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Pacific Malaria Drug Resistance Monitoring Network Meeting, Manila, Philippines, 08-09 August 2011 : report

31 декабря 2011 г. Всемирная организация здравоохранения

Полный текст

Meeting Report

Pacific Malaria Drug Resistance Monitoring Network

Pacific Malaria Drug Resistance Monitoring Network Philippines

Malaysia Papua New Guinea Indonesia East Timor Vanuatu Solomon Islands

Manila, Philippines 08–09 August 2011

Participants of the Pacific Malaria Drug Resistance Monitoring Network 08–09 August 2011, Manila, Philippines

WPR/DCC/MVP(03)/2011 RS/2011/GE/45(PHL)

English Only

REPORT

PACIFIC MALARIA DRUG RESISTANCE MONITORING NETWORK MEETING

Convened by: WORLD HEALTH ORGANIZATION Western Pacific Region

Manila, Philippines 8-9 August 2011

Not for sale Printed and distributed by: World Health Organization Regional Office for the Western Pacific Manila, Philippines August 2011

NOTE The views expressed in this report are those of the participants in the Pacific Malaria Drug Resistance Monitoring Network Meeting and do not necessarily reflect the policies of the Organization.

This report has been printed by the World Health Organization Western Pacific Region for governments of Members States in the Region and for those who participated in the Pacific Malaria Drug Resistance Monitoring Network Meeting, held in Manila, Philippines from 8 to 9 August 2011.

TABLE OF CONTENTS

ABBREVIATIONS EXECUTIVE SUMMARY 1. INTRODUCTION ................................................................................... 1 1.1 1.2 1.3 1.4 2. Objectives:...................................................................................... Welcome remarks ............................................................................. Opening remarks .............................................................................. Appointment of Chairperson, Vice-Chairperson and Rapporteur ...................... 1 1 1 2

PROCEEDINGS ..................................................................................... 2 2.1 Technical Session 1: Role of antimalarial drug efficacy monitoring .................. 2 2.2 Technical Session 2: Country Updates on the Malaria Situation, Treatment Policy, Drug Resistance Situation and Monitoring .......................... 6 2.3 Technical Session 3: Update on technical issues to strengthen drug resistance monitoring ........................................................................ 8 2.4 Group Work: Development of Pacific Malaria Drug Resistance Monitoring Plan .............................................................................. 10 2.5 Consensus on the need for a Pacific Malaria Drug Resistance Monitoring Network ......................................................................... 10 2.6 Technical Session 4: Establishment of the Pacific Malaria Drug Resistance Monitoring Network ............................................................ 11 2.7 Training Session and Group work ......................................................... 13

CONCLUSIONS AND RECOMMENDATIONS ............................................. 14 3.1 Conclusions ................................................................................... 14 3.2 Recommendations ............................................................................ 14

ANNEXES Annex 1 Annex 2 Annex 3 Annex 4 Annex 5 Annex 6 Annex 7 Annex 8 - TIMETABLE - LIST OF PARTICIPANTS, TEMPORARY ADVISERS, OBSERVERS, AND SECRETARIAT - CURRENT AND FUTURE TES PLANS - REQUIRED INPUTS FOR COUNTRY TES PLANS - MALARIA DRUG RESISTANCE MONITORING NETWORK: SITUATION/GAP ANALYSIS - PACIFIC DRUG RESISTANCE MONITORING NETWORK MEETING: GOALS, TERMS OF REFERENCE AND RECOMMENDATIONS - LIST OF DOCUMENTS DISTRIBUTED - LIST OF DOCUMENTS ON USB

Keywords: Malaria - prevention and control / Drug Resistance / Antimalarials - therapeutic use

ABBREVIATIONS

ACPR ACT AL AMO API ASU AusAID CLO CQ DHA-PIP Doxy ERC GCP Global Fund GMS IMR IRB IRS L1/L2 LLIN NIHRD PacMISC Pf Pv PCR PI QA QC QN RBM RCC RDT SAE SOP SP TA TCN TES TOR TWG WHO

Adequate Clinical and Parasitological Response Artemisisin-based Combination Therapy Artemether-lumefantrine Amodiaquine Annual Parasite Incidence Artesunate Australian Agency for International Development Country Liason Officer Chloroquine Dihydroartemisinin-Piperaquine Doxycycline Ethics Review Committee Good Clinical Practices Global Fund to Fight AIDS, Tuberculosis and Malaria Greater Mekong Subregion Institute of Medical Research Institutional review board Indoor residual spraying Level 1/2 (malaria microscopist accreditation) Long-lasting insecticidal net National Institute of Health Research and Development, Indonesia Pacific Malaria Initiative Support Center Plasmodium falciparum Plasmodium vivax Polymerase chain reaction Principal Investigator Quality assurance Quality control Quinine Roll Back Malaria Rolling continuation channel Rapid diagnostic test Severe adverse event Standard operating procedure Sulphadoxine-pyrimethamine Technical assistance Tetracycline Therapeutic efficacy study Terms of reference Technical working group World Health Organization

EXECUTIVE SUMMARY

The Pacific Malaria Drug Resistance Monitoring Network, aimed at strengthening antimalarial drug efficacy monitoring in the Pacific, was launched at an intercountry meeting held in Manila, Philippines from 8 to 9 August 2011. The meeting was attended by two temporary advisers, three observers, 16 WHO secretariat staff and 13 participants from six countries: Indonesia, Malaysia; Papua New Guinea, the Philippines, Solomon Islands and Vanuatu. The objectives of the meeting were: (1) to review countries’ national malaria treatment policies and antimalarial drug efficacy, and data and monitoring systems and identify key issues and gaps; (2) to review and develop country plans for antimalarial drug efficacy monitoring for the next two years; and (3) to discuss terms of reference and partner cooperation within the proposed Pacific Malaria Drug Resistance Monitoring Network, including resource mobilization and linkages with other existing networks. The meeting included country presentations, technical presentations by the participants and WHO staff, and group discussions. The participants noted that, while countries have performed well in reducing malaria cases, constraints still exist and there are several aspects which require attention. Some of these aspects are local capacity-building, standardization of therapeutic efficacy studies, improved information sharing, and harmonization of treatment policies across countries. After discussing the varying challenges and the gaps they would like to be addressed, all countries present concurred that there was a need for a regionwide monitoring network to support their efforts. A working group was formed to draft the terms of reference and recommendations for the proposed Pacific Malaria Drug Resistance Monitoring Network. These terms of reference and recommendations were then discussed in plenary session and modified. The agreed terms of reference for the Pacific Malaria Drug Resistance Monitoring Network are: (1) to support countries (programmes and research institutions) to implement the WHO standard protocol for routine monitoring of antimalarial therapeutic efficacy of the first and second line treatments for Plasmodium falciparum and Plasmodium vivax; (2) to identify training needs and coordinate capacity-building for high quality drug resistance surveillance; (3) to coordinate laboratory support to countries and facilitate the use of WHO recommended standard procedures, and contribute to the development of new procedures where they are not available; (4) to coordinate independent monitoring and review of therapeutic efficacy study (TES) data; (5) to facilitate the timely reporting and sharing of TES results; (6) to coordinate network activities and facilitate collaboration through regional informal consultations, regional planning, resource mobilization and review of progress;

(7) to support countries in reviewing national malaria treatment policies (if requested); and (8) to facilitate operational research and address knowledge gaps related to antimalarial drug resistance monitoring. The following were the recommendations of the meeting: (1) With antimalarial drug resistance being a major threat in the Region, antimalarial drug resistance monitoring efforts led by country programmes need to be strengthened, intensified and properly coordinated. (2) The Pacific Malaria Drug Resistance Monitoring Network should be established and coordinated by WHO (with a full-time Secretariat). (3) WHO and partners should immediately start mobilizing adequate resources for establishment of the Secretariat and its core activities. (4) The draft for a two-year national drug efficacy monitoring plans should be finalized and endorsed by each country by the end of 2011. (5) Countries should follow the latest WHO protocol for the antimalarial drug efficacy monitoring. (6) Countries should identify their capacity-building and technical assistance needs and seek assistance from the network partners. (7) Country data should be regularly reviewed (including for Day 3 positivity as an early warning sign for emerging artemisinin resistance) and shared within the network. (8) The network should convene a TES workshop for all Pacific country focal points and principal investigators within one year of its inception, and hold a full network meeting every two years, to review progress and support high-quality TES implementation.

