OCP epidemiological evaluation proposal from an expert group: revision 1

Onchocerciasis Control Programme in West Africa Programme de Lutte contre I'Onchocercose en Afrique de I'Ouest rolNr PfRoGRAil%l"r.,lYyIrrEE Jpc - ccp coMrrE coNJorNr DU pRocRAMMEBureau du Pr6sident JOINT PROGRAMME COMMITTEE Fourteenth session Luxembours. 7-10 December 1993 JPCl4.l0(ocP/EACl4.l0) ORIGINAL : ENGLISH September 1993 Provisional aeenda item 5 OCP EPIDEMIOLOGICAL EVALUATION PROPOSAL FROM AN EXPERT GROUP Revision I EXECUTIVE SUMMARY At the recommendation of the l3th session of the Joint Programme Committee (JpC) anExogrt group set up by the OCP Director in consultation with the Chairman of the Expert Advisory Committee to reflect on all aspects of epidemiological evaluation in the OCp reviewed: - The aims of OCP as the elimination of onchocerciasis as a public health problem in the Programme area and the maintenance of this achievement, and - The various control strategies - large-scale ivermectin treatment, vector control with or without ivermectin treatment and detection of and control of possible recrudescence of infection and disease in the programme. The group determined the objectives and methods for epidemiological evaluation in the OCP as follows: l. Obiectives a) To evaluate the impact of ivermectin treatment with or without vector control on onchocercal ocular disease. b) Evaluation of transmission and/or parasite control ie. i) to evaluate the effectiveness of control in interrupting transmission and ii) to evaluate the decline in the parasite reservoir and to determine when it is sufficiently low to allow the cessation of vector control. c) To detect at an early stage, renewed local transmission and the subsequent increase in theinfection in areas where transmission control has stopped. d) To monitor short, medium, and long-term effects of ivermectin treatment. e) To evaluate the cost/effectiveness of the different modes of ivermectin distribution. f) To evaluate the accessibility and acceptance of ivermectine trearment in the different member states. JPCl4.l0(ocP/EAcl4.l0) Page 2 g) To detect the possible development of ivermectin resistance in areas where large-scale chemotherapy is undertaken. 2. Methods The various methods for epidemiological evaluation, their appropriateness and applicability for the OCP situations and their disadvantages were summarized as follows: a) Clinicat examination. Ophthalmological examination is the most important clinical examination carried out at OCP and is the recommended method for evaluating the impact of ivermectin treatment, vector control, or both on onchocercal ocular disease. The method is expensive and requires highly skilled personnel. b) parasitologr. This method in the form of skin snips to determine prevalence rates. and trends, incidence ind intensity of infection is at the moment the method of choice to assess the impact of vector control on transmission. For areas of combined ivermectin and vector control' incidence of infection in non-ivermectin treated individuals could be used to assess the impact of this combination on transmission. Similarly in areas where ivermectin treatment is the only means of control, parasitological examination should be used to detect incidence of infection in a cohort of children. The limitations of this method of diagnosis are the lack of adequate sensitivity in very light infections and possible patient resistance to the procedure. c) Serodiagnosis. In the absence of a more sensitive and specific method of diagnosis the parasitological method of diagnosis is to be used in the detection of possible recrudescence of infection in the now oncho-freed areas. The preferred tool for diagnosis would be a serological test (now at the operational testing stage) able to detect pre-patent and early infections' d) polymerase chain Reaction (PCR). The decline in the parasite reservoir would depend on the status of the adult worm. The assessment of this status could be done through the detection of parasite products such as antigen or DNA. The novel PCR method for such a detection would be the method of choice when and if it is fully developed. e) Entomotogical approach. The possibility of using simple entomological techniques to calculate the rates of inf.itiuity in caught flies, to complement the epidemiological evaluations with a view to the early detectiln of poisible recrudescence of infection needs to