterior shins of

older adults. The inguinal regions and external genitalia may also be affected. Patches of
complete pigment loss are seen with perifollicular "spots" or islands of normally
pigmented skin giving rise to the so-called "leopard skin" appearance. Atrophy and
depigmentation are not usually itchy.
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Systemic manifestations — In a study in Malawi, generalized musculoskeletal complaints,

backache, and joint pains were more frequent in infected than uninfected individuals. In
addition, infected individuals weighed significantly less than uninfected individuals [41].
Inguinal and femoral herniae are common.

Nodding syndrome, an epileptic disorder of uncertain etiology that occurs in children in East
Africa, has been associated epidemiologically with O. volvulus infection; the association has
been controversial. A systematic review and meta-analysis of eight studies noted that
onchocerciasis is associated with epilepsy, with an average increase in epilepsy prevalence by
0.4 percent for each 10 percent increase in onchocerciasis prevalence [42]. However, a
subsequent study in an endemic area of Tanzania noted no difference in microfilarial density
between individuals with or without epilepsy [43]. A later systematic review and meta-analysis
of 11 studies supported the hypothesis that intensity of infection with O. volvulus is involved in
the etiology of epilepsy [44]. Neurotoxic autoantibodies to leiomodin-1 have been found more
abundantly in patients with nodding syndrome compared with unaffected village controls and
were cross-reactive with O. volvulus tropomyosin/troponin, suggesting that nodding syndrome
is an autoimmune form of epilepsy caused by molecular mimicry with O. volvulus antigens [45].

A 2017 international workshop on onchocerciasis-associated epilepsy concluded that infection

with O. volvulus is associated with a spectrum of epileptic seizures, mainly generalized tonic-
clonic seizures, but also atonic neck seizures (nodding), myoclonic neck seizures, and absence
seizures. Typically, the onset of seizures is between the ages of 3 to 18 years [46]. Two
additional studies provide further evidence of a temporal relationship between onchocerciasis
and epilepsy [47,48]. A minority of individuals have concomitant severe stunting with no delay
or delayed puberty (the so-called Nakalanga syndrome) [49].

Data from the Onchocerciasis Control Programme in 11 countries in West Africa have shown
that mortality was significantly associated with increasing microfilarial load but not with
blindness per se (after controlling for other variables) [50]. The relationship between
microfilarial load and mortality appears to be nonlinear [51].

Travelers — Onchocerciasis among returned travelers from endemic areas is relatively rare; a
minimum stay of 12 months in endemic areas is generally necessary to acquire infection. If
infection does occur, it tends to manifest with itching and/or a subtle itchy papular rash, which
is often concentrated on one limb. There may be accompanying limb edema [52] and swelling
may also occur without any rash. Other early manifestations include transient urticaria,
arthralgia, and fever. The chronic skin changes and eye changes typically seen in long-term
residents of endemic areas are generally absent. Symptoms develop in a median period of 18
months from the time of exposure (range: three months to three years) [53-55], so a detailed
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travel history is important. Persons who have spent many years in endemic areas (though grew
up in a nonendemic area) may present with symptoms within shorter times of leaving endemic
areas. Ocular signs are relatively rare in patients with imported onchocerciasis. When long-term
residents of endemic areas migrate to nonendemic areas, they may manifest more chronic skin
and eye pathology [56-58].

HIV coinfection — HIV may affect the clinical presentation of onchocerciasis, as well as the
immune response to infection [59,60], although there does not appear to be an effect of HIV on
onchocerciasis prevalence or vice versa [61] or on response to treatment [61]. Consequently,
one would not expect HIV-infected individuals to be at greater risk of infection. Among six
individuals with HIV in a hyperendemic area of Uganda where onchocercal skin disease is
common, the burden of skin disease was higher than among patients with onchocerciasis in the
absence of HIV infection [40,62]. Inclusion of HIV-infected patients in mass treatment
campaigns for onchocerciasis appears to be safe [63].

SOCIOECONOMIC AND PSYCHOSOCIAL ASPECTS

High levels of blindness in African savanna regions resulted in desertion of affected villages
with resettlement to less fertile areas, with serious adverse economic consequences. In a study
in highly endemic areas of Guinea, blindness (and, to a lesser extent, visual impairment) were
associated with substantial mobility and occupational impairments [64]. Rates of celibacy,
widowhood, and divorce were higher among patients with ocular onchocerciasis than
uninfected individuals.

Onchocercal skin disease is also a significant cause of stigma, disability, and diminished
agricultural productivity throughout much of sub-Saharan Africa [65-67]. Even after 10 years of
community treatment with ivermectin in southeast Nigeria, the most worrisome consequence
of onchocerciasis for those with symptoms and signs was social seclusion or stigmatization
(affecting 34 percent of individuals) [68]. Severe onchocercal skin disease in heads of
households is associated with a higher school dropout rate among children, especially girls [69].
The Global Burden of Disease Study 2017 estimated a total of 1.34 million years lived with
disability (YLDs) for onchocerciasis of which 96,100 YLDs were caused by onchocercal eye
disease and 1.25 million YLDs were caused by onchocercal skin disease [1].

DIAGNOSIS

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The diagnosis of onchocerciasis is based on a history of compatible epidemiologic exposure,

clinical manifestations as described above, and supportive laboratory evidence of infection. The
clinical picture may be difficult to distinguish from loiasis and from infection due to Mansonella
species. Nonspecific laboratory findings in patients with onchocerciasis may include peripheral
eosinophilia and hypergammaglobulinemia. However, eosinophil counts are normal in up to 30
percent of infected individuals from endemic areas. (See "Loiasis (Loa loa infection)".)

