Applied modelling: progress report and proposals for further research

WORLD HEALTH ORGANIZATION ORGANISATION,V\OND|ALE DE LA. SANTE OiTCI]OCENCI/TSIS COIfIEOL PROGRAI'O@ I}i TI]B VOLTA RIVER BASIN AREA ocB/srrrr/PRl35 .2 AP?LIED I4ODELLI}TG PROGRESS REPORT A}ID PROPCSALS I'OR FUPJ}IEP, PJSEAPCFI 1. Backqrounl In the past epidemionetric models have been of little use to Onchoccrci-asis ConErot Progranune (OCe1, oartly because rnodelling tended to be rathcr acaCeni-c ryhile Ehere has been virtuaLly no contact between the rirodelars and Ehe CCi' staff involved in Efue realities of vcctor ccntrol and epiCerniological field rescarch. Honever during the year L9S3|J984 OCP enbarked also on Eha developraent of a model following some practical questions concerning the analysis and interprc - tation of the epideniological evaluation data. It r.ras realised that the epidemiological indices used were not sensitive enou3h todescribe the actual epidenriological trenis afcer vector control because they failed fo take into account irnportant factors such as superinfecEion, prod.uctive lifespan of tj,e adult $rorm, prepatenE period and age-specifie exposure. Afurce cf infection moclel was developed to predict the pre and post eontrol age-specific tren:ls after taking these factors into account, The results ir"re tested against the observed data and the general trends were in good agreencnt raith the predicticns. As a result tl-re force of infection rnodel has leil to a better understanding of the age specific trends 3nd nr-rst iroportantly to the develop- ment of appropriate and sensitive statistics for the analysis. Having serveC its purpose, the nno,1el was not further used, but the new statistics are now the basis of the routine analysls of thc epider:riological evaluation data and Ehe philosophy behind the model is used in Ehe interpretation of the results. A detailed {escription of tho force of infection model and the resulEing statistical pethodology waa presented at the fifth rneeting cf the Experr Advisory Corimiitee (EAC). It r,r.?s stresseC that the ain of the model develcl- ment had been the general reorientation of the analysis .:nd that ths force of infection model r.ras conf ine,l ro the main host aspects of onchoccrciasis and was Eherefore not a full transnission :nodel nor a complete nodel for the host. Further Cevclornnent of applietl nodelliug was planned and contacts ha'l been nade with sorae exDerts in this fiel,1" Ii{ -2- The EAC expressed consiJerable interest in the progress made so far an4 supoorted efforts for the rapid development of complete epidemiological rnodels which shoulj include all aspects of transmission of O. volvulus and the d1'narnics and bionomics of its vectors. After field testing of these models they should be used in future plannine and to determine che possible effect of different intervention strategies. ?-, Applied rnodelling and data analysis A priority in data analysis is the integrated analysis of the evaluation data for the comprehensive assessment of the impact of vector control on disease transmission and of the epidemiological changes following control. Sevaral different types of data have been collecEed since the start of OCP, i.e. parasi'- tological, ophthalmological, nodutectomy and various entomological data. Different approaches can be used in the integrated analysis of atl these data. One option, which is presently used, is to analyse each data set separa- tely, to compare the results anC to draw general conclusions based on the total of the different.findings. The disadvantag,e of this approach is that it does not allow a full quantitative assessment of the consistency between the Cifferent data .anr] that the conclusions and hygotheses tend to be more of a qualitative than a quantitative nature. A good examole of this oisad-.rantaBe r^ras already encountered during the integrated analysis of the epideniological data. In the central OCP area where the conrmunity microfilarial load has