be considered' The following would have to be determined beforehand a) the correlation between presence of parasites in flies and human infection in an area and b)the level of infection in flies at which a particular action needs to be undertaken. I. TNTRODUCTION Following the recommendation of the JPC at their last meeting in Geneva, E-ll December 1992, that an expert group be set up by the Programme Director in consultation with the chairman of the iip.i, ed-visoiy committei to examine epidemiological evaluation in the OCp, the Director appointed such an expert group to consider this issue with the following terms of reference: to reft-elt on all aspects of epid-emiological evaluation, and make recommendations as regards the OCP concept and strategy in the field. This report sets out the conclusions of the meeting of the expert group which took place on March 25,1993 at the OCP headquarters in Ouagadougou' 2. OBJECTIVES OF CONTROL The group examined the purpose for the Onchocerciasis Programme and underlined the main objective of the Programme as two-fold: JPCl4.l0(ocP/EAcl4.l0) Page 3 a) the elimination of onchocerciasis as a public health problem in the I I Participating Countries b) the maintenance of this achievement 3. CONTROL STRATEGIES For the purpose of achieving the above objectives, the group observed that the OCP has drawn up three control strategies each aimed either individually or in combination at achieving a specific objective as indicated below. 3.1. Large-scaleivermectintreatment The primary aim of the large-scale ivermectin treatment is to control onchocercal morbidity. This control strategy was adopted by the Programme after the successful field triats of ivermectin in 1987. At present it is the only control strategy used directly against the morbidity, in particular ocular disease, in the OCP area. The large-scale treatment is undertaken in specified areas either alone or in combination with larviciding. This strategy is an OCp responsibility even though the actual distribution of the drug is carried out by national onchocerciasis teams with OCP support. 3.2. Vector control, with or without ivermectin treatment The vector control strategy , with or without ivermectin distribution is to interrupt transmission for a long enough period to achieve the virtual elimination of the parasite reservoir. Vector control is used singly to achieve the above in the remaining river basins still under larviciding in the original OCP area. A combination of vector control and ivermectin distribution for the above objective is carried out in the southern part of the western extension, southern extension, some parts of the original OCP area and in the intermediate zone in Cote d'Ivoire. This control strategy is considered as an entirely OCP responsibility. 3.3. Detection and control of possible recrudescence of infection and diseesc This control strategy is aimed mainly at the detection of any possible recrudescence of the infection and disease, and is possible control through large-scale ivermectin treatment. This strategy is adopted, or will be adopted, in areas that have been cleared of the initial infection with almost near zero prevalence of infection. The responsible actors are the participating governments with or without technical support from the OCP. 4. OBJECTIVES OF THE EPIDEMIOLOGTCAL EVALUATION The meeting discussed the important need for the evaluation of these control strategies and agreed that for epidemiological evaluation of the impact of these control strategies, the objectives should be as set out below: 4.1. To evaluate the impact of ivermectin treatment with or without vector control on ocuhr disease. The group identified two areas where this type of evaluation would be carried out. These were: the areas where there is ivermectin treatment only, identified as the river basins to the north of the Tinkisso river in Guinea, west of Mali, Senegal and Guinea-Bissau. a) JPCl4.l0(ocP/EACr4.l0) Page 4 b) areas where both ivermectin distribution and larviciding are undertaken. These are the western extension, specifically in Sierra Leone and the area south of the Tinkisso river in Guinea, the intermediate zone in COte d'Ivoire, the previously re-invaded zones in the west and east of the original OCP area, the southern extension and in certain specified areas in the original Programme area- Evaluation of transmission/parasite control4.2 With respect to the