Skin snips — Skin snips are the gold standard for investigation of an individual patient. A skin
snip may be performed with a corneoscleral punch or with a small needle and disposable razor
blade ( picture 4). It should be a bloodless specimen from the level of the dermal papillae. The
site of the skin snip is selected on the basis of the site that is likely to give the highest numbers
of microfilariae. In Central America, the best site is over the scapula or iliac crest; in Africa, the
pelvic girdle, buttocks, and external thigh; in Yemen, the lower calf. In early infections and in
localized light infections, the site selected should be that in which the dermatitis is most
marked.

A minimum of two snips should be taken; the sensitivity of the test increases if more snips are
taken. For investigation of a returned traveler, often a set of six snips are taken, one from over
each scapula, each iliac crest, and each calf. The biopsy specimen should be incubated in saline
for up to 24 hours before evaluating for presence of motile microfilariae. Hematoxylin and
eosin staining of the specimen may be required for species identification, particularly in areas
where other filarial species are also endemic. O. volvulus microfilariae characteristically have no
sheath and no nuclei in their tails ( picture 5).

It takes approximately 9 to 15 months for the worm to mature and release enough microfilariae
to be detectable by skin snip. Skin snips are inadequate for detecting early or light infection,
and they are often negative in expatriates and in patients with sowda. (See 'Onchocercal skin
disease' above.)

In highly microfilaremic L. loa-infected individuals, L. loa microfilariae in skin snips may be

misidentified as O. volvulus microfilariae. In one study including 41 skin snips from patients in
Cameroon evaluated with species-specific quantitative polymerase chain reaction, 12 percent
were O. volvulus microfilariae, 75 were L. loa microfilariae, 12 percent were Mansonella perstans
microfilariae, and one sample had both O. volvulus and L. loa microfilariae [70].

Improved methods of diagnosis are needed for evaluation of individual patients and
monitoring of onchocerciasis elimination programs. Alternative approaches based on
amplification of parasitic DNA in skin snips remain research tools [71,72].

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Slit-lamp examination — Slit-lamp examination can be used to look for wriggling microfilariae
within the anterior chamber of the eye. Prior to slit-lamp examination, patients should be asked
to sit forward (with the head between the knees) for at least two minutes to improve the
likelihood of visualization. Transparent live microfilariae may also be seen coiled in the cornea.
Punctate keratitis represents dead microfilariae surrounded by an inflammatory infiltrate; it is
easier to see than live organisms.

Mazzotti test — The Mazzotti test should not be used as a routine diagnostic test; it may be
considered if onchocerciasis is suspected in the absence of findings on skin snip or slit-lamp
evaluation. It is contraindicated in heavily infected individuals (who will have positive skin snips)
and individuals with optic nerve disease.

The Mazzotti test consists of a 50 mg oral dose of diethylcarbamazine (DEC), which leads to
microfilarial death and associated symptoms of worsening pruritus about 20 to 90 minutes
later; an acute papular rash with edema, fever, cough, and musculoskeletal symptoms may also
occur. Symptoms generally reach a peak at about 24 hours and then subside over the next 48 to
72 hours. In some cases, severe systemic reactions can develop, including pulmonary edema,
visual loss, collapse, and death. In the United States, DEC is not available for this indication.

Patch test — DEC can be administered as a topical preparation to a small area of the skin to
assess for local skin reaction. In a study of untreated children in Cameroon, Gabon, and Central
African Republic, the proportion of children who tested positive with a 10 percent DEC solution
ranged from 25 to 77 percent; this finding correlated closely with the prevalence of nodules (a
reflection of the level of endemicity) [73]. Sensitivity may be greater with a 20 percent DEC
solution [74].

Patch testing is a useful alternative to skin snipping in low-prevalence areas, since it is

noninvasive, inexpensive, and more sensitive than skin snipping. The African Program for
Onchocerciasis Control recommended its widespread use as a preferred alternative to skin snip
for epidemiologic evaluations [75]. The test is not available in the United States.

Serology — Serology is not uniformly reliable. In addition, the prevalence of positive serology
among nonendemic adults returned from endemic areas is extremely high in the absence of
active infection and can remain positive for many years [54]. Standard antifilaria enzyme-linked
immunosorbent assays (ELISAs) have significant cross-reactivity between filarial parasites.
Some recombinant purified antigens, ELISAs, and Western blot techniques with very good
sensitivity and specificity for O. volvulus have been developed, but they are not routinely
available for clinical use.

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Detection of antibody subclass IgG4 may enhance specificity. An immunochromatographic card

test detecting IgG4 against recombinant Onchocerca antigen Ov-16 (Ov-16 card test) had very
good sensitivities in West Africa field trials (81 and 77 percent in two villages). Test specificity
was 100 percent (using the skin snip test as the gold standard) [76].

A serologic test using a multi-antigen quick luciferase immunoprecipitation system and four
recombinant antigens has been developed for diagnosis of O. volvulus. Sensitivity and specificity
for detection of O. volvulus compared with control sera were 100 percent, though it is not widely
available [77]. For distinguishing O. volvulus from Wuchereria bancrofti, Loa loa, and Strongyloides
stercoralis, specificities of 76, 84, and 93 percent have been reported. The assay could be used
for diagnosis of individual infections, for early detection of recrudescent infections in control
areas, and for mapping new areas of transmission.

