The Bui ivermectin trial: preliminary results

1t MBMORANDUM To: Cliief VCU Date: 18.11.87 Attention: Subject: The Bui Ivermectin TriaIPreliminary Results I rc'ur : Dr.' . VCIJ (',11 )' f't--f : i'r'lr.tt: t',:f : R A. Baker h:c)1]t,()uBA 87 /vAr /B^t4/6tD . l t-tt'i gi rrat,,,r l.rr. 1'rl I . 11J,1,1;lLrprUr..T,t0N ltr ,-rt'clt--'t' l,r-> :Lttd.v t,hcr ef f ect of ivernectih on transmission in[lr': Erri.tiorEj (B].ach V,-rlta River on the Ghana/C6Le d,Ivoire border), l-t " ':;l!>t,trre tf,-, i trt,s-i ( Agl-r,:rehame and Akanyakrom) were monitored dairyrr'"r)) i.6. Fi7 31. 10.87. (jne hunr1red anr-l f orty eight capture days Lt/\r-itt'',lr::i,;an)e 1.rrl',i1i111-,'.-',J ,l'/41 f l ies and 6SB3 f Iies were caught atAl'.lrny;rllr,_iur irr l4ll rla.yr=r. Over gBZ., r>f these f lies vgere savanna members ,.-rf t.lrt: i:i - .d_.au[t:_qit_r.tr_u t:,..rlnpIr:x . AI I tir,.: s;1.irirr'rr.l irr I'l i trft:r:1, i r:,rt - .;AF''IIIIiE: l'(, 1 l,l'l' F AIt'.)r.lll Ii'l'A I ltlljIr II'li,'[]tj]'Etr ALL 3RD] NFIjCTIVE STAGES %PAROUSINTECTIVE %PAROUS il ,f parolr:i f Lies at both points were kept in g0% arcohor,i/'-'rii i\,-:icl l]aenral-um and dissected to revear onchocerca]rt: f,-,1L()wir1g results were r>btained: I'IEAD L3S A(iD0t,E[( AI'tt] AKAI.lYrli.RO[J :]399(;|7 !) 408454 1.20t22 190189 200206 3. 5%2.Oyo 91.2%92.4% J'[)Trtl, 3,17 8 862 242 379 406 2.6yo 33), j-vermeetin was to include 85.6% of the 92.4% AS C;n l,Ire 1 .3 t,h arrci 1 4t,i.r Augr:st ( week rl is;t-,r'ibt.it.,;,1 L<_> 1(i61, people, estimatedpopu1;rt.ittrr (-)\,i-rr 5 year,s o.1.d. :t. A-l'lal.,J$rIt [],-'1.7 l.--,iti I./(], t r.lrr i:: tn.i :i.s i,-, r r'i I rrlr..t.Lun -L98:t Iii Ir;t,l.t'. wr: rralr t-'ofi)pare l.,ransnrission in 1g87 bef ore and afteri,,,,;1'111,.,;I i11 rlL:I iv,.,,l']'. Llr-t,.:)i (lonlpari:j()lrS ]tave to be dOne Wlth gfeat ,jar.'e- Er:,t:t,tst] tho: river r.ras treated nlore or less successfullyt,)rr,:rrglr.)LrL, l,lrere rvil I lrave b'een seasonar changes in the sourcei:r't:etlirrg sit,cs of tire bitine .f ly populations. other f actors, suchi-I.v r'rrrplr:vi1;p' and age-specif ir: biiins patterns which can greatryirrf Ir)t;11r;1: Lhr: c,l::iervecl transnrission iul*=, wilr also vary on asel35,fllil I l"ra:_; i lr . r"ri l.h F'rer,,i r>rr s Years!.-o-.tUP-e.L]Igjjl tell whe,1;her i.zerlnectin itas had an effect on Ieasol)s, we must also compare transmission withBer:ar-rse ivermectin treatment was carried out inlook nrost carefulry at the months of september andnr',t herve access to pre-1997 weekly rlata for the Buiso tlris preliminary anarysis is confined to monthiy ah/1, I Iior t,hese L)revicrtts year.:l. Arrgr.r:.; 1,, we rnrrst (-l<,: l,crber- . We cic, G,.r r'Ba i tr Banralq,,L .),)ptLrir t- i S,tt.ts . Pwr 4zzr /,Lr t( ) D:i. l-!E!