138 Tt.
e Nematodes
...... run.... s...1rnaOilcJ:131·152.1980.
22.Kazu,aJW.~J.Pw,yR.et•I.Com~ot.itlgle
"°"':~•nd~lorlf-albe,-.
"'"JTropMedH)'II
23. Onchocerca vo/vu/us
(Leuckart 1893)
Introduction
Onchocerca volvutus is a 118CIOf-borne filarial
nematode. The adult worm locates to a single niche
In the subcutaneous tissues. Its offspring. micmlilar-
iae, migrate throughout this tissue, inducing Injury
to a variety of ana tomical sites contiguous with that
tissue. There are no reservoir hosts fo, lhis para-
site. The blackfly, Slmulium spp., is the vector of O.
vo/vulus. This lilarial parasite occurs in Africa, and
throughout Latin America. Onchocerciasls used to
bo the major cause of blindness• throughout sub-
Saharan Africa. often affecting ITIOfe than 50% of the
Inhabitants of towns and villages in endemic areas.
The advent of the ivermectin program, administered
jointly by the World Health Organization, The Clark
Foundation, and Merck & Co., has seen the inci-
dence and prevalence of onchocerclasis reduced in
Africa by more than 90% in many regions. JI was
once so prevalent thal people could not live in many
places along r1verbanks. Hence, the turnabout in thls
disease over the last five years has been nothing
short of a miracle in the annals of International public
health practice.
With the intensified effo,ts to eradicate river blind•
ness. public health officials have started lo enter
regions not p(evioosly under surveitlance. It has been
pointed out that because of this new intense scrutiny
of the infection, there has been a paradoxical rise in
the global estimates of prevalence.' Approximately
18 mlllion people are infected with 0. volvulus, world-
wide. Nearty all of them live in Africa {with about one-
h 31f In Nigeria and Congo), with about 150,000 cases
In the American tropics.' An estimated 270,000 per-
sons have been blinded as a result of onchocercia-
sis, almost all of whom live in sub-Saharan Africa.
Onchocerciasis rs stilt the fourth leading cause of
bUndness in the woricP The disease also causes a
disfiguring dermatitis that is second only to polio as
a cause of long term disability In endemic areas.
Historical Information
Onchocerca volvulus was first described in Africa
by Louckart. He recounted hls discovery of the para-
site to Patrick Manson, who. in turn, published the full
description in 1893, glvingLeuckartfullcredit.'Ear-
lier. O'Neill" observed the micmli1ariae of this filarial
nematode in the skin of a pa tient from West Africa.
Onchocerciasis In Lalin America was not reported
until 1917. when Robles• found ocular disease asso-
ciated with the presence of nodules on the fo«1-
head of a smaN boy. He dissected the nodule and
found that it contained tho adult worms. Later Robles
desaibed the worm, the pathology of the disease,
and epidemiology of the Infection. MOfeover, he sus-
pected that the blackfly was the vector. which was
proved by Blacklock' In 1927.
Life Cycle
Adult femc1les measure about 40 cm in length
and 0.3 cm ln width, while the male measures about
3 to 5 cm in length. Both sexes lie entwined about
each other. locating to subcutaneous fibrous nod-
ules, onchocercomas (Fig. 23. 1), which vary In slze
depending on the number of adult worms In them.
Some nodules are so small that they cannot be pal-
pated.' Mlcrofilariae are produced within the nodules,
and leave these sites to migra te throughout the sub-
cutaneous tissues ( Fig. 23.2, 23.3). The blackfly (F,g.
39.5) acquires the larvae while taking a blood meal.
The Immature worms penetrate the insect's hemo-
cele, and the muscle fibers of the flight wing bundles
in the thorax. After 6-8 days of development, during
which the lar,ae molt twice, the now infective larvae
leave the muscles, enter the cavity of the proboscis,
and are deposited on the skin when the fly bites.
Lar,ae enter the bite wound after tho fly withdraws
lts biting mouth parts. The imma ture parasites invade
the subcutaneous tissues with the aid of a prote-
ase.' and take up residence there. After completing
their development, lhey mate. Adults produce hun-
dreds to thousands of mlcrolilanae during their life
span (about 700 mlcrolilariae per day) of 8-10 years.
Growth and molting of worms in the subcutanoous
t'.ssues induces fOJmatlon ol the fibrous nodules, and
also elicits an angiogenic response, resultlng In the
productioo of a network of vessels, the funclioo of
which is presumably to supply nutrients to the par-
asites and carry away metabolic wastes. A similar
anglogenic response is induced by the Nurse cell-
parasite complex of Trichina/ls spJra//s.
Cellular and Molecular Pathogenesis
Q 'l'Olvu/us has Impressive lmmuno-modulatory
propertios, with the capacity to bias h ost responses
to a Th2 type pattern. By this mechanism host cell
 Onchocerca volvulus