In a study including 285 patients with epilepsy in an ivermectin-naïve, onchocerciasis-endemic

region in the Democratic Republic of Congo, serologic results obtained with the Ov16 rapid
diagnostic test (Ov16 RDT) and the Ov16 ELISA test were compared with skin snip results [78].
The sensitivity and specificity of each test was calculated with the other assays as a reference.
The Ov16 ELISA had the highest sensitivity (83 percent), followed by Ov16 RDT (74.8 percent)
and the skin snip (71.4 percent). The Ov16 RDT had a higher specificity compared with the Ov16
ELISA (98.6 versus 84.8 percent).

In the United States, the National Institutes of Health and the Centers for Disease Control and
Prevention may be of assistance with diagnostic testing.

Antigen testing — Antigen tests may be more useful than antibody detection assays for the
diagnosis of individual infections and for monitoring the success of therapy, since they are
positive only in individuals with active infection. Further research is required for additional
development of antigens tests before they can be available for routine clinical use.

A study of an Onchocerca antigen detection dipstick test for urine or tears in Cameroon
reported sensitivity of 100 percent and 92 percent in urine and tears, respectively; specificity for
urine and tears was 100 percent [79]. Major sperm protein 2 (MSP2) has also been proposed as
a potential diagnostic antigen; preliminary studies appear promising [80].

Mass spectrometry, bioinformatics, and molecular techniques have been used to characterize
additional diagnostic antigens detected in the in vivo nodular fluid [81]. Liquid chromatography
and mass spectrometry on blood samples from O. volvulus–infected and –uninfected individuals
revealed a set of 14 biomarkers that showed excellent discrimination between infected and
uninfected persons [82].

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Polymerase chain reaction — Highly sensitive polymerase chain reaction (PCR) tests based
upon DNA amplification have also been developed but are not yet available for general use. In a
Cameroonian study comparing skin snip PCR and urine PCR with antigen detection, the skin
snip PCR had higher sensitivity than the urine PCR (>90 versus 14 percent), and the PCR tests
were generally equal to or more sensitive than antigen tests [83]. In a study in Guinea with low
prevalence of disease after >10 years of control by the Onchocerciasis Control Programme, skin
snip PCR and the DEC patch test were more sensitive than skin snip microscopic examination
[84].

Ultrasonography — Ultrasonography of subcutaneous nodules may be used for identification

of adult worms. Deeper, nonpalpable nodules can be also detected. Ultrasound may also be a
useful tool for the longitudinal observation to monitor adult worm viability after macrofilaricidal
therapy [85].

DIFFERENTIAL DIAGNOSIS

The differential diagnosis of onchocercal skin disease is summarized in the table ( table 1).

Other differential diagnoses to consider in onchocerciasis include:

● Loiasis – Clinical manifestations of loiasis include transient subcutaneous Calabar

swellings and migration of the adult worm across the subconjunctiva of the eye. The
diagnosis is established by identifying a migrating adult worm in the subcutaneous tissue
or conjunctiva or microfilariae in the blood. Coinfection with onchocerciasis can occur,
which is important for decisions regarding treatment. (See "Loiasis (Loa loa infection)",
section on 'Onchocerciasis coinfection'.)

● Mansonella infection – Mansonella infections are often asymptomatic, but clinical

manifestations can include transient subcutaneous swellings similar to the Calabar
swellings of L. loa, pruritus, papular eruptions, urticaria, and hypopigmented macules as
well as ocular symptoms. Unlike O. volvulus, the Mansonella adult worms do not form
subcutaneous nodules. The diagnosis is established by identifying the microfilariae in the
blood or on skin snip. (See "Mansonella infections".)

TREATMENT

Clinical approach — The clinical approach varies for treatment of individuals within endemic
areas, individuals outside endemic areas, and mass treatment.

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Within endemic areas

Individual treatment — Treatment of individuals within endemic areas with relatively

high levels of ongoing transmission consists of ivermectin (150 mcg/kg) administered orally as a
single dose, on an empty stomach with water. Treatment should be repeated every three to six
months until the patient is asymptomatic ( table 2) [86]. Thereafter, indications for repeat
treatment include recurrence of pruritus, presence of a typical rash, or eosinophilia. Treatment
with ivermectin may be required for 10 years or more [87].

Adverse effects following ivermectin administration are usually mild and are thought to occur
as a result of the host immune response to released Wolbachia antigens [88]. Symptoms usually
develop within three days of treatment and include fever, rash, dizziness, pruritus, myalgia,
arthralgia, and tender lymphadenopathy. Severe reactions including systemic postural
hypotension can also occur. The incidence of these symptoms correlates with burden of
infection prior to treatment. Symptoms can usually be managed with analgesics and
antihistamines.

The safety of ivermectin in young children (height <90 cm) and pregnant women is uncertain.
Ivermectin has been administered inadvertently to pregnant women during mass treatment
programs, and no increased rates of congenital abnormalities were observed [89]. Ivermectin
may be given after the first week of lactation and no adverse effects in lactating women have
been documented.

Administration of ivermectin every six months results in greater reductions in microfilarial loads
than annual treatment; it is possible that even more frequent treatment could provide
additional benefit. In a study of 657 patients with onchocerciasis, those who received treatment
every three months had fewer remaining female worms than those treated annually [86]. In two
Mexican communities, administration of treatment every three months appeared to rapidly
suppress residual transmission [90].