{ILTx .'i . t Wt_t_ll-ii, _l_g$j Fje' l' slit''ws Ltrat, tlre percentage of infective parous flies '-lr-')l)l-)e(1 f r-,-rru 1.4% 1,,,-r ijero two weeks utt., ivermectin dellVery and didlrr',t, t'i:-i,: irl)r,,,,,-' it .ll?r, I'or t,hc foll.owing g weeks. Ilow rnUCh Of th1St"lrlrlr.':t'it'rtl was dttc t,o iver-nrectin and how much to a natural faII ini trfr:r-'t, i r-rtr ra{.,:s'j IiiE' ir .;hi,rv:r the percentages of parous f lies which werejrrf':cLjr,'e, infe,.'teci or infected with oirly L1s- and LZs during the May(rct-'ob'jr' pert''i-od. Trarrsniisston irad clearly bqg:n- at its height duringt.,i1r'1 1r+r'-i'-".1 rr-,-,nr rvecrr z:-) (beginning of June) to weeks 311l-rr'f irrnitrrl ,rf ArrBu::1,) ancl fri,f ,lr.oipetl before ivernrectin was given.Tlt'r PtlL"''.rlrLagr-"rf pa.oLrs flies wiiir onfy i,fs and L2s did dropirnnrt'rli.at,elv r-r",->nr 5.6:4, t,c- 2.8% in week 34 but .o=.-.s"in to 4.7% lnrvr:'-rl: 31, bef ,-rre s;tal--ri r j sing around z. s?6 f rom week 3T]. rf rvermectinlrarl i-rr-)r'1',,:',1 -,,1 i L :-ilrorrld, ,,,.*- rvor:1cl }r.ave expecterl an immediate andI)errnalr(af1 t, r".-:r-lrrr [,i,rrr i.rr t]re perLrentage of f ries with L1s and L2s. F'ig. li sh,:,ws i;lraL rielivery of ir,,ermectin coincided with a: r-rl_rri*-arrt tarl f trl I i rr f f y lunrbe.rs at both Agbolekame and Akanyakrom,r'*e"lti trt: e tnittirtrltttr iti wt:ek:i 35r anrl :l 6 Cen,l ,rf August/early September)wlrr-'rr r,r'r-,r ,.';rt,,,-irls .r.t)r-e r,r,-:,,rrrieci rln s days at Agborekarne. Ery numbers 'rl' li'''llr r'''irrt,:i !,''g"rr t,,-r pir:rr uL) i:lgain fi.onr week 3g (week 3? atAlrarrS':rkr',,,ril) r.ri.r,rr :1 nraxinrirnr of i-r.r.i roo-per day at Akanyakrom in weeks41 nnr,l 4;l ( r:;rr L.v t.o rui,l- oct,rber-) . wrien f 1y nunrbers are row,irrf:':ti'2.it,5, r.'ater: are rikery to be instauie, so this courd exptalnthir s+-ahilit.i' 'rra:r obser..'ed o^.ly from week 38, 5 weeks afteri v,; r'rrrt:,.-l t, i tr ,le I i ,ze ry . Val'yitrg t'rff i'lr'rr:y c,f vector r:ontrol corrlrl also have played al"'''le' Fle' 4 srir'-'t'rs h'rw 1;lt,-' pal'ous rate changed rluring thls perlo,l . -Itp.