Organisation mondiale de la santé (OMS) · Technical Documents

Second Biregional Meeting of Malaria Drug Resistance Monitoring Networks, Bangkok, Thailand, 24-26October 2016 : meeting report

31 décembre 2016 Organisation mondiale de la santé

Le texte intégral est hébergé par l’organisation qui le publie. lawenc.com indexe les métadonnées et renvoie vers la source officielle.

Texte intégral

Meeting Report

SECOND BIREGIONAL MEETING OF ASIA-PACIFIC MALARIA DRUG RESISTANCE MONITORING NETWORKS

24–26 October 2016 Bangkok, Thailand

Second Biregional Meeting of Asia-Pacific Malaria Drug Resistance Monitoring Networks 24–26 October 2016 Bangkok, Thailand

WORLD HEALTH ORGANIZATION REGIONAL OFFICES FOR SOUTH-EAST ASIA AND THE WESTERN PACIFIC Report Series No. RS/2016/GE/68(THA) English only

MEETING REPORT

THE SECOND BIREGIONAL MEETING OF ASIA-PACIFIC MALARIA DRUG RESISTANCE MONITORING NETWORKS

Convened by: WORLD HEALTH ORGANIZATION REGIONAL OFFICES FOR SOUTH-EAST ASIA AND THE WESTERN PACIFIC

Bangkok, Thailand 24–26 October 2016

Not for sale Prepared by: World Health Organization Regional Offices for South-East Asia and the Western Pacific Bangkok, Thailand December 2016

NOTE The views expressed in this report are those of the participants of the Second Biregional Meeting of Asia-Pacific Malaria Drug Resistance Monitoring Networks and do not necessarily reflect the policies of the World Health Organization.

This report has been prepared by the World Health Organization regional offices for SouthEast Asia and the Western Pacific for those who participated in the Second Biregional Meeting of Malaria Drug Resistance Monitoring Networks held in Bangkok, Thailand, 24–26 October 2016.

CONTENTS

ABBREVIATIONS ................................................................................................................... 4 SUMMARY .............................................................................................................................. 5 1. INTRODUCTION ................................................................................................................. 7 1.1 Background .............................................................................................................. 7 1.2 Objectives................................................................................................................. 7 2. PROCEEDINGS.................................................................................................................... 7 2.1 Opening session ....................................................................................................... 7 2.2 Review of recommendations from 2015 and progress (Dr Rabindra Abeyasinghe) 8 2.3 Antimalarial drug resistance monitoring in the GMS, BBINS and Pacific networks: progress and implementation challenges; monitoring quality control templates (Dr Maria Dorina Bustos) ...................................................................................................................... 9 2.4 Presentations by principal investigators on TES results: GMS network................ 10 2.5 Presentations by principal investigators on TES results: BBINS network ............ 14 2.6 Artemisinin resistance: global situation, update and next steps (Dr Pascal Ringwald) ............................................................................................................................ 16 2.7 Presentations by principal investigators on TES results: Pacific network ....... 19 2.8 Updates on the Strategy for Malaria Elimination in the Greater Mekong Subregion, 2015–2030 (Dr Fred Binka) ................................................................................................ 22 2.9 Summary of country results and discussions (Dr Pascal Ringwald) .................. 22 2.10 Country TES Plans 2016 –2017 ........................................................................... 23 3. CONCULSIONS AND RECOMMENDATIONS .............................................................. 26 3.1 Conclusions ............................................................................................................ 26 3.2 Recommendations .................................................................................................. 27 ANNEXES .............................................................................................................................. 29 Annex 1. TES Country Plans, 2017-2018 ........................................................................... 29 Annex 2. Agenda................................................................................................................. 39 Annex 3. List of participants ............................................................................................... 42

Asia, Southeastern / Drug resistance / Malaria / Regional health planning

ABBREVIATIONS

ACPR ACT AL AM API AS+AQ AS+SP AS+MQ AS+PYR BBINS BVBD CNM CQ DHA+PIP DRS ERAR G6PD GFATM IMR K13 MEF NIMR NIRTH NMPE NMCP NVBDCP ODPC Pf Pm Po Pv PMI PQ PSA RAI RDT TES UNOPS USAID WHO

adequate clinical and parasitological response artemisinin-based combination treatment artemether+lumefantrine (Coartem ™) artemether annual parasite incidence artesunate+amodiaquine artesunate + sulfadoxine-pyrimethamine artesunate + mefloquine artesunate+pyronaridine (Pyramax™) Bangladesh, Bhutan, India, Nepal, Sri Lanka Bureau of Vector Borne Diseases Cambodia National Centre for Parasitology, Entomology and Malaria chloroquine dihydroartemisinin+piperaquine drug resistance surveillance Emergency Response to Artemisinin Resistance Glucose-6-phosphate dehydrogenase Global Fund to Fight AIDS, Tuberculosis and Malaria Institute of Medical Research Kelch 13 mefloquine National Institute for Malaria Research National Institute for Research in Tribal Health National Institute of Malariology, Parasitology and Entomology National Malaria Control Programme National Vector Borne Disease Control Programme Office of Disease Prevention and Control Plasmodium falciparum Plasmodium malariae Plasmodium ovale Plasmodium vivax President’s Malaria Initiative primaquine piperaquine survival assay Regional Artemisinin Initiative rapid diagnostic test therapeutic efficacy studies United Nations Office for Project Services United States Agency for International Development World Health Organization

SUMMARY The Second Biregional Meeting of Asia-Pacific Malaria Drug Resistance Monitoring Networks was convened in Bangkok, Thailand on 24–26 October 2016. This was the second such meeting organized to bring together participants from three drug-resistance monitoring networks: the Greater Mekong Subregion (GMS) network, the Bangladesh, Bhutan, India, Nepal and Sri Lanka (BBINS) network and the Pacific network. It followed the success of the first meeting held in Siem Reap, Cambodia in November 2015. The meeting provided an opportunity for participants to build upon discussions from the 2015 meeting and to review the results and experiences of implementing therapeutic efficacy studies (TES) over the past 12 months. In addition, participants were able to further explore common challenges arising during the implementation of TES, particularly in complex country settings. Despite the fact that some countries are facing situations of malaria endemicity in the pre-elimination and elimination phases at national or subnational level, the increasing risk of artemisinin and multidrug resistance remains a serious challenge. Countries were able to engage in fruitful discussions on cross-border collaboration and share experiences and approaches to defeating malaria. The meeting was organized by the WHO South-East Asia and Western Pacific regional offices in coordination with WHO headquarters and the Emergency Response to Artemisinin Resistance (ERAR) hub in Phnom Penh, Cambodia. At the end of the meeting participants were expected to have:  received an update on the recommendations of the 2015 meeting;  reviewed and discussed implementation and results of the recent TES;  discussed the role and results of Kelch 13, the molecular marker for tracking artemisinin resistance, and of other molecular markers for monitoring malaria drug resistance; and  developed work plans and budgets for each country and the networks for TES monitoring in 2017–2018.

Conclusions  Most countries have continued to strengthen implementation of high-quality TES. Nearly all countries implemented TES for 2016 with the exception of Papua New Guinea and Bangladesh where ethical approvals were still being finalized. Technical assistance will continue to be provided by WHO staff as relevant. Countries that would like to seek training and certification for microscopists can make a request through their WHO country office. WHO recognizes the need to increase the numbers of expert microscopists within countries, particularly as countries move to pre-elimination and elimination. This is part of strengthening their national malaria microscopy quality assurance system. Effective surveillance systems are the backbone of ensuring malaria elimination in both the Pacific and GMS regions, and specifically case-based surveillance systems. This becomes more important as countries with very low numbers of cases can integrate drug efficacy monitoring into the national surveillance (or vice versa). Drug resistance is more challenging in the Greater Mekong Subregion. There are four artemisinin-based combination treatments (ACT) failing in Cambodia and also partner drug failures in Viet Nam. The Lao People’s Democratic Republic is



borderline (10%), with artemether+lumefantrine (AL) still working. In Thailand the situation is patchy, and in Myanmar the situation is good regarding partner drugs, though artemisinin resistance is a challenge. The threat does not appear to have spread beyond the Mekong, but it is important to remain vigilant.    Countries need to test alternative ACTs: artesunate+pyronaridine (Pyramax™) for Cambodia, Myanmar, Thailand and Viet Nam. The Pacific and BBINS countries do not have a problem with ACTs or K13. India’s changing drug regimen shows how useful monitoring drug efficacy is. For GMS countries, information on artemisinin (K13) and also piperaquine (P14) and mefloquine markers (pfmdr1 copy no.) for resistance are equally important. Molecular genotyping results from D0 filter paper would provide a good mapping of the situation. Continued monitoring will lead to action – that is, to the timely review and change of drug regimens. There are currently no replacements for artemisininderivative drugs, so we must continue to use ACTs. WHO is working with partners like Medicines for Malaria Venture (MMV) in the development of a non-artemisininbased drug.

Recommendations for Member States: 1) Countries may continue to strengthen implementation of high-quality therapeutic efficacy studies (TES) using the standard WHO protocol. Countries may continue to strengthen and support laboratory capacities: strengthen overall malaria microscopy quality assurance systems including refresher training for TES microscopists; and implement quality control for molecular assays with reference laboratory (Institute Pasteur Cambodia), technical training and exchange of samples. Alternative ACT regimens need to be tested before deciding on a drug policy review as soon as signs of declining efficacy manifest. Countries are encouraged to maintain regular monitoring visits to TES sites, using quality control monitoring forms. Countries are encouraged facilitate integration of monitoring of drug efficacy into routine surveillance systems in pre-elimination settings.

Recommendations for WHO: 1) Tasks for the networks focus on coordination, information sharing and technical support for the activities outlined above, with particular emphasis on strengthening cross-border information sharing and coordination, and laboratory Quality Control for microscopy and genotyping assays. WHO is requested to provide continuous updates on artemisinin resistance and especially in the Greater Mekong Subregion. WHO is requested to provide support for countries moving into elimination as they adopt new approaches to monitoring and surveillance beyond the routine TES.

1. INTRODUCTION 1.1 Background The Second Biregional Meeting of Asia-Pacific Malaria Drug Resistance Monitoring Networks was convened in Bangkok, Thailand on 24–26 October 2016. This was the second such meeting organized to bring together participants from three drug-resistance monitoring networks: the Greater Mekong Subregion (GMS) network, the Bangladesh, Bhutan, India, Nepal and Sri Lanka (BBINS) network and the Pacific network. It followed the success of the first meeting held in Siem Reap, Cambodia in November 2015. The meeting provided an opportunity for participants to build upon discussions from the 2015 meeting and to review the results and experiences of implementing therapeutic efficacy studies (TES) over the past 12 months. In addition, participants were able to further explore common challenges arising during the implementation of TES, and particularly in complex country settings. While Sri Lanka recently received the WHO certification as “malaria free”, other countries are still facing varying situations of malaria endemicity, pre-elimination and elimination contexts all within the same country. In addition, the increasing risk of artemisinin and multidrug resistance remains a serious challenge, especially in the GMS.

1.2 Objectives The objectives of the meeting were: 1) to follow up on the recommendations of the 2015 meeting; 2) to review and discuss implementation and results of the recent TES; 3) to discuss the role and results of Kelch 13, the molecular marker for tracking artemisinin resistance, and of other molecular markers for monitoring malaria drug resistance; and 4) to develop work plans and budgets for each country and the networks for TES monitoring in 2017–2018.