There is considerable variability in reduction of microfilarial densities between individuals

following treatment with ivermectin [91]. Development of ivermectin resistance has been
suggested in Ghana [92], but it remains controversial. Suboptimal responses may be
attributable to host factors, including polymorphisms in host multidrug resistance (MDR1)
genes. In a Ghanian study of 42 patients treated with ivermectin, a difference in MDR1 variant
allele frequency was observed between suboptimal responders and responders (21 versus 12
percent) [93]. A mathematical model has been developed for analyzing drug efficacy, which may
be used to investigate atypical responses to ivermectin in onchocerciasis [94].

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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 [95].

Loa loa coinfection — In the setting of coinfection with L. loa, treatment of

onchocerciasis with ivermectin can facilitate entry of L. loa microfilariae into the central nervous
system, leading to encephalopathy, potentially severe neurologic sequelae, and death [96,97].
The number of people estimated to be coinfected with onchocerciasis and loiasis by 2025 is
31,000 [98].

In areas where both onchocerciasis and L. loa are endemic, blood should be obtained to
evaluate for evidence of L. loa microfilariae prior to administration of ivermectin.

The optimal approach to the treatment of onchocerciasis and loiasis coinfection is uncertain;
one approach consists of doxycycline (200 mg orally once daily for six weeks) plus albendazole
(400 mg orally with fatty meal twice daily for three weeks) [99].

Mass treatment — Mass drug administration programs consist of ivermectin

administration at 6 to 12 monthly intervals for 10 to 16 years [100]. The African Program for
Onchocerciasis Control (APOC) treated hyperendemic and mesoendemic areas (hyperendemic
communities have a prevalence of palpable nodules among a sample of 50 adult males of >40
percent; mesoendemic communities have a prevalence of 20 to 39 percent). The Onchocerciasis
Elimination Program for the Americas administers treatment in all areas with the goal of
complete elimination.

Mass treatment programs have had significant impact on the burden of disease due to ocular
onchocerciasis, including reduction of ocular microfilarial loads and regression of early anterior
segment lesions such as punctate keratitis and iridocyclitis [101-105]. Ivermectin also has a
beneficial effect on the incidence of onchocercal optic nerve disease [106] and visual field loss
[107]. These improvements have been observed to occur more rapidly with mass drug
treatment than with vector control alone. In one cohort study evaluating mass treatment in
eight Nigerian villages, gross visual impairment decreased from 16 to 1 percent after eight
years of annual ivermectin treatment [105].

Mass treatment has also reduced the burden of onchocercal skin disease. Reductions in the
prevalence of severe itching (4 to 1 percent after five years of annual treatment) [104,108],
nodules (59 to 18 percent after eight years of annual treatment) [105], and papular dermatitis
(15 to 2 percent after eight years of treatment) [105] have been observed. A study in Nigeria
noted reduction in itching (19 percent), reduction in skin rash (17 percent), and darkening of
leopard skin (7 percent) following 10 years of annual ivermectin treatment [109].
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A multi-country report of the community impact after five or six years of annual ivermectin
treatment noted substantial reduction in clinical symptoms and onchocercal skin disease [110].
There were significant reductions in itching, acute papular onchodermatitis, chronic papular
onchodermatitis, lichenified onchodermatitis, depigmentation, and nodules (odds ratios [OR]
0.32, 0.28, 0.34, 0.54, 0.31, and 0.37 respectively). In a report including more than 1400
individuals from the Yeki district in Ethiopia treated with successive annual community-directed
treatment with ivermectin for 15 years, the prevalence of infection (by skin snip) dropped from
81 percent to zero. Furthermore, papular dermatitis had reduced by 95.9 percent, palpable
nodules by 90.5 percent, and atrophy by 30 percent [111]. Overall, it was estimated that APOC
had cumulatively averted 8.9 million disability-adjusted life years (DALYs) due to onchocerciasis
up to 2010 and would avert another 10.1 million DALYs between the period of 2011 and 2015
[112].

Elimination of onchocerciasis with ivermectin treatment in hyperendemic areas with efficient

vector transmission appears to be feasible [113]. Data from Mali, Senegal, and Nigeria suggest
15 to 19 years of uninterrupted treatment may be required [113,114]. Further study is needed
to establish the point at which the number of parasites or parasite density falls so low that
infection cannot persist [75,115]. Studies in Burundi, Chad, and Ethiopia suggested that the foci
evaluated had reached elimination thresholds; entomologic confirmation is awaited.
Elimination is considered within reach for Côte d'Ivoire, Malawi, Mali, Niger, Senegal, and
Uganda [116].

Loa loa coinfection — In areas where both onchocerciasis and loiasis are endemic, the
rapid assessment tool for loiasis should be employed prior to mass treatment with ivermectin.
This tool delineates communities at high risk of loiasis using geographic information systems to
identify potential vegetation areas for vector breeding together with a history of eye-worm.
(See 'Loa loa coinfection' above and "Loiasis (Loa loa infection)".)

A mobile phone–based video microscope (termed a LoaScope) has been developed that is
capable of counting L. loa microfilariae in peripheral blood collected in disposable rectangular
capillary tubes. In a Cameroon field trial, the device was used to identify individuals with L. loa
microfilaremia levels ≥20,000/mL [117]. Among more than 16,000 individuals who underwent
testing, approximately 2 percent were excluded from ivermectin distribution because of a L. loa
microfilarial density above the risk threshold. More than 15,500 individuals (95 percent of those
tested) received ivermectin for treatment of onchocerciasis; no serious adverse events were
observed. (See "Loiasis (Loa loa infection)", section on 'Other tests'.)