-,il'1, Ir',rrrr t lro ]a:it, tw,-r weeks of october, tlr.e period after lvermectinr'l':ri'zt:t'.'' rr'Iali tltar-'i'-6'';11 by very higlr parous rates close to 100%, whereas;r m(5srl r_-,f arr-ru])Ll il0?d was observed before delivery. If the presence "f rrrr'l I i l)i-lr''-)rl:: f I i es is arI iurli c:ator of some insecticide treatmentf ailuIe, i'l-i':t't ve'.': 1,ot' contro1 was more successful" after ivermectin 'Je-l i*er'.v. I,il: rlreref ore neecl to l<.ow ilre origin of the friesbi1,i'g in tlrt'. Rtri bef ore and af ter iverrnectin treatment. Irig. f) /-r(-,rrrpares the nrean nr:mber of fries caught per day for 'rnclr r.rtlr;li r_rrr tir.:: IlLri (niean of Agbolekame and Akanyakrom), atAlll(',u,=1[:t,ulqt',, r,n t,h-.. Comt_.r* Rivr:r. and at C]ruteS GaUthier On the BandamaI'-i'".1" Ilcil,lr [,lt'lse p,.ritrt,s li.: to the sotrL]r-west of the Bui Gorge, intlie rlLre,:Li,-,n c,f Lhe nr,--,rrsoon wj_nds which brow during the rainyr'/::as/ir). Tlrc:l-e: i s; .r ,-:1. crst: rel-ationship between biting at chutes(iarrtlritr- anr-l Attiot;al'^,-,ittl..r'o in .Iune,/JuIy-*itr, peaks in weeks ZS and zT.In l- -- _lll"5e p':-aks in f 1v ttuntbers cor-respond approxi-mately to those observedr'l.r 1,lrr-' Er-:i, f]1,.r1gh r,vrt,h a J.ag crf l-z **.k=. The mtst rikely(.r()l)Lrl-rrsirrr is trrat. trre major:ity of fries bitins man on the Bui in "Tr111''' 'z'Itt I .r' .'an)e f rr-rnt t,lrr: Banclanra E.i ver in southern C6te rl , Ivoire andtlri,rl, 1.,jr<'r.;t' f f ir:r-'- wel'() rrrir:ging infection into the Bui. rn week 26,Ir'r' r-'v.,'1 111 1-'.1 ''. ):,. r2', <-rf t,]re pi.or= f ries at Taabo and chutes Gauthieri,rrr'.1 3.c)",, r-t7-'tlr'.: rlal.()us flies at Amouakoukro were i"f;;i;; "'.-"' Tlt': :ieLr(/n'J pe,all -irt f J-y nurnbrlrs on the Bui in September,/October1.'ar)t){.rt, tre,-:xpIain.:rl irr t}re same bray. There were few flies on theIt-'rqe-I' Banrlanr;r at t,iris t j.rne, trre 1ai.ge nunrbers on the como6 were arrl:::.::l.sPer:iis inr'st, prr:bably S--i".d;""Ii) and aII our work onr Irr/'-i:i-r()n prrriudir:ity' has shown that this is not a tirne when f lies 3tr:arzel l.ong di:itances in a north-€]astwards direction. We must thus 1,:,r>I.. J',,,r';trLotht-+r s(:,urLte of flies at this season - presumably one wltich is r:l')scr to Alranyaiqrom than Agbolekarne. The hish parous rates :-irtgge::t. 1,tra t, tlre s,-rur(je is son)e cl j.stance away ( or that nulliparousl'l ies w('l'(j ,.-rtily bitirLg ahray from Lhe river bank - rather unlikety). .l f 'l.,hc :iL,ur,lt) br",:eding siLes were f ar away f rom the Bui, j-vermectin ,'rrtl Itl ,-nIy l-r,: r:,f f .lctivr.r in cont r.-:Iling transmission on the Bul if 1 lrel'' e/il:r rr,) ,/ne ll(./c)L-rciasis in Lhe source areas. 3. 