2. PROCEEDINGS 2.1 Opening session Dr Daniel Kertesz, WHO Representative to Thailand, delivered the opening address on behalf of Dr Poonam Khetrapal Singh, WHO Regional Director for the South-East Asia Region. Dr Kertesz noted that all 20 malaria-endemic countries in the South-East Asia and Western Pacific regions had achieved the malaria-specific targets of the Millennium Development Goals. By 2014, the goal of a 75% reduction of malaria morbidity compared with 2000 had been achieved by 14 of 20 countries, and malaria mortality reduced by more than 85% in 2014 compared with 2000 in both regions. Recently, Maldives and Sri Lanka have been certified by WHO as malaria-free countries. Dr Kertesz called upon all countries to maintain this momentum and to build upon the excellent progress made, as the serious threat of artemisinin and multidrug resistance remains.

Dr Sombat Thanprasertsuk, Deputy Director of the Department of Disease Control, Ministry of Public Health, Thailand, delivered welcome remarks on behalf of Dr Jessada Chokdamrongsuk, Director General, Department of Disease Control. He noted that malaria is still a significant public health problem in this region. As outlined in the Strategy for Malaria Elimination in the Greater Mekong Subregion (2015–2030), ensuring universal health coverage for all, including mobile and migrant populations, will be critical if the GMS countries are to achieve the goal of malaria elimination by 2030. The GMS countries belonging to the WHO South-East Asia and Western Pacific regions share many commonalities in relation to eco-epidemiological and socioeconomic settings, and collectively, collaboration needs to be strengthened. Chair and co-chair appointments were as follows: Dr Chinanonwait, Thailand as Chair and Dr Shamsudin, Malaysia as Co-chair (Day 1); Dr Leo Makita, Papua New Guinea as Chair and Dr Sher Singh, India as Co-chair (Day 2); and Dr Aung Thi, Myanmar as Chair and Dr Samad, Indonesia as Co-chair (Day 3). The rapporteurs were as follows: Dr Leang Rithea, Cambodia (Day 1); Dr Abu Nayeem Md Sohel, Bangladesh (Day 2); and Dr Hong Quang, Viet Nam (Day 3). The meeting agenda is available in Annex 2 and the list of participants in Annex 3. 2.2 Review of recommendations from 2015 and progress (Dr Rabindra Abeyasinghe) Since the 2015 meeting in Siem Reap, Cambodia, countries have continued to strengthen implementation of high-quality TES. Countries in both regions are implementing TES for 2016 with the exception of Papua New Guinea, where ethical approvals are still pending. WHO has provided continuous technical support to strengthen national programme capacities. In 2015, the quality of microscopy was noted as an issue of priority and WHO responded by developing and sharing microscopy standard operating procedures (SOPs). These SOPs have been used as a platform for training national focal points for both the Western Pacific and South-East Asian countries. Other key recommendations for Member States were as follows: 1) ensure that alternative artemisinin-based combination treatment (ACT) regimens are tested and available as soon as signs of declining efficacy manifest; 2) maintain regular visits to TES sites; and 3) facilitate the integration of monitoring of drug efficacy into routine surveillance systems in pre-elimination settings. As countries move towards pre-elimination and elimination, they face challenges in collecting adequate numbers of patients for TES. As such, WHO is considering alternative approaches. For example, Malaysia’s approach is currently being considered as a model to adopt in other near-elimination countries. Key recommendations for WHO were: 1) share the finalized monitoring tools and reporting guidelines with in-country and external monitors, and 2) provide support for countries moving into elimination as they adopt new approaches to monitoring and surveillance beyond routine TES. WHO is setting up a regional data-sharing platform to facilitate the sharing of information and will continue to strengthen data sharing with Member States through this platform. Guidelines will be shared with Members States once they are finalized at WHO headquarters.

2.3 Antimalarial drug resistance monitoring in the GMS, BBINS and Pacific networks: progress and implementation challenges; monitoring quality control templates (Dr Maria Dorina Bustos) The standardized in vivo protocol for the assessment of therapeutic efficacy was reviewed. It remains the gold standard to monitor drug efficacy, and results are used to update drug policies as it is based on the clinical and parasitological response of patients. The protocol was designed for P. falciparum (Pf) and P. vivax (Pv) malaria for all drugs, including chloroquine (CQ). The protocol involves 28-/42-day follow-up according to the half-life of the drug, is based on radical cure, and has been adopted by ministries of health, national malaria control programmes (NMCPs), and research institutions. Every six months, the WHO Global Malaria Programme releases an update on artemisinin and ACT resistance with a specific focus on the latest validated TES results and genotypes for molecular markers. Other tools involved in the assessment of therapeutic efficacy include in vitro tests and pharmacokinetic assays. In the GMS, TES commenced in 2008 with 32 sites and increased to 52 sites in 2016. Within the TES sites, the challenge remains of determining where artemisinin resistance has spread and when it has emerged independently – and the definition of artemisinin resistance itself is still evolving. The initial definition of suspected/confirmed resistance, which was based on TES, was more than 10% of patients still positive on day 3 (D3). With the validation of Kelch 13 (K13), retrospective analysis indicated a higher percentage of more than 10% positivity on D3. A snapshot of artemisinin resistance in the subregion revealed that by 2014–2015, there were three sites with confirmed resistance in Viet Nam: Binh Phuoc, Dak Nong and Gia Lai. Although all sites had 100% adequate clinical and parasitological response (ACPR), partner drug resistance by 2016 had occurred in Binh Phuoc with 50% D3+, 65% ACPR, 83% K13 mutations and 56% PIP resistance. In Cambodia, between 2014 and 2015, there were seven sites of confirmed artemisinin resistance with validated K13 mutations around the country. In 2014–2015, these situations in the Lao People’s Democratic Republic showed confirmed resistance in Champasak: 22% D3+, 90% ACPR; 54% C580Y, 23% R539T; and in Sekong: 20% D3+, 86% ACPR; 54% K13 mutations. Results from 2014–2015 also showed K13 mutations present in several sites in north-west and north-east Myanmar; however, clinical response remains good at this stage. TES sentinel sites in the Pacific network are found in Malaysia, the Philippines, Indonesia, Timor, Papua New Guinea, Solomon Islands and Vanuatu. Within the BBINS network there are six sentinel sites in Nepal, Bangladesh, Bhutan (2016) and 11 active sentinel sites in central and NE India (2016). Bhutan is in the elimination phase and focuses on case-based surveillance. Sri Lanka has been declared malaria free and also focuses on case-based surveillance. All countries across these two networks have close to 100% efficacy of artemether+lumefantrine (AL) against falciparum malaria. Challenges of monitoring the therapeutic efficacy of antimalarials Countries across the three networks experience similar challenges in terms of TES implementation. These include insufficient time in the study preparation phase for protocol development, site selection, ethical approvals process, training for TES teams in the field and delays in release of funds. During the study process itself, challenges include follow-up of

study patients (28/42 days), particularly in remote areas. Other problems include a failure to adhere to study protocol such as recruitment of non-eligible patients, failure to obtain consent, and poor documentation. Multiple issues with laboratory protocols include proper slide validation; timely genotyping of malaria parasites – Msp1, 2 and glurp – (to differentiate recrudescence from re-infection) as part of quality control (QC); molecular markers for antimalarial drug resistance to include pfmdr copy numbers in countries with mefloquine use / resistance (especially in the GMS); and quality assurance (QA)/QC of molecular procedures. In addition, adherence to data-entry protocols and quality control and validation of the study data were highlighted. Finally, QC monitoring templates were presented including the QC reporting form by the external clinical monitor. Discussion Regarding the challenges associated with recruiting sufficient numbers of cases for TES, WHO noted that the national principal investigators could adjust sample size according to reported cases. In other words, recruitment has to be handled on an annual and country-tocountry basis. It was suggested that countries either start the recruitment process during the transmission season or wait another three months if case numbers were insufficient. In terms of the time frame, the protocol covers two transmission seasons over a 12-month period. The ethics approval itself is valid for one year only. At most, WHO will grant a six-month no-cost extension. Evaluating the efficacy of single-dose primaquine (PQ) was another issue raised. WHO responded that for P. falciparum, primaquine is given at the end of 28- or 42-day follow-up, not immediately after ACT. It was emphasized that when assessing the efficacy of chloroquine (CQ) in vivax patients, PQ when given 28 days after CQ treatment, has to be specifically stated. 2.4 Presentations by principal investigators on TES results: GMS network Cambodia (Dr Leang Rithea) Malaria incidence has generally declined over the past 16 years, with the exception of peaks in 2004, 2006 and 2009. Results from the 2015 TES show that dihydroartemisinin+ piperaquine (DHA+PIP) resistance has spread to north-east Cambodia. In terms of drug efficacy, artesunate + mefloquine (AS+MQ) has been highly effective in areas where DHA+PIP resistance levels were very high last year. AS+MQ and DHA+PIP should continue to be closely monitored not only in the sentinel site but also in health centres without evidence of drug resistance in order to measure the spread of ACT resistance in the country. In 2016, an alternative ACT – artesunate+amodiaquine (AS+AQ) – is being tested in two sites that showed resistance to ASMQ and DHA-PIP. Ongoing challenges include low transmission, patient loss to follow-up and difficult road conditions. However, data quality have improved and studies can be started earlier compared to last year. Cambodia would appreciate additional technical support from WHO. A representative of the President’s Malaria Initiative, which is led by the United States Agency for International Development (USAID/PMI), was encouraged by the results presented by Cambodia and commended the achievement of the sample size. It was noted that

as countries move towards elimination, however, the relevance of TES must be revisited. Improved routine surveillance systems must include monitoring and case-based surveillance, and surveillance approaches must be relevant to specific country situations. WHO noted that the regional offices are working on new strategies with the Global Malaria Programme. With the combination of ACTs and primaquine, the proportion of P. falciparum has been plummeting but P. vivax is increasing. Keeping the focus on vivax malaria is also critical because falciparum tends to disappear much faster and is easier to control. It will be important to remain aware of the scale of intervention and vector control as it has an impact on transmission and treatment guidelines. China (Professor Tang Linhua) China has made important progress towards achieving the target of malaria elimination by 2020. Local transmission of cases sharply decreased between 2010 (4262 cases) and 2015 (40 cases). By the end of 2015, local transmission occurred only in Yunnan, Hainan and Liaoning provinces and Tibet Autonomous Region, mainly in four counties near the China–Myanmar border. Preventing imported cases is now the key challenge. In 2015, 3285 imported malaria cases were reported. Of 300–400 cases of imported malaria reported in Jiangsu and Henan provinces each year, more than 95% were P. falciparum cases from Africa. Yunnan Province reported 516 malaria cases: 70 falciparum and 442 vivax, of which 96% were imported cases. The TES in 2016 was expanded to include an additional four surveillance sites, and covered the following: CQ tested in Yingjiang county; and DHA+PIP tested in Yingjiang, Tengchong, Longyang, Ruili, Menglian, Pu’er, Kunming and Luliang counties. Regarding K13, a total of 12 types were found along the China–Myanmar border. Half of the cases show wild type (52%), with F446I (33%) and P574L (5%) being the most common K13 mutation types. Yingjiang and Ruili showed more polymorphism of K13 gene. The characteristics of K13 types in Yingjiang were the same as in Myanmar, mainly F446I and F574L. The D3 positivity of enrolled cases showed a relationship with F446I. Overall, CQ and ACTs are still efficient in treating uncomplicated P. vivax and P. falciparum, respectively. No artemisinin resistance to falciparum was observed in China. However, there were two cases of Chinese nationals from Myitkyina, Myanmar, with highly suspected artemisinin-resistant malaria. A major issue for China is tracking traders travelling to Myanmar and Africa. Using the surveillance tracker as well as 7-day follow-up and sharing information across borders continue to be priorities. Artemisinin resistance occurs on the Myanmar side of the border. More research is needed to determine if resistance is also occurring in China. Additional training on diagnosis in low-transmission areas is needed as delayed treatment contributes to deaths. At township level, China uses a 1-3-7 malaria surveillance strategy, which refers to case reporting within one day, case investigation within three days, and complete investigation within seven days. Cross-border communication needs to improve. It was noted that Chinese workers crossing to Myanmar for woodcutting and forestry work use no preventative measures. It would be advisable for China to implement some measures for prevention and to have rapid diagnostic tests (RDTs) available.