Doxycycline may be effective for community-directed treatment in areas where both

onchocerciasis and loiasis are endemic. In a Cameroon study evaluating the efficacy of
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community-directed treatment with doxycycline for six weeks among 104 individuals in
communities coendemic for onchocerciasis and loiasis, doxycycline alone was effective for
reducing microfilaremia and the viability of adult worms [118].

Outside endemic areas — Treatment of individuals outside endemic areas or in areas with
relatively low levels of transmission consists of ivermectin (150 mcg/kg orally) every three to six
months until asymptomatic (ie, resolution of signs of infection such as rash, pruritus,
eosinophilia, microfilariae in skin biopsies, or microfilariae on eye examination) ( table 2).
Treatment should be repeated if there is recurrence of clinical symptoms [119,120]. Ivermectin
does not kill the macrofilariae (adult worms) but does sterilize female worms.

Doxycycline is an emerging treatment. Published protocols have given a six-week course of

doxycycline 200 mg orally daily followed by ivermectin four to six months later, hence the safety
of simultaneous treatment is unknown. Doxycycline does not kill the microfilariae so, for a more
rapid relief of symptoms, it is reasonable to treat with ivermectin one week prior to starting
doxycycline. Doxycycline is contraindicated in pregnant women and children <9 years of age (
table 2) [121,122]. (See 'Targeting Wolbachia' below.)

Therapeutic approach — Potential therapeutic targets include microfilariae and adult worms
(macrofilariae).

Microfilaricidal therapy

Ivermectin — Ivermectin is a semisynthetic macrocyclic lactone derivative. Itis a selective

inhibitor of neurotransmission in invertebrates, is microfilaricidal, and also appears to impair
release of microfilariae from gravid female worms. Within one week following a single dose,
ivermectin can reduce skin microfilarial counts by 90 percent, with prolonged suppression for at
least a year.

Ivermectin also may have some direct effects on adult worms, but it does not eradicate
infection [123]. Multiple doses of ivermectin may have a partial macrofilaricidal effect and a
modest sterilizing effect after four or more consecutive treatments, with the life expectancy of
adult worm reduced by approximately 50 percent after three years of annual ivermectin
treatment [124].

Addition of albendazole to ivermectin does not appear to confer treatment benefit. In a

randomized trial including more than 270 patients with onchocerciasis in Ghana, combination
therapy with ivermectin and albendazole was no better than ivermectin alone for sterilizing,
killing adult worms, or achieving sustained microfilariae clearance [125].

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Within the setting of control programs, ivermectin treatment usually has to be repeated
throughout the 10- to 14-year life span of the adult worms to eradicate infection in the
population. However, in general, it is not necessary to treat infected individuals for the life span
of the worm if they are removed from the endemic setting [54]. Most individuals become
asymptomatic after a few years of therapy.

Moxidectin — Moxidectin has a longer half-life than ivermectin (20 to 43 days versus <1
day), is more efficacious than ivermectin in reducing skin microfilarial loads, and may be
capable of interrupting the transmission cycle within six rounds of annual treatment [126,127].
In a randomized trial (performed in Ghana, Liberia, and the Democratic Republic of Congo)
including 1472 patients with at least 10 O. volvulus microfilariae per mg skin treated with
moxidectin (978 patients treated with 8 mg single dose) or ivermectin (494 patients treated with
150 mcg/kg single dose), the skin microfilarial density was 7.5 times lower among patients
treated with moxidectin (0.6 versus 4.5 microfilariae per mg skin) 12 months later [127].
Moxidectin was approved by the US Food and Drug Administration in 2018 for treatment of
onchocerciasis in adults; further study is needed to delineate how it should be used in mass
drug administration programs.

Macrofilaricidal therapy

Targeting Wolbachia — Wolbachia is the endosymbiotic bacteria within O. volvulus

required for embryogenesis and survival [128,129]. Doxycycline has activity against Wolbachia
and has been shown to induce sustained sterility of female worms with a dose-dependent
macrofilaricidal effect [130-133]. In one study including 167 patients in Ghana treated with
doxycycline (100 mg/day orally for six weeks), followed by ivermectin at 3 and 12 months, the
percentage of living female worms containing Wolbachia was substantially reduced (from 80 to
5 percent) [131]. The greatest efficacy has been observed with administration of doxycycline
200 mg/day for six weeks [134].

Doxycycline, followed by ivermectin, can be used for treatment of individuals in areas of

relatively low transmission and for treatment of individuals outside endemic areas. Doxycycline
cannot be used for treatment in areas of ongoing transmission because new infections would
require repeated courses of doxycycline; in such circumstances, repeat dosing of ivermectin is
the preferred approach.

Rifampin and azithromycin have in vitro activity against Wolbachia, although five-day courses do
not appear to be effective for clinical management of onchocerciasis [135,136]. Rifampicin may
prove to be an alternative to children who cannot be treated with doxycycline or may be used in
the future in combination with other drugs; further study is needed.

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The heme [137] and lipoprotein [138] biosynthetic pathways of Wolbachia have been proposed
as potential candidate drug targets for future research.

Other approaches — The veterinary anthelminthic drug closantel is a potential new

therapy; it is an inhibitor of filarial chitinases and inhibits molting of L3 larvae [139].

Removal of adult worms via nodulectomy is another therapeutic option, particularly in lightly
infected individuals such as expatriates. However, nodulectomy alone cannot be considered an
effective strategy for cure since many worms lie deep and may be undetected.