evaluation of transmission and/or parasite control, further sub- objectives of epidemiological evaluation were identified. These were: 4.2.1. To evaluate the effectiveness of vector control in interrupting transmission. This evaluation would be carried out in the areas where only vector control is undertaken as in certain parts of the original OCP area. 4.2.2. To evaluate the effectiveness of combined vector control and ivermectin distribution in interrupting transmission. As indicated above, the areas concerned would be in the specified areas in the western extension, the intermediate zone, the southern extension and the original OCP area. 4.2.3. To evaluate the decline in the parasite reservoir and to determine when it is sufficiently low to allow the cessation of vector control. The group recognized that this domain of evaluation pertains specifically to vector control and, in the first instance, refers to the vector control activities in tne orijinal OCP area. In the extension areas where both ivermectin distribution and larviciding are undertaken the situation becomes rather complex. 4.3. In areas where transmission control has been stopped, to detect at an early stage renewed local transmission, and the subsequent increase in the infection The evaluation in this respect witl be focused in areas of virtually zero prevalence, and/or zero incidence of infection at the time of its being instituted. This will be in areas of full devolution, such as Burkina Faso and Niger, and thl oncho-freed areas of the other original participating Countries. This objective of epidemiological evaluation will become more and more important as more areas become devolved. 4.4. In areas where large-scalc chemotherapy is underteken, to detect the possible development of ivermectin resistance In view of the fact that ivermectin is and will be very widely used, the group considered the possibility of the development of parasite resistance to the drug with time. In this respect the group considered the evaluation of such a phenomenon zN an important objectivc of epidemiological evaluation in the OCP area. 5. RECOMMENDED METHODS FOR EPIDEMIOLOGICAL EVALUATION IN THE OCP In recommending the appropriate method for epidemiological evaluation in the OCP the group reviewed the variois toots ior diagnosis in respect of what is currently available, potential 6n., "t the point of operational testing, a-nd others yei to be developed. The performance of these tools, their applicabiiity to rhe various objectives of the epidemiological evaluation in the OCP and their limitations were also considered. Th. grorp set forth the following recommendations: 5.1. Impact of large-scale ivermectin treatment on onchocercal ocular disease With respect to the evaluation of the impact of ivermectin treatment with or without vector control on onchocercal ocular disease it was recommended that ophthalmological examinations be the prescribed method of evaluation. Such ophthalmological evaluations would JPCl4.l0(ocP/EAcr4.l0) page 5 preferably be carried out at less intervals than have been done previously. In addition the group recommended that photographic recording of findings be included in these ophthalmological evaluations in view of the problem of inter and intra-observer variations in ophthalmological findings. 5.2. Vector control to interrupt transmission The group recommended that, in the absence of other more specific tools of diagnosis at the moment, parasitological diagnosis in the form of the skin snip method continue to be usedto assess the impact of vector control on transmission of the disease in the areas where only larviciding is used as the method of control. In this respect the trends in the decline of prevalence and where possible the measure of incidence in the younger age group should be of more importance than a single prevalence value. The limitations of this method of diagnosis in its lack of adequate sensitivity in very light infections are recognized. Where both larviciding and ivermectin distribution are undertaken the group recommended the use of parasitology as the means of diagnosis but only as far as the measure of incidence is used. The measurement of incidence of infection in a cohort of children in areas where only ivermectin treatment is undertaken was also recommended. This, however, would be useful only after many years, at least 5 years, of ivermectin distribution in the areas concerned. When the serological test becomes operational and proven to be specific enough, this may also be used in such areas. 