1. INTRODUCTION

Antimalarial drug resistance is a major public health problem hindering the control of malaria globally. The rapid spread of resistance to antimalarial drugs during the past few decades calls for intensified efficacy monitoring. The intensified action will ensure proper management of clinical cases and early detection of changing patterns of resistance in order to update and revise national malaria treatment policies. Surveillance of therapeutic efficacy over time is an essential component of a malaria programme. It is a key strategy to detect, monitor and prevent the spread of antimicrobial resistance. All Pacific malaria-endemic countries are monitoring antimalarial drug efficacy, but there is a need to: (1) strengthen planning and implementation; (2) update country programmes on new monitoring procedures; and (3) ensure sharing of information and effective coordination of efforts, as it is being done in the Mekong malaria-endemic countries. The threat of emerging artemisinin resistance in neighbouring countries calls for immediate action to step up malaria drug resistance monitoring efforts in the Pacific. The intercountry meeting in Manila, Philippines, aimed to strengthen antimalarial drug efficacy monitoring in the Pacific through the launch of the Pacific Malaria Drug Resistance Monitoring Network. The meeting brought together national malaria programme managers and focal persons on malaria treatment from six countries: Indonesia, Malaysia; Papua New Guinea, the Philippines, Solomon Islands and Vanuatu. It also brought together other stakeholders, partners and technical experts to explore collaboration and define the way forward. Timor Leste was invited but could not attend. The WHO Regional Office for the Western Pacific, in collaboration with the WHO Regional Office for South-East Asia, and its partners organized the meeting. The meeting took place from 8 to 9 August 2011 in Manila, Philippines (for programme and list of participants, see Annexes 1 and 2). 1.1 Objectives: (1) to review national malaria treatment policies and antimalarial drug efficacy data, country monitoring systems and identify key issues and gaps; (2) to review and develop country plans for antimalarial drug efficacy monitoring for the next two years; and (3) to discuss terms of reference and partner cooperation within the proposed Pacific Malaria Drug Resistance Monitoring Network, including resource mobilization and linkages with other existing networks. 1.2 Welcome remarks

Dr Eva Maria Christophel, Team Leader, Malaria, other Vectorborne and Parasitic Diseases, WHO Regional Office for the Western Pacific, welcomed all attendants to the meeting and expressed her enthusiasm for the opportunity for the six countries from the Western Pacific and the South-East Asia Regions to come together and discuss the monitoring situations prevailing in each country and the possibility of establishing a Pacific drug resistance network. 1.3 Opening remarks

In his opening address, Dr Shin Young-soo, WHO Regional Director for the Western Pacific, remarked on the tremendous and sustained progress made in malaria control and elimination among the Western Pacific countries. Nine of the ten countries have pledged to eliminate malaria. Yet, the Western Pacific has been the epicentre of malaria drug resistance since the 1960s, and the emergence of artemisinin resistance could jeopardize the progress made.

A malaria monitoring network that builds on the example of the Mekong network is needed. The network would assist member countries in planning and implementing highquality efficacy studies. The main focus would be on training and capacity-building for national staff. It would also provide assistance on data analysis and interpretation, and assist countries in reviewing and updating their national treatment policies. While WHO is strongly committed to establishing this network, this also requires strong political commitment from Member States, high-quality technical expertise from technical partners and adequate financial resources from donors. This network will have a positive impact on achieving the malaria-related targets in the Millennium Development Goals and those set in the Regional Action Plan for Malaria Control and Elimination in the Western Pacific (20102015). 1.4 Appointment of chairperson, vice-chairperson and rapporteur

Dr Shin Young-Soo called for the nomination of chairperson, vice-chairperson and rapporteur. Dr Mario Baquilod, Medical Officer, National Center for Disease Prevention and Control, Department of Health, Philippines, was nominated as chairperson. Dr Tenneth Dalipanda, Director of Public Health, Ministry of Health and Medical Services, Solomon Islands, was nominated as vice-chairperson, and Dr Christina Rundi, Senior Principal Assistant Director, Disease Control Division, Ministry of Health, Malaysia, was nominated as rapporteur. 2. PROCEEDINGS

2.1

Technical Session 1: Role of antimalarial drug efficacy monitoring

2.1.1 Resistance of Plasmodium falciparum and Plasmodium vivax malaria parasites to antimalarial medicines: a global overview (including the role of networks) Ms Amy Barrette, Technical Officer, Global Malaria Programme, WHO, gave an overview of drug resistance and treatment failures and reviewed tools used for monitoring drug efficacy and resistance, including the 2009 WHO standardized protocol. Ms Barrette also discussed the evolution of the protocol and how its use in countries over the years has led to changes in malaria treatment policy. The types of support provided by WHO were also outlined. WHO provides technical support for data analysis, monitoring, report writing and publishing, and financial support for medicine procurement and quality control. Ms Barrette also described the WHO database and gave examples of how data from the drug resistance database could be presented. The data in the database is compiled from three main sources: published journal articles; reports by ministries of health, national malaria control programmes and research institutions; and raw data from surveillance studies. Ms Barrette summarized the benefits of regional and sub-regional networks in monitoring and controlling drug resistance. The networks can facilitate the implementation of the WHO protocol and standard operating procedures (SOPs), exchange of information and experiences, and help to inform treatment policy change. 2.1.2 Overview of malaria situation and drug resistance in the Western Pacific Region and meeting objectives Dr Eva Maria Christophel, Team Leader, Malaria other Vectorborne and Parasitic Diseases, WHO Regional Office for the Western Pacific, presented an overview of antimicrobial drug resistance, why it is a major concern, and expressed the urgency of

implementing the six-point policy package to combat drug resistance in all member countries. The policy package urges the participating countries, partners and donors to: (1) commit to a comprehensive, financed national plan with accountability and civil society engagement; (2) strengthen surveillance and laboratory capacity; (3) ensure uninterrupted access to quality essential medicines; (4) regulate and promote national use of medicines, including in animal husbandry, and ensure proper patient care; (5) enhance infection prevention and control; and (6) foster innovations and research and development of new tools. She then gave an overview on the malaria situation in the Western Pacific countries and remarked that, although malaria transmission and incidence rates are decreasing trend, they are still too high in several Pacific countries and represent a major health problem. She went on to review the drug resistance situation and national drug policy in the Region, and the emergence of artemisinin resistance in Cambodia. 2.1.3 Antimalarial drug resistance in the South-East Asian Region

Dr Md Mushfiqur Rahman, Malaria Unit, WHO Regional Office for South-East Asia, presented an overview of the situation of antimalarial drug resistance in the South-East Asia Region. He mentioned antimalarial drug resistance as a major public health problem as evidenced by Plasmodium falciparum (Pf) resistance to chloroquine and sulfadoxinepyrimethamine (CQ and SP). Plasmodium vivax (Pv) also showed resistance to chloroquine in Indonesia. He discussed the serious issue of emerging resistance of Pf against artemisinin at the Thailand-Cambodia border and potential spread of the same and vulnerability in Myanmar, Bangladesh and some northeastern states of India Dr Rahman presented in detail the country-specific drug resistance status and concluded his presentation with an overview of the current drug policy per country in the Region which has been updated/changed based on the results of the therapeutic efficacy studies (TES) in South-East Asian countries such as: Bangladesh, Bhutan, India, Indonesia, Nepal, Sri Lanka, Timor Leste, and the Democratic People’s Republic of Korea. 2.1.4 Lessons learnt from the Greater Mekong Subregion: antimalarial drug resistance, artemisinin resistance and containment, the role of the Mekong Malaria Programme network Dr Charles Delacollette, Coordinator, WHO Mekong Malaria Programme, WHO Regional Office for South-East Asia, presented lessons learnt from the Greater Mekong Subregion. He focused on the need for programme managers and researchers to agree on the use of standardized study protocols across study sites and countries in order to compare outcomes, map results and take appropriate actions. There is still some disconnect among individual researchers and institutions, which may make results difficult to analyze and interpret. Dr Delacollette noted that having a good monitoring and surveillance system goes hand in hand with a response system, and there is a need to turn research into policy change by increasing connection between researchers and programme managers. He emphasized that because malaria cases and artemisinin resistance are concentrated in border areas, the regional network plays an important role in the monitoring and surveillance of artemisinin resistance across countries. This enables a better coordinated effort

to elaborate common strategies to contain and combat artemisinin resistance. Finally, he summarized the role of the drug resistance monitoring network to contribute to the following activities: (a) agree on the use of standardized tools; (b) increase the capacity of investigators to perform quality studies; (c) exchange data and information; (d) strengthen good practices; and (e) provide incontrovertible evidence for action. Successful networking models such as the Mekong in vivo TES model help to attract donors’ interest and additional funding to develop and support multipartners’ supranational interventions, for example the bi-country/bi-regional artemisinin resistance containment project along the Cambodia-Thailand border. 2.1.5 Containment of artemisinin resistance on the Cambodia-Thailand border

Dr Najibullah Habib, Technical Officer, Malaria, other Vectorborne and Parasitic Diseases, WHO Cambodia, made a presentation on the artemisinin resistance containment project on the Cambodia-Thailand border, of which he is the manager. The containment project is a multi-pronged emergency intervention to eliminate falciparum malaria in target areas. A map of the malaria containment zones was presented. Zone 1, where artemisinin resistance is confirmed, is targeted for malaria elimination, and Zone 2 is targeted for intense malaria control. Both zones are located mainly along the Cambodia-Thailand border. The targeted population in 10 provinces in Cambodia and seven provinces in Thailand consists of over five million people. Dr Habib described the seven pillars of the containment strategies: (1) to eliminate resistant parasites by detecting all malaria cases in target areas and effective treatment and gametocyte clearance; (2) to decrease drug pressure for selection of artemisinin-resistant malaria parasites; (3) to prevent transmission of resistant parasites by mosquito control and personal protection; (4) to limit the spread of resistant parasites by mobile /migrant populations; (5) to support containment/elimination of resistant parasites through behaviour change communication, and advocacy; (6) to undertake basic and operational research to fill knowledge gaps and ensure evidence-based strategies; and (7) to provide effective management and coordination for rapid and high quality implementation. The containment project involves multiple avenues and approaches. It engages village malaria workers (VMW) who are able to diagnose malaria with the help of rapid diagnostic tests (RDTs) and treat with artemisinin-based combination therapy (ACT) malaria cases in the community; the anti-economic crime police, appointed to inspect drug outlets for artemisinin monotherapies and fake and substandard drugs; and taxi drivers who can reach out to migrant populations. Dr Habib also demonstrated Thailand’s malaria information system or BIOPHICS. This system consists of: real-time mapping, case tracking and follow-up, SMS reporting, monitoring situations and trends, and summary reporting, among others. Finally, a summary of the lessons learned from this project was presented. Overall, the containment project is having a positive impact; its flexibility and responsiveness are appreciated by partners, and good collaboration along with strong management helps in the effective implementation of containment efforts. The project demonstrated the important role of

monitoring resistance in detecting artemisinin resistance, and the experience is extremely useful for the countries in the WHO Western Pacific Region. 2.1.6 Wrap-up