PREVENTION AND ELIMINATION

There is no vaccine to prevent onchocerciasis. A number of onchocerciasis control programs

have been implemented worldwide:

● The Onchocerciasis Control Programme (OCP, 1974 to 2002) – The OCP was an
international partnership that used aerial larviciding of rivers for vector control in 11 West
African countries. The program was highly successful in interrupting transmission and led
to economic redevelopment of fertile areas previously deserted due to high rates of
blindness [140]. The OCP also distributed ivermectin to control recrudescence. In
extension areas, ivermectin was used either alone or in combination with larviciding.

● Mectizan Donation Program – Merck, the manufacturer of ivermectin (Mectizan), pledged

to donate all drugs necessary to overcome onchocerciasis and established the Mectizan
Donation Program in 1987. Collaboration was established with the World Health
Organization (WHO), health ministries, and nongovernmental organizations to distribute
ivermectin using a sustainable community-directed approach [141].

● The Onchocerciasis Elimination Program in the Americas (OEPA, 1991 to the present) – The
OEPA consists of partnerships between the governments of the endemic countries, the
Pan American Health Organization (PAHO),the Carter Center, Lions Clubs International,
the Bill and Melinda Gates Foundation, and the Mectizan Donation Program. The goal is to
eliminate onchocerciasis from the region via mass ivermectin therapy every six months; it
aims to reach at least 85 percent coverage of the eligible population. In 2008, a resolution
adopted by the PAHO called for the regional elimination of ocular morbidity caused by
onchocerciasis and interruption of transmission by 2012 [142,143].

By the end of 2012, transmission was interrupted or eliminated in 11 of the 13 foci in the
Americas [144]. Colombia was the first country to achieve country-wide interruption of

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transmission, and ivermectin distribution was discontinued in 2008. Surveillance is

required three years following cessation of treatment to achieve certification of
elimination, and Colombia subsequently completed the WHO verification process.
Ecuador, which has highly endemic transmission with a highly efficient vector Simulium
exiguum was the second country to suspend treatment, in 2010. Post-treatment
surveillance was completed in 2012, and Ecuador was the second country to be declared
free of onchocerciasis in 2014. Subsequently, elimination of transmission in Mexico was
confirmed in 2015 and in Guatemala in 2016 [4].

Active transmission is ongoing in two foci, the Venezuelan South Focus and the Brazilian
Amazonas Focus, where Yanomani people live deep in the rain forest. Communities with
the highest infection prevalence are being targeted with quarterly treatment to try to
expedite elimination of onchocerciasis in the Americas.

● The African Program for Onchocerciasis Control (APOC, 1995 to 2015) – APOC initially
aimed to control onchocerciasis as a public health and socioeconomic problem. After
2009, however, the treatment goal shifted from control toward elimination. The program
covered 19 African countries using annual ivermectin treatment delivered by community
distributors chosen by the communities themselves. The communities also controlled the
timing of the intervention, taking into consideration issues like weather, religious events,
and cultural events. By 2009, more than 68 million people were treated in 15 endemic
countries; the average therapeutic coverage was 77 percent in countries with a stable
security situation and 64 percent in post-conflict countries [145]. During 2013, seven
countries (Burkina Faso, Burundi, Cameroon, Liberia, Malawi, Mali, and Sierra Leone)
achieved the minimum requirement of 80 percent therapeutic coverage deemed
necessary for eventual onchocerciasis elimination.

Local vector eradication was used in combination with ivermectin treatment in a small
number of APOC projects [146,147]. The APOC Trust Fund was supported by a range of
partners from the public and private sectors; the program was executed through the
WHO, with the World Bank as the fiscal agent. Elimination of onchocerciasis transmission
has been reported for the Wambabya-Rwamarongo focus in western Uganda using twice-
yearly treatment with ivermectin combined with vector control [148].

Further prevalence of infection surveys were conducted in 2014 with the aim of re-
evaluation of villages previously classified as hypoendemic (with precontrol nodule
prevalence ranging from 5 to 19 percent) and therefore not previously included in APOC
treatment programs. The surveys identified the need to extend areas of treatment in the
Democratic Republic of Congo and the need to initiate mass treatment in Gabon [116].
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The community-directed intervention approach has been integrated successfully with

other primary health care interventions, such as management of malaria, distribution of
insecticide-treated bednets, and vitamin A supplementation, with the support of
community-directed distributors [149]. African universities and nursing schools are
including the community-based strategy in their curricula to broaden use of this effective
technique for health care interventions. In 2013, a total of 15 countries coimplemented
treatment of onchocerciasis with ivermectin with treatment of lymphatic filariasis with
albendazole. Other coimplemented activities include treatment of soil-transmitted
helminthiasis, schistosomiasis control, sensitization on HIV/AIDS, and primary eye-care
activities.

● The Expanded Special Project for Elimination of Neglected Tropical Diseases is a program
established in 2016 to coimplement control activities of onchocerciasis alongside other
neglected tropical diseases; specific aims include elimination of lymphatic filariasis by
2020 and onchocerciasis by 2025. Elimination of onchocerciasis requires hypoendemic
areas not previously considered for treatment to be mapped by onchocerciasis elimination
mapping (OEM), but the prevalence thresholds of positive Ov16 serology and sampling
strategies for OEM await confirmation.

SUMMARY AND RECOMMENDATIONS

● Onchocerciasis is caused by the filarial nematode Onchocerca volvulus. It is also known as

"river blindness" because the blackfly vector breeds near fast-flowing streams and rivers.
The disease affects rural communities and is a major cause of blindness and skin disease
in endemic areas, as well as onchocerciasis-associated epilepsy. (See 'Introduction' above.)