Lao People’s Democratic Republic (Dr Viengxay Vanisaveth) Between 2010 and 2016, the Lao People’s Democratic Republic saw a decline in falciparum cases while vivax cases rose since 2011. Malaria is concentrated in four southern provinces: apart from Phongsaly, all northern and central provinces recorded an API <1 in 2014, while four southern provinces showed an API ≥10 per 1000. The malaria drug treatment regimen changed in 2016: first line: uncomplicated Pf malaria, AL + single dose PQ; severe cases, injectable artesunate+AL; second line: quinine + doxycycline + single dose PQ. For treatment of uncomplicated Pv malaria, first line: AL + PQ; second line: oral CQ+ PQ (with G6PD test). TES progress in the past 12 months included testing AL in Salavanh province and DHA+PIP in Chamapsack – this is ongoing with military and civilian groups. A review of national malaria treatment guidelines is planned for 2017 after results of TES are confirmed. Primaquine is now used on a small scale for Pv and in a single low dose for Pf treatment. In the TES sentinel sites, low-dose PQ is being used to prevent relapses. It was questioned why the Lao People’s Democratic Republic would consider changing to DHA+PIP when the drug is failing across the border in Cambodia. It was clarified that the change would only occur in some areas and not the whole country. It was also noted by WHO that in the context of changing a drug regimen, the number of D3 failures would predicate such a change, with results from 50–100 cases per site on which to base such a decision. At this point, it is still necessary to test and know the results of alternative ACTs in the event a drug policy review/change is made. Myanmar (Dr Khin Lin) Myanmar has made significant progress in reducing the malaria burden across the country, although each region/state still has foci of transmission. Falciparum malaria accounts for the highest percentage of malaria cases (64%), but it markedly declined between 2012 and 2015. In 2015, TES were conducted in Muse, Paletwa and Myitkyina. Results from Muse showed 96.7% (58/60) PCR-corrected ACPR for AL, 100% (60/60) for DHA+PIP and 100% (68/68) for CQ. In Myitkyina, results for AL were 96.5% (54/56) PCR-corrected ACPR, 100% (56/56) for DHA+PIP and 100% (66/66) for CQ. Finally, in Paletwa, results showed 97.2% (35/36) PCR-corrected ACPR for AL, 100% (13/13) for DHA+PIP, and 100% (7/7) for CQ. For 2016, studies are ongoing in Ta Beik Kyin and Tamu sites and are expected to commence in three more sites (Rakhine, Kayin and Mon states). Regarding K13, it remains unclear whether the mutations are de novo or have spread. The mutation F446I is the most common, occurring in 38.56% of cases found from northern and eastern Myanmar, with none (yet) in the west. The second most commonly found mutation is A676D (2.38%). However at the present time there is no significant relationship between mutations and therapeutic outcomes. Myanmar has a highly mobile and migrant population and is critically located on the western border of the Mekong region, so TES and K13 mapping remain important programme activities and should continue. Measures taken to address malaria in migrants travelling to and from malaria-endemic areas include mapping of the migrants, malaria prevention guides published in many languages, setting up of border screening points, work site interventions to provide access to malaria services, and operational researches to assess the most effective interventions. The majority of migrants are unofficial workers, so monitoring is challenging. It was also clarified that even if 12

50% of the D3-positive cases were mutant, there was no significant association with the outcomes. Reference was made to a study conducted with researchers at University of Maryland, which noted that F446I is characterized as contributing to an intermediate resistance, so not all mutants have the same correlation contributing to D3 positivity. There are different levels of virulence. It was noted that Cambodia also had the F446I mutation, but it was not yet clear whether it was spreading or not. It was also noted that the sample size for F446I, which was around 293, was a lot less than the average sample size of 1000 for other K13 mutations. Sample size is important for mutations related to D3 positivity. Myanmar confirmed that further studies would be undertaken. Thailand (Mr Theerayot Kobasa) From 2015 to 2016, confirmed malaria cases declined from 24 850 to 12 339. P. vivax cases accounted for 68% of total cases in 2016 with the highest burden being in Tak Province (5609 cases), which borders Myanmar, and Ubon Ratchathani Province (1342 cases), which borders Cambodia and the Lao People’s Democratic Republic. Current treatment guidelines for uncomplicated Pf malaria are as follows: first line: DHA+PIP + PQ; for P. vivax malaria; CQ + PQ 14 days; for severe malaria with supportive care; injectable AS followed by DHA+PIP + PQ. Results from TES conducted in 2012–2015 indicate a problem with efficacy of AS+MQ for treatment of Pf in Kanchanaburi and Tak provinces, showing ACPR between 75% and 80%. For the TES in 2016, AS+MQ studies are still on going in Songhkla and Yala. In Sisaket, results show a 100% ACPR. For 2015-2016 TES testing of DHA-PIP, Ubon Ratchathani showed ACPR of 100%. Results for CQ against Pv are ACPR of 98% and 100% for Kanchanaburi and Sisaket, respectively. The presence of K13-resistant mutation was confirmed: C580Y in Tak, Kanchanaburi, Ranong, Ubon Ratchathani, Sisaket and R539T in Ubon Ratchathani. Associations with six other mutations – R539T, 441L, 446I, 449A, 458Y, 561H and 574L – were found in four provinces. The focus for the future will be on TES for alternative ACTs; drug resistance surveillance for the current antimalarial drug in lowprevalence provinces; K13 monitoring, molecular QC and continued QC/QA system for malaria diagnosis; and strengthened networking and coordination with the provincial health offices, district promoting hospitals, and malaria posts. It was noted that the current Mahidol study in Sisaket on DHA+PIP shows a 10% failure rate. As this has occurred together with C580Y, it is concerning because of the intention to change to DHA-PIP. WHO noted that the situation makes sense as AS+MQ is highly efficacious when DHA-PIP is failing, which is important to note when choosing first-line drugs. For Thailand, choosing a first-line drug is complicated due to the erratic data and results. Porous borders, population movements and other factors affect molecular and efficacy results at different time points. An issue of concern raised during discussion was the low case numbers in the studies presented, and whether conclusions could still be drawn. Thailand noted that future studies would combine clinical studies and routine surveillance. Information on patients enrolled in TES and the disaggregation of Thai or M1 patients is available. Multiple data sources are used to inform drug policy change, not just a single study.

Viet Nam (Dr Bui Quang Phuc) The malaria epidemiology has changed significantly over the past 15 years in Viet Nam. Although the primary vectors remain the same – Anopheles minimus, dirus and epiroticus – the proportion of malaria parasite species has changed. In 2000, P. falciparum accounted for 77.5% of cases, while P. vivax represented 21.4%. In 2016, the percentages changed to 46.4% for P. falciparum and 50.9% for P. vivax. Overall, confirmed cases have declined from 74 329 cases in 2000 to 9331 in 2015. The number of malaria deaths during the same period declined by 97.9%. In 2016, the efficacy of DHA+PIP for P. falciparum infections was assessed in Binh Phuoc (27 enrolled); Dak Lak (3); Khanh Hoa (9); and Dak Nong (5). Antimalarial drugs currently in use include DHA+PIP (Arterakin™, procured by NIMPE) against Pf malaria; and CQ 25mg/kg for 3 days against Pv malaria. Key results from TES indicate that DHA-PIP is still highly efficacious (95.5–100%) in Dak Nong, Gia Lai, Quang Nam and Khanh Hoa. In Binh Phuoc, the low efficacy of DHA+PIP in 2015 (61.1% cure rate) served as a serious warning of the importance of testing alternative ACTs. The proportion of positive asexual falciparum parasites on D3 is high, ranging from 10.8% to 46.3% in six provinces. The high proportion of D3 positivity and the presence of K13 propeller mutations, such as C580Y and R539T, indicate confirmed resistance in several sentinel sites. Viet Nam will test artesunate+pyronaridine (Pyramax™) in 2017. 2.5 Presentations by principal investigators on TES results: BBINS network Bangladesh (Dr Abu Nayeem Md Sohel) Bangladesh is currently between the pre-elimination and elimination phase. As of 2015, the situation in the country is as follows: at-risk population is 13.25 million with 13 endemic districts, of which three are highly endemic, one is moderately endemic and nine have low endemicity. All of the districts are located close to the border with north-east India and western Myanmar. Total cases numbered 39 719 with nine deaths in 2015. The current API is 3.00 per 1000 population with mortality at 0.068 per 100 000 population. A key challenge is reaching the remote hill tribe villages. The case numbers further declined in 2016. The malaria treatment regimen was updated in 2016: AL for uncomplicated Pf malaria; and alternative treatments: AS+AQ; AS+MQ; DHA+PIP. The protocol for mixed malaria infections is: AL+ PQ 0.25 mg/kg for 14 days; and for severe malaria: injectable artesunate + PQ 0.25 mg/kg for 14 days. Neither K13 nor resistant cases have been reported in the 20142015 drug efficacy studies done in Upazilas (subdistrict) sentinel sites at the Chittagong Hill tracts close to the border with Myanmar. Bhutan (Mr Tobygel) Between 2000 and 2015, malaria cases in Bhutan declined from 1868 to 104, with P. vivax accounting for 63% of all cases. From 2013, P. falciparum malaria increased, accounting for 41% of all cases by 2015. Imported cases accounted for 70/104 cases in 2015, indicating a problem in controlling malaria along the border areas, particularly the border with the Indian state of Assam. This is a very porous border with thousands of workers crossing daily. Since 2008, TES has been carried out in five sentinel sites: two hospitals and three Basic Health Units to monitor ACT and CQ efficacy against P. falciparum and P. vivax malaria, respectively. TES results from 2008–2013 show 100% ACPR for AL and CQ, against Pf and

