Всемирная организация здравоохранения (ВОЗ / WHO) · Technical Documents

Report on a 3-years follow-up of ocular onchocerciasis in an area of vector control

Всемирная организация здравоохранения
Открыть оригинал документа

Полный текст размещён на сайте публикующей организации. lawenc.com индексирует метаданные и ведёт на официальный источник.

Полный текст

{WORLD HEALTH ORGANIZATION ffi-,{rd" dt-J't ORGANISATION MONDIALE DE LA SANTE 0nchoceroiasj.s Control Programne in the Volta Sasin Area. n@oRT 0N A '-YEAX IOLLo\I-UP 0F oCUI,An oNCHoCmCL{Sffi]}I AI'[ AREA OT'VECTOR COMN.Of, Elid.omiological E\raluation Uni t Tlchnlcal Doc. 0CPr/Bt/7a.42 ')i r )i-)i'3. T}lylefors & A.l,Io Tdnjr.rm Ophthalmologist, IIEO Onchocerclasis Control Programme in the Volta River Basin Area, W 5491 0ua6adougou, Upper Volta. -)Hr Q66sultant Ophtahalnologist i'j'HO, assoclate professor in ophthal- mo1ory, University of 0s1o, Nomay. 3[, \II{IR.O]IICTION fhe l-urpact of ocula onclrocenciasls ln te:ms of severe eye leslone emd. blintlness is lnfl-uer:cetL by the intensity of infection and. tr -sns- misgLon of ttre tllseaser The d.evelopment of omohoce:scaI eye lesions j:t areas of orrgoLng transmiEsion has been stud.Led Ln ltrest Africa A2A) u'rt very Umrtsd d.ata are available frour areas where the vectorr the @}Bxg flyr ha.s been elimlnated (, or r:ncler control measu:res 6). n" course of oncho- cerciasle may ohang€ signlfioantly when a control of the vector is establlshed.. An lnterzrrpted. or heavil-y reduoed. transmlgsion of Onchocerca volvulus w111 break off ttre accr:mulation of parasites ln tlre hruran body amd. tlnrs initiate a st{€B of sLow1y decrea,sLng intensity of lnfection TLre lnfluer:ce of t}ris on existing eye leslons and. tJte risk of blindness is not hrownr hrt ls of imnediate Lnterest for estimates conoerrri"ng the pretli.ctable a,nwrt of blindnese dn€ to onohocerciasis. TLre Onchocerciasls Control Programroe ln the Volta lli.ver Ba,sln Area. is based on rector control, whioh was in-i.tlated ln 1975. A cletaiLed ophthal- nologtca.l evaluation of patients living 1n selected. rilla6ee in the progr€me area wa.s qa.rried. out Ln 1975 ana agaln in L!JB, i.e a,fter a J-year perlod. firrlng whioh there wa,s aJr almost complete internrption of transeLsslon of ftehooerq.s, vo.lv.qIus according to availabLe entomolog:ical resultsr fhe J-yea foI1ow-+rp of the d.evelopment of ocular onchoeerciasis in such an area of vectcrr oontrol ls presented. in this :seport. I'IATtrRIAIS A$D ]'I TI{ODS A tota-1 of 5 vllIages situated. w:ithin the Onchocerciasls Control 1>1'ogramne area J,n the Vo1ta, ILlver Basin were exa.ninod. ophthalnologica.Lly Ln 1975 and L97Bt correspon&ing to a J-year period of yector control. [tre uillages lncluded. in the stuqy were, Itouvi6lo (ro'46t't, ,oo8li) at tlre Upper Sougor:riba, river ln Upper Volta. - Itinp6o (to'4rtl, 5"t2w) also at the Upper Sowpr:riba river. Pend:[6 (tt"o4lt, 4'41\r) at a tritnrtarry to the mack Volta in Upper Volta. GengBnloe (too4gtl, 2'501^I) at tlre 31aok Volta in Gha.na,. widnaba (tOo57tl, o"l4w) at the RecL Volta ln Ghana. flh.e vector conf,rrcl in the ar€a ooncezned. was measrujned. by means of regular catches of @ a.t catchlng polnts sitr:ated. cLose to tfte vi[agps em,lLined. in this str:dy. TLre results, presented, as Annual thans- mission Potentials, showed for the concerr:ed catohing points dr:ring the obseffiation poriod AIPS rcng:ing from 0 to 188 infective ira*ne/^ory'yea*" . fn this reporb these values are consiclered. as incLicators of a relevant vector contrrol, and. the complex interpretation of avai-Lab1e entcrmolo€J.oal clata is not further &iscussed.. A locaI oengus was carefuJ.ly prepared. ln each village to ensu.re a representative proportion of the population belng exa.ulned. .../ -r1 "from the Vector Control Unite O'rchocerciasis Control Programne in the Vo1b, River Sasin Ar€a. 2 The vlsual acudff was tested for each eye separately without glass co:Epec- tlonr usi.ng ar: illitexate ttEtr or iland.