● Humans are infected with O. volvulus via the bite of a blackfly of the Simulium genus (
figure 3). The blackfly deposits infective third-stage larvae into the human skin, which
mature into adult parasites (macrofilariae) over the next 6 to 12 months. The females live
in subcutaneous or deeper intramuscular tissues and are surrounded by a fibrous capsule.
The males migrate between nodules to fertilize females. Approximately 12 months after
initial infection, the adult female worms begin to produce microfilariae, which migrate
through subcutaneous tissues, dermal, and ocular tissues. When an infected human is
bitten by another blackfly, the fly takes up dermal microfilariae. (See 'Life cycle' above.)

● Clinical manifestations of onchocerciasis include eye involvement, subcutaneous nodules,

skin involvement, and systemic manifestations, including onchocerciasis-associated
epilepsy. Manifestations of ocular onchocerciasis include punctate and sclerosing keratitis,

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uveitis, optic atrophy, and chorioretinitis. Manifestations of onchocercal skin disease

include acute and chronic papular onchodermatitis, lichenified onchodermatitis, skin
atrophy, hanging groin, and depigmentation. (See 'Clinical manifestations' above.)

● The diagnosis of onchocerciasis is based on a history of compatible epidemiologic

exposure, clinical manifestations, and supportive laboratory evidence of infection. A skin
snip biopsy is the gold standard for investigation of a patient. Slit-lamp examination can
be used to look for wriggling microfilariae within the anterior chamber of the eye.
Mazzotti testing should be performed only in certain clinical circumstances. Serology,
antigen testing, and polymerase chain reaction are useful tools though are not routinely
available in endemic areas. Ultrasonography of subcutaneous nodules may be useful for
identification of adult worms. (See 'Diagnosis' above.)

● For individuals with onchocerciasis in endemic areas with high levels of ongoing
transmission, we suggest treatment with ivermectin (150 mcg/kg) administered orally as a
single dose ( table 2) (Grade 2C). Treatment should be repeated every three to six
months until the patient is asymptomatic; treatment may be required for 10 years or
more. In areas where both onchocerciasis and Loa loa are endemic, blood should be
obtained to evaluate for evidence of L. loa microfilariae prior to administration of
ivermectin. (See 'Individual treatment' above and 'Loa loa coinfection' above.)

● For individuals with onchocerciasis in areas with low levels of transmission and for
individuals outside endemic areas, we suggest treatment with ivermectin every three to
six months until asymptomatic ( table 2) (Grade 2C). Doxycycline is an alternative
treatment. (See 'Outside endemic areas' above.)

● Mass drug administration programs consist of ivermectin administration at 6 to 12

monthly intervals for 10 to 16 years. In areas where both onchocerciasis and loiasis may
be endemic, assessment for loiasis should be made prior to mass treatment with
ivermectin. (See 'Mass treatment' above.)

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island of Bioko as a result of larviciding by the WHO African Programme for Onchocerciasis
Control. Acta Trop 2009; 111:211.
147. Garms R, Lakwo TL, Ndyomugyenyi R, et al. The elimination of the vector Simulium neavei
from the Itwara onchocerciasis focus in Uganda by ground larviciding. Acta Trop 2009;
111:203.
148. Katabarwa MN, Habomugisha P, Khainza A, et al. Elimination of Simulium neavei-
Transmitted Onchocerciasis in Wambabya-Rwamarongo Focus of Western Uganda. Am J
Trop Med Hyg 2020; 103:1135.

149. CDI Study Group. Community-directed interventions for priority health problems in Africa:
results of a multicountry study. Bull World Health Organ 2010; 88:509.
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Topic 5683 Version 34.0

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GRAPHICS

African Programme for Onchocerciasis Control (APOC) and ex-

Onchocerciasis Control Programme (OCP) countries

Reproduced with permission from: World Health Organization. African Programme for Onchocerciasis
Control (APOC).

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Geographic distribution of onchocerciasis in the Americas, 2014

* Have requested World Health Organization (WHO) verification of elimination.

¶ WHO has verified elimination.

Reproduced with permission from: Onchocerciasis Transmission in the Americas 2015. Copyright © 2015 The Carter Center.

Graphic 63640 Version 4.0

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Life cycle of Onchocerca volvulus

During a blood meal, an infected blackfly (genus Simulium) introduces third-stage filarial
larvae onto the skin of the human host, where they penetrate into the bite wound (1). In
subcutaneous tissues, the larvae (2) develop into adult filariae, which commonly reside in
nodules in subcutaneous connective tissues (3). Adults can live in the nodules for
approximately 15 years. Some nodules may contain numerous male and female worms.
Females measure 33 to 50 cm in length and 270 to 400 micron in diameter, while males
measure 19 to 42 mm by 130 to 210 micron. In the subcutaneous nodules, the female
worms are capable of producing microfilariae for approximately nine years. The
microfilariae, measuring 220 to 360 micron by 5 to 9 micron and unsheathed, have a life
span that may reach two years. They are occasionally found in peripheral blood, urine, and
sputum but are typically found in the skin and in the lymphatics of connective tissues (4). A
blackfly ingests the microfilariae during a blood meal (5). After ingestion, the microfilariae
migrate from the blackfly's midgut through the hemocoel to the thoracic muscles (6). There,
the microfilariae develop into first-stage larvae (7) and subsequently into third-stage
infective larvae (8). The third-stage infective larvae migrate to the blackfly's proboscis (9)
and can infect another human when the fly takes a blood meal (1).

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

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Punctate keratitis

Onchocercal punctate keratitis with dead microfilariae in cornea

surrounded by white cell infiltrate.

Reproduced with permission from: Murdoch ME, Murdoch IE. Onchocerciasis. In:
Principles of Medicine in Africa, 3rd Ed, Parry E, Godfrey R, Mabey D, Gill G (Eds),
Cambridge University Press 2004. Copyright © 2004 Cambridge University Press.

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Sclerosing keratitis

Sclerosing keratitis affecting entire cornea.

Reproduced with permission from: Murdoch ME, Murdoch IE. Onchocerciasis. In: Principles of
Medicine in Africa, 3rd Ed, Parry E, Godfrey R, Mabey D, Gill G (Eds), Cambridge University
Press 2004. Copyright © 2004 Cambridge University Press.

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Onchochorioretinitis

Onchocercal chorioretinitis with optic disc pallor.

Reproduced with permission from: Murdoch ME, Murdoch IE. Onchocerciasis. In: Principles of
Medicine in Africa, 3rd Ed, Parry E, Godfrey R, Mabey D, Gill G (Eds), Cambridge University
Press 2004. Copyright © 2004 Cambridge University Press.

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Skin snip in onchocerciasis

Taking a skin snip using a corneoscleral punch.

Reproduced with permission from: Murdoch ME. The skin and the immune response
in onchocerciasis. Tropical Doctor 1992; 22(Suppl 1):44. Copyright © 1992 The Royal
Society of Medicine Press.

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Onchocerca volvulus microfilariae

Microfilariae of O. volvulus from a skin nodule of a patient from

Zambia, stained with hematoxylin and eosin. Image taken at 1000x
oil magnification.

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

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Differential diagnosis of onchocerciasis

Category of Main
onchocercal differential Distinguishing features and remarks
skin disease diagnosis

Acute papular Miliaria APOD vesicles are larger and more widely scattered over
onchodermatitis the trunk, whereas miliaria is usually limited to flexural
(APOD) sites.

Bites of Simulium These papules are small, closely clustered and many have
and other insects a tangential punctum.

Chronic papular Scabies* Involvement of extremities and presence of burrows (thin,

onchodermatitis grayish, reddish, or brownish lines that are 2 to 15 mm
(CPOD) long) indicate scabies. Examine other family members.

Eczema¶ Eczema is rarely limited to the buttocks, the commonest

site for CPOD. The flat-topped papules of CPOD are
characteristic.

Lichenified Lichenified eczema Eczema and scabies tend to be symmetric, unlike LOD
onchodermatitis which may be limited to one limb.
Lichenification
(LOD)
secondary to
chronic scabies

Atrophy Senile atrophy Atrophy associated with old age is usually generalized,
whereas onchocercal atrophy may be limited to a
particular region (eg, the buttocks). Reserve a clinical
diagnosis of onchocercal atrophy to patients <50 years.

Depigmentation Other post The shins are common sites for trauma. Onchocercal
inflammatory/post- depigmentation is often quite extensive and bilateral with
traumatic "spots" of normally pigmented skin centered around hair
hypopigmentation follicles.

Repigmenting Vitiligo typically begins in an acrofacial distribution.

vitiligo Repigmentation of patches of vitiligo may give a "spotty"
appearance initially.

* Refer to the UpToDate topics on scabies, section on typical infestation, and the etiology and
patient evaluation of pruritus.

¶ Refer to the UpToDate topic on the epidemiology, clinical manifestations, and diagnosis of atopic
dermatitis (eczema).

From: Murdoch ME, Hay RJ, Mackenzie CD, et al. A clinical classification and grading system of the cutaneous changes in
onchocerciasis. Br J Dermatol 1993; 129:260. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-
2133.1993.tb11844.x/abstract. Copyright © 1993 British Association of Dermatologists. Modified and reproduced with

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permission of John Wiley & Sons Inc. This image has been provided by or is owned by Wiley. Further permission is needed
before it can be downloaded to PowerPoint, printed, shared or emailed. Please contact Wiley's permissions department
either via email: [email protected] or use the RightsLink service by clicking on the 'Request Permission' link
accompanying this article on Wiley Online Library (http://onlinelibrary.wiley.com).

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Treatment of individuals with onchocerciasis

Individuals in endemic areas with high levels of ongoing transmission

Ivermectin 150 mcg/kg orally (single dose); repeat every three to six months until asymptomatic

Individuals outside endemic areas or in areas with low transmission

Ivermectin 150 mcg/kg orally (single dose), PLUS

Doxycycline* 200 mg orally once daily for six weeks (start one week after administration of
ivermectin)

* Several studies support use of doxycycline, although it is not standard therapy. Treatment with
ivermectin should be administered one week prior to treatment with doxycycline to provide
symptom relief. Doxycycline is contraindicated during pregnancy. 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.
[1]

Reference:

1. American Academy of Pediatrics. Red Book: 2021-2024 Report of the Committee on Infectious Diseases, 32nd ed,
Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH (Eds), American Academy of Pediatrics, Itasca, IL 2021.
Source: Hoerauf A. Filariasis: new drugs and new opportunities for lymphatic filariasis and onchocerciasis. Curr Opin Infect
Dis 2008; 21:673.

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Contributor Disclosures
Michele E Murdoch, BSc, FRCP No relevant financial relationship(s) with ineligible companies to
disclose. Peter F Weller, MD, MACP Consultant/Advisory Boards: Genzyme [Eosinophilia];GlaxoSmithKline
[Eosinophilic diseases];Knopp Biosciences [Hypereosinophilic syndrome treatment]. 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
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.

Conflict of interest policy

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