5.3. Impect of vector control on the decline of peresite reservoir Whereas it would be useful to know the decline and levels of parasite reservoir to determine when this is sufficiently low to allow cessation of vector control, the group recognized that none of the present tools of diagnosis has this capability of detection. The group, however, showed a keen interest in the possible development of the Polymerase chein reection (PCR),DNA method for the detection of parasite products, such as antigens, a method which could help determine level of parasite reservoir. 5.4. Dctcction of early stagc of lnfectton (recrudescence) 5.4.1. In areas where the objective of evaluation is to detect at an early stage renewed local transmission and the subsequent increase in the infection, the ideal method of diagnosis would be thc serologicel test when it becomes operational. In the meantime the skin-snip (persitologicet) tcst would be recommended bearing in mind its limitations in very light and early infections. 5.4.2. There are some entomological techniques which could complement the epidemiological tests with a view to the early detection of a possible recrudescence of onchocerciasis, for example: Collection of flies by trained villagers. A technician will identify the parasites in the head of the parous flies. ii) Mass identification of the parasite using DNA-probe technique For more details on this point see document JPCl4.9. 5.5. Monitoring of effects of ivermectin In as much as at present there are only minimal side effects with the use of ivermectin, the group nonetheless recommended that the present method of monitoring for any possible serious short, medium and long-term effects of ivermectin be continued. i) JPCl4.l0(ocP/EAcl4.l0) Page 6 5.6. Cost effectiveness of different modes of ivermectin distribution. The group recognized that, at present, the main mode of distribution of ivermectin is through the laige-scale riethod. There is however the emergence of other modes of ivermectin distribution, as for example, the community self-treatment. It was recommended that the cost/ effectiveness of these various delivery systems be evaluated. 5.7. Accessibility and acceptance of ivermectin. Due to different conditions in the Participating Countries, the group recommended that the accessibility and acceptance of ivermectin and different modes of distribution in these countries be evaluated. 5.8. Detection of parasite resistance to ivermectin For the detection of parasite resistance to ivermectin the group recommended the use of the skin snip method to determine changes in the skin microfilarial load after drug therapy, as an in vivo method for the detection of drug resistance. The attached table sets out the summary of the main conclusions of the group. PARTICIPANTS Dr. L. Osei - Consultant in EPI Unit ( Chairman) Dr. A Seketeli Dr. D. Quillevere Dr. \Y. Soumbey - Rapporteur Dr. B.A. Boatin - RaPPorteur Co-ooted members Dr. J.H Remme - TDR Geneva Dr. K.Y. Dadzie - PBL Geneva JFCI4.10(ocP/EAC14.10) page 7 tF .J E a) q, oo o ! xo -EEE: oiR! Svoct @ '= {) a!? a5 7 t! r.rtrEaod 3; 9, .i !o =Xoo! u.s 'l O XobEsB F--e;* H g () -oO .=G -Ei;o- q)O 6F !v-P.o^6.FrrctE - - r) > seEd cO '= I E; oJi o oE PbYo e, o.!9u)o6 6 EI o G E rl o ooo .= cr.= .FrGHh ^.!= .i: >9 .l 9E x 6EIEY(.,QE'- b Ir= E r.EllJO H6F c .v=XF .EE 'i;rto ctrEr)-O h .=': I o.8 \EC oOt= -'= .=I95aE '=o- cc79.9 u] 8.Eo Xc(! ! o9nAC -t OE "'frqY E6 -dO (J6 ErHE -49- '-'i o.UsJ;= .9.E=_fr E -! aJ # E-E E. o t)oc() a) O6 :o -6U.q 6'-3r 2c (, -Eta a) .oL o.E9EUt{ \raa $EtsE.: = o-> o.9-O =1q9.^e r s 8t SEEeg € EAE;gls i;E*E s!loE o3oc,c> 8Eoe-E - i*o o.= '=9 oU- ae.6 dY o >:.i ze! oc() -oo9trE69 o.r G, GIth zo. EF tr a, 3 ,0r IIo-: =dnx -E .' =-EBo'& .n o 'to 9p9.; .r fl E.sJ! XJrrarUt hs *'=ara E€ o0g! -9ooE- p 10;E';E z *'=rr; (J'; co ur 9t,oE- 'E s.€E';9o.=E E8E .E? $Eior{o o C)der o.= o -E6€ -ooa (JE fil6ocEGI o E Gi c o (J(t (, o a.) c1)o.i r -doHFAo.(I|u sE s 9> OrrGtso ! o.E= 6 --'=9UEt =sAxc o o a=8 .9€= o8ti F E6E.E '=G=o E-.-:iyEe ,S;E E h i.sq2B 9 ,D,!o E=OE =EE E=6gE E E E a.?bE9+= -?grsfe 6a E E*OrOI.=€ o s EE=€'E E.E E TE JigEE .9 - 4.I H.9Ena E.E E E.3 F6-:i "E: E tC,-\ar=+ E.:zEi55Ec E;E:E E E€ EJieE t! o tr & AU o tIl a d Q odA J o&F oo cr) (n oc EIo o Uz o ]L o z o F J EI J I(, 3 o t! o o.tlt