Adults shed microfilariae

into subcutaneous tissues

\Q
Infective larvae
develop ,n blackfly ;- ;::::; _,,___ __, , "

Blackfly takes first

blood meal , ingests larvae

PATHOLOGY
140 The Nematodes
Those areas In which peripheral lymphatics converge
(e. g .• occipot, suboccipital areas, in tercostal spaces.
axilla, and iliac crests) have the higheSt predi~
for oodutes. The body regions most affected differ
according to geographic locales. In Africa, for exam-
ple, the nodules predOr.lina<e in the lower part of the
body, whereas in Central America they tend to be
found moJe often In the upper portions of the body.
This difference is related to the biting habits of the
vector insects, and the styles of clothing worn by the
inhabitants of each endemic area.

Clinical Disease
Clinical onchocerciasls includes dermatitis, eye
lesions, and onchocercomas.

Onchodermatltls.
Mild infection (less than five nodules per infected
Figure 23. 1. Cross section of nodule (onchocer- Individual) Is usually asymtomatic. In contrast, mod-
coma) Induced by ()nchocerca volvulus. Nun:ierous erate to severe infection {ten Of more nodules, with
sectlOns of adult worms are seen. 2.5 cm in diam. many in the head and neck region) produce corre-
mediated Th1 type immunity is suppressed leading spondingly more serious and more numerous symp-
to impaired respooses to PPO skin testing fOf tuber- toms. Involvement of skin is characterized by intense
culosis," and even Increased susceplibility to Inter- Itching. which is associated with a rash consisting of
current inrections with lepromatous leprosy." numerous small. circular, elevated papules 1-3 mm
The degree of pathogenesis varies directly with in diameter. On white skin , the papoles artl reddish,
the intensity of lnfectioo and the degree of host but on black skin, they tend to be dark brown. The
responsiveness lo dying adult worms and microfilariae pruritus of onchodermatitis is inlense and disabling.
and their secretions. Dead microfilariae induce inflam- Occaslonal suicides result from the extreme discom-
matory reactions that become more sovcre as the fort associated with it.' Tho affected areas of skin
infection JM"ists. This point is important v.1len consid- become edematous end thickened. and It looses its
ering therapy. The lesions, primarily Involving the skin elasticity. The skin can take on an orange-peel qual-
and the eyes, oc:aJr as a consequence of cell-medi- ity. Over time. the skin win atrophy. especially over
ated immunity to parasite antigens. Individuals with the buttocks, with appearance of wrinkles. Oeplg-
the most vigorous ceU-mediated immune responses
develop the most severe manifestations. '· u, ••
The ma)or ocular leslons occur in the cornea to
produceakeralitis. lnthiscasethekeratilisresults
from an accumulation of punctate opacities in the
cornea that arise from a unique lmmunopathologic
damage to microfilariae in the eye. This is a Th2-
dependent process with a heav)· reliar10e on host
Interleukin 4." In the skin, similar Immune responses
lead to pru ritus and angloedema.
Subcutaneous nodules, the other hallmark of clin-
lcal onchocerdasls, vary in size from barely discern-
able to approximately 5 cm In dlametet Nodules
develop OV8f an 18-month period depeoding on the
n11mbef of adlMI worms in each. The numbe< of nod-
ules also varies, from an occasional one to several
hundred, occupying large areas of subcutaneous
tissue. In the latter Instance, blackf!ies biting such
individuals may actually expire, due to theoverwhelm-
ing nature of the infection in their ftlght wing muscles.