Dr Qin Cheng of the Australian Army Malaria Institute commented on the speakers’ review of the situation of malaria drug resistance, and highlighted the importance of drug resistance monitoring as well as the effectiveness of a monitoring network. Overall, the malaria incidence rate is on a decreasing trend, yet malaria is still a major health problem in the Western Pacific countries. With drug resistance becoming widespread, ACTs were introduced to all countries over the past five years. As ACTs are the cornerstone of malaria programmes, resistance to ACT poses a threat to all recent gains. Therefore, countries must continue their drug resistance monitoring efforts, and a network will give the countries a greater chance of succeeding in the fight against drug resistance. The benefits and role of the network are summarized below. Benefits of a regional drug resistance monitoring network:  standardized study design, protocols, methods, SOPs;  availability of comparable data;  sharing and exchange of information and experiences;  better control of border malaria;  coordinated efforts and policy changes;  better country support and capacity-building;  sharing human resources, connecting research and operational teams; and  liaising with donors and seeking funds with one voice. Role of a regional drug resistance monitoring network:  to identify problems and prioritize activities;  to bridge different WHO Regions;  to standardize study design, protocols, methods and SOPs;  to share and exchange information, experience and human resources  to coordinate efforts and policy changes;  to connect research and operational teams;  to liaise with donors and seek funds; and  to document good practice and coordinate publications.

2.2 2.2.1

Technical Session 2: Country updates on the malaria situation, treatment policy, drug resistance situation and monitoring Philippines

Dr Mario Baquilod, Medical Officer, National Center for Disease Prevention and Control, Department of Health, Philippines, presented drug resistance monitoring data from the Philippines. The Philippines has moved into micro-stratification of the endemic areas to better target control interventions (to village level). Dr Baquilod also presented graphs depicting the decrease of malaria morbidity and mortality over the past ten years. Therapeutic efficacy studies (TES) were regularly performed in the Philippines until 2009, showing more than 95% efficacy of arthemeter-lumefantrine (AL) and chloroquine (CQ). 2.2.2 Malaysia

Dr Christina Rundi, Senior Principal Assistant Director, Disease Control Division, Ministry of Health, Malaysia, described the national strategic plan for malaria elimination. The plan consists of seven elements: (1) surveillance system; (2) integrated vector management; (3) early detection and prompt treatment; (4) preparedness and outbreak response; (5) communication and social mobilization; (6) capacity-building; and (7) operational research. At present, Malaysia has moved into micro-stratification of the endemic areas. The national antibiotic guideline and the national guideline on the management of malaria were also discussed. Dr Rundi informed that the national guideline on the management of malaria is currently under revision. The national antimalaria drug response surveillance programme began in 2003 in eighteen sentinel sites in the country. As of 2006, there was some evidence of treatment failure with chloroquine and sulphadoxine-pyrimethamine. However, the programme is also currently under review as the number of falciparum malaria cases is on the decline, and there is the need to include other antimalarial drugs. 2.2.3 Papua New Guinea

Dr Inoni Betuela, Head of Vectorborne Disease Unit, Papua New Guinea Institute of Medical Research (PNG-IMR), presented the data on the current situation in Papua New Guinea. Papua New Guinea is endemic to all four human malaria species and remains a high-burden country, with a higher prevalence in those older than 15 years old. The data show the P. vivax peaks in age groups less than four years. Although bed net/long-lasting insecticidal net (LLIN) coverage is more than 50% at household and village levels, surveys have shown less than 40% bed net use among the high-risk groups of pregnant women and children under five. There is less than 20% availability of diagnostic services and drugs in health facilities. Baseline TES of artemisinin-based combination therapies (ACTs) in 2005– 2007 by PNG-IMR showed high efficacy: 90% of artesunate-sulfadoxine-pyrimethamine (ASU-SP), as well as dihydroartemisinin-piperaquine (DHA-PIP), and 95% of arthemeterlumefantrine (AL). A concern for the country is the wide availability of antimalarial monotherapies (CQ, SP and artemisinins).

2.2.4

Solomon Islands

Dr Lyndes Wini, Medical Officer, Malaria and other Vectorborne Diseases Control Program, Ministry of Health, Solomon Islands, presented on the malaria situation in Solomon Islands, their current treatment policy and drug resistance situation. Over the past ten years, confirmed malaria cases have decreased. In the provinces, there have been decreased incidence rates from 2009–2011, and Isabel and Temotu provinces are now targeted for malaria elimination. Currently, all health facilities have ACT supplies and are provided with treatment guidelines. With CQ and SP still widely available, there is still a high proportion of presumptive treatments in the private sector, including among pregnant women. TES has been performed since 1994 and continues to the present. In 2008–2009, an AL efficacy study was conducted in Malaita province, demonstrating 100% and 96% adequate clinical and parasitological response (ACPR) in P. falciparum and P. vivax, respectively. There are still major challenges faced by Solomon Islands. Due to diverse malaria profiles, remoteness and scattered populations, malaria stratification has yet to be performed. Laboratory diagnosis is limited to only 58% of health facilities, and there is a low uptake of RDTs, which may be due to the historical use of microscopy as a way of diagnosis since people are not yet used to RDTs. Also, regular drug resistance monitoring has yet to be institutionalized. 2.2.5 Vanuatu

Dr Edward Tambisari, Malaria Case Management Officer, Malaria Unit, Department of Health, Vanuatu, presented on Vanuatu’s current malaria situation, treatment policy and drug resistance and monitoring. According to the World Malaria Report 2010, the annual parasite incidence (API) in Vanuatu ranges from 10–50 cases per 1000 population across its islands. Overall, confirmed cases within the past ten years have decreased and API among the six provinces have also decreased between 2005–2010. For treatment policy, the first line treatment for falciparum and vivax malaria has changed from CQ+ SP to AL. Also, since the introduction of RDTs from hospital to community level, diagnostic coverage has increased to greater than 90% as of May 2011. TES has been performed since 2001. Vanuatu is showing an increasing proportion of vivax cases in recent years. CQ+ SP was still effective (95% ACPR in 2005) when the country shifted to AL in 2007. There is an on-going P. falciparum and P. vivax therapeutic efficacy study in progress that started in March 2011, with four P. falciparum and 34 P. vivax cases enrolled so far. 2.2.6 Indonesia

Dr Worowijat, National Malaria Control Programme, Ministry of Health, Indonesia, discussed the malaria epidemiological profile of Indonesia. Malaria is the sixth leading causes of mortality by communicable diseases among all age groups (based on basic health research in 2007). There are a number of areas throughout Indonesia which have CQ or multidrug resistant malaria. A 2010 study showed that DHA-PIP was safe and effective for P. falciparum and P. vivax, with adequate clinical and parasitological responses (ACPR) of 100% and 97.6% respectively. To combat malaria, Indonesia' s national malaria elimination strategy has four objectives: (1) to decrease villages with five or more per 1000 population malaria incidence rate by 50%; (2) to ensure all districts and cities are able to conduct confirmation of suspected malaria cases and treat 100% of these cases with ACT; (3) to ensure all endemic areas intensify and integrate malaria control; and

(4) to begin step-wise elimination of malaria by islands. To combat and eliminate malaria, Indonesia has adopted an approach to guarantee that diagnosis is confirmed by either microscopy or RDT; ACTs are prescribed; bednets and indoor residual spraying (IRS) are used for prevention; and intersectoral collaboration and community participation are recognized as necessary. 2.2.7 Wrap-up

Dr Dorina Bustos noted that most countries have moved to ACTs and are using parasite-based diagnosis, either microscopy or RDTs. It is noteworthy that Solomon Islands and Vanuatu have successfully rolled out ACTs and RDTs in the last two years with Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund) support, and are now showing significant decreases in the morbidity and mortality rates. In general, country updates showed that there is a significant variation among countries that conduct TES: different protocols, different reporting systems, and different capacities. The disparity calls for harmonization. 2.3 Technical Session 3: Update on technical issues to strengthen drug resistance monitoring