decreased by more than 702 after 8 years of control, the oercentage of dea{ worms fcund in nodulectomies was about 352" compared to 102 in a non-controlled area, while the productivity of the livin:z female wortrs r,ras only marginally reduced. The ouantitative consistency beEween those findings is not clear and the only conclusion dratim so far is that the percentage of dead worns was satisfactory (i.e. around 3-52) in all villages surveyed in the central area. Eurther:more it has been hypothesized thaE the relatively slow increase in the percentage of dead worrls is due to the fact that the nodulectony data are cross-sectional and noE longitudinal data, and that a large nurnber of worms dissolve after death and cannot be traced anymore afEer a number of years of control. -1- hs illustrated above it is not comrrletely sati.sfactory to just an1I)'.se the different data sets independently and formulate raEher vague hypotheses r^*.ich may explain certain observed differences. It raould be much more convincing if comgasite hypothescs on the underlying nhencrnena are fornulaicd., if attempts are maJe to ouantify these hyootheses and if these are teste3 against.sll the relevent data EoEether. In other tsoEds, it rvould be better to develop models and to use them in the integrated analysis. It is this aperoach to modelling whieh we c.a1.1 appli-ed modelling in th,: rrresent reoort. Modellinl in this sense is a necessary tool for the integrated anatysis and can even serve as a guide for the more classical analysi-s of seoarate data sets, like the force of infection nodel vras useful in the develorrnent of the- statistical indices for the aarasitological and ophthalnologicaL data. SuL'se-= quent further analysis can then result in nore refined hypotheses and in improved mo<lels for a<ldi-tional analyses" To our Doint of vier^,, applied. urcdetling is a requirement for the analysis, and models should be developed and improved in close associat:Lon with every new ohase of Cata analysis. The advantage of this stenwise approach is that applied modelling will imredi.ately serve as an analytic tool, rnd that ruith further analysis and testing the rnodels rril1 become mnre an,l more valid for other epplicaticns such as nredicticns and testing of the pcssibl+ effect of alternative interventien straEeqies. The diss..lvanta?e cf this aoproach is fhat nodel develrpment will not be as rapid as reccr-rrrlendod by the EAC. 3. Prenaratory neetin=qs on further nodel developnent Turo preoaratory meeEi-ngs on frrrEher model development '..rere held vrith the particioation of biorqathematicians and biostatisticians of the universities of Ttibingen and P-otterd,un, who are all axperienced in mo,Jelling anrl its aoolication to disease control proqranmes. The first neetinz was held in fiibineen in June 1984, and this meeting i'as also attended by several entorleloqists and aarasitologists fron the universi-ty of Tiibingen. It was stressed that if nodels are to be of practical value to OCP,. it vrill be necessary that these rnodels are based on the latest findings and that they shoutd be sufficiently flexible to assist in data analysis and future planning. -h The dyra:r,i,cs of onchocerciasis vrerc revi-cwecl anJ it wes an,reed that a conD'l:Ee but flexthle transmission nodel r.,ou1"1 be very conplicatecl and that it woul-i' t'e ncre realistic to contin'-16 sls:^pi-se rrrith the develoDnerlt of sub--rnodels., '+hi'cl: can t,e uscd an,l Eeste{ i,r tho tnal)rsis., anC to inEegrate these sub-:lodels onlv r'.t a later st36e inEo a ful-l trans::i-ssioh nodel . It was Droposed to lrocee' in three main :ha.ses: -e) ievelor:nent of r- host-n.