Pv respectively. In 2015, all health centers were designated as catchment sites for all malaria cases to be reported and followed up at days 7, 14, 21 and 28. For the first three days, Pf and Pv patients are admitted in the health centres for supervised treatment. Migrant workers are screened at entry points; blood samples are collected for diagnosis and PCR; and treatment is given for positive cases. Much progress had been made on surveillance as Bhutan has moved towards using health centres to monitor drug efficacy. Follow-up of migrants beyond three days remains challenging. Bhutan focuses on a 1 km radius and attempts to screen all people using RDTs within that radius. In the case of positive results, blood samples are taken for microscopy, and then followed up. One participant commented that more use of microscopy should be made since Bhutan is a small county. With low-density parasitaemia, and as the country reaches elimination, maintaining expert microscopists at provincial level will be more cost effective. India (Dr Neelima Mishra and Dr Neeru Singh) India’s national drug policy was presented. For P. falciparum, the first-line ACT is AS+SP throughout India, with the exception of the north-eastern states where AL is used, plus single dose PQ. For P. vivax, CQ 25mg/kg over 3 days + PQ 0.25 mg/kg for 14 days is used, with G6PD test if facilities are available. Prevention for travellers includes personal protection measures and chemoprophylaxis, but for migrant labourers and military personnel, doxycycline or mefloquine (MEF) are reportedly prescribed. All fever cases are investigated for malaria by microscopy or RDT. In 2013 there was a change in the drug regimen for the northern states after high failure rates of AS+SP, with triple mutations (dhfr and dhps) for SP resistance showing a sharp increase through the years. The efficacy of AL in Pf (2014–2016) in north-eastern India was 96.1– 100%; efficacy of CQ in Pv (2009–2015) was 100%. In four sites in central India, efficacy studies with AS+SP and AL from 2013 to 2015 showed 95–100% and 92–100% cure rates, respectively. No delayed parasite clearance or early treatment failures have been observed with AL. Limited non-synonymous K13 mutation (F446I) was found only in the north-eastern state of Tripura and central state of Madhya Pradesh at a very low frequency (1–1.5%). In order to monitor emerging resistance in the future, regular monitoring of antimalarial efficacy as well as K13 markers for AS resistance will continue to be required. It was pointed out that with continued use of AS+SP, dhps and dhfr mutations are seen in low frequency, but it is a triple and quintuple mutation. India confirmed that for vivax case management, G6PD deficiency analysis was being carried out. Participants from India and Bangladesh agreed that more studies should be carried out in the common borders of Mizoram and Tripura. It was noted that falciparum cases are increasing, and that proportionally it has always been higher in some states. However, the change in drug policy and ACTs has helped to reduce total case numbers, also reflected in the declining number of deaths. At community level, ACTs are available and surveillance is good. The proportion of vivax has always been higher, but it does vary from state to state due to the climate and ecological variations.

Nepal Total malaria cases in Nepal declined from 4969 in 2006 to 1352 in 2015. No malaria deaths have been reported since 2012. Several factors have contributed to the decline in deaths and cases, including: increased coverage of early diagnosis by RDT; prompt treatment by effective antimalarials (preventing further transmission); improved socioeconomic status; and increased long-lasting insecticidal net (LLIN) coverage in high and moderate risk areas, following completion of the micro stratification of risk areas in 2013. The national treatment guidelines were recently updated in 2015 and are as follows: for uncomplicated P. falciparum: AL for 3 days and single dose PQ 0.25 mg/kg; for P. vivax/malariae/ovale: CQ 25 mg/kg for 3 days + PQ 0.25 mg/kg for 14 days; test all P. vivax cases for G6PD deficiency before initiation of PQ. For severe P. falciparum malaria: injectable artesunate; injectable artemether; injectable quinine. TES in 2013–2014 in two sentinel sites in south-eastern and south-western districts bordering India showed 100% ACPR to AL and no K13 mutations. Since 2015, every case is reportedly being followed up. TES and other evidence-generating operational research should be continued for timely and successful elimination. Sri Lanka (Dr Hetti Priyani Ranjanaprabha Dharmawardena) Sri Lanka was certified malaria-free by the WHO in September 2016. Activities to sustain prevention of re-introduction of malaria are done by the central and 22 regional offices of Anti- Malaria Campaign of the Ministry of Health. Government health facilities are provided with diagnostic and treatment capacities, with staff in charge of all malaria-related activities throughout the country. By 2012, only 23 indigenous cases had occurred in Sri Lanka, and since October 2012, only imported cases were found (mostly from India and Africa). The malaria drug policy changed in 2014 to treat P. vivax with CQ and P. falciparum with ACTs and PQ. Treatment and follow-up is done for all patients admitted to hospitals from D0 to D3 until patients are discharged when negative. Health workers follow up with patients either at clinics or at the patients’ homes. Over-the-counter medications are unavailable; therefore, the use of substandard drugs is minimal. In 2015, 71 cases were followed up (31 P. vivax) and treated with ACTs. Twenty-six people were followed up until day 28. Between 2015 and October 2016, 34 Pf cases were recorded, 13 of which were severe. Of these, 21 were treated with ACTs, and six were lost to follow-up. All patients responded well. The malaria case review committee, a subcommittee of the Technical Support Group to sustain malaria-free status, with the technical staff of Anti-Malaria Campaign decides if cases are classified are imported or not. To date, this management system works well. Sri Lanka confirmed that good collaboration with the armed forces as well as screening of people arriving to the country at different ports of entry were key components of the system. In addition, regional-level authorities carry out follow-up if patients develop fever. To prevent the reintroduction of malaria, routine microscopy, visits to locations with high numbers of foreign workers, asylum seekers, etc., will help to prevent the reintroduction of malaria. 2.6 Artemisinin resistance: global situation, update and next steps (Dr Pascal Ringwald) Definitions of artemisinin resistance, multidrug resistance, ACT failure and ACT resistance were reviewed. It was reiterated that ACT failure is not necessarily linked to

resistance. The rationale for conducting TES tests was also reviewed. TES remain essential for determining whether first- and second-line drugs are still effective. They also serve as an important evidence base for ministries of health to update their national malaria treatment policies. WHO currently recommends monitoring the efficacy of firstand second-line ACTs every two to three years in all falciparum-endemic countries. In the Asia-Pacific region, these data have not always been available because countries have been missing the beginning of transmission seasons due to administrative delays. In addition to TES, in vitro tests, molecular markers and pharmacokinetic tests are also useful tools for confirming resistance. Currently, resistance to artemisinin is partial, i.e. affecting only the ring stage. It is possible that artesunate resistance could become total. Artesunate resistance could also increase the risk of de novo resistance to the partner drug and/or facilitate the selection of partner drug resistance leading to ACT treatment failures. In areas of artemisinin resistance, artesunate and quinine should be combined for the treatment of severe malaria. Based on recent TES data, Viet Nam will need to change the treatment regimen in Binh Phuoc because of the failure of DHA+PIP, which has also occurred in Cambodia. It is not possible to have PQ resistance and MEF resistance at the same time. When PQ fails, it happens very quickly and spreads very rapidly, as is currently the case in Siem Reap. Mutations of both artemisinin and partner drug resistance lead to high levels of treatment failure. However, the biggest issue with resistance remains in Cambodia and its borders. Regarding K13, not all mutations lead to delayed clearance in the same manner. Currently, 250 mutants have been recorded; in eastern GMS (Cambodia, Lao People’s Democratic Republic and Viet Nam), C580Y, R539T, Y493H and I543T mutations were frequent or specific; in western GMS (China, Myanmar and Thailand), F446L, N458Y, P574L and R561H mutations were specific; P553L allele was distributed in the two areas. It is complicated to validate a specific mutant as it requires transfection studies and specific in vitro tests in addition to delayed clearance during clinical trials. 2.6.1 A surrogate marker of piperaquine-resistant P. falciparum malaria in Cambodia (Dr Didier Menard) An overview of studies describing novel tools to detect piperaquine-resistant P. falciparum malaria was presented. One new in vitro assay – piperaquine survival assay (PSA) – looks at the number of parasites able to survive to 48 hours exposure of 200 nM piperaquine. This novel assay was challenged in two studies: 1) in a retrospective study, they tested 32 culture-adapted, C580Y-K13 mutant parasites collected at enrolment from patients treated with a three-day course of DHA+PIP and having presented or not with a recrudescence at day 42; and 2) in a prospective study, they assessed ex vivo PSA survival rate alongside K13 polymorphism of isolates collected from patients enrolled in an open-label study with DHA+PIP for uncomplicated P. falciparum malaria in Cambodia. They found that all parasites from recrudescent cases had PSA survival rates ≥10%, a relevant cut-off value for piperaquine resistance, and concluded that the PSA assay adequately captures the piperaquine resistance/recrudescence phenotype, a mainstay to identify molecular marker(s) and evaluate efficacy of alternative drugs.

The goal of the second study was to use the phenotypic information from the PSA to identify genetic marker(s) of piperaquine resistance and study their association with DHA+PIP treatment failures. Using a next generation sequencing approach, researchers identified amplification of the plasmepsin 2–3 gene cluster encoding proteases involved in haemoglobin degradation as the most significant molecular signature associated with in vitro resistance to piperaquine. Using a large longitudinal collection of samples from clinical efficacy studies of DHA+PIP done across Cambodia since 2009, they examined 725 falciparum isolates and found that an increased plasmepsin 2 gene copy number was strongly associated with DHA+PIP treatment failures. Patients harbouring multicopy plasmepsin 2 parasites had a 20 times higher risk of recrudescence during the 42-day post-treatment follow-up (94% sensitivity and 77% specificity). The retrospective analysis of samples collected in Cambodia during the last decade before and after introduction of DHA+PIP as first-line treatment showed that the proportion of multicopy plasmepsin 2 parasites correlated with the increase of DHA+PIP treatment failure rates, from 2009 to 2015 in western Cambodia and during 2014 –2015 in eastern Cambodia. In areas of artemisinin resistance, the efficacy of DHA+PIP at day 42 fell under 90% when the local proportion of multicopy plasmepsin 2 parasites rose above 22%. They also confirmed that when a parasite is resistant to piperaquine, it becomes sensitive to mefloquine, and when a parasite is resistant to mefloquine, it becomes sensitive to piperaquine (opposite mechanisms of resistance). Researchers concluded that multicopy plasmepsin 2 constitutes a surrogate molecular marker to track piperaquine resistance and a molecular toolkit combining plasmepsin 2 with K13 and mdr1 monitoring should provide timely information for antimalarial treatment and containment policies. Dr Menard also mentioned the possibility of sharing SOPs and validating procedures with interested country research groups, also as part of QC of genotyping results. 2.6.2 Malaria microscopy - updates on QA activities in the regions (Dr Rabindra Abeyasinghe) WHO is focused on strengthening diagnostics and QA in microscopy in Asia and the Pacific to ensure high-quality services for the public. Activities include biregional training for the establishment/strengthening of malaria microscopy QA in countries; external competency assessments of microscopists; external quality assessments of national malaria laboratories; refresher training of microscopists; support for to the establishment of national malaria slide banks and maintenance of a regional malaria slide bank; and assistance for the procurement of supplies and reagents for national laboratories. Microscopy is critical for the exclusion of the irrational use of antimalarial drugs in a patient and is important for maintaining the efficacy of existing drugs, as well as ensuring that the correct drugs and dosage are used for patients. Countries are strongly encouraged to move away from presumptive treatment and to ensure they are utilizing laboratory diagnoses. Support provided for malaria microscopy QA in the past year included: reviewing/updating the national QA systems in Vanuatu (April 2016), Myanmar (February–March 2016) and Thailand (May–July 2016); following up national QA plans and activities (as listed during the biregional training in June 2016) and providing technical assistance as needed; and conducting field and training activities (i.e. slide bank collection, refresher trainings, supervision) in collaboration with the WHO Collaborating