2.3.1 Update on methods for antimalarial drug resistance monitoring and use of the WHO standard protocol Dr Lasse Vestergaard, Medical Officer, Malaria, other Vectorborne and Parasitic Diseases, WHO Country Office in Vanuatu, made a presentation on the methods for drug resistance monitoring and the WHO standard protocol. Because many factors affect antimalarial treatment efficacy, standardization of methods and outcome classification are critical. Therapeutic efficacy studies are the most important to guide national treatment policy. In order to obtain high-quality results, quality assurance of procedures, continuous training and capacity-building are critical. The WHO protocol for assessment of therapeutic efficacy is the gold standard for treatment policy change. Dr Vestergaard then reviewed the definitions of different test outcomes based on clinical and parasitological criteria. He also mentioned parasite genotyping, mandatory with the 2009 protocol, to ensure correct interpretation of therapeutic efficacy results. Lastly, he acknowledged that in many countries, monitoring is already in place. The network would provide better coordination and standardization of work which are already in progress. 2.3.2 Practical issues of using the WHO standard protocol

Dr Dorina Bustos, Technical Officer, WHO Mekong Malaria Programme, WHO Regional Office for South-East Asia, examined the practical implications of adherence to the TES protocol. She discussed the WHO Ethics Review Committee (ERC) requirements in the submission of a protocol. A full protocol, signed by the principal investigator and endorsed by the Ministry of Health or director of the institute, an informed consent form in English and the local language, clearance from the national ethics committee, and annexes are required for submission of a protocol. She also spoke about the various sections of a study protocol, and considerations for each section, including challenges of selecting appropriate sentinel sites and achieving adequate sample size in low-transmission settings. Adherence to standard laboratory practices was also mentioned. Technical and administrative constraints such as data management, technical report writing, and re-training of TES field implementers and microscopists are required to ensure good clinical practices. Dr Bustos also reviewed important lessons learnt from performing TES in Mekong countries and made seven recommendations: (1) TES staff of the national programmes should be trained in quality control procedures in general.

(2) Mid-level management skills of the TES leader:    a wide supervisory role the ability to take stock of project logistics, manpower needs; and familiarity with timelines, procedures and requirements of overall implementation

(3) Timely data analysis should be ensured. (4) Coordination/meetings with border provinces/countries should be conducted regularly. (5) Cross-country monitoring by principal investigators should include careful observation and learning of best practices. (6) Countries should have a core of “qualified microscopists” (WHO certified) assigned to the sentinel sites who periodically undergo proficiency assessment and re-training to ensure quality assurance in malaria diagnosis and parasite counting. (7) Study drugs that have undergone quality control in an external laboratory should be available for TES. 2.3.3 Use of laboratory methods to monitor antimalarial drug resistance

Dr Qin Cheng of the Australian Army Malaria Institute provided a comprehensive review of the tools used to monitor antimalarial drug resistance from the perspective of the laboratory including TES, in vitro susceptibility testing, molecular markers and measurement of blood drug concentrations. It was acknowledged that for all tools, the methods are often more developed for P. falciparum than P. vivax. Dr Cheng gave an update on the genotyping methods for both P. falciparum and P. vivax used to support TES, and also asked participants to consider how to classify patients who are found to be positive by PCR but negative by microscopy during TES. In vitro tools remain imperfect, due to the wide variation in use of methods, and the lack of standardized thresholds. Since many of the molecular markers are only available for a limited number of drugs (e.g. molecular markers for artemisinin resistance are still unknown), molecular makers are currently useful for monitoring the spread of resistance for only some companion drugs of ACTs. Importantly, samples should be saved for future analysis, when molecular markers become available. 2.3.4 Health research involving human subjects: ethical considerations and procedures to follow Dr Jun Nakagawa, Technical Officer, Malaria, other Vectorborne and Parasitic Diseases, WHO Regional Office for the Western Pacific, presented an overview of the current research protocol and the ethical considerations when conducting research involving humans. Researchers conducting TES in the Pacific need to be cognizant of ethical considerations and procedures because therapeutic efficacy studies involve human subjects; hence, the need for an ethical review of protocols. Background information on why ethical reviews are conducted and guidelines and best practices concerning human subjects were reviewed. The function and structure of the ethics review committee (ERC) of the WHO Regional Office for the Western Pacific was also discussed. Dr Nakagawa explained the process of submitting a protocol and the required documents for submission to the ERC of the Regional Office. He concluded with proposals on how to improve protocols for submission and the submission process itself.

2.3.5

Wrap-up

Therapeutic efficacy studies remain the gold standard which guides national treatment policy change. Other tools (e.g. molecular markers, in vitro and pharmacokinetic studies) exist to help detect and confirm drug resistance. Adherence to good clinical practices, standardized methods, and quality assurance of laboratory methods are critical for the early detection of antimalarial drug resistance. 2.4 Group work: development of Pacific malaria drug resistance monitoring plan

The tasks of the groups were to formulate a two-year national therapeutic efficacy study plan for each country, identify the role of partners and envisage the role of a proposed Pacific malaria drug resistance monitoring network. Participants were divided into two groups: Group 1: Papua New Guinea, Solomon Islands and Vanuatu, facilitated by Dr Lasse Vestergaard Group 2: Indonesia, Malaysia, Philippines, and (on behalf of WHO Regional Office for South-East Asia), facilitated by Dr Dorina Bustos. 2.4.1 Presentation of group work

Each country presented its current and future TES plans, the required inputs for TES plans, such as human resources, technical assistance and capacity-building, and gaps that need to be filled in order to improve its programme along with WHO’s or other partners' role in filling these gaps. The results of the group work are presented in Annexes 3 to 5. 2.4.2 Wrap-up

Dr Inoni Betuela, Head of Vectorborne Disease Unit, Papua New Guinea Institute of Medical Research (PNG-IMR), summarized the TES that the countries have worked on. Dr Betuela noted that due to the different needs and stages of ACT, member countries need to take country-specific approaches, with the help of WHO. Also, funding for new clinical trials and the sustainability of the existing or established trials is a major issue as many countries are dependent on donor funding. Lastly, he commended WHO for the standardizing the TES protocol and expressed that it is now up to countries to follow and implement. 2.5 Consensus on the need for a Pacific malaria drug resistance monitoring network

Dr Eva Christophel led a discussion on the need for a malaria drug resistance monitoring network in the Pacific and the possible added value of such a network, in addition to what is already being performed at the country level. The discussion included therapeutic efficacy studies and training needs, as well as a possible extension of the network to include China, the Republic of Korea and the Democratic People’s Republic of Korea. Dr Christophel emphasized that the focus for the Pacific is on producing high-quality and regular therapeutic efficacy studies. Possible and current partners for technical support were mentioned for different areas of need, such as training, clinical monitoring and laboratory support. The question of one designated network laboratory was broached since there are multiple partners supporting this need but with varying methodologies. Working together to harmonize and standardize protocols is therefore a necessary step.

A consensus was reached on the establishment of a Pacific malaria drug resistance monitoring network, comprising of seven countries: Indonesia, Malaysia, Papua New Guinea, the Philippines, Solomon Islands, Timor Leste and Vanuatu. It was also decided that the group would ask China, the Republic of Korea and the Democratic People’s Republic of Korea whether they would be willing to join the network. The representatives of the Member States present expressed their wish for WHO to lead the network and to establish a full-time Secretariat. 2.6 Technical Session 4: Establishment of the Pacific Malaria Drug Resistance Monitoring Network

2.6.1 Proposed terms of reference, members, partners, coordination and communication mechanisms Dr Lasse Vestergaard presented a draft of the goals, objectives, functions and outputs of the proposed Pacific Malaria Drug Resistance Monitoring Network. The proposed goals are: (1) to provide the best evidence for treatment policy; and (2) to allow early detection of any emerging artemisinin resistance in the countries. The proposed objectives of the network are: (1) to support member countries towards the implementation of routine monitoring of antimalarial therapeutic efficacy studies of first and second line treatments; (2) to support countries in the collection and management of antimalarial drug efficacy data, review of data and reporting, maintenance of the national and Pacific network databases, and mapping of drug resistance; (3) to support countries in reviewing and implementing national malaria treatment policies; (4) to identify training needs for data collection, data analysis and reporting; (5) to assist coordination of regional efforts in support of antimalarial drug efficacy monitoring in Pacific countries, such as: establishing linkages with other similar networks; convening meetings to review progress made; assisting in planning, budgeting and coordination of future antimalarial drug efficacy monitoring activities, including review of sentinel sites; establishing a network of reference laboratories; and (6) to provide additional support as relevant regarding malaria treatment, including improving access to appropriate and good quality antimalarials (i.e. ACTs), improving parasite-based diagnosis, improving prescribing and rational use of antimalarials, and enforcing regulations and legislation (e.g. against the use of artemisinin monotherapies).

The functions of the network include: (1) setting up an office with a full-time or part-time coordinator (WHO staff member) to provide technical support and day-to-day running of network activities including reporting; organizing network meetings every two years for network countries to present results and discuss any technical or operational issues, and facilitating intercountry communication and collaboration; organizing relevant training seminars and technical workshops; supporting countries in developing and updating their national TES plans and budgets; supporting countries in TES protocol development and facilitation of ethics reviews; facilitating coordination of country support from reference laboratories; providing clinical monitoring visits and other technical support to ongoing studies, and assist in analysis and reporting of results to Ministries of Health and regional databases; assisting countries in reviewing and updating national malaria treatment policies; facilitating information sharing within the network, e.g. through a dedicated website; assisting in resource mobilization, e.g. contributing to writing funding proposals; assisting in advocacy, awareness raising, and political support; and linking the Pacific region to other regions and networks, and ensuring rapid exchange of relevant news and lessons learned.

