"/ W,ORLD HEALTH
ORGANIZATION ORGANISATION MONDIALE
DE IA SANTE
Onchocerciasis' control prograrame -iie-thc volta Ri-ver Basln Area
Epideniological Evaluation Unit
Teehnj-ca1 locuri6 it' Ocy/:rI/TB .43
TIM EFFECI OF A COIfrBI1MD TNTER}ITTTNNI TRX,',T}ENT,
USIIIG D]]C AND IDVi.iIrZOIi OII OCUI*R ONCHOCXRCIJSTS.
by
B. THYU]TJORSX
Jr Oncho
3.P. cerej-asig 549, Ouagadougou, Control Progrdr.e Upper-Volta.in the Volta. River Basin Area.
Page 1
Introd.uction
In a pre'rious chemotherapeutic study of onchocerciasis, under- taken by OCCGE Centre I'turaz in ooLlaboration with OCp, it was found
that a combined. treatment using cliettrylcarbamazine (l:lc) and levanizole
gave a relatively good raicrofilaricid.al- effect but no aclverse treatment
reactions*. fhe two dnrgs were then given tluring a ] week period vyith
a maxirun tlose of 60 m{aay of levamizole and 2oo mg/aay of Dtrc. .
However, Levanlzole alone showed no significant effect on ooular oncho-
cerciasis in airother group treated with l2O ng/d,ay maximum dose d.uring
5 weeks. l'Ievertheless, a possibl-e interaetion between DllC antl levamizole
merits to be furtirer investlgated, especially as there was a oonplete absence of adverse reactions to ti:e treatment given in the previous
trials.
trevamizole nay possibly have an lmmunostimulant action, even lf tolerable doses of tire drug have not shovrn any significant effect on
0. volvulus (luae 1975; I{aertens & \Tery ]:gr1:). However, the combined use of levamizole and a nicrofilaricide may be of interest as a possl- bIe synergistic interaetion between the two dnrgs may peralt reduced.
and. intemi-ttent tloses.
?opulation examined.
A1J- patlents i-n the present study came from the vl1Iage Kolo-Ko1o, situated south-west of Bobo-Dioulasso. In ord.er to reduce as much as possible tlrop-outs, all examinations and. treatrnents rrere
camied out in the village itself. rwo groups were Lncluded ln the
stuttye one treatment group and one plaeebo group. The composition of the groups was !
DEC + levami-zo1e Placebo
L2 nales (mean age z L6 females (mean age 28
59fi
yrs) z 44t6 yrs)11 l,,Ia1es (mean age i
IJ females (mean age 24
5016 yrs)
z 4L2O yrs)
)F (see reports OCCGI and. OCt/tt?t/ll.2Z and, 75)
Page 2
lhe placebo group ineluded from the beginning J more females and, z ma1es,
but those patients never showed up at any examinatj-on and were ti:.erefore excluded froin the group. The parasitological results wil-l bc given in a separate report (Centre Lluraz).
The ophthalnologlcal exaiair:.ati on techni_que was the same as for the Ie chni c aI llocr"merr_t s
previous drug trlals. Reference.is mad.e to the ocp/Epr/77 .22 and, Oc?/ttpr/77 .15.
Treatment
Both DIIC and levamj-zo1e were initlally given at increasing
d.oses, according to the follorving scheme :
!e.r
1 2 3
4-7
TohL - 6/L2 - TT (initiar z/l-la (naintenance d.ose
6/+-ta (
r/6-T8 (
t/t-ze
(t/g-te
(D]]C
25 mg
50 mg
1OO mg
200 ng
treatra. )
after 5 months)
,,4r,) r6t,) t'7") ug,r)
pre-treatnent) post-treatnent) folIor,v-up exam.
levanizo].e 30 mg
6O ng 90 ng 120 mg
The maintenance d.ose consisted of a single dose of 2oo mg DDC + 6o ng levamizole, vrhich was given on 6 oecasions dr,rring the
observation period. Treatment and fo1Iov,r-up exarainations took place
in tire village aceord.ing to the following scheme 3
Treatment 0phth. examina'cion
il il
ll
??
?I
29/tL
-
77Lt/t -
78z/l -
782o/+ - TB
t1/a2
-
78 final fo1lov-up) ) ) (
( ( ( (
i? rl
[he placebo gro,"lp was treatecl wlt]r DEC during 7 daJrs in
October 1978. The dosage giveir rvas 25 mg + 50 ng + 1OO mg + 4 x 2OO-mg.
lhe treatment vras unfortunately carried out before the final fo11ow-up
of the trial_.
Pagc J
Obserrrations
In table 1 the number and distribu-tion of cases with slgns of ocular onchocerciasis is shown for the two groups. The vast majority of the patients were only lightly infected fron the ophthalmological poin,c of rriew, but with a slight tendency for more microfilariae and lesions -
ln the eyes of the treated group. Hotrvever, the mild ocular onchocercj-a-
sis found in the two groups together with a relatively high mean age, especially for the na1es, reduces considerably the reliability of conclusions concerning treatment effeets. rn this context it must also be ,oted that the Drtrc-treatment of the placebo group, which took place before the final fo1low-up exanination, renders impossible comparisons betvreen the groups coneerning octilar parasite loacl ancl anterior segrnent
lnvolrnaent.
