Report: meeting on onchocerciasis surveillance tools, 30-31 January 2008

MULTI DISEASE SURVEILLANCE CENTRE (MDSC) OMS/AFRO. CENTRE DE SURVEILLANCE PLURIPATHOLOGIQUE Avenue Naba Zombre N'1473 - 01 BP 549 OUAGADOUGOU 0l - Burkina Faso Tel. : (226) 50 34 29 53159160 - Fax : (226) 50 34 28 75 - 50 34 36 47 E-mai I : ndsc (rr,)oncho. a{io. rvho. int Dfeeting on onchocereiasis surveillanee tools (3O.31/Ot /2OOB| Report 1 February 2008 : :. !: 11u,t'Av r-igiurr:ri prrur l' 1ti'ir1ur i 2 Table of contents Introduction and opening remarks Background and objectives of the meeting Background Objectives of the meeting....... Review of onchocerciasis surveillance tools .. Epidemiological surveillance tools: Skin snips, DEC patch test.... I Skin snip ... 2 DEC patch test 3 Discussion .... Review of entomological surveillance tools: black fly dissection and pool screening 3.3 Constraints in the operational implementation of the entomological and epidemiological tools. .. 3.4 Serological evaluation of the transmission of Onchocerca volvulus after large scale ivermectin treatment 4. Possibilities of improvement of pool screening (Present status and future development) 5. Decisions making tools . 5.1 ONCHOSIM Model : usefulness and challenges in the present context. 5.2 Other methods of analysis and decision making 6. Building capacity in onchocerciasis endemic countries 7 Group discussions .... 7 .l SOP of epidemiological surveillance of onchocerciasis in the present context (Report and recommendations) . 7 .1.1 Definition of early detection 7 .1.2 Review and update the available guidelines on epidemiological surveillance . 7.1.3 Data handling and storage and use for making decision 7.1.4 Define the use of the tools: Skin snip and DEC patch test 1 .1.5 Capacity building in onchocerciasis endemic countries. 7 .l.6 Decentralization of laboratory / molecular biology: conditions, how can it be done? ....... 7 .2 SOP of entomological surveillance of onchocerciasis in the present context 7 .l.l Definition of early detection 7 .1.2 Pool Screening Methodologies and Sampling Schemes 7 .1.3 Laboratory and Collection Logistics I .1.4 Data analysis and reporting 1 .1.5 Alternative Methods. 8. RECOMMENDATIONS 9. Closure of the meeting..... Annex 1: WORK GROUPS Annex 2: List of participants ..... 3 J J 4 4 4 4 4 5 5 1 2.1 2.2 J I J 3 3 2 3 J ,9 10 11 l1 12 t2 t4 .14 .1,4 .14 .15 .15 ,15 .15 .16 16 l6 t6 17 L7 18 t9 2I 23 2 1. Introduction and opening remarks The opening session was co-chaired by Dr U.V. Amazigo (Director of African Program for Onchocerciasis Control) and by Pr M. K. KONDE (Acting Director of the Multi Disease Surveillance Centre). In her opening note, the Director of APOC, Dr Amazigo, rvelcomes the participants at Ouagadougou on behalf of the Director a.i. MDSC and her name. She stresses the importance of the surveillance in ex OCP countries and for APOC countries. She reminded the participants the expectations of APOC and MDSC of that meeting. The onchocerciasis surveillance tools should be simple, low cost for countries and operational. She wished the participant a fruitful meeting. Dr Richard Ndjomodjenyi, National coordinator of Uganda was elected chairman. Dr Laurent Toe, Dr Aim6 G. Adjami and Dr Albert Akpoboua were designated rapporteurs. After discussion, the agenda of the meeting was amended and adopted 2. Background and objectives of the meeting 2.1 Background As the Onchocerciasis Control Programme in West Africa (OCP) succeeded in the elimination of the disease as a public health problem, the present challenge is to maintain the gains and achievements of OCP through an effective surveillance system. A new paradigm resulted for the surveillance activities. The facies of onchocerciasis has changed: the prevalence of the disease is low in human population; the microfilarial load is very low in human populations resulting in a decrease of the sensitivity of the skin snip. This test is the standard epidemiological diagnostic tool for O. volvulus infection in humans. It is invasive, painful and carries with it the risk of transmitting infections such as HIV and hepatitis; the invasive nature of the skin snip leads to a decrease in the compliance of the population. The prevalence of infection in the vector population is also extremely low and conventional dissection techniques are inefficient to detect infection. The change of scope within the active control to surveillance brought in new needs and challenges for the detection and diagnosis of O. volvulus transmission and infection. The pool screening method was developed in this epidemiological context. Based on the participation of communities and national surveillance structures, the method allows an assessment of transmission level in vector population by screening rapidly large numbers of flies. The topical application on the skin of DEC patch was developed and proposed by the OCP to replace the skin snip. It was shown safer, more sensitive and minimally invasive. In addition, the program has developed policies and standard operating procedures to monitor the resurgence of the disease. Five years after the closure of OCP, onchocerciasis surveillance in the ex OCP countries, current methods and tools for surveillance have shown their limitation. It was therefore necessary to review, update and upgrade their implementation or look for alternative methods. It is necessary to correct the deficiencies to better safeguard the gains from the success of this program and set up an entomo-epidemiological surveillance in APOC countries. J '2.2 Objectives of the meeting Based on the need for effective surveillance tools of onchocerciasis, the meeting was called to work on the following main objectives: Review and analyze the current status of onchocerciasis surveillance tools for early detection of recrudescence. 2. Review and analyze the process of decision making and the actions to be taken 3. Review any other altemative to the present tools (e.g. pools screening) 3. Review of onchocerciasis suryeillance tools 3.1 Epidemiological surveillatrce tools: Skirt sttips, DEC patclt test A review of the epidemiological surveillance tools was carried out with a background on historical strategies carried out in OCP and criteria of use during the post OCP period. Throughout the whole control period, OCP has done epidemiological evaluation with standardized methods to evaluate the impact of vector control measures. 