(2)

(3) (4) (5) (6) (7)

(8) (9) (10) (11) (12)

The outputs of the network would be: (1) availability of high-quality antimalarial drug efficacy data through harmonization of procedures between network countries; (2) relevant technical assistance for standardized TES implementation at country level and data management; (3) organization of reference laboratory support; (4) timely reviews of efficacy results to inform national treatment policies; (5) effective information sharing between countries to alert them of the need to revise TES plans in the case of signs of emerging artemisinin resistance; (6) effective QA systems in place at all levels; (7) continuous training and capacity-building of national staff; and

(8) mobilized resources. These proposed terms of reference were broad and many were interlinked. A plenary discussion followed on needs and priority actions. The finalization of the TOR and the recommendations were referred to a working group (see 2.7.2). 2.7 2.7.1 Training session and group work Training on data entry and analysis

Dr Dorina Bustos presented during a training session an excel file which is currently being used for inputting malaria TES case data. This file can be adapted to each country in order to simplify and standardize data collection and analysis. 2.7.2 Group work: Refining terms of reference and recommendation for the Pacific Malaria Drug Resistance Monitoring Network Dr Christina Rundi, Senior Principal Assistant Director, Disease Control Division, Ministry of Health, Malaysia, presented the outcome of the group work on defining the terms of reference for the Pacific Malaria Drug Resistance Monitoring Network, and a consensus was reached in the plenary session (Annex 6). Goal: To support countries in the Pacific to generate and share up-to-date, high quality evidence on antimalarial drug efficacy to inform malaria policies. Network objectives: (1) to support countries (programmes and research institutions) to implement the WHO standard protocol for routine monitoring of antimalarial therapeutic efficacy of first and second line treatments for P. falciparum and P. vivax; (2) to identify training needs and coordinate capacity-building for high-quality drug resistance surveillance; (3) to coordinate laboratory support to countries and facilitate the use of WHO-recommended standard procedures, and contribute to the development of new procedures where they are not available; (4) to coordinate independent monitoring and review of TES data; (5) to facilitate the timely reporting and sharing of TES results; (6) to coordinate network activities and facilitate collaboration through regional informal consultations, regional planning, resource mobilization and review of progress; (7) to support countries in reviewing national malaria treatment policies (if requested); and (8) to facilitate operational research to address knowledge gaps related to antimalarial drug resistance monitoring.

3. CONCLUSIONS AND RECOMMENDATIONS

In the plenary discussion, Dr Christophel presented the draft conclusions of the meeting and recommendations. These were discussed and refined by the participants. 3.1 Conclusions

The first half of the meeting focused on reviewing drug resistance data from each country and the issues with drug resistance monitoring. Artemisinin resistance is becoming a palpable threat in the Region. As the threat of resistance grows, there is a call for harmonization of protocols and quality assurance capacity-building across countries for therapeutic efficacy studies. The need for networking and improved coordination between countries, regional research institutions and WHO, was evident. The overarching objective of the meeting focused on the need and added benefits of a malaria monitoring network for the Pacific. A consensus was reached to create a Pacific Malaria Drug Resistance Monitoring Network. This network will be comprised of five countries in the WHO Western Pacific Region (Malaysia; Papua New Guinea, the Philippines, Solomon Islands and Vanuatu) and two countries in the WHO South-East Asia Region (Indonesia and Timor Leste). Member States wanted WHO to lead this network and establish a full-time secretariat. Terms of reference of the network and recommendations for the network were agreed upon by the meeting participants. 3.2 Recommendations (1) With antimalarial drug resistance being a major threat in the Region, antimalarial drug resistance monitoring efforts led by country programmes should be strengthened, intensified and coordinated. (2) The Pacific Malaria Drug Resistance Monitoring Network should be established and coordinated by WHO (with a full-time Secretariat). (3) WHO and partners should immediately start mobilizing adequate resources for establishment of the Secretariat and core activities. (4) The draft two-year national drug efficacy monitoring plans should be finalized and endorsed by each country by the end of 2011. (5) Countries should follow the latest WHO protocol for the antimalarial drug efficacy monitoring. (6) Countries should identify their capacity-building and technical assistance needs and seek assistance from the network partners. (7) Country data should be regularly reviewed (including for Day 3 positivity as an early warning sign for emerging artemisinin resistance) and shared within the network. (8) The network should convene a TES workshop for all Pacific country focal points and principal investigators within one year, and hold a full network meeting every two years, to review progress and support high-quality TES implementation.

TIMETABLE Day 1 Registration Opening Ceremony Opening remarks by the Regional Director WHO WPRO Self introduction of participants Nomination of Chair, Vice Chairs and Rapporteur Group photograph 9:15 9:45 Coffee Break Technical session 1: Role of antimalarial drug efficacy monitoring 10 minute presentations followed by 5 minutes discussion P. falciparum and P. vivax resistance to antimalarial medicines: a global overview (including the role of networks) – Amy Barrette/Pascal Ringwald, WHO GMP/HQ 10:0 0 Overview of malaria situation and drug resistance in the Western Pacific Region, and meeting objectives – Eva Christophel, WPRO Antimalarial drug resistance in the SouthEast Asian Region – Mushfiqur Rahman, WHO SEARO 10:1 5 10:3 0 Lessons learnt from the Greater Mekong Subregion: antimalarial drug resistance, artemisinin resistance and containment, the role of the Mekong Malaria Programme network – Charles Delacollette, WHO MMP Containment of artemisinin resistance on the Cambodia-Thailand border – Najibullah Habib 10:30 11:00 Discussion Wrap-up & recommendations - Dr Inoni Betuela, IMR/PNG Coffee Break Technical session 4: Establishment of the Pacific Malaria Drug Resistance Monitoring Network 10 minute presentations followed by 5 minutes discussion Proposed Terms of Reference for the Pacific Network, members, partners, coordination and communication mechanisms – Lasse Vestergaard, WHO Vanuatu, Walter Kazadi – Mulombo, WHO Solomon Islands TA and financial gaps, next steps – Dorina Bustos, WHO MMP Wrap-up & recommendations – Charles Delacollette, WHO MMP and Amy Barrette, WHO GMP Day 2 Summary of Day 1 by Walter Kazadi-Mulombo, WHO Solomon Islands and Seyha Ros, WHO Vanuatu Presentation of Group work: - country work plans for routine efficacy monitoring - role of partners - Pacific network

8:00 8:30

8:30 8:45

10.4 5 11.0 0

Discussion Wrap-up & recommendations - Qin Cheng, AAMI Technical session 2: Country updates: Malaria situation, treatment policy, drug resistance situation and monitoring 10 minute presentations followed by 5 minutes discussion - Philippines, Malaysia - Papa New Guinea, Solomon Islands, Vanuatu

11.1 5

12:30 1:30

Lunch Technical session 2: continued - East Timor, Indonesia Discussion Wrap-up & recommendations - Dorina Bustos, WHO MMP Technical session 3: Update on technical issues to strengthen drug resistance monitoring 10 minute presentations followed by 5 minutes discussion Update on methods for antimalarial drug resistance monitoring and use of the WHO standard protocol – Lasse Vestergaard, WHO Vanuatu Practical issues of using the WHO standard protocol, including sentinel site selection, frequency of studies, data analysis, monitoring; Challenges and ways forward for anti-malarial drug efficacy monitoring in settings with decreasing malaria transmission – Dorina Bustos, WHO MMP Use of laboratory methods to monitor antimalarial drug resistance

12:30 1:30

Lunch Training on data entry and analysis – Dorina Bustos

2.00

2.15

2.30

2.45

3.00

(including molecular markers of resistance, in vitro testing) – Qin Cheng, Australian Army Malaria Institute Health research involving human subjects: ethical considerations and procedures to follow – Jun Nakagawa, WHO WPRO

3.15 Discussion Wrap-up & recommendations - Amy Barrette, GMP/HQ 3:30 3:45 4:15 Afternoon Tea Group work: Development of a 2-year Pacific Malaria Drug Resistance Monitoring Plan Introduction to group work Closing Tasks: 1. 2-year national plans (where, what, who) 2. role of partners 3. role of Pacific network Groups 1: Papa New Guinea, Solomon Islands, Vanuatu + partners – Facilitator: Dr Lasse Vestergaard 2. Philippines, Malaysia, Indonesia + partners – Facilitator: Dr Dorin Bustos 5:30 Close for the Day Refreshments hosted by WHO 5:00 3:30 4:00 Afternoon Tea Plenary session: Meeting conclusions and recommendations - Eva Christophel, WHO WPRO

ANNEX 2 LIST OF PARTICIPANTS, TEMPORARY ADVISERS, REPRESENTATIVES/OBSERVERS AND SECRETARIAT

1. PARTICIPANTS

INDONESIA

Tel No. E-mail

Dr Pranti Sri Mulyani National Malaria Control Programme Ministry of Health Jalan HR Rasana Said Blok X.5 Kav 4-9 Jakarta : +6221 4287 1369/+62811 896032(mob) : Pranti68@yahoo.com Dr Worowijat National Malaria Control Programme Ministry of Health Jalan HR Rasana Said Blok X.5 Kav 4-9 Jakarta : +6221 4287 1369/+62856 7203454(mob) : vizz2vizz@yahoo.com Dr Jenarun Jelip Principal Assistant Director Jabatan Kesihatan Negeri Sabah P.O. Box 11290, 88814, Kota Kinabalu, Sabah : +608 8724 122 : drjenarun@gmail.com Dr Christina Rundi Senior Principal Assistant Director Disease Control Division Ministry of Health Malaysia Level 4, Block E10, Complex E Federal Government Administrative Centre 62590 Putrajaya : +603 8883 4268/019 5839528 : +603 8888 6215 : drchristinarundi@moh.gov.my Mr Leo Makita Department of Health P.O. Box 807 Waigani : +675 3013819 : +675 3253523 : makitals@global.net.pg