-test at ! meters. [tre ophtha"lmologtcal e:raraination took place j.n a dark room, witl: a slitfanp (Uaag-Shelt 90Or magrriflcatlon x15 and r€5) a.r:d ophthalmoscoplr lbfore the e:raroination of the anterior segnent of the eye, each pau.ent ha.d. his head. bent d.onn for a nialnum of I minute. TLie rumber of living microfilarlae in tho anterlor chanber $as then counted., always startlng with the right eye. Dead. an6 Li- wing mi.crofilariae in the cornea and onohocornea,l opaclti.es rnrere a-1so cowrted. [lhe pupils were then tilated with troplcamide Ud eye drops, if no oonka- lnd.ioation, and. direct or ind.:ireot ophthalmoscopy of the funclus wae oarsled out when posslble. In L9T5 one obse:srer oamied out all the ophtha.lmolog:iea.1 exami- r:a,tlons whereas during 1978 at the folIow-up trro more obse:srers were inyolved. in the evaluation. 4NESULTS the population e:ram-lned i.n each ui11a6e in 1975 and 1978 ls shoulx in Table 1. The re-attend.ance ratel ioo. patients e:ca,roined. on both occasions, ranged trcn 4715 to 16150,3 when caloulated, on the basis of the 1,)lJ seff'Tle. However, no co:rection for population movements or d.eaths has been mad.e. [he overall prevalence of ocular onchocerciasis, d.efined. as the pregoaco of ,microfllariae kn the anterior segnent of ttre eye, has not changed. significantly over the J-year period. even if there is a tend.ency for lower prevalences per village in 1978. However, the age-speciific pre- valence for ttre a€e-groups below 1! years showed. a d.ecrease because of non- infected. individuals being gradually included. in the saarple after 5 years of vector control. Table 2 shows the d.istributlon by age and. sex of the patients ttrat were exarolned ophthalmologically both in 1975 and, !978, [Lre composition of the erca,roined. population resembles closely a lceovn stand.ard. population from the a,rrea concervred. A1so, the preva-1ence and. d.istribution of severe ocular onchocercal lesions in the non-attend.ing and. attend.ing populations were sj.mi1ar, thus ind.icating tl:at there $ras no iiryortant bias in the exa- mined. population concerning intensity aied. gravity of infection. fabIe J shows the incid.ence and d.i.sappearance of signs of ocu-Iar onchocerciasis in the anterior seguient of the eye. The incidenco of visible microfilariae ana/or cozrreal opacities shows a slight d.ecrease by age above llte 15-29 year group, sj.nilar in both sexes. ilowever, these ocular signs d.i-sappeared. evenly in all ag:e groups and. with a slight female pred.ordnance. fn [able 4 the quantity of rnicrofilariae and. onchocorneal opacities in the anterior seggrent of the eye is shown. fhe rn:mber of livitlg nicrofilariae i.n the anterior ohamber of the eye sholrs no si8rrificant change betrueen the exaarinatLons in l%5 and. 1978e whereas the quantity of both d.ead. and. livi-ng nicrofilarj.ae and. their opacities ln the oornea ha^g d.ecneased. sj-gniflcantly over the 1-year period.. An arralysis of obserrer variation d.emonstrated. a clear d.ifference between t*ro obse:rrers corrcernir:g the nu.mber of mierofilarice in the anterior chanber, but no such inter-obsenrer variation was found. concern-ing the cozrrea"l signs. [he lrrcidence of severe ocu]ar onchocercal lesions