3.1.1 Skin snip The principle of the test is the detection of the presence of O. volvulus parasite by taking two small skin biopsies (over the left and right iliac crests respectively) and examining them microscopically. The living microfilariae are easily observed emerging from the biopsies. Skin biopsy has been used as pre treatment, control and surveillance tools to assess the indicators such as prevalence, incidence and CMFL. Prevalence is the proportion of persons in the community who are carrying the infection as proved by a positive skin snip. It is expressed in percentage and it shows the current level of the infection in a population. Incidence is the proportion of persons in a community who have become infected in a year after having negative skin snips in the previous two years, which have now become positive; children bom after control measures started, who have now become positive. Community Microfilarial Load is the average number of microfilariae per skin snip for a community. The CMFL gives an indication of the strength of infection in infected persons.The conditions of field implementation were presented base on the guidelines defined by the OCP. 3.1.2 DEC patch test The DEC patch test is based on the detection of the presence of O. volvulus parasite by applying DEC (diethyl-carbamazine) to the skin over each of the two iliac crests, and examining the skin under the patches after 24 hours, to see if there is an inflammatory reaction. The description of the test as perfonned by OCP and the last development concerning a monotest were done. The performances of each test were described. 4 3.1.3 Discussion Skin snip remains the standard tool for epidemiological surveillance. It is the only test giving a direct proof of the presence of the parasite and so of the disease. Populations do not accept this test any longer because it is invasive; moreover there are risks of transmission of disease such as HIV or hepatitis if sterilization is not well performed. The skin biopsy is not routinely use in APOC area. In case of a routine use in APOC countries, the threshold of the indicators should be adapted. DEC patch test is a potential candidate to replace skin biopsy. The test is being standardized by a German company "Lohmann Therapy System". The participants expressed their concern about the specificity of the test in areas where Mansonella, Perstans and Loa loa co-exist and their antigen cross-reacts with those of O. volvulus leading to false positive reactions. The efflcacy of DEC patch test in areas under ivermectin is also questionable and need to be investigated. It was also advised to take advantage of the results of ongoing TDR study on Bakoye, Faleme and Gambia rivers to assess the efficacy of the DEC patch test in areas where only CDTI is being used. It was agreed that more research is required to make the DEC patch test applicable for onchocerciasis diagnosis or to be used as surveillance tool. 3,2 Revtew of entomological surveillsnce tools: black fly dissection and pool screening Dissection of flies The most direct method of surveillance for O. volwlus recrudescence is to detect new infections in the endemic population. Onchocerca volvulus transmission has historically been measured through dissection of wild-caught vector black flies. This method is efficient in monitoring transmission in areas in which onchocerciasis is hyperendemic or mesoendemic because the prevalence of infection in the vector population is usually high. However, in the face of a successful control program, the prevalence of infection in the vector populations is drastically reduced. The classic dissection method to determine the prevalence of infection becomes progressively less efficient in areas where control has been successful. Dissection requires freshly caught flies and must be performed at or near the capture site. This introduces costs associated with the travel of a trained technician to a location near each catching site, or the transportation of the freshly caught flies to a nearby laboratory. An additional cost related to the classic dissection method will be for the employrnent of fly catchers, who will also need to be paid salaries. Pool screening Entomological surveillance of onchocerciasis is carried by collection of blackflies, screening pools of flies in the molecular biology laboratory to determine infectivity rates, and then make decision considering that the threshold is 0.5/1000 flies caught. The entomological surveillance gives an alarm signal that should warn for epidemiological investigations. 5 A review of the technique as it is used was made. The entomological surveillance through the assessment of prevalence in vectors is more sensitive than epidemiological surveillance by skin snip. If it is well applied, entomological surveillance could provide early warning that new infection may be developing. The objectives of entomological detection of the recrudescence in onchocerciasis freed area aims at: . checking and comparing the current level of infectivity of the simulium to the level at the time of cessation of vector control; . Using it as a signal to suggest the start of epiderniological investigations (especially parasitological surveys). . Following the trend of infection in the fly population could be a useful indication of infection in the human population. The number of infective blackfly females per thousand parous females (infectivity rate) has been adopted as the sole entomological index to be used. It can be generated by classical dissection of blackflies and also by pool screening method. The number of infective blackfly females per thousand parous females (infectivity rate) has been adopted as the sole entomological index to be used. It can be generated by classical dissection of blackflies and also by pool screening method. The last one have several comparatives advantages as his implementation is less constraining and may also have cost advantages. Furthermore, as the prevalence of infection is generally low in ex OCP area,large numbers of insects need to be examined to obtain an accurate estimate of infections levels, and examining individual insects becomes very inefficient. In spite of its perfornance, pool screening needs to be improved. One of major constraint is the minimum number of 6000 flies required to get results statistically valid. National coordinators reported several time the difficulty of getting this sample size during collection at some breeding sites. However, by analyzing the data of flies collection of the period 2002- 2007 produced by the MDSC, it appears that about 40oh of catching sites have produced less than 6000 flies. This result indicates that several problems intervene in the resolution of this situation: suitability of capture points, supervision and motivation of village capturers. Discussion The participants highlighted the need to improve the pool screening to make it more operational. That includes: . Definition of a more operational threshold levels of infectivity to enable an appropriate response; . Analysis of the trend of infectivity rate which has more importance than the infectivity rate in absolute terms; . To find more reliable and sustainable circuits to deliver samples flies to the MDSC's laboratory; . To reduce delays in the delivery of results to the countries by improving the feedback circuit. Till now, there is no alternative technique for early detection of a possible recrudescence of infection in human population. 