Figure 23.3. Higher magnification of a microfilaria of
0. volvulus In skin. 310 µm x 7 µm.
mentation can also occur, especially c,,,er the shins.
Sometimes this is known as "leopard skin". These
sequelae are more convnon in Ahica than in Cen-
tral America, bt!I Central American children who are
infected may have facial lesions, reddish In colof.
described as erislpela de la costa.
Lymphadenopathy
Lyrnphnodelrr.otvement inAfricaisusuallyfoundin
the inguinal and femoral nodes, 'Nhereas In the Ameri-
can tropics it is in lhe head and neck. Advanced lymph
node irNONemeflt can lead to adenocele formation.'
Ocular l esions.
All parts of the eye are affected in chronic, long-
term infections. lnitiaUy, there may be conjunctivitis,
with irritation, lacrimalion, and photophobia, a reac-
tion analogous to the defmatitis in respon se to dead
mlaofilariae. The cornea at this time reveals the
puoctate lesions of keratitis. Slit-lamp examination
reveals motile or dead microfilariae in the conjunc-
tiva. A long-standing infection produces sclerosis and
vasculartzation. Sclerosfng keratitis is the leading
cause of blindness due to onchocerciasis, and devel-
ops c,,,er a 20- to 30-year period. Onchocercal blind-
ness peaks in those between 30 and 40 years of
age: individuals most responsible for taking care of
their families.' The anterior chamber is also Invaded,
and microfilariao can be seen there with a s!it lamp.
FlnaUy, there may be lritis, iridocyclitis, and second-
ary glaucoma. Invasion of the posterior segment of
the eye causes optic neuritis and papillitis; the cho-
roid and the retina are also Involved.
Diagnosis
Because of its highly focal distribution, a traVel
historyiscritical inordertoentertalnaclinicalsuspi-
cion of onchooerciasts. A definitive diagnosis is usu-
ally made by examining a piece of skin (2-5 mmi) dls-
seded from the affected part of the body. In Mica,
the specimen should be obtained from the lower part
of the body, and In Ceotral America from the upper
23. Onchocerca volvu/us 141
part The skin should be alcohol-cleansed, elevated
with a needle, and cul with a scalpel blade. Next, a
preferably bloodloss piece should be placed in warm
physiological saline and examined microscopically for
motile mlcrofilariae within 10 minutes. A reprasenta•
tive sample of skin can be weighed and the nllllber
of miaofilartae per mH!lgram of tissue calculated as
an index of the intensity of infection. In addition, the
piece of skin can be pressed against a dry micro-
scope slide, and the impression stained with Glemsa
solution and examined microscopically for miaofilar-
iae {Fig. 23.4). Histologic sections of a subcutaneous
nodule (F"igure 23.2, 23.3.) may also reveal mlcrofi•
lariae. The sensitivity of skin snips has recently been
improved by PCR amplification using primers tha t
encode portions of a 150 bp repeal' 1
The Mazzotti Test is a provocative challenge test
using a SO mg dose of diethylcarbamazlne (DEC).
Within 3 hours after lreatmenl, patients wtth O. volvu-
fus infection will develop pruritus. In heavily infected
patients, the Mazzotti reaction can be seve<e and
may exacerbate the ocular pathology in a patient.
As an alternaUve, some physicians perform a type of
patch test by applying DEC to a small region in order
to eliclt a 1ocal Mazzotti-like reaction.'-••
Serologic tests that measure lgG antibodies to 0.
volvu/us are sensitive, but their specificity Is poor. and
not yet useful to the diniclan. Efforts are underway to
develop recombinant immunodiagnostic reagents.
Treatment
lverrnectln is the drug of choice foronchocerci-
asis. lvermectin inhibits the release of microfilariae
from the female.11 Usualy, a single oral dose of 150
mcg/kg administered every 6 months will slOw or
reverse the progression of both ocular and cutaneous
.-;iii -,., - ·--~
. /'-b>:__~--J
. ·..J . .. . ·0'. -·- .
... r . ,..1 • 0 1 .~ ·
• t.·. .., .
.
cw--"il .r--.
: ·-~',.;;;f)
" . ;r,..
'·ti •. .
. --~- .
' ..:.
<"' • . ,.
•. ·,
._,, ..~ 'i. '
Figure 23.4. Impression smear of a skin snip from a
patient heavily Infected with a votvulus. Mlcrofilariae
-....ere visualized with Giemsa stain.
 142 The Nematodes

diseases." The dnJg Is available through the Mectizan grams of onchocerciasis.u The onchOOerciasis con-
Donation P:-ogram es!atlished in 1986 by Merck & lfol program inoorporates elements of vector control,
Co. tvem1ectl n doeS not kiU the adutt worms encased chemotherapy with tvermectin treatment and surv&11"
in a nodule. Therefore, repeat dosing Is necessary \o lance. Tll6 control program in Africa will nan through
suppress the release of mlcrofilariae In some patients 2007. So far. Merer. and Co. has oommitted OYer 400
2
more frequent Interval dosing Is required in ordtlf miRlon ivefmedin tablets valued at over $200 miUion.
to suppress pruritus. Community-wide chemotherapy
lnterrupls transmission of onchocerclasls.•o. 11 The References
major toxicity of tvermectin is generally not from the 1. 0,...,.8M.Modetnmeclidne--an-,l(:iant10CMgr.~
drug itself but rather from its abiflty lo increase the --.iaanl"Old~Jlrlad.Ola111S:15-21,1119'2.
antigen load from dead and dying parasites, leading 2. F.-..an 0. In: Tn,pe:all~ DIIOJSH.
PnndplN..Pll!he91N,&Pffdlce.\obt.rne2j~RLWlliw
lo fever, angioedema and prurituS. These symptomS Dt-1.w.larPf~ -~Ch,orct,ll~pp.873-886,1999.
usually occur within 24 hours of treatmenl In those
patients with oono.irrent Loa loa infection, ivermeclin ,...._on c«wd.. WCl'ld
RllpS.asl:1-1o.t.1995.
can elicit sev8re reactions. including encephalopa-
thy!' This point is especially critical In areas such as
West and Central Africa. where there is epldemlologic: 5. J. On the PNHIIC8 al a 1llarla In "e111waaw." lanc:91 1:
over1ap between the two helminth Infections. In Latin 265-26&.1175,