Tel No. E-mail MALAYSIA

Tel No. Fax No. E-mail PAPUA NEW GUINEA

Tel No. Fax No. E-mail

Tel No. Fax No. E-mail PHILIPPINES

Professor Peter Siba Director and CEO Papua New Guinea Institute of Medical Research P.O. Box 60, Goroka, EHP : +675 532 1998 : +675 532 2800 : pmaxsiba@gmail.com Dr Mario S. Baquilod Medical Officer VII National Center for Disease Prevention and Control Department of Health San Lazaro Compound, Sta Cruz, Manila : +632 743-8301 to 23 : +632 711-6744 : marbaquilod@yahoo.com Dr Fe Esperanza Caridad J. Espino Head, Department of Parasitology Medical Specialist Research Institute for Tropical Medicine FILINVEST Corporate City, Alabang, Muntinlupa City, 1781 : +632 807-2628 to 32 loc 227/804 : +632 842-2245 : fespino_2000@yahoo.com Dr Albino Bobogare Director VBDC Program VBDCP, Ministry of Health P.O. Box 349 Honiara Tel No. : +677 39748 Fax No. : +677 30655 E-mail : abobogare@gmail.com Dr Lyndes Wini Medical Officer - VBDC Program VBDCP, Ministry of Health P.O. Box 349 Honiara : +677 30410 : +677 30655 : lyndes.wini@gmail.com Dr Tenneth Dalipanda Director of Public Health Ministry of Health and Medical Services P.O. Box 349, Honiara : +677 23205 : +677 20085 : tdalipanda@moh.gov.sb

Tel No. Fax No. E-mail

Tel No. Fax No. E-mail SOLOMON ISLANDS

Tel No. Fax No. E-mail

VANUATU

Tel No. E-mail

Mr Esau Naket Malaria Case Management Nurse - Malaria Unit Ministry of Public Health Ministry of Health Simbolo Redlight, P.O. Box 394 Port Vila : +775 2427 : enaket@vanuatu.gov.vu

Tel No. E-mail

Mr Edward Tambisari Malaria Case Management Officer - Malaria Unit Department of Public Health Department of Health P.O. Box 1116 Port Vila : +678 592 8487 : dredwardt@gmail.com

2. TEMPORARY ADVISERS AUSTRALIAN ARMY MALARIA INSTITUTE Dr Qin Cheng Head Drug Resistance and Diagnostics Weary Dunlop Drive, Gallipoli Barracks, Enoggera, Brisbane, Qld 4051, Australia : +61 7 3332 4834 : +61 7 3332 4800 : Qin.Cheng@defence.gov.au Dr Inoni Betuela Head – Vectorborne Disease Unit P.O. Box 60, Goroka, EHP : +675 532 2800 : +675 532 1998 : ibetuela@gmail.com

Tel No. Fax No. E-mail PAPUA NEW GUINEA INSTITUTE OF MEDICAL RESEARCH Tel No. Fax No. E-mail

3. OBSERVERS AUSTRALIAN AGENCY FOR INTERNATIONAL DEVELOPMENT (AUSAID) Ms Joanne Greenfield Health Adviser Health and HIV Thematic Group P.O. Box 887 Canberra ACT 2601 : +61 2 6206 4600 : +61 2 6206 4878 : Joanne.Greenfield@ausaid.gov.au

Tel No. Fax No. E-mail

BILL AND MELINDA GATES FOUNDATION

Tel No. Fax No. E-mail SECRETARIAT OF THE PACIFIC COMMUNITY

Dr Thomas Kanyok Senior Programme Officer P.O. Box 23350 Seattle, WA 98102 : (206) 709-3100 : +1.206.494.7039 : Thomas.Kanyok@gatesfoundation.org Mrs Lilian Sauni Grant Coordinator - Malaria Grant Management Unit Floor 3, Anthony Saru Building Hibiscus Avenue, Honiara : +677 38022, 25543 or 25574 : +677 25547 : lilians@spc.int 4. SECRETARIAT

Tel No. Fax No. E-mail

WHO/HQ

Tel No. Fax No. E-mail WHO/SEARO

Ms Amy Barrette Technical Officer Global Malaria Programme World Health Organization Avenue Appia 20 1211 Geneva 27 : +41 22 791 1648 : +41 22 791 4824 : barrettea@who.int Dr. Md Mushfiqur Rahman Temporary International Professional (Malaria) Malaria Unit, Department of Communicable Diseases World Health Organization Regional Office for South-East Asia I.P. Estate, New Delhi -11002 : +911123370804, ext 26694 : +911123378412 : rahmanmdr@searo.who.int Dr Charles Delacollette Coordinator WHO Mekong Malaria Programme Faculty of Tropical Medicine, Mahidol University 420/6, 7th Floor, New Charlermprakiat Building Ratchawithi Road, 10400 Bangkok : +66 2 643 5860 : +66 2 643 5870 : Delacollette@searo.who.int Dr Dorina Bustos Malaria Technical Officer WHO-Mekong Malaria Programme 7th Floor, New Chalermprakiat Building (60 years) Faculty of Tropical Medicine Mahidol University 420/6 Ratchawithi Rd., Bangkok 10400 : +662 643 5859 : +662 643 5860 : bustosm@searo.who.int

Tel No. Fax No. E-mail WHO/SEARO/MMP

Tel No. Fax No. E-mail

WHO/WPRO

Tel No. Fax No. E-mail

Dr Eva Maria Christophel Team Leader Malaria, Other Vectorborne and Parasitic Diseases The World Health Organization Regional Office for the Western Pacific P.O. Box 2932, 1000 Manila : +632 528-9723 : +632 521-1036 : christophele@wpro.who.int Dr Bayo Fatunmbi Technical Officer (Monitroing & Evaluation) Malaria, Other Vectorborne and Parasitic Diseases The World Health Organization Regional Office for the Western Pacific P.O. Box 2932, 1000 Manila : +632 528 9725 : +632 521 1036 : fatunmbib@wpro.who.int Dr Budiono Santoso Team Leader Essential Medicines and Health Technologies WHO Regional Office for the Western Pacific 1000 Manila : +632 5289846 : +632 5211036 : santosob@wpro.who.int Dr Najibullah Habib Technical Officer Malaria, Other Vectorborne and Parasitic Diseases World Health Organization No. 177-179 corner Streets Pasteur(51) and 254 Sankat Chak Tomouk, Khan Daun Penh Phnom Penh : +855 23 216610/+855 12 505566 (mob) : +855 23-216211 : habibna@wpro.who.int Dr Harpal Singh National Professional Officer World Health Organization 1st Floor, Wisma WN, Block C, Komplek Pejabat Damansara, Jalan Dungun, Damansara Height 50490 Kuala Lumpur : +603-20939908 : +603- 20937446 : singhha@wpro.who.int Dr Zhang Zaixing Malariologist World Health Organization P.O. Box 5896 Boroko, NCD Papua New Guinea : +675 325 7827 ext. 418; : +675 325 0568 : zhangz@wpro.who.int

Tel No. Fax No. E-mail WHO/WPRO

Tel No. Fax No. E-mail WHO REPRESENTATIVE'S OFFICE, CAMBODIA

Tel No. Fax No. E-mail WHO REPRESENTATIVE'S OFFICE, MALAYSIA

Tel No. Fax No. E-mail WHO REPRESENTATIVE'S OFFICE, PAPUA NEW GUINEA

Tel No. Fax No. E-mail

Tel No. Fax No. E-mail WHO REPRESENTATIVE'S OFFICE, PHILIPPINES

Dr Rabindra Abeyasinghe Technical Officer (Malaria) World Health Organization P.O. Box 5896 Boroko, NCD : +675-3257827 : +675- 325-0568 : abeyasingher@wpro.who.int Dr Jeffrey Hii Scientist World Health Organization National Tuberculosis Centre Building Second Floor, Building 9, Department of Health Sta. Cruz, Manila : +63 2 528 9061 : +63 2 731 3914 : hiij@wpro.who.int Dr Walter Kazadi-Mulombo Medical Officer World Health Organization Ministry of Health Building Chinatown, Honiara Tel No. : +677 23406 Fax No. : +677 21344 E-mail : kazadimulombow@wpro.who.int Mr Kwabena Larbi Scientist Malaria, Other Vectorborne and Parasitic Diseases World Health Organization Ministry of Health Building Chinatown, Honiara : +677 23406 : +677 21344 : larbik@wpro.who.int Dr Lasse Vestergaard Medical Officer Malaria, Other Vectorborne and Parasitic Diseases Country Liaison Office World Health Organization P. O. Box 177 Port Vila : +678 27683 : +678 22 691 : vestergaardl@wpro.who.int