6 3.3 Constraints in the operational implementution of the entoruologicsl and ep id em io lo g ical to o I s. Before the closure of the OCP, a suitable network of sentinel villages (often first line villages) was created in each country. All the onchocerciasis foci were covered. The village was the epidemiological unit. The size of the selected villages was not exciding 300 inhabitants. The calibrated and standardized skin snip was the epidemiological evaluation method. The targeted village population was composed of all persons aged above one year. The frequency of visit was three years per village and every year per basin with a turnover. The typical evaluation team requires at least 6 persons (1 for census, I skin sniper, I microscope agent, I for visual acuity and ivermectin treatment, I supervisor and I driver). The difficulty of implementation of the surveillance tools are classified by level: 1. The management of surveillance a. Integrating onchocerciasis surveillance to the national surveillance system is difficult because it is an active surveillance that needs a specific equipment and that cannot be done routinely b. The respect of a 3 years periodicity for the same village in a basin c. How many villages should be evaluated on a basin to better assess the epidemiological situation on the whole basin? An operational sfudy in collaboration with the ONCHSIN users could propose a solution. d. The network of surveillance is not well known by the national team (number of villages to be evaluated on ayearly base). e. Epidemiological surveillance of onchocerciasis requires important resources (material, funds and human resources) 2. The use of skin biopsy a. After 28 years of control and the rollback of the disease, onchocerciasis is no more seen as an important heath problem. It is difficult to mobilise population. The fact that skin snip is invasive and painful make the population refuse progressively the test. The compliance is getting low. More effort is needed to sensitize the population. b. The field teams have often to face problem of accessibility to some villages during most part of the year in the onchocerciasis areas. c. The large number of forms for data collection conducts the teams to work late in the nights. d. Skin snip is able to quantify the disease. It is difficult to conduct it simultaneously with CDTI. l1 months break is needed to obtain good statistical results. The skin snip is less sensitive in the hypo endemic areas where microfilarial loads are low. 3. The pool screening a. The technique requires six months covering the high transmission period which is also the time for farming. This makes the mobilisation of villagers difficult for participating to the vector collection. b. The technique requires an important number of flies (at least 6000 per point). It was difficult to supervise efficiently the vector collectors during six months. c. To be correctly carried out the pools screening the management needs important financial resources to provide incentive to vector collectors, supervisors and ensure transport at national and international levels. 4. Human resource: the group of entomologists is getting old and need to be replaced to carry out the implementation of the surveillance activities. The Ministry of heath does 7 not give a high priority to their activity. It is noted that the entomologists are getting older progressively; several entomological technicians are on retirement. Replacement is needed. 5. Decision making: An important delay in the analysis of the specimens is noticed in the processing at the laboratory with important consequence on feed back of the results to countries. The importance of Pools screening as an alert tool is not yet perceived by the countries. Discussiott The meeting reviewed the entomological and epidemiological surveillance tools available and presently operational. Their definition and context of application was revisited. It is considered that the standardized skin biopsy and the pool screening remain the surveillance tools in Africa. An advocacy should be made using ONCHOSIM model to show the level of risk of recrudescence and the necessity to invest in surveillance. In order to determine the minimum and representative number of villages and vectors collections sites per basin the participants call for an operational research on a certain number of basins to collect a maximum of data and information that could be analysed using ONCHOSIM. It was highlighted the fact that entomologists and entomology technicians of the ex-OCP be mobilized in due course to set up an entomological surveillance network in APOC countries. They will train local technicians to carry out the surveillance activities. A list of available ex- OCP technicians should be prepared to that effect. It was also brought up the fact that most entomologists and entomology technicians in the ex- OCP are old and need to be replaced to carry out the surveillance activities in the onchocerciasis freed zones. The meeting was informed that two academic training centres (one in the University of Abomey Calavy / Benin for French or English speaking candidates; and another one in Khartoum / Sudan for only English candidates) are highly qualified for such training. The meeting was informed that in a near future, the use of human bait to collect Simuliurn flies will no longer be accepted by ethical committees. To that effect it was advised to start researching for altemative methods for fly collection like the use of traps. The capacity building in the onchocerciasis endemic countries was discussed. It was suggested that decentralization of the molecular biology laboratory be considered. The idea of strengthening the capacity (human resource and updated technology) of the molecular biology laboratory of the MDSC as a central and reference laboratory should be considered. Other operational molecular biology laboratories in the sub-region can be identified and their capacity strengthened to process samples locally and from neighbouring countries. The new method of Pool screening in use in OEPA countries to assess the Annual transmission Potential (ATP) was found attractive and it was advised to test the method in the ex OCP area to evaluate the usefulness of this method against the current one which is used to assess the infectivity rate. 8 3,4 Serological evaluation of the trunsmission of Ortchocercu volvulus after large scale iverruectirt treutment The objectives of the presentation were to evaluate the utility of an ELISA using recombinant antigens (Ov16, Ov7, Ovll) to estimate incidence of exposure in a sentinel cohort of individuals in a community after ivermectin treatment, and to perform serologic follow-up studies (using the ELISA -cocktail or IgG4 Ovl6), as part of a series of periodic prospective in-depth surveys evaluating the impact of mass distribution of ivermectin, in sentinel cohorts of individuals in communities of the three endemic foci in Mexico. A review of the WHO criteria for intemrption of transmission in OEPA was done. It is based on the absence of detectable infection in untreated children reaching the age of 5 (i.e. those rvho are about to take their first dose of ivermectin). A 5-year cumulative incidence rate of < I new case per 1,000 susceptible children is acceptable (provided a population of this size