America, the surgical removal of palpable stJbculane. 87-\15, 1917.

ous nodules has led to successful resolution of the 7. 6la,;kl0ck08. Thelnsedll'.,,.,,._,,,,,,~~
Infection In some instances. (l...,.:u,1 IH3). The.....,_dW0ffllnocllAnlllmaninA!tb.
BMJ I 1n.133.1927.

Prevention and Control o,e.....,_._._

Onchocerca vo/Vu/us distribution follows that of
the dlpteran vectors. Blackflles bfeed In fast-naming
water of mounlalnous stteams In regions of Africa
and South and Central America, and they have a
falr1y long flight range. Thus. onchocerciasis can be
8.0Ub80.Th9popul11Jondynarnicld~rea~III
Trcc1Mec1Parn11o1 « ,e1.e. 1993.
9. ~A.JamnER.s.i,.,\alllA.elllL~p,oleues
d0:'ICl'l0Cffl:8. & ; : , ~ 6 e:17~11S,1989.
akln1ui:.n8CGv-=:c:inalionln~WNoloncho-
_...,.~M). 1:309. 19n.
11. PrOIIA.NIC<:uM.fbJglfflar(A.~~y.-,clon;n;>,
Cltdnil. 8MJ1:$39-90, 1979.
12.Pll-,manE. l.l»JH. ~OS.etlll.lni.leudn-41ndT

OJ
found several miles from the nearest endemic bfeed•
ing site. Because much of the coffee of the world is
grown on mountainous hillsides, th& prevalence of
onchocerciasis among workers on coffee plantations
Is high. Control of tho diseaso should first employ the
use of lvermectin to reduce mict0filarial WOfm bur-
dens ln infected poople. By 1995. over 9 miAion lver-
helps~ 2 -~ b al e,,;pern,enlll
182:931..-.0. 1995.
13. Nulmln Tit SIMI C. Wn Ot. et IL Immunity l o ~
~o111rv11..-.i.,tu,w._p.Q~inwn.nel0
Clncl-,;a~w.,;cion. J ~Ois\83:11 2$-1133,19111 ,
14.Chllncnaneu, R. 09......-AF.Nvar~z RM . Ci't>Jllltlngffi,
mune ~.-ocia!MI ,-alb antiganl In l'unan oncho-
CllfciM4. JlnlectOis 182:11SS.1164, 1990.

mectin doses per year were being distributed.' dor•;lw;1c1rdu1'.NN.Par-'ol37:57-106, 1998.