Tel No. Fax No. E-mail COUNTRY LIAISON OFFICE, SOLOMON ISLANDS

Tel No. Fax No. E-mail COUNTRY LIAISON OFFICE, VANUATU

Tel No. Fax No. E-mail

COUNTRY LIAISON OFFICE, VANUATU

Tel No. Fax No. E-mail

Dr Ros Seyha Scientist Country Liaison Office World Health Organization P. O. Box 177 Port Vila : +678 27 683 : +678 22 691 : ross@wpro.who.int

CURRENT (2010-2011) AND FUTURE (2012-2013) COUNTRY TES PLANS

Country

Parasite species

Current sentinel sites 2010-2011

Drugs tested 2010-2011

Current funding available 20102011

Proposed sentinel sites for 2012-2013

Drugs to be tested in 2012-2013

Anticipated funding available for 2012-2013

Pf Timor Leste

Nil

Suai Vila and Comoro Community Health Centres in Covalima and Dili districts

Funding available from GF (amount not known)

Nil

Aileu Vila and Formosa Community Health Centres in Aileu and Dili districts

Funding available from GF (amount not known)

Peninsular Malaysia: 8sites: Gua Musang; Raub; Lipis; Jerantut; Muadzam; Tapah; Gerik; Kemaman Malaysia Pf Sabah: 4 sites: Telupid; Kota Marudu; Bangi; Pitas Sarawak: 2 sites: Seri Aman; Serian

CQ: Peninsular Malaysia and Sarawak SP: Sabah

Peninsular Malaysia: 5 sites: Penang; Johor; Selangor; Kelantan; Kedah Malaysian Government Sabah: 4 sites: Keningau; Tawau; Kudat; Ranau Sarawak: 2 sites: Sibu ; Miri Artesunate – mefloquine or AL Malaysian Government (except for assets)

Country

Parasite species

Current sentinel sites 2010-2011

Drugs tested 2010-2011

Current funding available 20102011

Proposed sentinel sites for 2012-2013

Drugs to be tested in 2012-2013

Anticipated funding available for 2012-2013

Peninsular Malaysia: 5 sites: Penang; Johor; Selangor; Kelantan; Kedah Pv NA NA Sabah: 4 sites: Keningau; Tawau; Kudat; Ranau Sarawak: 2 sites: Sibu; Miri Pf Philippines Pv Palawan CQ GF/RBM project Palawan Same sites (ethical amendment to be in line with WHO current protocol) Same sites (ethical amendment to be in line with WHO current protocol) 2 sites: Malaita and Kira Kira Palawan AL GF/RBM project Luzon (Zambales)

CQ: Peninsular Malaysia Artesunate – mefloquine or AL: Sabah and Sarawak

Malaysian Government (except for assets)

AL, quinine AL (2012)

GF RBM project

Pf Papua New Guinea Pv

2 sites

Ongoing (under GF)

AL (ongoing)

GF/WHO

2 sites

Ongoing (under GF)

AL (ongoing)

GF/WHO

Solomon Islands

2 sites: Tetere and Munda

AL (ongoing)

Country

Parasite species

Current sentinel sites 2010-2011

Drugs tested 2010-2011

Current funding available 20102011

Proposed sentinel sites for 2012-2013

Drugs to be tested in 2012-2013

Anticipated funding available for 2012-2013

2 sites: Tetere and Munda 1 site 1 site 1. Lampung province (Sumatera 2010), by Prof Inge; 2. Kalimantan and Sulawesi, by Dr Emiliana;

AL (ongoing)

2 sites: Malaita and Kira Kira 1 site 1 site

Pf Vanuatu Pv

AL AL

GF/AusAID GF/AusAID

AL AL ASU-AMO & DHA-PIP: - 1 site in Lampung - 2 sites in Kalimantan & Sulawesi - 3 sites in East Nusa Tenggara (West Sumba, Flores & Atambua) - 1 sentinel in North Maluku DHA-PIP: - 1 site in Papua

GF GF

DHA-PIP (sites 1&3) ASU-AMO (site 2); DHA-PIP and ASU–AMO (sites 4 & 5)

Malaria Transmission Consortium (1); GF R8 (2); AusAid and Wellcome Trust; GF; WHO (3); WHO (4&5)

1 site in Lampung 2 sites in Kalimantan & Sulawesi; 1 site in Papua; 3 sites in East Nusa Tenggara (West Sumba, Flores & Atambua); 1 site in North Maluku

Indonesia

3. Timika (Papua), by Dr Jeane Rini; 4. East Nusa Tenggara (Dr. Syaffrudin from Eijkman and Dr Asep from Hospital); 5. North Maluku

WHO, GF, AusAID, Wellcome Trust

Country

Parasite species

Current sentinel sites 2010-2011

Drugs tested 2010-2011

Current funding available 20102011

Proposed sentinel sites for 2012-2013

Drugs to be tested in 2012-2013

Anticipated funding available for 2012-2013

1. Lampung Province (Sumatera 2010) by Prof Inge; 2. Kalimantan & Sulawesi, by Dr Emiliana; Pv 3. Timika (Papua) by Dr. Jeane Rini; 4. East Nusa Tenggara (Dr. Syaffrudin from Eijkman & Dr Asep from Hospital); 5. North Maluku Idem Pf AusAid & Wellcome Trust; GF; WHO (3); WHO (4&5) Malaria Transmission Consortium (1); GF R8 (2); Idem Pf Idem Pf Idem Pf

REQUIRED INPUTS FOR COUNTRY TES PLANS Country Human resources Already trained Transportation Supplies Technical assistance Yes Other components QA system Supervision Capacity building Yes Laboratory support Yes

Timor Leste

Yes

Malaysia

MOH, State, district, Institute of Medical Research

Staff travel, transport means; transporta-tion of samples

Microscopes; filter papers; packaging materials for samples; motorbikes Drug supplies (quality assessed), other drugs; laboratory supplies and consumables for malaria blood film, blood spot assays (genotyping); haemoglobin testing, pregnancy test; office supplies

Training (national; regional)

Progress meetings

Slide crosschecking (ongoing)

Site visits

Training at State level

Probes & primers, reagents, consumables

Philippines

Fulltime: experienced nurse/study coordinator (1) and medical technologist (1); Part time: data manager/encoder; driver (travel to site); barangay health workers

Airfare, vehicle hire for travel to site; local travel follow ups and home visits

Statistician, Molecular biology laboratory procedures

IRB review fee; patient costs; community incentives; communication; courier services; meetings with stakeholders; report writing; scientific presentations

Malaria microscopy QA; GCP site monitoring visits (by local independent group); sitespecific and site monitoring visit SOPs

WHO; malaria program coordinator

Orientation and training; assessment and reassessment of malaria microscopy proficiency; GCP training course

Molecular biology procedures; chloroquine metabolite assays

Papua New Guinea

Increase capacity

Add to fleet

Increase and add microscopy

Retraining of microscopy staff

Needs improvements

Improve on site

Clinical trial monitoring

Improve and set up in sentinal site

Solomon Islands

1. Principal investigator 2. Parasitologist x1 3. Field microscopists (WHO L1/L2) x 2 per site 4. Clinical staff x 2 per site 5. Field/ Community liaison x 2 6. Driver/ Logistician x1 per site 7. Site Coordinator 8. Admin x1 9. Coinvestigator x 1 10. Medical Monitor x 1 per site 11. Data Manager

1) Vehicle x3 2) OBM x 1 3) Canoe x 1 4) Safety at sea equipment

1) Reagents for BSE 2) Microscopes 3) Glass slides 4) Lancets (spring loaded) 5) Filter paper

1. Training (protocol implementation, data analysis and scientific report writing) 2. External QA (data validation, clinical monitoring, slide crosschecking & PCR)

1) Internal QA 2) External QA (see TA)

1. Site: local site coordinator 2. National: site visits twice a month

See TA (internal & external) (role of network)l)

See TA (internal & external)

Vanuatu

1. Principal investigator 2. Parasitologist x1 3. Field microscopists (WHO L1/L2) x 2 per site .

1) Vehicle x1

1) Reagents for BSE 2) Microscopes 3) Glass slides 4) Lancets (spring loaded) 5) Filter paper 6) Hemocue cuvettes 7) Thermometers 8) Weighing Scales 9) Stationaries 10) Desktop (central) 11) Laptops (field)

1. Training (protocol implementation, data analysis and scientific report writing) 2. External QA (data validatioin, cllinical monitoring, slide crosschecking & PCR)

1) Internal QA 2) External QA (see TA)

1. Site: local site coordinator 2. National: site visits twice a month

See TA (internal & external) (role of network)l)

See TA (internal & external)

Indonesia

NIHRD; Parasitology Department (University); Eijkman Institute; Hospital

self travel, public transport

Microscope, including supplies and reagents; stationery & others supplies

Training for technical asistant national level, training for microscopist

Mapping, data management, meeting, hospital fee & patient cost, publication

slide crosschecking by NIHRD; data validation, PCR

Visits; clinical, lab, protocol adherence, data management

Training, networking'

NIHRD, Eijkman Institute, Parasitology Department (University), Hospital & Regional Laboratory

MALARIA DRUG RESISTANCE MONITORING NETWORK – SITUATION / GAP ANALYSIS S/ No. Coun try NMCP TES Focal Point Principal Investigator & Institution Protocol used Data managemen t Reporting & Publications Last Treatment Guidelines Review Present source(s) of funding and amount available per year GF (amount not known) What is needed to improve TES / DRM? Measures to fill gap WHO’s role in gap filling?