is available). The prevalence of antibodies is equivalent to the cumulative incidence rate. The sample size required to calculate a one-sided 95% CI for a prevalence that excludes 0.1% is 3,000 if zero positives are found. Sero-conversion measured by cocktail ELISA can assess infection incidence as accurately as skin biopsy in the sentinel group as all individuals became positive to both tests simultaneously. In the Oaxaca focus, all persons in a cohort consisting of ll7 children in the sentinel communities remained serologically negative for antibodies recognizing a cocktail of antigens in ELISA over a four-year period (2001-2004), which indicate an exposure incidence of Oo/o. The serologic data suggest that transmission may have been brought to undetectable levels throughout much of Oaxaca. The monitoring could be easier to maintain if based on serological tests. However, antibody tests do not provide precise estimations of infection rates because some persons exposed to the parasite may develop specific antibodies but never get infected. Thus, detection of circulating antibodies in an exposed population cannot be used to define the presence and level of infection, but the serological data do have potential utility as an epidemiologic tool to provide an estimate of exposure. When to stop treatment in a focus in OEPA? [n Oaxaca focus, even when transmission has been suppressed, treatment has not been discontinued immediately. It is considered that transmission may be suppressed by treatment, but it may rebound if the pressure on the population is removed. It is admitted necessary to maintain control activities until the level of transmission is so low that any rebound in transmission that occurs when control activities end will not reach a level that will cause the reproduction ratio to increase above the breakpoint. Unfortunately, it is difficult to predict to what extent transmission will increase once control activities are ended. Discusstort The experience of the OEPA was presented to show other alternative to the skin biopsy The experience of the OCP on the use of serological tests had revealed number of limitations including: - The low sensitivity of antigens cocktails in the West African context, - The production and availability of these antigen cocktails in the African context. 9 Technologies seem to have evolved and further tests in Africa is timely. But the fact that ' antibody tests do not provide precise estimations of infection rates is a real obstacle to their usefulness. 4. Possibilities of improvement of pool screening (Present status and future development) The prevalence of infective O. volvulus larvae in black flies is usually quite low in areas where control activities have been successful. The scarecity of flies carrying infective larvae makes analysis by conventional dissection impractical. As a result, PCR-based methods have been developed that permit one to screen large numbers of flies in a single pool, overcoming the difficulty of dissecting large numbers of flies. However, determining the prevalence of infective flies from PCR pool screen data is not a straightforward process. To overcome this obstacle, an algorithm was designed that permitted one to estimate the prevalence of infective flies from pools screen data, in which the calculation is based upon the number of flies per pool and the proportion of negative pools. This algorithm was incorporated into a computer program, Pool Screen 1.0. Pool Screen 1.0 was a useful tool, but contained some limitations. The two most significant of these were the need to use pools that all contained the same number of flies and the inability of the program to calculate an upper bound of the prevalence of infective flies when all pools tested rvere found to be negative. These deficiencies were corrected in an updated version of the program, Pool Screen 2.0, which allow the use of unequal pools and calculated an upper bound on the infection prevalence in those cases where all pools tested were negative. PoolScreen 2.0 was incorporated into the operational plan of the Onchocerciasis Elimination Program of the Americas (OEPA), which set its major entomological measure of the suppression of transmission as a prevalence of infective flies of less than l/10,000. Operational experiences have demonstrated that it is often nearly impossible to obtain a sufficient number of flies to meet this benchmark. It was recognized that transmission intensity was driven by three factors, which included annual biting rate, the prevalence of infective flies and the mean number of L3 carried by each infectious flies. As a result, OEPA recognized that it was necessary to develop a method to take all three parameters into account when measuring levels of transmission, as a low biting rate might mean that the density of the vector population was insufficient to maintain transmission, even in the case of relatively high infection prevalence. As a result of this need, a new version of Pool Screen (Pool Screen OEPA) has been developed. This program calculates the ATP with an associated 95o/o confidence interval. The program requires the entry of three data fields, including the number of flies per pool, the time over which the particular pool was collected and the results of PCR screening of the pool. It was emphasized that the results obtained by the program will only be as accurate as the quality of the data input into the program, and that effective use of the method requires that it be employed in the context of a sampling program that estimates the intensity of human / vector contact over the entire transmission season as accurately as possible. The design of such a sampling scheme will require balancing the optimal scientific procedures against the resources available to carry out the surveillance process. l0 5. Decisions making tools 5.1 ONCHOSIM Model : usefulness und challenges in the present context, A review of how the criteria for an intemrption of transmission was established and used in OCP was carried out with a background on historical strategies carried out in OCP. Throughout the whole control period, OCP has done entomological evaluation with standardized methods and on a large number of catching sites, to evaluate the impact of vector control measures. Epidemiological evaluation was done in a much larger number of villages. The use of standardized methods and availability of historical data regarding trends in entomological and epidemiological indicators of infection (infection and infectivity rate in flies, incidence of infection in human) have helped in establishing criteria for an intemrption of transmission. ONCHOSIM simulation model developed by the University of public health in Rotterdam helped to determine criteria for the cessation of control activities. The criteria were: if successful vector control had taken place over a period of l4 years, and trends in CMFL and mf prevalence in adults were consistent with ONCHOSIM predictions, and no infection was found in children bom after the start of the programme, then vector control could