-rrasite life iristory node1. Ti:is nodel coulrl trs.: the results of the f irst analysi-s of the epi-,1e-r:ni-ol ogi.eaL lata. b) ievelopnent of a vector-parasite lifc history norJel,. This rodel r'rcul:i be needed durinq the iietailed a.nalysj-s of tha- entonclogical 4tEa. c) i;eveloment of a full transmission rnode-l conbining (a), (b) an'1 .ar, extension for host-vector contacr- factors " IE rr,as also agreeJ tha.t these nodels should be develoletr i-n close collaborati-on r.rith the OCP staf,f of the lifterent uni-ts to ensure thp't the rroqielsra'oUl1}lereatistj.cancofnracticalvalue.rorthi.sr:asoiit'gas proPose<l to orqanize a meeting on noCellinp in t'raqaCouSou' wi-th the rartici- paEio;:, of staff fron the Eaiderri-clocical Evaluatton llnit (E?I) -en.: rhe Vectc: conrrol unir (VCiJ) . In the naanti:rlei ,levelonm.ent of sub-trodel (p-) shoulrl heg,in, p'?-rt1-'/ because this sub-model i-s already neede,l in the analysis ap,d nartly Lecause it woul'J benefit the meetinq i-n ftraeadouqou if same concrete exale',le of the use of reodelling in 3CP could bc demonstrated. Eolloyinq the anoroval of these prooosals by the Tlro-ralrL-le lirector, a seconrl neeEinq',ras hclC in'-ottar4-ar: in l"er-'t::nber 1??,,'+ t-o discuss the levelo:- ment cf the host..r-,a.rasite life history ro4.:1 . Thi-s meetini vras also attendel by an f?I staff ne-rqber: rrho a.l.rise<i on the oarasi-tological aspects. ?lie nai-n structure of the no.{el uas deciCeC uoou and a TSA r"ras establised tri-th tlie cotleagues of l.oEterd,am, r;ho further rlerrelored and nro"ramned the nodel" The first nnodel ,nras conDlete-,{ in -Eabruary 19.35 aa:l i-s now inolenentad on the nicro coursuters of OCP in CuagadouZou. q6" The host-tara-site Ii fe hi-stery model The hosE--parasi-te life history nociel i-s a micro sinulation no,iel rrhicl: sinulates the in;livi<lual life tiistories of all inhebitants of a villaie ,ropulation in a 26n9 r.lith enil.erric onchocerciesis during a neriod l-'efore 'ail1 after vector control lcr each rerson the model sir'rulates each infection and the tife history of the resulting a-lult ferna-le tTor'ro ir.cluding the period r,'hcn the wonn hes.lied buE not dissolved. For e:ch aCult female v:orm the':ro-lucti-' vity of microfil-aria-e is sirrulaie.l as well as their con.tribrrtion to thc- r:ic::o' filarial density in the skin and irr Lhe anterior cha:lber of the eye c,f the l:osi" The noiel has been designed in such a way that it enables the si-nuletion of actual indicator villaqe-s in CCI', rrhich are regularly examincd by "'he epideniological evalrration tearns. Once the age and- sex distribution for the villaqe h,as becn specified for the basetine stlrveye the model r+il1 further sinulate Ehe village population using birth and de.lth rates which a:e a"'1icable fcr ilost Africa. The proffra$ne calculates fcr the sirnulateC i:opuLaEi-ot the sarce statistics on i-nfection and on the.aCult lrorn ponulation as are used i-n the analysis of the epilernioiogical rlata an4 produces thesa results for exactl'/ Ehe sarne.iates at rrhich actual eri-iemiologi-cel surveys r^rere don.e in the villa'3e' thus enablinE a co.lnlete comnarison bet,rreen the observed and, simulated results' In ad.{igion the Eroqr?.-rre oroJ.uces the statistics al so for lo:le specifiei future riates. T,,:e si:r,-tlated rcsults depend on the various Dar.Tleters in the no'lel for which ostirnatas ha're to be nrovi.deC before each si'lulation. 3ne of the ::ost ir1rortant p4rameters is the average foree, of i':fection for adults durinq the pre-control perioC, which rieternines the enrlenicity level- and which is uresently estinaterl in,lirectly using the baseline cor'munity nicrof ilarial load (3'"1FL). The actual risl.