Timor Leste

WHO

WHO excel sheet

2007 (AL)

Support needed for PCR , QA etc

Mala ysia

Directo r of Diseas e Control , MOH Malari a control coordin ator

Philip pines

National Malaria Control Programme, MOH and Institute for Medical Research Department of Parasitology, or Medical Department, Research Institute for Tropical Medicine

WHO 2003 but plan to use 2009 version

Technical report for MOH and WHO; Scientific publication Depts. of Parasitology, and Epidemiolog y and Biostatistics Peer review in Technical Working Group (TWG) meetings, feedback to stakeholders, technical reports to WHO (peer review) and sponsors, publications/ draft

2011 (ongoing revision)

Government funding (USD100,000)

Training on update of new TES protocol

Need to identify lab for PCR. TA needed for QA Training on update of new TES protocol

To identify the lab and provide TA

Assist in training

WHO, investigato r authored

2009 (by TWG and professiona l medical societies)

GF (USD42,380 for AL for Pf); RBM project (USD40,000 for CQ for Pv)

Dedicated, well-trained team; technical supervision; referral system and support for SAEs; increase capacity of reference laboratory; training of sentinel site

Training, institutional collaborations , advocacy (national and sub-national), networking; incorporate in national and local (sentinel site) plans

Training; updated guidelines, logistics for supplies and GMP drugs; independent site visits; technical review of draft manuscripts and reports

manuscripts, IRB

PNG

Leo Makita

Dr Inoni Betuela, Dr Manuel Hetzel

WHO 2009

PNGIMR internal database

Ongoing and biannual progress reports

2009

AusAID and Global Fund, AU$ 350,000

Solo mon Island s

Albino Bobog are

Dr Lyndes Wini

WHO 2009

WHO Excel Spreadsheet

Requires capacity building

2009

Vanu atu

George Taleo

WHO 2009 protocol

WHO TES Excel table

2007 (2009)

GF-RCC (USD 120,000 annually), AusAID (funds held with PacMISC) Global Fund RCC USD 60,000 2009-2011

teams; GCP monitoring by independent trained monitors; national, subnational, and local agencies support Funding, Human resource, Updating new TES protocol, TA, incountry AC Capacity building , External monitoring & validation

Financial support, TA

Funding and updating TES & QA

Pacific Drug Resistance Monitoring Network

Coordination, TA

Indon esia

1. Dr. Emiliana/ NIHRD

WHO

WHO & MoH

ASU-AMO and DHAPIP

USD

Staff training Training (clinic staff, workshops, microscopist, TA for study data monitoring management), and data clinical analysis, monitoring and supervision Molecular 1. Network marker 2. Funding training, update to the protocol, networking

Assist in review of efficacy results, revising treatment guidelines, provide training, assist in QA

1. Network 2. Funding WHO support

2. Prof. Dr. Inge/PD

WHO

WHO & MoH

DHA-PIP

US $

3. Dr. Syaffrudin /Eijkman Institute 4. Dr. Asep/ Hospital NTT

WHO

WHO & MoH

ASUAMO, DHA-PIP

USD 95,000

Molecular marker training update, networking Molecular marker training update Molecular marker training update Molecular marker training update

Networking

1. Network 2. Funding WHO support

Networking

1. Network 2. Funding WHO support

WHO

WHO & MoH

ASUAMO, DHA-PIP

USD 95,000

Networking

1. Network 2. Funding WHO support

5. Dr. Jeane /Hospital

WHO

WHO & MOH

ASUAMO, DHA-PIP

$ US 339,400 (in vivo 150,000 + in vitro 189,400) from AusAID $US 100,000

Networking

1. Network 2. Funding WHO support

Key areas of need:  Coordination of TES processes: Protocol; proposal dev, ethical review, funding, training, supervision, reporting/ publication, etc  Capacity building – programme level; research institution level  Translating research results to policy and programming – communicating results for policy / programme use  Advocacy and resource mobilisation – technical and financial including logistics

ANNEX 6

PACIFIC MALARIA DRUG RESISTANCE MONITORING NETWORK TERMS OF REFERENCE

Goal To support countries in the Pacific to generate and share up–to-date, high quality evidence on anti-malarial drug efficacy to inform malaria policies. Terms of Reference 1. To support countries (programmes and research institutions) to implement the WHO standard protocol for routine monitoring of anti-malarial therapeutic efficacy of 1st and 2nd line treatments for Plasmodium falciparum and Plasmodium vivax 2. To identify training needs and coordinate capacity building for high quality drug resistance surveillance 3. To coordinate laboratory support to countries and facilitate the use of WHO recommended standard procedures, and contribute to the development of new procedures where not available 4. To coordinate independent monitoring and review of therapeutic efficacy study (TES) data 5. To facilitate the timely reporting and sharing of TES results 6. To coordinate Network activities and facilitate collaboration through regional informal consultations, regional planning, resource mobilization and review of progress 7. To support countries in reviewing national malaria treatment policies (if requested) 8. To facilitate operational research to address knowledge gaps related to antimalarial drug resistance monitoring.

ANNEX 7 LIST OF DOCUMENTS DISTRIBUTED       

Methods for Surveillance of Antimalarial Drug Efficacy 2009 (hard and e-copy) TES template protocol + summary cover sheet (hard and e-copy) Methods and Techniques for Clinical Trials on Antimalarial Drug Efficacy: genotyping to identify parasite populations, 2007 (hard and e-copy) Field application of in vitro assays for the sensitivity of human malaria parasites to antimalarial drugs, 2007 (hard and e-copy) Global Plan for Artemisinin Resistance Containment, 2011 (hard and e-copy) Global Report on Antimalarial Drug Efficacy and Drug Resistance (hard and ecopy), 2010 Monitoring Resistance of P. falciparum and P. vivax to Anti-Malarial Drugs in the Greater Mekong Sub-Region, Phuket/Thailand, 2007, Mekong Malaria Programme (hard and e-copy) Report of the workshop to review and plan therapeutic efficacy studies to monitor P. falciparum and P. vivax resistance to antimalarial drugs in the Greater Mekong Subregion, Mandalay/Myanmar, 2009, Mekong Malaria Programme (hard and ecopy) Responding to the challenge of antimalarial drug resistance by routine monitoring to update national malaria treatment policies. Vestergaard, Ringwald, 2007 (hard and e-copy) Report of the 14th South-West Pacific Malaria Meeting, Madang/Papua New Guinea, 2007 (e-copy) WPRO Ethics Review Committee Standard Operating Procedures, 2010 (e-copy) Containment Newsletters 1 + 2+3 (hard and e-copies)

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ANNEX 8 LIST OF DOCUMENTS ON USB   Timetable Presentations Technical Session 1 1. Pacific Drug Resistance, Ms. Amy Barrette 2. Overview of antimalarial drug resistance in the Western Pacific, Dr. Christophel 3. Overview of TES on antimalarials in SEARO, Dr. Rahman 4. Lessons learnt from the Greater Mekong Subregion, Dr. Delacollette 5. Containment project on the Thai-Cambodia border, Dr. Habib Technical Session 2 1. Drug resistance monitoring in the Philippines, Dr. Espino 2. Drug resistance monitoring in Malaysia, 3. Drug resistance monitoring in Papua New Guinea, 4. Drug resistance monitoring in Solomon Islands, 5. Drug resistance monitoring in Vanuatu, Technical Session 3 1. Methods for anitmalarial drug resistance monitoring, Dr. Vestergaard 2. Practical issues and operational challenges, Dr. Bustos 3. Monitoring drug resistance, Dr. Cheng 4. Health research involving human subjects, Dr. Nakagawa Summary of Day 1, Dr. Kazadi-Mulombo Group work outputs TES training, Dr. Bustos Do we need a network? Dr. Christophel Technical Session 4 1. Pacific Malaria Drug Resistance Monitoring Network TORs, Dr. Vestergaard Pacific Malaria Drug Resistance Monitoring Network TORs-REVISED, Dr. Rundi Pacific Malaria Drug Resistance Monitoring Network- Recommendations, Dr. Christophel  References 1. Methods for surveillance of antimalarial drug efficacy 2009 2a. TES dug efficacy protocol template 2b. TES summary cover sheet 2c. WHO Mekong TES template protocol

3. Methods and techniques for clinical trial on antimalarial drug efficacy 4. Field application of in vitro assays for malaria 2007 5. WHO Global Plan for Artemisinin resistance containment GPARC-DUP 2011 6. WHO Global Report on Antimalarial Drug Efficacy and Resistance 2010 7. Monitoring resistance of Pf and Pv to antimalarial drugs in GMS 2007 8. Workshop report to review and plan TES, Myanmar 2009 9. Responding to the challenge of antimalarial drug resistance by routing monitoring 10. 14th SWPMM 11a. WPRO ERC SOP 2010 11b. WPRO ERC Annex, Application form 12. Containment project newsletters  Background documents 1. Handouts for the Pacific Malaria Drug Resistance Meeting 2. Information Bulletin, general information 3. Information Bulletin, list of attendees

www.wpro.who.int

Основные сведения

Организация Всемирная организация здравоохранения (ВОЗ / WHO)

Тип документа Technical Documents

Дата принятия 31 декабря 2011 г.

Источник Всемирная организация здравоохранения