Centre for Malaria Diagnosis at the Research Institute for Tropical Medicine (RITM) and ACTMalaria. External competency assessments of microscopists will continue in 2016 and 2017. 2.7 Presentations by principal investigators on TES results: Pacific network Indonesia (Professor Din Syafrudin) Indonesia reduced malaria incidence by half with most malaria cases concentrated in a few provinces in the eastern parts of the country. National treatment guidelines were revised in 2008 to include DHA+PIP. As of 2013, the regimen for Pf malaria is: DHA+PIP for 3 days, and for Pv malaria: DHA+PIP + PQ 0.25-0.3 mg/kg daily for 14 days. DHA+PIP is still effective for the treatment of Pf and Pv malaria, and there is no evidence of possible artemisinin resistance. Results from the 2015–2016 TES in five sentinel sites are: East Nusa Tenggara, 100% ACPR for Pf and 94.4% for Pv; North Maluku, 100% ACPR for Pf and Pv; North Sulawesi: 88.9% (100% PCR-corrected ACPR) for Pf and 100% ACPR for Pv; Papua: 95.3% (PCR-corrected 97.6% ACPR) for Pf and 96.5% for Pv. The TES results in five sentinel sites revealed no delay in parasite clearance. To date, no polymorphisms of K13 gene were found in any of the isolates examined. Two studies recently approved by WHO Research Review Committee will be conducted in 2016 in Papua (at the border with Papua New Guinea) and the province of Bengkulu. Future efficacy monitoring is still required, but due to fewer eligible cases, it was suggested that any level of parasitaemia be considered as the inclusion criteria. National TES could be carried out every five years or when delayed parasite clearance is observed. Indonesia confirmed that the Government purchases DHA+PIP from Holley Pharm, under Guilin Pharmaceuticals. Regarding the 6% treatment failure, confirmation was requested whether this was due to low absorption of drugs or whether it was an early sign of resistance to piperaquine. An assessment of the pfmdr1 gene copy number as well as the plasmepsin gene was proposed. Five years ago, the team at Eijkman Institute conducted an analysis on piperaquine resistance in vitro using P. falciparum 3D7 clone cultured in the presence of increasing concentrations of piperaquine. It yielded P. falciparum isolates with IC50 for piperaquine 5–10 times higher than the control. When the isolate was analysed for CQ-resistant genes, no increase in the copy number was found at that time and it was not understood that this was a positive result. Malaysia (Dr Umi Kalthom Shamsudin) Malaria cases declined between 2001 (12 780) and 2015 (2311), with a slight increase in 2014 due to increased zoonotic (P. knowlesi) cases. Malaria mortality decreased 76% in 2014. Overall, indigenous malaria has declined since 2014, and imported cases now account for the highest proportion of cases. Success is due in large part to the VEKPRO Online Web-based Real Time Malaria Surveillance System. The system contains data on reported cases including: case investigations, vector control activities, treatment and case follow-up; drug resistance surveillance, malaria deaths and outbreak management. Results from the 2015 and 2016 drug resistance surveillance show 100% ACPR for AL with P. falciparum, P. knowlesi and P. malariae. Following the 2016 drug policy change to AL for P. vivax, the drug resistance surveillance will include follow-up on vivax cases in

2017. There is no evidence of artemisinin resistance in Malaysia. Drug resistance surveillance is carried out by Ministry of Health staff throughout the year at all hospitals in Malaysia, and all malaria patients must be admitted to hospital for treatment. The first-line treatment regimen for uncomplicated P. falciparum is: AL with PQ 0.75mg/kg added on D1 of treatment. For uncomplicated P. vivax / ovale: AL and PQ 30mg OD for 14 days. Treatment for severe malaria for both Pf & Pv is: injectable artesunate 2.4mg/kg (at 0H, 12H, 24H) and daily subsequently till D7 and switch to oral doxycycline 100mg; add PQ 0.75mg/kg (except pregnant / less than 1 year old). Treatment for uncomplicated P. malariae / knowlesi is AL and for severe malaria; treatment is the same as Pf. For follow-up of patients, the health inspector visits the patients’ homes (district health office personnel are under the Ministry of Health). The malaria web-based database used for drug resistance surveillance is integrated with the surveillance system of the vector programme of the Ministry of Health. Regarding diagnostic QC, all the falciparum-malaria positives undergo slide QC at state level. Once diagnosed as P. malariae, they undergo PCR confirmation for P. knowlesi. Despite the fact that the drugs are working well, there are still deaths due to late or incorrect diagnosis on the first visit. Papua New Guinea (Dr Leonard Nawara) Based on the latest studies, AL and DHA+PIP are still highly efficacious (98–100%), with no delayed parasite clearance in Papua New Guinea. The current treatment regimen for uncomplicated Pf, Pv, Po, Pm is: first-line treatment: AL tablets in Pf, Pm malaria; AL+ PQ for 14 days in Pv and Po; second-line: DHA+PIP in Pf, Pm malaria; and DHA+PIP + PQ for 14 days in Pv and Po. For severe malaria (both Pf and Pv): first line is injectable artesunate or artemether, followed by AL when patients can swallow; second line is QN injection followed by oral QN and doxycycline when patients can swallow. Since changing the drug regimen to ACTs in 2010, studies of antimalarials have been limited. TES was conducted in two sites from 2012 to 2014. The national malaria control programme (NMCP) plans to make TES a success and conduct it regularly with support from WHO. Operational research and other updates include: TES 2014 (completed in 2014); TES 2016–2017 (to start and to include K13 with assistance from WHO); and studies on histidine-rich-protein 2 (hrp2) deletions. Challenges to TES implementation include delays in ethical clearance, human resource limitation and misunderstanding of the purpose and processes of TES within the Department of Health. Philippines (Mr Sherwin Galit) Malaria mortality rates declined steadily from 286 in 2000 to 20 in 2015. However, case numbers have increased from 4972 in 2014 to 8321 in 2015, with falciparum malaria accounting for more than 77% of the malaria burden in 2015. Of 81 provinces in the country, 32 are malaria free and 49 are malaria endemic. Palawan province accounts for more than 75% of all cases, and infections by five plasmodium species have been recorded there. Palawan has been a TES sentinel site since 2009, and studies have been carried out as follows: in 2016, CQ vs Pv; in 2015, AL vs Pf; in 2013–2014, AL vs Pf; and in 2009–2012, CQ vs Pv. The current drug regimen for Pf is first-line: AL; second-line:

QN plus clindamycin; and for severe malaria is artesunate suppository or parenteral artesunate. AL is still effective against Pf, and CQ against Pv, and there is no evidence of K13 mutations. Although significant progress has been made in reducing malaria, the Philippines will continue with TES in Palawan. Timor-Leste (Ms Maria do Rosario de Fatima Mota) Over the past 10 years, Timor-Leste has successfully reduced the number of malaria deaths from 58 in 2006 to zero as of October 2016. P. falciparum accounts for the largest number of cases: 45 Pf cases compared to 6 Pv cases in 2016. Timor-Leste entered the pre-elimination phase in 2016. Results from the 2012–2013 TES, which assessed the safety and efficacy of AL for the treatment of uncomplicated P. falciparum malaria, showed PCR-corrected ACPR of 100%. The efficacy of CQ for the treatment of P. vivax malaria showed 82.4% ACPR and 85% PCR-corrected ACPR. Given the 15% failure rate, Timor-Leste is considering a change in the drug regimen. To select an alternative drug to chloroquine, additional therapeutic efficacy studies are planned to assess the efficacy of AL over CQ in the management of Pv infections in 2016. Given the challenge of enrolling sufficient numbers of patients, all cases in the entire country will be enrolled. It was surprising that Timor-Leste had higher numbers of Pf than Pv while entering into the elimination phase, as this is not usually the case. In the pre-elimination phase, the surveillance system should integrate TES rather than the other way around. All cases can be recorded and followed up. With 45 cases on an island, this should be easy to achieve. Timor-Leste responded that there had been issues with surveillance and with gaining access to the district that had the majority of cases. However, discussions were held with the referral hospital in the district to ensure that all patients will be admitted to hospital and enrolled in the study. Regarding the high level of transmission, as the area had recently been declared a new economic zone, adjustments were still being made to the new regulations. About 30% of cases were index cases. Indoor residual spraying and case investigation were done to control the outbreak. The vivax cases had been confirmed by microscopy and RDT at health facility level and validated by the national laboratory. Timor-Leste did not have the capacity to do the blood level measurements, hence cannot assess the 17.5% treatment failure of Pv. All vivax failures were treated with second-line AL. A final point from Indonesia was that Indonesia and Timor-Leste should work towards collaborating on TES, particularly along the border shared by the two countries. Solomon Islands (Mr Albino Bobogare) Although the annual malaria incidence has declined in the country, there have been fluctuations. The peaks in trend incidence were due to social unrest and the consequent limited ability for patients to access treatment. Trends in malaria deaths have also fluctuated but are generally decreasing. The 13 deaths in 2015 were reportedly associated with other illnesses, and the Ministry of Health has started the process of verifying the causes of these deaths. Vivax malaria has been more stable than falciparum over the years; however, the number of vivax cases increased again in 2015. The TES from 2009 in Auki, Malaita Province showed that AL was still effective for both Pf (ACPR 100%) and Pv (ACPR 100%); and in 2011–2013, TES results from Tetere, Guadalcanal Province confirmed that AL is still effective with ACPR of 100% for Pf and 94.6% for 21

Pv. Results of K13 2009 data are to be published and samples are being analysed by the principal investigator at the Walter and Eliza Hall Institute of Medical Research (WEHI), Melbourne. Solomon Islands will implement TES in late 2016. 2.8 Updates on the Strategy for Malaria Elimination in the Greater Mekong Subregion, 2015–2030 (Dr Fred Binka) The overarching goal of the subregional malaria elimination strategy is to eliminate malaria by 2030 in the GMS – to eliminate P. falciparum malaria by 2025 and to maintain malaria-free status and prevent reintroduction. The GMS has achieved a 54% reduction in the malaria burden in the past year. WHO has outlined key interventions for success including malaria case detection and management; malaria case and entomological surveillance; and disease prevention in transmission areas. Supporting elements include: innovation and research and enabling environment (including health systems strengthening, multisectoral engagement and governance). Regional support for countries provided by WHO includes: development of national strategic and operational plans (NSPs); functional elimination task forces; guidelines, manuals, implementation of core interventions; a regional data sharing platform; malaria drug resistance monitoring and insecticide resistance monitoring. Issues still to be addressed include: revisiting indicators for monitoring to reduce them and refine definitions; developing standard terms of reference to make elimination task forces functional; and developing generalized guidelines for best practices on eliminating foci. Community engagement will also be critical in moving towards elimination and/or maintaining this status. The regional data sharing platform, known as Mekong Malaria Elimination, was presented. This platform incorporates the District Health Information System 2 (DHIS 2), Malaria Module and Malaria Cased-based Surveillance Module. The three key objectives of the regional data sharing platform are: 1) to improve data management and sharing of standardize malaria data in the GMS; 2) to strengthen the capacity at all levels of the NMCPs for data analysis and response; and 3) to support detailed country-level surveillance including mapping in selected cross-border areas. In the discussion, India raised the issue of integrating cases from private practitioners into the regional data sharing platform. In addition, the question of engaging polio workers to be involved with malaria was raised. WHO responded that this has to be done in cases where the burden has already been reduced and depends on the resources countries have. A system for the regular monitoring of insecticide remains a priority for many countries, and a key challenge is insufficient numbers of entomologists. Collaboration with the nonhealth sector could be a viable solution. Regarding outdoor transmission, more work is needed to determine the scale of the problem – to define the burden, transmission and proportion. LLINs remain important but not sufficient. 2.9 Summary of country results and discussions (Dr Pascal Ringwald) Dr Ringwald congratulated all countries for the excellent work presented and noted that significant results had been achieved. He also thanked the donors supporting WHO. Dr Ringwald pointed out that it was important to distinguish between the Pacific and GMS regarding the problem with artemisinin resistance and partner drugs. India, Bangladesh, Nepal and Bhutan are not experiencing artemisinin resistance, which is a positive thing, 22