- of irrflction for an i-nCividual depends on his a3e, the sui:' populaCion to which he belongs (e.g" nales, females, fishermen eEc') anl or a r)arameter fcr variation i-n in,ii-vi.1.ral ri-sk within a subpooulation trhich rr:flects iro.runological or exnosure Cifferences betwaen indi-viduals. Other para'neters 1r? those which deterrnine the random distributions for the lon3evity of fenale worns, their pro,luctivity in relaticn t,o worTl age, the s'rread of rnicrofilariae to the region of the skin snip and the anterior chamber of the eye, calcification of th'e female worm and the perioC between -1eath ant dissolvement of calcified and for non''c'rlcif ied u'orrns . -5- The simulation ^Drogramre has been ,,rritten in FoF-TR'AN and has been clevelopeC on an IBI','-PC. Special attention has been Siven to optimisation in the rrro?ramring, which rirds D€cessary because of thc cornbination of hee"vy:rroc's-' sing and the use of the arogralnne on a nicro connuter' As a result of this optimisation the si;r.ulation cf an averaqe villaqe pooulation over a nerio'i of /r0 years takes less than 10 iainutes' The ''lror,,raqnce ,aiLl !o'- activety used in' the inteErated analysis of, the eoidem:i.clogical clata. The most innortant anplicatj'ons for the near future are: a) The furthe;r anal;'sis of the norlulectomy data r'''i-th err'chasis on the prcportionsoftleadr,rornns.Testingcfvaricustrypothcsesonlongevity and calcification' b)TheEestingoftheconsist.,l:ncybetweenthel:resenthypothesesand- the observe'. c:.i:lernio1o3ica1 trenCs, and Ehe proie-ction of epidenioi:' gical trends after 10 years of vector control' c)Sensitivityanalysisofthcnostiilport'antDaran2tersincr,ierto determi-ne which range of estirtates and vrhich alternative hyrr:t-heses are conpatible r;ith the observei results ' The sirrulation ?rof,risme is presently being used in the integtatei' analysis of tire epirleniological date and the rcsults of a first test of the no{'el r'rere ruite satisfactory. Prelininary results of the analysis r'rill be preseaLed to the EAC in June. 5. OC,: rrneeLin3 on aoplied :rcdelling anC proposals for further research The propose,l 'neetin3 on aoolied r'.ocelling in ccP r'ras held in ouaga;lou8ou froa 25-28.liarch 1935. Darticioants r'.,ere oCP staff fro",r VGIJ, EPI ap'd STAT anJ the bionathenaticj-ans/biostatistician's fron the universities of P-otterdan an<1 Ttibingen. After a revicvr oc previous ruork on nodelling for onchocerciasis' the host-'parasite nodel rras introduce'l and an example of its use in the integrate-{' analysis of the enideniolo3lical clata r'ras demrrnstrate'i' The model vr'as further discussed and the rneeting a?reed that the n]oCel shoul4 b'e adopred and extensi"- vely used in the analysis of the epilerniological data' Some extensions of the morlel- t^rere a1s<: prog'osed, such ac the inclusion cf blinCness in the Preseot moCcl-' -7- The meeting sunporte,f the proaosal for a steprvise approach to further mocel deveroomenE in close association with data analysis" 1liven the '-;ro3ress r.rith the host-narasite model anC the fact that the detailed an'alvsis of the entomoteqical <iats ruill soon take off, it ',ras agreed that it woull be timely to start r,rorking on the second phase, i.e. the rlevelopiaent of a vector'-oa;:":site model " the meetinq discusseC in consi.'Jerable detail the various factors whicr'r should be taken into account in rhe analysis of Ehe entomological data and jn the ,rector..parasite rno,lel" This discussion included a reviers of the avai'labl-e knor^rledge an.l requirencents f or future f ield research on solln'e of the key f actors ' A first outline of the ve.ctor-parasite mcdel "ras develooed durinS the discussions anri rvas endorsed bY the meeting. Consideratrle attention was atso given to host-'vector contact and its imporEance both for transmi.ssion and for variation in the epicemiolo."ical ^attern' It,.ras agreed that a r:rioritT in the inEegrated analysid shoul'l be the analllsis of the relation between pre-control ATPs and epiderniological ind'ices for speciaLly selected co:nbinations of villages and caEching Ooints' Iiowever it was reaiised thaL the a,railable data are lj.nite,r and that Eh"y contain no informatj.on on c,.ifferential exfrosure. Some special joint EPI-VCU stu:lies !'ere ProPose'i for the western extension zone in orcer to iinprove our knou,lecae of the epidemiolo - gical significance of (1or,r) Eransnission potentials' Several other :"rotosals for relevant field ::esearcir were also made and forwarded to the OCP researcr' meeEinfl. Finally, the