2 J.J_qmpatjs:ll_t. qitlr Frevior.rs Years fl'.r'; t,-, i.he r.trtknorvn origin of the f Iies biting man in Septenrber nrrd o,: t,r.,[-,,,:r' 1987 wlren t]re ef f ect of ivermectin on transmlssion :;lt,rlt1r.1 ii,'t'.',-: Lec;r'r r)r-)rit rLr-'t-ic:eabl-e, w€ ntust contpare transmission 1nt,lrrse lrr.rrrLlr:', wit,lr thal, recorded irr previous years. Because l,r'c'ilt,ur,.:nL, ,-^if i{-'a(:y l.arie:r-l f rt:m y(lar to year, these comparisons musti.;'rk.: irrt-,, i'I,),'',-)rlrlt, f I), l-ri t,ing numbers. We cannot therefore use slmple ,'lr-\rrrlr-:r irr t'lrI .,r.'IIIEE: t,o:ihor.r the effect of ivermecti.n. Other l--)tt]'i1nret,,:rt's :ill1.:i) A:f t,ir,: per.'cent"tge of infective parous f Iies and the rr'u))l).':r' ,-,f irrft:',-'t,j-rr:- f lir:s or. infec--Live larvae per 1000 parous flies 'll'C nl'-)f(:' Ul-ir:f tr1. Flg. 6::hr-rt.rr: Itt:w t.Jrt: nr:niber r>f parous flies and parous rates inI)':plenbt-r:' arrl L)t:tober ha.re varied f rom year to year. It can be '',br;er'\'e';t-l t,hat illB5 and 1967 were nrost courparable in the numbers and F)/1r'(t{-lnt aEir_1s of l)ar'ous f lies . Comparisons between tgBZ and 13'/ll , lftlit , 131-l I , 1lls3 ancl 1984 are nrost dif f icr:1t because so f ewpaICru:; f l.i,.r:.i rvrlrt-\ ,::aught in tlrose yeaIS rig. 7 ::hriws tire percentage of infective parous frles in l.iept'-'nrl-rer,/r)<:.t<-,[,re]' jn ea(ljr year'. T]re lgBz figure of o.4% is ir-tblil.,enl-,ia ll:.' ,l r:,r^rtlr t,h.an al1 previous years. The next lowest was r'.:r.:or,l,:d i rr LllBIi ( 1 . 4:d ) . Iiitl ,':l ::Ir,-,ws l.he perc:ent,age r:hange in the nunrber of infectivet'I L,-:i 1,.-r' l(.1 ()() l).jr)',)u:r f l.ies in sept/oct for each year compared tol3tl7 Wi i,tr {)Ii1.t' 4 .irrf et:ti-ve f lies per 1000 parous f Iies, over 8O% r'(-'(lLlL:t,it-,r-is wer'+ rec,)r-Lled in lgBZ ,,:ompared to aII prevlous years rrlir.:r)[)t, 198fi vrirr--r-'r-r r^ri L]r, 14 per 1000, the reduction wag 6A%. L)r:tupalaLr,l.: f igrrr',:s e.tn be ,-:alculated for L3s per 1000 parous f lies.l,c',":n L,3s !.,')r- i000 p,--11',rus f lies wcre recordeci f or sept /oct, lggT rr(,ln)l-\,'tl'(r(-i t,/) :.a4 Ltt 19BS and [r6 in 1986. Reductions of over 80% were t',:c,',i-r1.,'r-l f .-,r' ;tl I l/,e;ir.if e)i(.jept 1gB5 (7l.Zyr) and 1980 (?9.0%). ,1 . ijl=ti-r-'Ll_rll 1( )_lilr Ii'r.rr"11111,11, iy.1 rn ry lrar'.: retlrre ed tr.ansntissiotr at 1t:ar=, t, 7r):?. duling Septenrber/October l gBZ . the Bui Gorge by at 1','(irllerlt.ir) rleli\rory will have no substantial ef fect on annualtransnri:lsi'n at, Bui r:ntil peopre riving beside the sourcebrr:r:r-lirrg :iiLt-=:; on the Bandanra and Conro6 are also treated. Flies i r:r,'ading the Eui in the May - early Auguft,-period are responslblel',-,r' 60-70?t, r:f errlnual transrnission. ii'urrthel