and India has demonstrated that monitoring drug efficacy provides very useful information for changing the drug regimen. The situation in the GMS is more challenging, with four ACTs failing in Cambodia and also failures in Viet Nam. Although AL is still working in the Lao People’s Democratic Republic, it is at the borderline of 10%. In Thailand the situation is patchy, and in Myanmar the partner drugs are working. While the threat does not appear to have spread beyond the Mekong, the situation is critical and complicated and requires a lot of attention. Countries need to think about testing alternative drugs: Viet Nam, Thailand and eastern Cambodia could test artesunate+pyronaridine (Pyramax™) in 2017; and Myanmar will also start testing Pyramax™ shortly. It is very important to have alternative drugs available if the situation arises where and when it is necessary to quickly jump to another drug. Regarding K13, this research needs to be done systematically within TES. P14 and Pfmdr1 copy number can give information on piperaquine or mefloquine. With D0 filter paper samples, it is possible to get a good mapping of the situation. It is monitoring that leads to action – that is, to the changing of drug regimens. There is currently no replacement for artemisinin derivatives, so it is not possible to do anything else but use ACTs. We need partners to develop a drug that is not artemisinin based. 2.10 Country TES Plans 2016 –2017 Bangladesh In 2017, Bangladesh will conduct TES studies on the efficacy and safety of AL for uncomplicated P. falciparum malaria in two sites: 1) Nykhonchori subdistrict, Bandarban, which is close to the Myanmar border; and 2) Ramgarh subdistrict, Khagrachari, which is situated close to the border with India. In 2018, CQ and PQ for the treatment of P. vivax malaria will be tested in three sites: 1) Ramu in Cox’s Bazar district; 2) Kalmakanda in Netrokona district; and 3) Sreemongol in Moulvibazar district. The studies will be conducted during the malaria transmission season – usually from May to September. If sample size is insufficient during this period, the study will be extended and the area will be expanded to the adjacent upazilla (subdistrict). The TES implementers will be NMCP, Department of Medicine, Chittagong Medical College and National Institute of Preventive and Social Medicine. Cambodia For 2017, Cambodia has planned TES in seven sites. AS+MQ will be tested in Siem Pang (Stung Treng), Veal Veng (Pursat), Ksem (Kratie) and Buosra (Mondulkiri). In the other three sites, namely Kg. Speu, Kg. Thom and Stung Treng, AS+PYR (Pyramax™) will be tested. For 2018, AS+MQ will be tested in Kg. Speu, Rattanakiri, Maung Russei (Battambang) and Preah Vihear. In the remaining three sites of Kvav (Siem Reap), Veal Veng and Oddor Mean Chey (Anlong Veng), the ACT to be tested will depend on TES results from the previous year. The implementer for all TES will be the Cambodia National Malaria Program. Monthly monitoring and supervision will be provided.

China China has planned TES for nine sites in Yunnan in 2017–2018 to test the efficacy of DHA+PIP and CQ and 10 sites in Jiangsu and Henan provinces to test the efficacy of DHA+PIP. The nine selected sites in Yunnan are: Tengchong, Baoshan; Yingjiang Dehong; Ruili Dehong; Menglian, Puer; Longyang, Baoshan; Cangyuan, Lincang; Longling, Baoshan; Luliang, Qujing and Kunming. In Jiangsu and Henan provinces, the 10 sites comprise five counties in Jiangsu and five counties in Henan. Sites were selected on the basis of strategic location – the Yunnan-Myanmar border is 1997 km long. Tengchong, Yingjiang and Ruili City, which belong to Baoshan and Dehong Prefectures respectively, are located in west Yunnan bordering with Myanmar, and have the highest malaria incidence rates in China. India For 2017, India has planned TES to assess the efficacy of AS+SP in Lakhimpur Kheri (Utar Pradesh) and North 24 Parganas (West Bengal) and to test AL in three sites: Kokrajhar (Assam), Dhalai (Tripura) and Lunlei (Mizoram). For 2018, four sites have been identified: Udalgiri (Assam); South Garohills (Meghalaya); West Garohills (Meghalaya) and Churachandpur (Manipur). The TES implementers will be National Institute for Research in Tribal Health (NIRTH) and National Institute for Malaria Research (NIMR) with monitoring and supervision provided by National Vector Borne Disease Control Programme (NVBDCP). Indonesia As a result of delays to the commencement of TES in 2016, Indonesia will conduct TES in late October 2016 thru October 2017 in Papua (north-east, Jayapura /Papua New Guinea border) and Bengkulu (North Bengkulu district). The TES for 2017-2018 is planned to be conducted between July 2017-December 2018 in West Papua; Molucca (Seram district), East Nusa Tenggara (districts at the border with Timor-Leste and North Moluccas (Morotai districts). The sites were selected due to the high/moderate malaria incidence in eastern parts of Indonesia, unconfirmed reports of DHA-PIP treatment failure from the area, and to explore cross-border collaboration on malaria with neighbouring countries. Lao People's Democratic Republic For 2017 TES, the Lao People’s Democratic Republic has planned to assess the efficacy of DHA-PIP for the treatment of uncomplicated P. falciparum in Champasack. In addition, the efficacy of AL for Pf malaria will be assessed in Attapeau. For 2018, AL will be tested in Savannaketh, and DHA-PIP in Salavan. The implementers of TES will be the Centre for Malaria Parasitology and Entomology (CMPE) and the provincial health offices. Malaysia Malaysia will continue its drug resistance surveillance nationwide on all malaria cases, using the VEKPRO online web-based real time malaria surveillance system, fully integrated with the surveillance system of the vector programme of the Ministry of Health. With the 2016 drug policy change to AL for P. vivax, the surveillance will include follow-up on vivax cases in 2017 and onwards. 24

Myanmar For 2017, Myanmar has planned to test the efficacy of AS+PYR and CQ in Kayin State and in Kawthaung, Tanintharyi Region. Likewise, the efficacy of AL, DHA+PIP and CQ will be tested in Myit Kyi Nar, Kachin State and in Muse, eastern Shan State. In 2018, AL and CQ will be tested in Beelin, Mon State, and AS+PYR and CQ in Tandaung, Kayin State. In addition, AL, DHA-PIP and CQ will be tested in Tamu, Sagaing Region, in Tabeikkyin, Mandalay Region, and in Paletwa, Chin State. The TES implementers will be the Department of Medical Research together with NMCP. Papua New Guinea For 2017, Papua New Guinea plans to implement TES in one site, Alotau, to test the efficacy of AL. In 2018, AL and DHA+PIP will be tested in the following two sites: Vanimo Green (border province) and Lae. The NMCP will be the implementer and the M1 and M2 slide readers will be CPHL/PNG-IMR. Papua New Guinea requires training for field officers, medical monitor, Co-Principal Investigators and Principal Investigators. Philippines Despite the success in managing malaria, the Philippines will continue TES in 2017 –2018. The efficacy of AL for falciparum and CQ for vivax will be assessed in Palawan in 2017 and in 2018, respectively. The implementer will be the Research Institute for Tropical Medicine for both 2017 and 2018 TES. There will be an internal TES monitor, Mr Erick Ocampo and a WHO external monitor. The NMCP in the Department of Health plans to “reactivate” the drug resistance surveillance in the current surveillance system in near-elimination provinces. Solomon Islands Solomon Islands has planned TES with AL in one site in 2017: Tetere, Guadalcanal Province. In 2018, AL will be tested in Auki, Malaita Province. The TES implementers will be Dr Lyndes Wini, Adam Fafale and Leonard Boaz, in collaboration with WHO and WEHI. Dr Lyndes will provide monitoring and supervision. Thailand Thailand has selected one site (Tak province) for TES implementation in 2017, to test AS+PYR (Pyramax™). In addition, drug resistance surveillance of DHA- PIP will be carried out in five sites: Mae Hong Son, Kanchanaburi, Surathani, Srisaket and Sakaeo. The implementers will be the Bureau of Vector Borne Diseases (BVBD) and the Office of Disease Prevention and Control (ODPC). The drug resistance surveillance was chosen for the following reasons: low cases, 100–200 cases/year from malaria clinics (need at least 50 cases for analysis), both Pf and Pv (no inclusion criteria), 42- day follow-up possible (Thai and M1with more chance to complete follow-up), to look at the resistance trend in international borders, and in areas with good malaria information system management (IT staff available).

Timor Leste With the low number of cases, the country plans TES with AL nationwide on Pf and Pv laboratory-confirmed malaria, with focus on out-break prone resettlement/development areas. The program needs TA on PCR and K13 confirmation, and TES refresher training. Viet Nam Viet Nam selected the following sites for 2017: Binh Phuoc and Dak Nong to test AS+MQ and Pyramax™; Khanh Hoa to test AS+MQ and CQ; Gia Lai to test AS+MQ and Pyramax™; Phu Yen to test DHA+PIP; and Ninh Thuan to test DHA+PIP and Pyramax™. For 2018 TES, AS+MQ and Pyramax™ will be tested in Binh Phuoc, Ninh Thuan and Quang Nam. In Dak Lak and Quang Tri, DHA+PIP will be tested. Finally in Gia Lai, AS+MQ and CQ will be assessed. Suggestions for improving TES implementation include more technical support from WHO such as training on K13 analysis and technical support for laboratory staff; assistance to get certificate of K13 analysis as reference laboratory; refresher training for microscopists; refresher training of good clinical/good laboratory practices (GCP/GLPs) for all staff in charge of TES (2 years certificate validity, Ministry of Health rule); software to calculate half-life clearance time (t1/2); strengthening of QA/QC system in microscopy; and adequate study duration for minimum required sample size. Network plans The key priorities identified by the networks were:  QA / QC system for diagnosis on yearly basis o identification of reference laboratories; o SOPs and refresher microscopy; o national slide banks and external competency assessment (ECA) course;  Subregional activity coordination o inter-network cooperation across borders; o information sharing of malaria index; o different national antimalarial drugs policy (treatment used near border); o molecular and pharmacokinetic technology; o transition to the establishment of web-based data management, and early warning system.

3. CONCULSIONS AND RECOMMENDATIONS 3.1 Conclusions Most countries have continued to strengthen TES work. Nearly all countries implemented TES for 2016 with the exception of Papua New Guinea and Bangladesh where ethical approvals were still being finalized. Technical assistance will continue to be provided by WHO staff as relevant.