The treatn:ent was v,reIl accepted by the patients and no specific conplaints concernlng the eyes lvere pu.t forl,rrard.. similarly, no systeuic adverse reactions were encounterecl . iro addj-tj-onal topical treahaent r,,ras
indicated or given.
The visual acuity did not c.ange si3nificantly.in any of the
patients during or after treatment iir. flre present study. The visual fields were not exanined. systematically but constricted fiel-ds were
found in one ease of suspect optic atrophy, lrhich remained unci:anged
during the observation period.
rn the anterior segmeq! of the eye there was a slight red.uction
of the number of rcicrofilariae in the anterior chamber after tire inltial treatment' Hor'vever, in ahnost all of those pattents a few microfj-lariae renained in the chamber throughout thc observation peri_od. rri the
corneat a few more rnicrof ilarlae appcared immedi-ate1y af ter ttre first - treatnent scheme, and there was subsequently a slight increase in pre_
valence and quantity of onchocorrreal opacitles. fhe nobj-lizing effect of Dllc treatment on microfilariae anci their rapld death in the corTLea ls well-knovm, and explains fuI1y the corneal changes seen in the
present study.
-__
Pa3e {
ilowever, corneal microfilaria.c re-appeared in 6 treated patients at irregular intervals, thus indicating that the treatment was insrifflcient, especially the maintena.noe cl-ose. In no case the anterior segment got cleared from microfilariae during the wi:o1e treatment period.
An anterior uveitis in forra of a ni1d. torpid iritis was present
in 4 treated patients but onI;' one placebo case. the iritis sho.vred no
exacerbations in any of these cases, anrL even dlsappeared in 2 eases.
rn one womanr 50 year oIc1, a falnt flare appeared in the anterior
charober at the last control, which can however harclly be relatecl to the treatment.
Cataracts of senile or cornplicated. nature were eolunon in both groups under study, which is logical considerinll the high mean
age of the patients. The inpli_cation of several cases of incipient cataract being included iii the stucly is that the fundus could not be
relevantly exami-ned- for choroidoretinitis in 19 eyes in the treatnent
Sroup and B eyes in the placebo group. Ihis fact renders unreliable conclusions concerning the incidence of posterior segment lesions,
lhe cataractous r-enses did not show nuch s16ns of progressin3
opacities in Selreral, bu-t uade the fundus examinatior-r. inpossj_b.e at the last fo11or,v-up of iL ZO-year o1d. treated man.
fn tite posterior segnen!1 an optic atrophy of post_ner-rri_bic
na'ture vras founcl in I mlLles ancl 2 females before treatnent, anc. those
case$ remained stable during thc observation period. I{owever, one r1e!r
case of optic atrophy r-ras founcl in e. DT-year o1d. man in 6e treated.
group. rhe atrophy shorved. r-rp.at the 5-month control after treahrent and then persisted unchanged.
demonstrated in this patient,
Severe visual field defects coulcl be thus confirming the diagnosis.
fn the placebo grou,o there were 2 patients shovring an optic atrop[y from the beginninl, of t,r,e observat;.on period. The atrophy i11
those two cases renainec seeirringly unchanged throughout the study, anci
no new eases of optic atrophy appeard. 1n that group.
?age 5
Choroic'loretj-naI lesions existed in j patints before treatnent
and no nev'r sucli lesions were found durin,3 the folIow-up period. rn.all J cases the choroidoretinitis lvas associated with an optic atrophy.
In the placebo group tLrere ',ras on1;. one case of choroidoretinitis in the beginning, but a discrete nottling of the retinal-pigment epitheliwa
was seen in a lf-year olcl patient at the final f oIIorv-up. Ilolvever, a
co-existing complicated cataraet mad.e the fr.rndus examinatioii difficult,
and it can therefore not be excluded that the leslon did not exist before.
a
Page 6
Conclusions
A conbined treatlent using 2oO mg DEC + 60 mg levamizole given as lnterni btent single doses at 1-2 months intervals shovred the foll_o-
w'ing effects on patients with ocular onchocerciasis 3
- The ocular parasi_te load vras slightly reduced
riae persisted in ttre anterior segment.of the
patients duri_ng the observati-on period..
but nicrofila- eye in most
- Existing posterior segment lesions t1y.
did not ehange significan-
- one new case of optlc atrophy appeared in the treated group, br'.t the presence of cataract made the fundus exanination unreliable in several treated and control cases.
The general acceptance of t:re treatrnent was
systemic adverse reactions were encountered.
good and no
Definite conelusions concerning treatment effects in the present study are complicated by the fact that most patients were only lightly infectecl and relatively o1d. I{ov,rever, there is no Ophthalnologlcal errid'eirce that levamizole has had any effect at the dosage used.. Higher doses of DDC and levarnizole may be moz'e efficient but may then also i_m-
p1y a risk of adverse reactions.
a
Page 7
Table l-
fire distribution of ophthalmological signs and
lesions in the tre:.-tec1 and control group.
Fundus
bi1at.
not exam.
nicrofilariae in the anterior segment of the e;re.
sclerosing keratitis iri ti s
optlc atrophy choroid o re tinitis
Z
1
tiIAS :
TD
0A!
nT)
GROUP I.[FAS IIFAS
5nf SK-TR OA-CR
DDC + I.,evamizole
i,Iales Females
Total
I[a1es Females
Total
PIACEBO
o
10 15
+ 2)
7
1
4 5
1 2 5
I
7 15
2 1
2
1
I
2 1 7
1 1
t