an,erl,ses mu.st be made comparing biting, parous andirif ,:r.:tit,rr ratr:r. per weeh between years at each site. Weekly anal;,3;.1s.ar:e t:r'rrcial, to these and many other VCU activities. tle rrr-'E:ent,11, rtr=eel ar'l Ento Weekly Data Systenr. Furt,]ttr t=ff'-rrt;s .rre tteeded to determine the source breeding sltesi,f t,irr: f lics biLing at Bu.i in Sept,ernber,/October - the f lies whoset,rair:;rnissic,n lras apparently been affected by i ,l ,_t ,7 ivermectin dellvery I\r' I-l r' . lt r' . I).r; Itr'. Dr. (lt''trrer.r;r I rl t,irri 1 l-,-t, It,'1".,,1,,'l i 2',,' l'1,, , Wa I :;ir ['i u r" 1., ir ]r I *--.t'r:,::tttag^, ,,if Fayous Ipf ective Flies at Agbolekame and ,rtk'-rlr,'akrt,nr (Etri Gorge) for each week, May - september lggz f'r.'l',j,'r.rL;rgt,-s of f'ar,:,r-rs Infective Flies, parous Infected Flies .'-:rr,,l I''firoLrs ELie:s with onlSr 1,1 or L2 Onclrocerca at Agbolekatne nnt-l Altan.r,al,.y,.,.rltr (Erri Gorge) for each week, May - September r3i,7 E_t!LiI{E}=s I'irI. I [. j { Irie. .'l l),'rily Flii,irrg i-i,:,1.F-le ) , l,{al, [iate p--r,Week at Agbolekame and Akanyakrom (Bui Septenrbt: r 7987 Akanyakrom (BuiI,'irt ,l I'4,.;rrr 14,,'kli' 1r-q1-rrus Iilat,e ,1f, A6;brtlekanlrl arrd( l, r 1.1,,.i, I , I'1.11, l_;el, l,,.in)bc L. 198,1 li i t:. i' l,'i rl M, irrr ltai'ly Eit,i.ng Rate per Week at Agbolekame ( Ilr"r i (l,rr'gt") ) , Chut,es Gauthier. ( R. Bandama ) and( ti: (''r;rylr',ri .) I May - Septernl;er lgeT and Akanyakrom Amouakoukro Fig rj T'-'t,trl tiunther ,-'tttd pert:entage of Parolrs FIies collected at A6;l-,,'1,,'113p11-- rrn,-l Ak;rnyakronr in september and october 1gz6 I 9i.l'i . l'1",rrr l"'r,'(::rrt.,rg.-^ pirl'(-)rl:i inIective rates at Agborekame and A1.,,-rrr-y,rhr',-,ru i. Septenrber and October 1gT6 - 1ggZ. I i tl . ti l'.: r-(_:e]it.,-lEje r:]rangr: i n nuurber of inf.ectivepaI'ol.l:r fIir:s f6r Septelrber/October lgBZ g.r.-1-j r,rrJ in previous years. flies per 1000 conlpared to the same =- 'rl ,F'PERCENTAGT PAROUS INFECTIVE (., ;1 I .l\\oo\ I LJ)a l N)\oo\ I Ni I O\oo\ Co N ! N _l O)\oo\ I N)O N) I\) IJ$ I I h-P o Ed O r{ 15X .F\ 15 R- X z X :d o>l>r I Il- l\l cI) ).. -l 1. ( l\) CO Lr.lO (, t\) (-l I' Irl i rl ;>i L,') (o o ! ? I-TIn rn C) .--t Z a"- J- \- r iE* (, CT) f_n r_n -{: a) -{\ l\_) .E -1 . I r , r. I i I I Il I lt rp l\) N) O) N trl ED o ri r{X ?)