Countries that would like to seek training and certification for microscopists can make the requests through their WHO country office. WHO recognizes the need to increase the numbers of expert microscopists within countries, particularly as countries move towards elimination. This is part of strengthening their national malaria microscopy quality assurance system. Effective surveillance systems are the backbone of ensuring malaria elimination in both the Pacific and GMS regions, and specifically case-based surveillance systems. This becomes more important as countries with very low numbers of cases can integrate drug efficacy monitoring into the national surveillance (or vice versa). Drug resistance is more challenging in the GMS. There are four ACTs failing in Cambodia and also drug failures in Viet Nam. The Lao People’s Democratic Republic is borderline (10%) with AL still working. In Thailand the situation is patchy, and in Myanmar the situation is good regarding partner drugs, though artemisinin resistance is a challenge. The threat does not appear to have spread beyond the Mekong, but it is important to remain vigilant. Countries need to test alternative ACTs: artesunate+pyronaridine (Pyramax™) for Cambodia, Myanmar, Thailand and Viet Nam. The Pacific and BBINS countries do not have a problem with ACTs or K13. India’s changing drug regimen demonstrates the importance of monitoring drug efficacy. For GMS countries, information on artemisinin (K13) and also piperaquine (P14) and mefloquine markers (pfmdr1 copy no.) for resistance are equally important. D0 filter paper would give a good mapping of the situation. Continued monitoring will lead to action – that is, to the timely review and change of drug regimens. There are currently no replacements for artemisinin-derivative drugs, so we must continue to use ACTs. WHO is working with partners like Medicines for Malaria Venture (MMV), in the development of non-artemisininbased drugs. 3.2 Recommendations 3.2.1 Recommendations for Member States 1) Countries may continue to strengthen implementation of high-quality therapeutic efficacy studies using the standard WHO protocol. 2) Countries may continue to strengthen and support laboratory capacities: Strengthen overall malaria microscopy quality assurance systems including refresher training for TES microscopists; and implement quality control for molecular assays with reference laboratory (Institute Pasteur Cambodia), technical training and exchange of samples.

Alternative ACT regimens need to be tested before deciding on a drug policy review as soon as signs of declining efficacy manifest.

4) Countries are encouraged to maintain regular monitoring visits to TES sites, using quality control monitoring forms. 5) Countries are encouraged to facilitate integration of monitoring of drug efficacy into routine surveillance systems in near-elimination settings. 3.2.2 Recommendations for WHO 1) Tasks for the networks focus on coordination, information sharing and technical support for the activities outlined above, with particular emphasis on laboratory QC (microscopy, RDT and molecular assays) and strengthening cross-border information sharing and coordination especially in TES areas. 2) WHO is requested to provide continuous updates on artemisinin resistance as they evolve especially in the Greater Mekong Subregion. 3) WHO is requested to provide support for countries moving into the elimination phase as they adopt new approaches to monitoring and surveillance beyond the routine TES.

ANNEXES Annex 1. TES Country Plans, 2017-2018 2017 Name of site Drugs to test Proposed budget Name of site 2018 Drugs to test Proposed budget Funding Source Implementer Refresher Microscopy training M1 & M2 slide readers Monitoring and supervision Other needs/gaps, capacity building

Bangladesh Ramgarh, Khagrachori District Nykhonchori, Bandarban District AL 48,228 USD AL GFATM MOH & NMCP - TES team Training - Training/ Collaboration for K13 assays - Cross border bilateral meeting with India and Myanmar - Data Sharing and networking - ECA for Microscopist

Needed for CMRL and Study sites MT lab

MT lab of UHC/ MT lab of Brac/ MRG

UHFPO and CS, PI, CoInvestigators

Ramu, Cox's Bazar Kalmakanda, Netrokona Sreemongal, Moulvibazar

CQ & PQ 49,500 USD

CQ & PQ

Cambodia Siem Pang (Stung Treng) Veal Veng (Pursat) Ksem (Kratie) Buosra (Mondulkiri ) Kg. Speu AS+MQ 3000035000 USD 3000035000 USD 3000035000 USD 3000035000 USD 3000035000 USD 3000035000 USD Kg. Speu AS+MQ 3000035000 3000035000 3000035000 3000035000 3000035000 3000035000 WHO CNM Yes Yes Monthly

AS+MQ

Rattanakiri Maung Russei (Battambang) Preah Vihear Kvav (Siem Reap) Veal Veng

AS+MQ

WHO

CNM

Yes

Monthly

AS+MQ

WHO

CNM

Yes

Monthly

AS+MQ Pyramax ™ Pyramax ™

AS+MQ ACTs (to be confirmed) ACTs (to be confirmed) AS+MQ (Drug Resistance surveillance )

WHO

CNM

Yes

Monthly

WHO

CNM

Yes

Monthly

Kg. Thom

WHO

CNM

Yes

Monthly

Stung Treng

Pyramax ™

3000035000 USD

Oddor Mean Chey (Anlong Veng)

25000030000

WHO

CNM

Yes

Monthly

China Tengchong, Baoshan Yingjiang， Dehong Ruili， Dehong Menglian, Puer Longyang, Baoshan Cangyuan, Lincang Longling, Baoshan Luliang, Qujing DHA+PIP CQ DHA+PIP CQ DHA+PIP CQ DHA+PIP CQ DHA+PIP CQ DHA+PIP CQ DHA+PIP CQ DHA+PIP CQ DHA+PIP CQ 20000 USD Tengchong DHA+PIP, CQ DHA+PIP, CQ DHA+PIP, CQ DHA+PIP, CQ DHA+PIP, CQ DHA+PIP, CQ DHA+PIP, CQ DHA+PIP, CQ DHA+PIP, CQ 20000 USD 30000 USD 20000 USD 15000 USD 15000 USD 15000 USD 15000 USD 15000 USD 15000 USD WHO/TES YIPD, County CDC YIPD, County CDC YIPD, County CDC YIPD, County CDC YIPD, County CDC 2 1

30000 USD

Yingjiang

WHO/TES

20000 USD

Ruili

WHO/TES

15000 USD

Menglian

WHO/TES

1 NIPD or YIPD, 2 times/yr K13 test and analysis and QC; TES refresher training

15000 USD

Longyang

WHO/TES

15000 USD

Cangyuan

1 Require Chinese Gov’t support

15000 USD

Longling

YIPD, County CDC

15000 USD

Luliang,Qujing

15000 USD

Kunming

County 1 Jiangsu

DHA+PIP 12000 USD Cty. 1Jiangsu

DHA+PIP 12000 USD 1 1 - TES and microscopy training - Training for K13 and analysis and QC

County 2 Jiangsu County 3 Jiangsu County 4 Jiangsu County 5 Jiangsu County 1 Henan County 2 Henan County 3 Henan County4 Henan County 5 Henan

DHA+PIP

12000 USD

Cty. 2Jiangsu

DHA+PIP

12000 USD JIPD, County CDC

1 NIPD or JIPD, 2 times/yr

DHA+PIP

12000 USD

Cty. 3Jiangsu

DHA+PIP

12000 USD

DHA+PIP

12000 USD

Cty. 4Jiangsu

DHA+PIP

12000 USD Require Chinese Gov’t support

DHA+PIP

12000 USD

Cty. 5Jiangsu

DHA+PIP

12000 USD

DHA+PIP

12000 USD

Cty 1 Henan

DHA+PIP

12000 USD

1 - TES and microscopy Training ‘- training for K13 test and analysis and QC

DHA+PIP

12000 USD

Cty. 2 Henan

DHA+PIP

12000 USD HIPD, County CDC

1 NIPD or HIPD, 2 times/yr

DHA+PIP

12000 USD

Cty. 3 Henan

DHA+PIP

12000 USD

DHA+PIP

12000 USD

Cty. 4 Henan

DHA+PIP

12000 USD

DHA+PIP

12000 USD

Cty. 5 Henan

DHA+PIP

12000 USD

India Lakhimpur Kheri (UP) Kokrajhar (Assam) 24 Parganas North (WB) Dhalai (Tripura) Lunlei (Mizoram) AS+SP 38,433 USD 38,433 USD 38,433 USD 38,433 USD 38,433 USD Udalgiri (Assam) South Garohills (Meghalaya) West Garohills (Meghalaya) Churachandp ur (Manipur) AL 38,433 USD 38,433 USD 38,433 USD 38,433 USD WHO NIRTH Proposed NIRTH NIRTH, NIMR NIRTH NVBDCP Needs/ Gaps shall be identified in the due process of study. Capacity building is a continuous process

WHO

NIRTH, NIMR

Proposed

NVBDCP

AS+SP

WHO

NIRTH

Proposed

NVBDCP

WHO

NIMR

Proposed

NIMR NIMR, NIRTH

NVBDCP

WHO

NIMR, NIRTH

Proposed

NVBDCP

Indonesia West Papua (Manokwari ) GCP and Microscopy training for MD and Lab technician GCP and Microscopy training for MD and Lab technician

DHA+PIP

West Papua (Manokwari)

DHA+PIP

169,000 USD

WHO

Eijkman/MOH-BTKL

Yes

TBD

3 times

Maluku (Seram Barat) Nusa Tenggara Timur (Belu & other border districts)

DHA+PIP

Maluku (Seram Barat)

DHA+PIP

WHO

Eijkman/MOH/BTKL

Yes

TBD

3 times

DHA+PIP

Nusa Tenggara Timur (Belu and other border Districts

DHA+PIP

WHO

Eijkman, MOH/BTKL/Collabora tive work with East Timor

Yes

TBD

3 times

North Maluku (Tobelo and Moeotai)

DHA+PIP 4

North Maluku (Tobelo and Moeotai)

DHA+PIP

WHO

Eijkman, MOH/BTKL

Yes

TBD

3 times

Lao People's Democratic Republic Champasac k Attapeau DHA+PIP 52,069 USD 49,119 USD Salavan Savannaket h DHA+PIP 50,519 USD 50, 669 USD WHO CMPE and Province CMPE and Province Yes Yes Monthly

Yes

Monthly

Myanmar Kyar Inn Seik Kyi, Kayin State Kawthaung , Tanintharyi Region Myit Kyi Nar, Kachin State Muse, Eastern Shan State AS+PYR (Pf) & CQ (Pv) AS+PYR (Pf) & CQ (Pv) 35,000 USD 25,000 USD Beelin, Mon State Tandaung, Kayin State AL (Pf) & CQ (Pv) AS+PYR (Pf) & CQ (Pv) AL, DHA+PIP, CQ(Pv) AL, DHA+PIP, CQ(Pv) AL, DHA+PIP, CQ(Pv) 25,000 USD 25,000 USD WHO DMR (HQ)

WHO

DMR (HQ)

AL, DHA+PIP, CQ(Pv) AL, DHA+PIP, CQ(Pv)

30 000 USD 25,000 USD

Tabeikkyin , Mandalay Region Tamu, Sagaing Region Paletwa, Chin State

25,000 USD 30,000 USD 50,000 USD

WHO

DMR (POL)

WHO

DMR (POL)

WHO

DMR (HQ)

Papua New Guinea 111,040 USD Vanimo Green, Border Province AL, DHA+PIP CPHL/ PNG IMR Training of field officers, medical monitor, PI, Co-PIs

Alotau

TBD

WHO

NMCP

Yes

Lae

AL, DHA+PIP

TBD

WHO

NMCP

Yes

CPHL/ PNG IMR

Philippines Palawan AL Php 4,222,848 ($84,457) Palawan CQ Php 4,300,000 ($86,000) Government of Philippines RITMDepartment of Health Yes Yes Mr. Ocampo & WHO RITM staff