Reducing larval vector populations using OOT
and other insecticides in streams and rivers has also
been tried, with variable success. Because al1 spe-
cies of macrolnvertebrates in the treated rivers are
affected by these ageols, severe, adverse effects on
food chains and food webs have often resulted. Sig-
nificant reductions In the incidence of onchocefcia-
sis has resulted in the resurgence of butckflies in
some regions. In these cases, Insecticide use has
been reinstated . Unfortunately, end quite predictably,
bladdlies In many areas have developed resistance
to a wide variety of insectlcides.
A mullidiscipli02ry program was :nitiated by the
World Health Organization in seven African nations
(Benin, Burkina Faso, Cote d'Ivoire, Ghana, MaU,
Niger, and Togo), OOY8fing almost 1 mlUion square
kilometers of land, to serve as a model for oontrol pro-
1e. KilianHO.Thevseot110pica1Manolll-klthe~d
ondloct,rciasil.TrOPMedl'llnllllol~238,Hl68,
11n...., n the 1tea1meot ot
N EnglJ Mid 313:133-138, 19M,
18.8urr>ha'nG.'-nlec:in 11UlnWltd~~INion&:
~Iron!. ~ e d . ~ In
Mlllwi. AmJTfflflM9<1ttyg52:27M,1995.
lrul-
mentdonchocetciaawltlMlmlldlnonlhe ~ o l
inllclion. Sdlnc:e250;11&.118,1 990.
Caln RC.et II. Theeffectsol
~~...,_.on...........,of~
~~~MIJTfflflM9<:llfl'll-47:17o.190.1992.
21 . ~J.P.&rwM:!J.C.GanionJ.e111. IY9tmldlnlreatment
dloinis.T,.,,.,R$oc:TropMedttyg86:289,1992.
22.WebbeG.The~c:onltO!progrwnma.TransRSoe
TropMedttyg86:113-114. 1992.
 24. loalo8 143

24. Loa /oa in some individuals the parasite can eficit a number
(Cobbold 1864) of Immune-mediated responses that have an allorglc
basis. There appear to be at least three major groups
Introduction of individuals who experience different lmmunopalh-
Loa /OD is a member of tho filarial group of nema- ological responses to the parasite. One of these
todes, and its distribution Is Nmilad to Central ar.d groups is comprised of asymptomatic individuals who
West Africa, where it infects up to 13 milllon lndivldu- have diminished anti-Loa allerglc responses. These
als. In some hyperendemlc regions, up to 40% of a groupstypicallyhavehighleYclsofclrculatingmlcrofi-
population may be clinically Infected.' Loiasis Is an lariae. The secood group Is typified by Individuals who
emerging infection in areas where the establishment develop pronounced immunopalhology with charac,.
of rubber plantations has altered lhe rain forest ecol- lcristicrecurrentangioodcmaandcalabrarswellings.1
ogy.1 Adult worms live In subcutaneous tissues. Their These individuals develop Calabar swellings as a local
main vectors are dipteran flies of the penus Chrys- Inflammatory reaction that may precede the migrat-
ops. Loa loa has no reservoir hosts. iog adult worms. It is presumed to result from vigor-
ous hosl lgE responses and lnterleukin-5 production
Historical Information in response to adult worm secretions, or even micro-
filarial antigen ntleased by female worms. Host ll-5
AII!yll-Robertson, In 1895,1 gave the first com- prodlJCtlon results in circulating eosinophi1ia.'-' The
plete description of the worm and the c~nlcal pre- Calabar swellings are typicelty more severe in visi-
sentation of the infection. The woman from Whom tors to endemic areas than in residents who live for
he removed two adult worms (one of each aex) had many years in these same regions.-. 11 Thefe Is still a
lived In West Africa In Old calaba~ Swellings in her third group of individuals who neither have circulating
arms accompanied her infection and were clesaibed
microfliariae nor Gala bar swellings. These are Individ-
In detail. These Inflammatory lesions are still referred uals who live in hypefendemic areas yet are believec
to as caIabar swellings. Leiper, In 1913,' desaibed to have developed protective Immunity. u. u
two species of dipterans, Chrysops dimidiete and C.
silacae, as the vectors of L. loe. Clinical Disease
Life Cycle Calabar swellings are 10-20 cm ~rythema
tous angioedematous swellings that last for a fev
Female aduts measure 0.5 rm, wide and 60 rm,
days. They occur most typically on the extremltie'
long; the males ara 0.4 rm, by 32 mm. Adult worms
and the face, particularly in the periorbital regioo
deposit mlaofilariae (Ag. 24.1), wtile they wanclef
tlYoughout the subcutaneous tissues. Microfilariao (80
µm long by 7 IJITI in <fsameter) penetrate capillaries
and enter the bloodstream, where they oo:ulate until
they bocx>me ingested In a blood meal by a mango fly
(Ch,ysop,s spp.). L loe microfilariae exhibit dh.rnal peri-
oclic:ity lhat ooincides with the feecfing habits of Chrys-
ops.1 l.afvae penetrate the stomach of lhe fly, and
locate to the fat~ Eight to ten days late(, the infec-
live lhird-stagelarvaemigrate tothecavityof the biting
mouth parts, and are released into the bite WOU'ld when
theftytakesaooiherbloodmeal. Thelarvae,rONinthe
subwaneous tissues of the host, develop slowly into
adults within 1-4 years. The adult worms can live in the
tissues for up to 17 years.• Mature worms mate, and
lhe females begin depositing rr.crofilariae. The nutri-
tional requirements of L loe are unknown.

Cellular and Molecular Pathogenesis

Neither the adult 'N(l{ms in the subartaneous tis-
sues of th'!I host nor the microfilariae in U'~ blood-