be intemrpted. ONCHOSIM clarified what would happen in case of different period of vector control and or ivermectin treatment: -if the control measures are intemrpted in areas where transmission is well controlled: the vector return will not be followed by any transmission; -in areas where residual transmission is ongoing, if the vector returns immediately after stopping, the intemrption of control measures could be followed by an increase in the vector population followed by an immediate increase of the ATP. Recurrent transmission then causes an increase in the worrn prevalence followed (in subsequent order) by increases in the mf prevalence, ATP and CMFL. Based on ONCHOSIM calculations, the following operational guidelines were developed and tested in different foci in the central OCP area: if the observed infectivity level was lower than the critical threshold of I L3 larvae in the head of female flies (F3h) per 1000 parous flies, the risk of recrudescence was negligible and no further entomological evaluation was required. If the infectivity level was higher than 2 F3h per 1000 parous flies, vector control had to be started again. In the range between I and 2 F3h per 1000 parous flies, the situation was undecided and additional information on the specific local situation had to be considered. The recrudescence of the infection defined by ONCHOSIM was: An annual incidence of l- l.5o/o in adults detected during 3 to 4 years of intensive epidemiological surveillance could be used as early sign ofrecrudescence ofinfection and / or Infection detected in children born at the end of the control. Long-term surveillance aims to make sure that the infection does not retum is done by the countries. The correctness of the decision to stop control was evaluated at three moments in oCP: o Decision making on stopping control using entomological and epidemiological evaluation criteria, and reference to model predictions. 1l Post-control entomological evaluation in each river basin to assess whether decision to stop was justified. Long-term surveillance by countries. Discussion The need to optimize capacity building and operational research in the APOC & ex-OCP countries is the key point to maintain onchocerciasis surveillance active. The following points should considered: a) Diagnostic tools, methods, and skills; b) Review of onchocerciasis surveillance guidelines; c) Training at all levels; d) IEC interventions, e) Integration in National Health Systems; f) Decentralization and networking The decision making was based on detection of early signs of onchocerciasis transmission and infection using ONCHOSIM. Subsequent in-depth epidemiological situation was carried out to determine the risk of recrudescence of infection. Previous knowledge on ivermectin treatment was considered in ONCHOSIM. There is a need to review ONCHOSIM based on new diagnostic tools and experiences on ivermectin treatment / distribution in ex-OCP and APOC. It was suggested to introduce or to use in the ONCHOSIM model the passive epidemiological surveillance data. It was also suggested to use all available entomological and epidemiological evaluation data collected by SIZ in the ONCHOSIM rnodel 5.2 Other methods of analysis und decistort tnoking In the context of post control of the disease, the following points should be considered in the implementation of the surveillance: . Patient level: existence of individual reservoir of parasites, migration of infected persons, and compliance to long term treatment with ivermectin; ' Country level: arrangements to ensure an efficient follow up of the control programme, of the trends of prevalence and incidence of the disease; comparative analysis of infectivity rate using as base line data the data of the end of the control era; data collected through the national information system linked with those collected during cross sectional surveys to allow an accurate evaluation of geographic and therapeutic coverage; study of population migrations to better understand the treatment data; adoption and implementation of entomo-epidemiological surveys as performed by the OCP; information of the national authorities of the real cost of surveillance activities because the disease is controlled but not eradicated. Risk of recrudescence still need to be considered. 6. Building capacity in onchocerciasis endemic countries The strengthening of national capacities in the country is a key point of the success of surveillance. The present context is unpaired by the aging of national staff in charge of onchocerciasis control and surveillance (especially in the countries of the ex OCP) and the insufficient number of staff to implement entomological and epidemiological surveillance in APOC's countries. o a t2 In order to prepare countries for ensuring the residual activities of control and monitoring, capacity building should cover areas as diverse as epidemiology, entomology, parasitology, molecular biology, modeling, etc. Several structures / personalities are already identified as potential partner or could give support to this activity: - MDSC, should carry training at technician's level in entomology and epidemiology. In-service training on practical subject and targeted short courses should be organized base on the Field Epidemiology and Laboratory Programme (FELTP). - APOC should be in charge of the training at academic level for epidemiologist entomologist and modeling. This training should be done in relation with universities, specialized institutions and programmes such as: the University of Rotterdam for training on ONCHOSIM, the Intemational Master of Medical and Veterinary Entomology (EIM), training by the University of Abomey Calavy (UAC) and the University Montpellie 12 (UM2). - Dr J-M. Hougard, former chief of the vector unit of OCP and now coordinator of the Intemational Master of Medical and Veterinary Entomology (EIM), University of Abomey Calavy (UAC) and the University Montpellie12 (UIll4Z); - Pr Unnasch, University of South Florida, Tampa (USA) formally at University of Alabama at Birmingham, due to his experience in the settlement of OCP's Molecular Biology Laboratory. - Etc. The national staff should be trained and operational before the end of APOC in 2015. Cross- border cooperation and surveillance will be their main activities. Such surveillance must be conducted with tools effective in detecting early resurgence of the disease. It was suggested to work out a road map of how this training process should be implemented before 2015.It was stressed on the necessity to aim at providing the onchocerciasis endemic countries with simple, operational, less expensive tools that can maintain in absence of donors. 13 7 Group discussions 7.1 SOP of epidentiological surveillartce of onchocerciusis in the present context (Report und recontmendatiorts) 7.1.1 Definition of early detection Concept definition: Timely detection of recrudescence of infection in the post-control era. Low levels of infection should be found so that it can be easily controlled before the disease becomes a serious heath problem. lnfective flies can be used as an alarm, but there is a need for further epidemiological investigation. Operational definition: In the OCP, recrudescence was defined as an annual incidence of l- 1.5% of infection in adults detected during 3 to 4 years of intensive epidemiological surveillance; or infection detected in children born after the end of the control. There was recrudescence if adult is positive in last survey, while he/she rvas negative in the two preceding surveys. The group considered that this definition is clear, based on ONCHOSIM simulations. It requires intensive surveillance schedule (survey a village every three years). The need of better/more acceptable tools than skin snips was stressed. DEC patch test, serological tests to help detect early infection recrudescence are opportunities that should be considered for future development. The present situation is characterized by the fact that skin snips will become less acceptable and DEC patch is not ready. Recommendations: I ONCHOSIM (or other modeling approaches) should be used to confirm this definition, based on data collected after the end of OCP 2 Investigate whether we can also use prevalence as indicator 3 Continue research on DEC patch test, antibody test and candidate antigen tests as altematives for skin snips 7.1.2 Review and update the available guidelines on epidemiological surveillance The group has discussed the available guidelines on epidemiological surveillance on the following points. The group noticed that for the frequency of evaluation of a village, every village has to be evaluated once per 3 year; every year l13 of the villages in the same basins could be visited. Concerning the sampling procedure and the choice of sentinel villages, no conclusion was made on the number of villages to be evaluated. It was agreed that the minimum depends on criteria for selection of sentinel villages. They should be first line villages, preferably near the breeding site (because they are usually hyper endemic); and the size of the sentinel village was discussed. ln the OCP area small villages considered while in APOC area the villages are much larger. The group agreed that skin biopsy is the only available test for detection of infection. The main indicator is the incidence of new infection in adults or children born after cessation of control. However the use of prevalence of the disease should be considered. The major problem identified was the lack of funds making difficult to perform surveys every 3 years in all villages. t4 Recommendations: l. Because of invasive nature and the risk of transmitting other diseases (like HIV, hepatitis B) of the skin biopsy, the group recommends the exploration of the use of other tests (like DEC patch test, serological antibody tests) as replacement. 2. The alternative tests (DEC patch test, antibody test) do not yet quantify the level of the infection as the skin snip. The group recommends that relation between skin snip mf test (mf prevalence, CMFL or geometric mean mf/s in entire population) and the alternative tests be quantify; preferably based on existing data. 3. The minimum number of villages to be surveyed needs to be determinate. The group recommends that APOC and MDSC ask statistician / field expert to make recommendations based on available epidemiological and/or entomological data and resources. 4. The group also recommends that MDSC reviews the guideline on epidemiological surveillance and disseminate it (or make sure that countries make their own guidelines) 5. For OCP countries: to update the network of villages for epidemiological surveillance 7.1.3 Data handling and storage and use for making decision The group noted the lack of standard forms for data-collection for surveillance. It also highlighted the need to use uniform software for data-entry and analysis. Every country should analyze their results as input for decision making. The group recommends to simplify existing forms and to develop simple applications. It is also recommended that MDSC keep a central role: to check availability of database, handling, storage in countries and at central level; and to provide guidelines for decision making. 7.1.4 Define the use of the tools: Skin snip and DEC patch test The group has not specifically discussed this topic, but touched upon this in earlier discussion. Skin biopsy is curently the only useful tool for epidemiological surveillance. DEC patch needs to be developed further, before it can be used on large scale. Also the antibody test should be considered for improvement to serve in the African context preferably as a card test to be used in the field. 7.1.5 Capacity building in onchocerciasis endemic countries The group recommends that APOC and MDSC work together to support the countries in building capacity. Training of epidemiologists at MoH level and (technical) assistants could be carried at decentralized levels for: field work; data analysis; quality control; impact assessment; decision making and logistics. Epidemiologists and technical assistants should be equipped with adequate material for epidemiological surveillance. 7.1.6 Decentralization of laboratory / molecular biology: conditions, hory can it be done? For serological tests we need labs (unless card tests become available); ELISA test can be done in non-specialized laboratories and can easily be decentralized 15 7.2 SOP of entomological surveillance of ortchocerciusis in the present context (Report and recommendations) 7.1.1 Definition of early detection Ensuring the time frame of the surveillance activities (from sample collection through analysis and reporting of results) is sufficiently timely to permit action using the current tools available to control any recrudescence before transmission reaches a level where it may present a public health risk. 7.1.2 Pool Screening Methodologies and Sampling Schemes Several disadvantages of the "classical pool screen" (i.e. PoolScreen 2.0) were noted l. The need for testing large number of flies. 2. The period of fly collection is logistically difficult given it's seasonality overlaps with the farming season. Recommendations The committee discussed the current sampling strategy and potential modifications to most effectively utilize the current limited resources. Should we concentrate upon times when flies are abundant and most likely to be infected? Or should we make a more distributed collection process to obtain an accurate measure of transmission level? This is a strategic question of what type of surveillance scheme that you are trying to design. The committee noted that the historical data and the surveillance needs may be different in the zones under treatment and in the onchocerciasis free zones, and require different strategies. One compromise is to use a two stage approach. The initial strategy would be a more directed approach. When potential recrudescence is detected, then a more detailed study may be undertaken to quantify the extent of the problem. The committee recommended that entomological evaluations conducted by APOC should be strengthened. Thus, the committee recommended establishing a limited number of catching sites in APOC to be visited more frequently than the five year evaluation cycle currently being conducted. Within the onchocerciasis free zones the designated catching sites should be re-evaluated to eliminate those where black flies are no longer present. The committee noted that the new version of PoolScreen carries some potential advantages, but that the utility of the program has not been shown in the logistical context of sub-Saharan Africa. The committee recommended that a pilot study be undertaken to evaluate the new pool screen method compared to established methods at two points (one OCP one APOC). This pilot should contain an epidemiological component to permit the programs to better elucidate the relationship between the incidence and prevalence of infection and the intensity of transmission. 7.1.3 Laboratory and Collection Logistics The committee noted that supervision and training of the local fly catchers was essential in ensuring quality data collection. The committee felt that this would be best served by the designation of a senior level medical entomologist in each country to oversee collection activities. These individuals must be capable of coordinating an effective team and of defending program at the national level. This person will bear primary responsibility for 16 getting flies collected and delivered to Ouagadougou. As trained medical entomologists are becoming ararity, the committee recommended that APOC and the international community encourage the endemic countries to support the training of additional medical entomologists, perhaps utilizing the two current Master's in Medical Entomology programs currently offered in Sudan and in Benin. Financial support for such training may be available from WHO, AFRO and EMRO. Short-term training opportunities should also be made available for field- level technicians, to develop a critical mass of individuals in the program. The committee noted that transportation of the flies from the field to the laboratory represents a significant bottleneck in this process. Streamlining this process as much as possible is critical. The committee recommends that the process of coordinating all shipments be the responsibility of the medical entomologist described above. The committee strongly recommended that the central laboratory in Ouagadougou be provided with the human and material resources necessary to process all samples in a timely manner, especially in the context of APOC derived samples. The committee recommended that the laboratory explore the use of alternative sampling handling techniques to streamline the process. However, the committee recognizedthat the black flies shipped to the lab are not evenly distributed throughout the year, but tend to arrive during a few months of the year. The committee recommended that the program explore enlisting endemic laboratories with experience to assist with the sample analysis process. The laboratory at MDSC would then assume the role of a central coordinating facility in this process. In addition to processing a significant proportion of the flies collected, the central laboratory would have three additional roles; l. Training of personnel from the satellite laboratories; 2. Development and distribution of new techniques; and 3. quality control of the satellite laboratories. The committee noted that financial resources are very limited for these activities. They recommended that a comprehensive cost analysis of the process be conducted, basing the costs on a per fly basis. This estimate should include the costs associated with collection and transportation into the possible extent. 7.1.4 Data analysis and reporting Data entry is currently done in a manual manner, and results are reported by hard copy. The committee recommended that the current data platforms, which were originally designed for identification of individual larvae isolated by dissection be modified to best serve data collected by the poolscreen method. This platform should be designed to integrate with the data input needs of the PoolScreen programs to the possible extent. Finally, the committee recommended to distribute the results from the laboratory using electronic means. 7.1.5 Alternative Methods Human bait capture methods are inefficient in terms of man hours needed and may become ethically impermissible in the near future. The committee recommends that APOC support the development of alternative trapping methods that may replace the human bait collections. t7 ;2 RECOMMBNDATIONS Continue research on the DEC patch test, reactivate antibody test and candidate antigen tests as alternatives for the skin snip. It will be necessary to quantify the relation between skin snip mf test (mf prevalence, CMFL or geometric mean mf/s in entire population) and the altemative tests (DEC patch test, antibody test); preferably based on existing data. (APOC, TDR, MDSC) Considering the fact that human bait capture methods may become ethically impermissible in the near fufure, the committee recommends the development of altemative trapping methods that may replace the human bait collections. (APOC, MDSC) Consider developing a two step strategy for surveillance for onchocerciasis: a) in onchocerciasis freed zones, with a first step relying upon entomological methods to identify areas with transmission, and a second step based on epidemiological methods to carry out an in depth analysis of transmission intensity at sites where evidence for ongoing transmission is found; b) in areas under ivermectin treatment, both entomological and epidemiological evaluation methods should be implemented to follow the trend of the transmission. The data produced should be integrated in order to better understand the relationship between transmission intensity and the importance of infection in the human population. (APOC, MDSC) Regarding the high number of flies required, MDSC should institute a pilot program to compare, in the context of the African operational perspective, the utility of the existing Pool screening (expressing the infectivity rate) and the Pool screening OEPA methods (expressing the Annual Transmission Potential). The results of the pilot program should be presented at the next meeting in February 2009. (MDSC) Develop a new data entry platform tailored for use with pool screen data and ensure that this platform is designed for easy importation of the resulting data into the PoolScreen programs. New simplified data input forms and database to record all epidemiological data collected in countries are also required. (MDSC) In line with resolution No AFR/RC57/R3 of the 57th wHo/AFRo Regional committee, the meeting recommends to APoc and MDSC to urge the member states to identify entomologists and epidemiologists in each country to bear primary responsibility for the control and surveillance activities. APOC should invest in training national entomologists and epidemiologists through academic courses, while MDSC should invest in training technicians in both domains. (APOC / MDSC). The meeting strongly emphasised the key role of the molecular biology laboratory at the MDSC for onchocerciasis surveillance and recommended that the necessary resources be provided to permit the timely analysis of the blackfly samples provided the participating countries. The MDSC should consider identifying existing laboratories with experience in PCR analyses in onchocerciasis endemic countries. The MDSC should take the role of central laboratory providing J 4 5 6 7 18 I technical assistance, training and quality control support to the above identified laboratories. (MDSC) ONCHOSIM (or modeling approaches) should be used to investigate what minimum levels should be used in surveillance in order to speak of recrudescence and re-implement control measures. Such thresholds have not been set for entomological measures, while previously-proposed thresholds for epidemiological measures need to be confirmed. (APOC) There is a need to work together to review, build and strengthen the capacity of national teams for active entomological and epidemiological surveillance in data collection involving the communities. Effort should be made by APOC and MDSC in collaboration with Member States to provide adequate resources (financial and equipment) to the communities for data collection, processing, analysis and use. (MoH, APOC, MDSC) 10 The network of villages of epidemiological and entomological evaluation should be revisited at the present stage of onchocerciasis control in the OCP countries' national programmes. The guidelines on epidemiological and entomological surveillance should be updated. This would concem the minimum numbers of villages to be surveyed and the periodicity of visits per basin and country. This should be done in collaboration and harmony with the entomological surveillance network. This joint exercise would greatly benefit from the input by specialists operating the ONCHOSIM model. APOC and the MDSC should assist with the funds in the implementation of the above activities. (MoHAIat. Coord, APOC, MDSC) ll In APOC countries, consideration should be given to the instalment of networks of epidemiological and entomological evaluations adapted from that operated in OCP countries. In OCP and APOC countries, evaluation should be considered in connexion with CDTI activities. (APOC) 9. Closure of the meeting In his closure note, Pr M.K. Konde Dir ai MDSC thanked the participants for their availability and their important contribution. He expressed his satisfaction for the collaboration between MDSC and APOC technicians to reach the same objective. He will ensure that MDSC will play its role in surveillance of onchocerciasis, making funds available for the implementation of activities. The participants indicated that the time devolved to such meeting was too short to deeply develop all the points. They wished that the meeting should be reconvened next year to evaluate the progresses made, constrains and challenges, and the axes of implementation of the challenges. The Director APOC and Director ai MDSC agreed to co-organized the next meeting as recommended by the experts during the first week of February 2009. Dr Amazigo thanked the participants and assured them of her availability to give the necessary means to implement the recommendations. She outlined the quality of their contributions, which has greatly enriched the debate. Their commitment was made clear for the poor communities affected by the disease and who will benefit of the outcome of the meeting. She declared to remain attentive to the suggestions of the experts on the issues of onchocerciasis surveillance. Their expertise is needed and she would contact them to t9 I 9 a'collaborate any time by mail or telephone. She ended by wishing a safe trip back home to each one. 20 Annex 1: WORK GROUPS Subject: Review and elaboration of standard operation Procedures (SOP) for onchocerciasis surveillance Subject of Group 1: Standard Operational Procedure of epidemiological surveillance of onchocerciasis in the present context l. Definition of the "early detection* 2. Review and update the guideline on epid eval: a. Frequency of evaluation b. Sampling procedure/ Choosing sentinel villages c. Diagnostic methods: Skin biopsy d. Indicators 3. Data analysis, storage and use for making decision 4. Use of the tools: Skin Biopsy and DEC patch test 5. Capacity building in onchocerciasis endemic countries 6. Improvement of Skin biopsy and DEC patch test I . Decentralization of laboratory: conditions 8. Investigate other alternative methods 9. Cost of epidemiological evaluation tools 10. Identify research priorities Outcome: Report und recommendatiotts Group I Epidemiological surveillance (Room 34) Facilitator: Dr W. Soumbey-Alley Rapporteurs: Dr WA. Stolk Members: Dr W. Soumbey-Alley Dr NK. Diallo Pr M. Rodriguez-Perez Dr R. Ndyomugyeni Dr WA. Stolk Dr M. Noma Mr M. Sanfo Dr L. Toe 1. 2. J. 4. 5. 6. 7. 8. 2t ) Subject of Group 2: Standard Operational Procedure of entomological surveillance of onchocerciasis in the present context I 1. Definition of the "early detection" 12. Review the guideline: a. Sampling/ Choosing surveillance sites b. Use of village vector collectors c. Role of the entomologists 13. Use of the tools: Pools screening a. Method : Period of collection, Nb days of collection and periodicity, financial implications, logistic); b. Applicability by countries of the new "pool screening" c. New software : the need of defining ATP in present context (post OCP/APOC) and implication; d. Advantage and disadvantage of the old vs new "pool screening": feasibility on the field 14. Laboratory analysis: communication with countries, transport of sample, feedback of results 15. Data analysis storage and use for making decision 16. Decentralization of laboratory analysis: conditions/ capacity of analysis of the lab 17. Capacity building in onchocerciasis endemic countries 18. Investigate other alternative methods 19. Identify research priorities 20. Cost of entomological evaluation Outcome: Report and recontmendatiotts Group 2 Entomological surveillance (Conference room) Facilitator: Dr J-M. Hougard Rapporteurs: Pr T. R. Unnasch Dr A. Akpoboua Members: I Dr B. Philippon 2 Dr J-M. Hougard 3 Pr T.R. Unnasch 4 Dr S. Wobo 5 Mr T. Lakwo 6 Mr A. Adzah 7 Dr A. Akpoboua 8 Dr A.G. Adjami 9 Pr S. Traore 22 Experts Annex 2: List of participants Dr Bemard Philippon Dr Jean Marc-Hougard Dr W. Soumbey-Alley Dr Wilma A. Stolk Prof Thomas R. Unnasch Dr Mario Rodriguez-P erez Coordonnateurs 7. Dr Nouhoun K. Diallo, Coordonnateur/Guinde Conakry 8. DrRichardNdyomugyeni,Coordonnateur/Ouganda Techniciens/Entomologistes 9. Mr Adza Alex, Ghana 10. Mr Tom L. Lakwo, Uganda I 1. Dr Sam Wobo, Nigeria MDSC l. 2. 3. 4. 5. 6. 12. 13. 14. 15. Prof M. Kader Kond6, DIR a.i./MDSC Dr Laurent To6, Molecular biologist Dr Aim6 G. Adjami, Assistant molecular biology laboratory Mr Moussa Sanfo, Assistant molecular biology laboratory Dr Uche Y. Amazigo, DIR/APOC Dr Laurent Yam6ogo, COORD/APOC Dr Mounkaila Noma, CEV/APOC Dr Albert Akpoboua SIZ Dr Sougalo Traor6 APOC t6 l7 18 l9 20 23