Solomon Islands Dr. L Wini, A Fafale, L Boaz, WHO (SI), WEHI, GSH,

Tetere, Guadalcanal Province

52,047 USD

Auki, Malaita Province

TBC

WHO

Adam Fafale, Eric Taraihaka

Dr. Lyndes

Accessing funds

Thailand Tak Mae Hong Son TES of Pyramax™ DRS of DHA+PIP 32,000 USD Sites to be determined WHO BVBD & ODPC BVBD & ODPC Refresher training for 16 participants 2 people for M1 & M2 ODPC every 3 months, BVBD every 6 months ODPC every 3 months, BVBD every 6 months ODPC every 3 months, BVBD every 6 months ODPC every 3 months, BVBD every 6 months ODPC every 3 months, BVBD every 6 months - QC for molecular marker - National core team meeting - NCA 16 participant - ECA 12 participants - Regional slide bank - Data training and analysis - Strengthen documentatio n & reporting

8,000 USD

GF-RAI

Kanchanaburi

DRS of DHA+PIP

8,000 USD

WHO + BVBD

BVBD & ODPC

2 people for M1 & M2

Surathani

DRS of DHA+PIP

8,000 USD

WHO + BVBD

BVBD & ODPC

Approx. 64 MC microscopists

2 people for M1 & M2

Srisaket

DRS of DHA+PIP

8,000 USD

WHO + BVBD

BVBD & ODPC

2 people for M1 & M2

Sakaeo

DRS of DHA+PIP

8,000 USD

WHO + BVBD

BVBD & ODPC

2 people for M1 & M2

Project management Training and Assessment

30,000 USD

18,000 USD

Timor Leste Whole country as one site National Malaria Control Programme (MoH) Yes: October 2428, 2016 Yes Next training: June 2018 Yes: October 2428, 2016 Yes Next training: June 2019 International TA and 2 Expert Microscopist PI and Co-I and National LAB / QC GabineteMoH / Ethical Committee, NMCP PI and Co-I and National LAB / QC GabineteMoH / Ethical Committee, NMCP PCR / K13 confirmation, & TES refresher training

Whole country as one site

$ 34,013.37

$34,013.37

GFATM & WHO

PI / CoInvestigators and WHO

Whole country as one site

$ 28,846.64

Whole country as one site

$28,846.64

GFATM & WHO

National Malaria Control Programme (MoH)

International TA and 2 Expert Microscopist

PI / CoInvestigators and WHO

PCR - K13 confirmation, & TES refresher training

Viet Nam AS+MQ; Pyramax™ AS+MQ; Pyramax™ AS+MQ; CQ AS+MQ; Pyramax™ 30-35,000 USD 30-35,000 USD 30-35,000 USD 30-35,000 USD 30-35,000 USD AS+MQ; Pyramax™ AS+MQ; CQ AS+MQ; Pyramax™ DHA+PIP Dak Lak AS+MQ; Pyramax™ 30-35,000 USD 30-35,000 USD 30-35,000 USD 30-35,000 USD 30-35,000 USD Microscopist level 1 for NIMPE/ IMPEs technician; Microscopist level 2 for Provincial staff; Giemsa staining slides & RDTs must be checked before TES. PI & Co-PI; 4-5 x per yr. PI & Co-PI; 4-5 x per yr. PI & Co-PI; 4-5 x per yr. PI & Co-PI; 4-5 x per yr. PI & Co-PI; 4-5 x per yr. Training on K13 analysis and technical support for lab staff; Refreshe r training of GCPs/ GCLPs for all staff in charge of TES (2 years certificat e validity, MoH rule)

Binh Phuoc

Dak Nong

Gia Lai

Khanh Hoa

Ninh Thuan

Gia Lai

Phu Yen

DHA+PIP

Quang Nam

DHA+PIP DHA+PIP; Pyramax™ 30-35,000 USD 30-35,000 USD PI & Co-PI; 4-5 x per yr.

Ninh Thuan

Quang Tri

Annex 2. Agenda

DAY 1 - 24 October 2016, Napalai Room Time Presenter

08:00 08:30

Registration of participants Welcome remarks Dr Sombat Thanprasertsuk, Ag. Deputy Director, Department of Diseases Control, MOPH, Thailand Dr Daniel Kertesz, WR Thailand (on behalf of RDs WHO SEARO and WPRO)

08:50

10:15 10:45 11:00

Self-introduction Review of the objectives and expected outcomes. Nomination of Chair and Vice chair Group photo / coffee break (Foyer) Review of recommendations 2015 and progress Anti-malarial drug resistance monitoring in the Greater Mekong Subregion, BBINS and Pacific Networks: progress and implementation challenges; monitoring QC templates Plenary discussion Greater Mekong Subregion (GMS) Network: Presentations by Principal Investigators on TES results of the last 2 years (15 min. presentation/country, followed by discussion) Cambodia China Lunch (Pavillion Restaurant, basement) Greater Mekong Subregion (GMS) Network: Presentations by Principal Investigators on TES results of the last 2 years – Cont. Lao PDR Myanmar Thailand Vietnam Coffee / tea break Country TES Principal Investigators Dr Viengxai Dr Khin Lin Mr Theerayot Kobasa Dr Bui Quang Phuc Dr Rabidra Abesinghe Dr Maria Dorina Bustos

Chair and Vice-Chair

Dr Leang Rithea Prof. Tang Lin Hua

12:00 13:00

15:00

15:30

BBINS Network: Presentations by Principal Investigators on TES results of the last 2 years (12 min. presentation per country, followed by discussion) Bangladesh India Nepal Bhutan Sri Lanka Closure of Day 1

Dr Abu Nayeem Md Sohel Dr Neeru Singh & Dr Neelima Mishra Dr Maria Dorina Bustos Prof. Din Mr Tobgyel Dr H. P. R. Dharmawardena

18.00

Day 2 (25 October 2016), Dusit Thani Hall Time 8:30 Schedule Presenter Updates on the Kelch 13 marker for artemisinin Dr Pascal Ringwald resistance and global malaria multi-drug Dr Didier Menard resistance situation – Q&A Updates on the Quality Assurance of Malaria Microscopy Pacific Network: Presentations by Principal Investigators on TES results of the last 2 years (15 min. presentation per country, followed by discussion) Indonesia 10:30 11:00 Coffee / tea break Pacific Network presentations continued: Malaysia Philippines Timor-Leste Papua New Guinea Solomon Islands Lunch Updates on the Strategy for malaria elimination in the Greater Mekong Subregion (2015-2030) Summary of country results and discussions Group Work  Introduction Country breakout groups to prepare/update 2017-18 country TES plans / budgets and define tasks of the networks

9:00 9:30

Dr Rabi Abeyasinghe

Country TES Principal Investigators Prof. Din SyaFrudin

Dr UmmiKalthom Shamsudin Mr Sherwin Galit Dr Maria Mota Dr Leonard Nawara

12.00 13:00 13.30 14:00

Dr Fred Binka Dr Pascal Ringwald Dr Dorina Bustos Facilitators (WHO staff)



15.30 17:30

Coffee/ tea break Group Work continued Closure of Day 2 40

Day 3 (26 October 2016), Dusit Thani Hall Time 8:30 -

Schedule Finalize country work plans/budget; group discussion among border countries; and group discussion on drug resistance surveillance Coffee / tea break

Presenter Facilitators (WHO staff)

9:45

10:00-12:00 Plenary presentations and discussion of country plans / budgets and network plans (10 mins / country) Greater Mekong Subregion Network Cambodia China Lao People's Democratic Republic Myanmar Thailand Viet Nam Network plan BBINS Network Bangladesh Bhutan India Pacific Network Indonesia Malaysia Philippines 12:30 13:30 Lunch Plenary presentations continued: Pacific Network Papua New Guinea Solomon Islands Timor-Leste 14.45 Partners' comments

Country TES Principal Investigators

Dr Leang Rithea Prof. Tang Lin Hua Dr Myat Phone Kyaw Mr Theerayot Kobasa Dr Huynh Hong Quang Mr Tobgyel Dr Abu Nayeem Md. Sohel Mr Tobgyel Dr Sher Singh Kasyotia Dr Din Syafrudin Dr Ummi Kalthom Shasudin Mr Sherwin Galit

ACTMalaria, BMGF, DFAT, GFATM, RTI, UNOPS, USAID/PMI

15:15 15.45 16.00

Coffee / tea break Conclusions, recommendations and next steps Closing remark Maria Dorina Bustos Dr Lin Aung

Annex 3. List of participants

BANGLADESH Dr M. M. Aktaruzzaman, Program Manager, BAN-MAL and Deputy Program Manager (Malaria and VBDC), National Malaria Control Program, Directorate General of Health Services (DGHS), Mohakhali, Dhaka. Tel No.: +88 0 17 1130 2584, E-mail: mmaktaruzzaman93@gmail.com. Dr Abu Nayeem Mohammad Sohel, Mal &VBC, DGHS, Mohakhali, National Malaria Control Programme, House-240, Lake Road, Lane-17, New DOHS, Mohakhali, Dhaka-1206. Tel No.: 88 0 2988 0948, E-mail: nayeemdr@yahoo.com. BHUTAN Mr Tobgyel, Deputy Chief Program Officer, Vector Borne Disease Control Program, Department of Public Health, Gelephu, Tel No.: +975 17604363, E-mail: rwtobgyel@yahoo.com. CAMBODIA Dr Chea Huch, Deputy Director, National Center for Parasitology, Entomology and Malaria Control, Corner street 92-93, Trapeng Svay Village, Phnom Penh Thmei Phnom Penh, Cambodia. Tel No.: +855 I 0 316 306, E-mail: huch@cnm.gov.kh. Dr Leang Rithea, Vice Chief, Technical Bureau, National Center for Parasitology, Entomology and Malaria Control, #92. Trapeang Svav Village, Sangkat Phnom Penh Thmey, Phnom Penh, Cambodia. Tel No.; +855 1271 5666, E-mail: rithealeang@gmail.com CHINA Dr Hu Tao, Bureau of Disease Control, National Health and Family Planning Commission of People's Republic of China, Ministry of Health, No. 1. Xizhimenwai, South Road, 100044, Beijing. Tel. No.: +86 10 6879 2697, E-mail: hutao@nhfpc.gov.cn. Professor Tang Lin Hua, National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, 207 Ruijin Er Road, 200025, Shanghai. Tel. No.: +86 21 64373359, E-mail: ipdtlh@sh163.net. Professor Gao Qi, Jiangsu Institute of Parasitic Diseases, Meiyuan, Wuxi, Jiangsu, 214064,China. Tel. No.: +861 38 1219 9327, E-mail: gaoqiS4@botmail.com. INDIA Dr Sher Singh Kashyotia; Deputy Director, NVBDCP, Dte. GHS, DMRC Building, BlockIII, Ground Floor, Delhi IT Park; Shastri Park, DELHI. 110053. Tel.: 09968283266; Email: nvbdcp.sher1@gmail.com INDONESIA Dr Iriani Samad, Head Section, Sub-directorate of Malaria Control, Ministry of Health, Republic of Indonesia. Tel No.: +62 85211804379, E-mail: iriani_smd@yahoo.com.

Dr Jeanne Rini, Principal Investigator , Mimika District Hospital (RSUD Mimika),Jl. Yos Sudarso, