The effect of a combined intermittent treatment using DEC and Levamizole on ocular onchocerciasis

"/ 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 Control Progrdr.e in the Volta. River Basin Area.549, Ouagadougou, Upper-Volta. 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 sprevious 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 - 77 Lt/t - 78 z/l - 78 2o/+ - 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 ofthe 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 alsobe ,oted that the Drtrc-treatment of the placebo group, which took placebefore 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,,rasindicated or given. The visual acuity did not c.ange si3nificantly.in any of thepatients during or after treatment iir. flre present study. The visualfields were not exanined. systematically but constricted fiel-ds werefound in one ease of suspect optic atrophy, lrhich remained unci:angedduring 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 inltialtreatment' 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 corTLeals well-knovm, and explains fuI1y the corneal changes seen in thepresent study. -__ Pa3e { ilowever, corneal microfilaria.c re-appeared in 6 treated patients atirregular 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 presentin 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 tothe treatment. Cataracts of senile or cornplicated. nature were eolunon inboth 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 atthe 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 i11those 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.allJ 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. aPage 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. aPage 7 Table l- fire distribution of ophthalmological signs andlesions 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 IIFAS5nf 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