and. blind.ness i.s shorrnl in Table 5. The j-ncj-d.ence of choroid.oretinal lesions d.ominates oompared. to other lesions, and. onchoceroal blindness shows a remarkably l-ow incid.ence wirich is confi.ne<l to +,'he 10-49 yea;rs age group. Table 6 shows the disf,ribution of imeversible eye lesions j.n the population e:ra,rnined.e and. tkrei-r tend.ency to d-eteriorate. fhere is a male d.onrtnance for severe ocuJ.ar 1esi.ons, especially for those deterloratinS. Choroid.oretinal lesions seem to be raore prone to d.eteriorate compared. to the otherg. DISCUSSIO}I [he tota.]. attend.ance rate in 1978 was 6tr595 as compared to the L975 sampler TLre re..attendanoe of pati.ents varied- congiderably in the dif- ferent vi11ages, but no systernatio j.nvestj.gations corrcezrr-ing the reasons for non-attend.ance ruas und.ertaken. However, it eee:1ed. that seasonal nS.gration in certain villages lras an important factor in t}:-ls context. A1so, t'he re- attend.ance rates are seemingly 1ow as population rnovements aad d.eatJrs were not corrected for. Attenrttng and. non-attend.ing populations were oonpared. concern-ing their d.istribution by a6e a,nd. sex as well as prevalence of severe e)re lesions. ITo blas regard.ing the re-a.ttend,fugrsample was found. using these pammeterse and lt is therefore assurued to be representative of the population ooncerned.. ftre overal.l- prevalenoe of ocular onchocerclasis varied. ln the 5 vi11ages lncIufled. in this study. fhe preiralence rates were slightly but consistently Lor,rer in 1!JB, with an avera€e difference of 2r6c,3. The d.ecrease is rnainly due to a considerably lower a€p-specific preva.lerrce of ocular onchoceroiasis in the ags-groups belcrw 1l years, because of more non-infected. ohildren in tkre sample as a result of ttie vector conf,rol. the incid.ence of ocular onchocerciasis in the populaticrn e:raoined. l7l5 and 1pl8 shous a slight d.ecrease by age after the 15-29 lra€rs a€p Sxeoup, and this was sin::ilar ln both sexes. The intensi.ty of infection ls of impor- tance ln this context, as the presence of nicrofilarlae in the eyes usually sigxrify a certain leveI of parasite 1oad. Tlrusl elderly patients have a higher 1eve1 of probabiliff to afueerady have established. a suffioiently in- tense infecf,ion ...r/ Ta:: inter:n:pted. or significantly reduced. b€.nsndssion will j.n thj.s context tend. to deIay the appearance of ocular signs of onchocerciasis or confino it to ind"ivicluals that trere lnfected, before the beginn-ing of the vcctor caa'rpaign. Th.e total incid.ence of ocular onohocerciasis in this study of or$J can be compared. to the hlgh incid.ence of ),9t,3 for onchocorrreal riacities alone, tl:at Anderson et a1. G) found. in a {-year foIIow-up of onahocerciasis in an area of ongning transnission. I:ne d.isappearance of visible microfilariae or corr:ea.l opacities from the anterior segment was found. in all age-groups and u-ith a slight female d.ominance. Agai.n, the intensity of infection is of importanoe and the vector control may possibly have g:iven a stable or in certain oases decreasing Le'"'el of jinfection. Obse:srer variation may be of i-nrportance concerr:i.ng the dia.6nosis of early or light ocular involvement in onohocer- ciasis. llowever, no slgrrificant obserrer variation rvas found concerni.ng cornea"l sigrrs in this study. r1:rthermore, the recluced quantiff of ni.crofi- lariae in the cornea found. in 197S supports or:r finding of an itanti-j.ncid.encetl of ooular signs. the incid.ence of j.:reversible eye lesj-ons cor*nor:Iy forrnd. ln onchocerciasis, i.G. sclerosir:g: tceratitis, antericr uveitis with sln:echlae, choroicloretlnltis and post-ner:ritj-c optic atrophy, shows a complex i:atter:r. Sclerosing keratitis was found. in only one patient, whereas ohoroj.d.oretinitis showed. a relatively high incid.ence and o?tic atrophy agaln was rare " 'Jhese find.ings are not in accord.ar:ce with the results of Ind.erson et a1. (f) wfro found. a sin'Li1ar lncid.ence of sclerosing keratitis and. choroid.oretinj.ti-s of 4fi13 respectively 4221J ovelr a rf-year period. One possi.ble erplanation for the finding in the present stu{y is that the reduced. treursrdssion of O. volvulus breaks off the build-up of orrchocersal infection and. ocular a a.l' and oorrlar lesl-ons that are assoclated hrlth htgh miorofjIarial loadg are then leos llJcely to appear. Sclerosing keratitis usually represents an Lntense infection wl.th high numbers of iriqfofilariae present ln the an- terior seglnent of the eyel whereas postericrr segment lesions a.xe mr:ch less comelated to tJre microfilarlal- Ioa.d. (1). Cnc,roid.oretj.nal lesions may there- fore ensue and. d.eteriorate even in less intense infections, and. tl:e lrrpor- tanoe of ro!,orofilmiae ln the anterior charnber as a risk slgn 1n tJtis context has been pointerL out Qr!r4). [kie nr:raber of lirning microfi-].ariae ln tJ:e antsrior cha.mber of the eye d.:ld. not change over the ,-year period. in ttris study. 3ut a h-ighIy significant decrease of the prevalence of such microfi- lariae has been reported. after a::. B-year period. of vector confuol (!). TLre slgrli.ficantly decreased quantiff of corneal microfilariae found. ln L97B 1n tJ:e trrresent study may well be in accord.a"::ce with tJre ve:ry 1ow j.ncld.ence of sclerosiqg kere.titls and. the relative stablIlty of that Lesion at the follow-up. tYre d.isff.bution patterre of i:reversible ocular lesions in the po- pulation exam:ined. ir: L975 end- l/lS shous an j.ncrease by age and. a male d.oni- nance, which .in accordamce rvith previous surrre1rso llor,revere the rate of d.ete- riorated. lesions is consid.erably higher in rnales, wh-ich may be due to their usually more lntense infection. TLre overall rate of deteriorated. lesions seems to be Low, but d.irect eomparisons with other stu.d-les ere complex as these lesions at a certaln stage tend. to be self-perpetuating regard.lesg of the intensity of ir:fection. Iloweverr lt should. be noted. that ,lnd.erson et a1 (f) in thoir 4-year follow-up found that sclerosing lceratitis was meet prorie to d.eteriorate, whereas in the present study choroid.oretin:ilis d.eteri.orated. to a hlgher extent thari the other lesionso Again, the d.ecreasirg n-icrofi- 1aria1 1oad. in the corrrea found. in th:is stildy j.s in accord.ance w:ith a ten- tend.cy for solerosing ke::atitis to remain stable. .n.,/ I 9ftre incid.ence of blindness due to onchocerciasis was liuited to one age-group in or:r sa,rple, and. there was a male d.oni.natrIce. [he overall rate seems to be 1ow, but the figures are too smal1 to a11ow a reliable sta- tistical analysis. However, it should be noted. that all the four patients going blind. in the present study showed. j-rreversible and severe eye lesions in 1975, whr-ioh is }<r:oun to signify an lmportant risk of blindness a,:oyhow €'4). The nurnber of microfilariae in the anterior segrnent of the eye has been shown to related. to the risk ofi d-eteriorating eye lesions and bllndness Gr_a) and. it may also be a useful indloator of the intensity of infection in tertns of severe ocuJ.e* lesj-ons G). tt=" analysis of the quantity of microfilaria.e in the anterior segrnent cf, the eye in the present stud.y showed. no significant change concerning the riumber of