>r r! R- X z X :do?l\ (o o\j I N) +\oo\ N N) \1 NO o\ d N ; N i N PERCENT INFECTION + N)\o o{ O \q CO N o) \q + \q o\ N)\oo\ O\o o\ r I I i I I I I I ___t_._lN)O t!N N) +' 'lI o Io c ([.t(Jr ( 'r -- N m Lt(f Ln l\) =IIIn TN C) -l ri rrlx U^' ot c( (r I('f o {o 'to o + .)J-t _t, l<r '-l(, o-t l:) -a, J, l:i lllo iti)qlq N -U -]J -D )JnxoooCCCaaa = o = =Z;rri a r.iC)1C) -'-r -l/-..Tn ri\ o t-N Ll C') <( $ :lII tl CO -tr Cr + I\) -F' +' I I ltI(^) DAILY BITING RATE PER WEEK NOOOO (o OCO \l OO)OtnO+OGtCfNOOO t__._t_ ___L___1__l_ _t_ _,1 _t_ I dl NO N] N) NJA N] C) tv CN (n(f (,r N) GJ5 Ln o_r Crl CO IO .+- r.r E I \ FJ -i! z :dO F\ R- o E! o r< r5 X )>r 14 (o @ ! I I s I I 6) ul or rnx rrl + ,\ Z x no 3 rn n rn(-){ z h I _-l G G t -.i ri ! Yl ^.\.r) \ ,d u_) N s -t't l, I:i n+ J: -----n ---_A -d'- I ltq3- 3O N (o O N CoO N \.] \q i o)O\oo\t t_ CNO\o I O \q o\ I LJO N I f\) C) \q I O\o I O N t t\lO N) N-l t\) + N CN N.) @ UJ C] (.r.J I! 6) ED O r-{ r{ 7l>t rlj k ,z X :dO > F>r (o m!t I '.4 -U no(: a i I + I 'q -U),n oCa 2 -rl t-rl C) '-l trl tl =rnD mo -{ z € rn rrlx(J) (rJ +\ L.J O) r-rl m + U +N tr +\ * .1. ) \ ) -rl .F'(, = N Cf)O N5O N NOt!OO)O+NO 3OCOOo)C)+NOC) rJ C) C) F-LIES CAUGHT PER DAY + _I_r__ t__ -i __ _L ___l _ ___l ____L___N)O N) N) N-)5 N) CD N CO L,JO LJ N OJ + (! o) (rJ LI) C) ,\ f\) .f' -f, -l + Tlr. b + +o----- z rlA(, LT o ED \_{ oO o r5 z a C) z 1-d i*L (o CO! l,l I l6+ti:l OCF d3 xvt;[oc)Cyrrl xCn --lo.r rrln d l' b+ € m rrl xa ot- -o (5 r1 - -o _tl e-- c( I + id 1'+ -!o=---:-----l-I 7 I,t 'rl i, ! ,,:l .l I T 6' O) 'lli o iC) N (o o N coo){ O)O \1 tnO Nt +o NT C"lO N NO N 6 N o N t t t I I It )o oo rn Aa o N) $ C)OO (.r.J O C)O LliN) ,OI ,oIIl,O lFa r-ft- ' slnj OOO O PERCENT PAROUS FLIES !o N - ? 7 -U noCa -rl r rrla o ! O) !! ! m !(o CoO ,.i t. l;r ' t,i 'tiT. ,'l{ ',$. ,ii i$ -'tll iH ,"ttl r*I _)l lil ).I I i : o. E!o r{ 15 X >l>r r4 R- X z X :U or>F] T n oCa 1]t- rrla, =a rrl -'ll -{, F o c) -l ,$.r, .JIT a I @ C, o5 m Ul m O) CO{ G o, .o o '.O ''fl.c*1 ,' .d :#i,lil :1,. ;ltr-t -t,;rt '1T , :'IJ: :+"lr r#l r: r{i it'# (, OOO iI .!/ tiI ii 'l ,\ I il 9, o tp Il ,t(, t'i \t T noC 1J'' -rl a rrla I '.. '1 ,,, ',t. r:.1 .ft ,,. ,itt . ,iI'i! SNOUVd JO U]BNNN l H ,,1 { q :fi ,ff ffi d frs -n ,F'{ -oo BED .oryr{ -{ElrX o.Ubrq -< R- rrl 3Z -u'1. -..,'l bp'-1: hE:Uio 7 F>i s ;1 PTRCENT PAROUS INFECTIVE N O N (o N o N ! N o) N N N)q O N CNN Gl+NN ..1___r__l!o, __t ! \] @ !(o @O q m N) co (.,J CO + =rrl na ,l*.2 co(, CO C') Co ! r I 't iii. 's; .J"r l1 a @ % CHANGE TNFECTIVE FLIES / 1000 PAROus (o co N (oq, N (o s N @ N) N (o O\co\ !O N o) @ N @ @ N -: !!!!@@@coN+CJ-)CoONSo)NN}qNNNNN __t -___l _ _l_- __t_ _r-____L _ L__L__!O) ! ! o ED o r{ FJX |>r r{ R- X z X FUo>i>t 7 2Tl rn c) -l rrl -rlr rna ooo 1l noCa I ;{ c)I z C) rfl =--{I (o co! { CO !(o @O @ @ N co UJ @ 5 CO(n @ o) rr-l na I