meetin,'; ,Ji-scusse,1 the possible risk of trensmission and recru-- descence of the disease in a Cisequilibriun situati-on such as after interruntion of vectcr control as foreseen in the Long Te:rn Strateg;r anC the re-infestation of a previ-ously endemic area by S. darnnosun. Accordine to scrne classical rnatlter'ra-' tical models,recrurlescence is virtual ly certain gi'ven the expected immiSration of infected individuals frorn outsije the OCP aree-. The problerr with those raathematical nodels is, however, that they a're time'-inci'ei'endent and ttrerefore irrelevant for the oractical rtuestions faciag oCP. It vras agree'J that an inporEant future app,lication of apnlied no<lel1ine ""ould be the study of the ti:ne-dynamics of possible recruJescence of onchocerciasis and subsequently to assist in the development of an apTrropriate surveillance and intervenEion systen for thc Particinatino countries 4uring the oost OcP oeriod. --B The neeting was concluded by an enthousiastic statement of sunport for the continued use and develocncnt of alplied rnodelling for data anallrsi.s and planning in OCP. The neeting felt strongly that modetling in the sense a.nri spirit of the neetinq should definitely be classified as applied research anC shoul<i have hJ-gh pri-cfity. Furthernore the particinants stressed. that the raeeting had beea an excellent opportunity to di.scuss jointly the ongoin.q an,i planned analysis of the epide:'.iologi.cal ancl entomological data anC the re<iuire* nents for joint research. Such neetings should be organised on a routine i:asi-s. Meetings on rqodelling vrith the participation of the external advisors shoul'l continue and be held',rhenever sorTre najor rrrcgress in rrodel developnent woulC. u/arrant further jci-nt discussions. The follouring specific recoqrnendations were maCe for further research on apnlied rqodellinq; a) The collaborative project tliat started with the host''rarasite model should continue as follows " - The host"'oarasite '-qodel should be arrnlied in the analysis with as priori-tir the f'rrther anal.r'sis cf the nodulecton], data. Furtirerrno::e the mcdel should be extende4 r.rith the inclusion of blinCness and inating of aiult Trorns" ..Ihen the onqoing analysis of eye lesions has sufficiently nro;;ressed, a seDarate ;xoCule for eye pathology shoul'1 be adcied to the rnodel" * A vector.'.oarasite ncdel shoutd be developed along the lines discussed 'Juring tire neeting" This moilel shoulC be extensively applied in the analysis of the entomological data and apcropriate modifications should be -ade whenevk')r necessary. - "ollor,ri-ng the experience r^'ith the host-parastte aild the vcctcr-r',arasite sub*nodels in the analysis, a full transmission ;nodel shoulC be develoned which will be nartl)' baseJ on these tr'ro sub-lao'Le1s' After thorough testing of the transnrission rnodel it shoulC be userl in the integrated analysis of the dat-e from the pro-forest zone and in :he development of an aDDropriate and lractical surveillance and inLcrven- ti-on system for the Farticinating Countries durinT the post L\CP pe:iod. -9 b) An existing model for schistosomiasis could be aCapted Eo onchocerciasis and used far a prelim:l,nary study of the nossible recrudesconce of thc disease during the post OCP perioC. Since this model will not be usci and tested in the analysis, its validity r^'i11 he limited. I{o'treverr glvert the iact that preoaration for devolution has already started, Eherc is a need for some firsE aoproximations cn the time-'dynar:rics of possibl-t recrudescesce. Since this ',:ork could be concleted in a retatively short period, tire neeti-irG suprrorted this nroposal on condition that thje coltaboratior. r"rouIC follow the ncrmal OCP Dr:iceCures for colLaboraEi're research. It was agreed to submit the prcposals on furEher modellinq Eo thii HAC JurinS its next neeting in June 19E5, If the EAC apprcves the proposals>. arr.1n'- gemerris should be rrade to continuc the project as soon as possible.