nr-icrofilariae in the charnber, but sig?Llficantly red.uced. numbers of microfilariae artd. onchocorneal- opacities in the coxneao Ttris may ind.icate that the aqueous humour is a more favourable nedium for the sr.usrival of nicrofilarias than the cornea.l stroma. Observer variation is an important factor to take j-nto consj-d.e- ration in a follow-up su.rvey. In the present study the sa.:ne ophthalmolog:ist carried. out all the era;ainatj-on in 1975, but trrro more observers participated. ln the 197E follo'w-up. It is therefore of utmost inportance to obtain an estimate of the correlation between the J observesg" llhere uas a good. inte.:- obse::rrer agreement concern-ing the m:mbers of living and. d.ead. mj-crofilariae in the cornea as well as onchocorneal opacities. Howeverr regard.ing the nu.mb':r of living mierofilariae in the anterior cha;irber of the eye, there were d.iffe- rences at the p- Orool 1eve1 of significance between two observers. But the variance of the mean values of each obserrrer was limited, ihus ind.icating that the number of microfi-lariae in t:e anterior cha.mber was in fact unchan- ged.. / 10 llre corned find.ir:gs are only related. to variance of id.entificatlon and. cor:rtting techrrigue, whereas the assessment of the quantity of micro- filarlae in the anterior rhaurber is J.ess accr:rate because of their mobility and. tend.ency to settLe in the chaa.rber ang1e. iiowever, it must be und.er1j.ned. that all ttrree obse:srers had consid.erably more experience in the special e:casdnation technique for n-iarofilariae in the anterior segnent dr.ring the fo11ow-rrp surrrey ln 1!lB which rather underllnes the sigrrificance of the decreased quantity of microfilariae in the cornea, for:nd. ln 1]/8. uCO}TCIUSIO}IS A folIow-up dr.rring l.97B of ocular onchocerciasis j:i ! villages situated. wlthi.n the onchoceroi.asis Control ProgEarnme area has d.emons- trated. the following effects of a J-),ear period. of vector contrroh - the overall preval_enoe. of ocular onchocerciasj.s has not cha4ged. striklngly, although the rates are consistently lower in 1fl8, especialiy for tpe age-groups below 1J years. - the total -lggidenc€ of ocular onchocerciasis in patients exa- nj.ned' both j-n L975 ond. 1978 was Br6i,i. Ilowever, there was also a disappearance of microfilarj.ae from the eyes ln a total of ll-fi15 of the ind.ividuals. 11he incid.ence of ocrrlar si.gns of the disease may be due to i.nfections esta- blished. before the begirurS.ng of the vector caapaign, arid. the nanti-lncid.encel due to d.ecreasing light infections as a resul-t of an inter:r:pted. transm:ission. - tho incid.ence of severe onchocercal eye lesions was consid.erably lor'rer than has been fowrd. i.n areas of ongoing transmi ssion. A1so1 the pattern of new severe e1'e leslons was d:lfferent with a particularly 1ow incidence of sclerosing lceratitis as compared. to choroid.oretinal lesions, - the tend.ency for eristi.ng severe eye lesions to deterj.orate was 1ow, especially in femaleg. - the overall inci_d.ence of blindness due to A11 patients golng bIind. had. severe eye man-ifestations are arryhow associated. with a high risk of blindness at tor control. onchooerciasis was OrJf5, already in 1975, w}::ich an early stage of vec- - the d-ecreased. intensity of ocular involvement due to orrohoce:nciasis was read.ily seen in a sign-lcantly reduced. microfilarial 1oad. in the corrrea. ,..]-rc, number of llrring microfilarlae in the a*terior chanrber was apparently u.ncha*ged. and. it was d-emonstrated. that observer variati.on nust be taken into consid.eration in th'is contert. ,..1/ L2 A0i0trOtrfIir'ncm'mIT !'Ie aclcroHrled€le the valuable parti.cipatlons in fieId. ovaluations by Dr A. RollantL and the etatistioa-l advice glven by I\tr T.F. d.e C. l,Iarshall. t1 1. 2. 4. I-?NFTRMICES And.erson, J. ET ALo Str:.d.ies on onchocerciasis j.n the United. Ca.rneroon Reoublic. III. A for.:r-yeax foIlow-up of 5 rain-forest arrd. 6 Sud.an- savanna viI1ages. Tra.nse rof,r Soc" f,rop. I,-ied. I{yg.; l9 162-171 (t976}. Bud.d.en, F.T{. The natr:raI }r-istory of ocufar onchocerciasis over a period. of 14-15 yeaxs and. the effect on this of a single course s1'suramin the- raly. Trarrs. r?oy. Soc. trop. lied.. IIyg.r 19, 454-491, (tgle). 1, lioberts, J,ii.I. l-II AL. Onchocerciasis-in l(enya 9, LA and. 18 years after clininaiion of the vector. 8u11. 1,,i:1d.. tsbnftf, Ote,'iJ, 195-2L2 (7967). Ro11and., A. },T AL. ,','volution sur ! ans d.e llonchocerecose oculaire dans une courmrnautd villageoise atAfrique 0""ia"rrta1e. 3ir11. irJ.Ld.. fieal-th 0rg.,b, (l), eol-ero (r97s). Thylefors, B. & Ro1land., lI. Situation dans un foyer d.tonchocercose du I{a1i aprbs treize ans cle contrdle anti-simu1id.ien. 2. ;Ispects oculaires ,krn. Soc. belge ]bd. trop., 5lL, 6t 577-5Bz (l.977), Thylefors, B. ii Brinkmarrnr U.K. The microfilarial Ioad in the anterior segrnent of the eye. A parameter of intensity of onchocerciasis' 8u11. ldlld. Health Org. 52, 71t-717 (J977), 6. t4 TalLe 1 Tkre population exa,mined. and preval"rr"u" of ocular onchocerciasis in 1775 and. 19TB per vi11age, The re-attend.ance rate is calculated. on the 1975 sa,srple without correctlon for cleaths or m-igration' -x-) Rates ad.justed. for age and. sex. t975 t97e Vil1a,ge &(a- Ccular mined. onchg- . cercaasr! Ilka- Ocular oncho- nl-neo cerciasis Re-attend.ance (i',i) I{ouvielo a56 6419'o IGmp6o 74 4tr4( Pend:[6 254 1or1i5 GenepnLrpd 2't2 4i rf,'o ilidnaba 1|1- 69rq'" Total = BBT 47ll5 151 60 rc)','r 69 firq( 187 Zer]:r| 142 17 rT5 1e9 55rE[ 718 45,jt)6 tzt (16r6lt) 54 0lra;!') t36 (>t,>y() 109 (+zrq;) ::26 (71r7"(') 546 ( 61,6i,j) tt5 Table 2 ?he d-istribution by age and sex of the sa'nF1e exa.mlned. both ln 1975 and 1978. :1i I'l:camined. o/ 75 92 14 5-].4 t519 10-49 J 50' (24,093) I q f (z5,cnJ) (26,1;(,) | t> lQa,o;[)(zg,tl I g, l3+,nt) (r9,oi5) | t,+ f(rz,p;) 27e (>o rn;) 268 (49 r:10,6) 546 69 71 81 55 Age I'Iales Ieinales Ehcaroined. (?3) (:;1 Total t6 Table 3 - Incid.ence and. d.j.sappear€rnce of vj.sible microfilariae -landrror onchoclgneal oltacj-ties in the anterior segnent of the eye. Age Inoi.dlence .{tnti-incid.ence I,taIes Females j'ia1es Females 5 -t4 ]q - 2q 10-49 + 50 Totala 6 (8,7t3) 10 (1r,7i5) 6 (t r+l;) I (>,s13) 25 0,q3) 7 2 22 (T r5o,51 (rc, p5) 0,e10 $ 'ss)(erzgi) B (il,6i6) 9 (l:zr1o,'o) 4 $,q5) 9 (t4?6i:) 2g (tor4i'o) s 0,>;:') rz (rergJ) t2 (t1r0l)(,) > (t+rT'") i4 (t2,7i3) +7 @,61(') ?, TABTE 4 PU}TCT,1.TE liio 0I llytrs uiici{1'{'TGItx 6>g 521 758 A\TM.AGE 6q 3,19 -26 1q? 82 rcl- TitrI (:U,,[ITITY OF i 0fiCH0CftCAL 1ICITIlIS II,I MM jtrU:C DItr'C IJ.MC 0P0 !.!2 (0.06 - t.4j) 5.82 (5.eT -11.80) ?-.zz (t.11 - 5"15) 1.78 - 6.60 P --l llTD Ifli\GE 200w ,J^ 1B Table 5d +aftre i-ncid.enoe of i:reversible ocular lesions and. blindness by age arid. sex. -:r d.efi.ned. as vi-sual acuity less than t/zo tettex el/e without cor"rection" Blindness Solerosi keratitis M06) F Choroid.o- retinitis r,1 (rii) 0ptic alrophy 1(115 - r (r,+) - | t3,7) r(r,r) z(t,til)- I r(r,ri;)r(0,+li) o,6t5 I orrS r(rrz) - r(0,49J)- o '2)! r(1rl) z(2 rl) 40,5) 6(7 ,5) l(arl) z(gr:--) s(+,r95) :-o(5,795) 5 )95 t5--29 10-49 50+ Totalt

Основные сведения
Тип документа Technical Documents
Дата принятия
Источник Всемирная организация здравоохранения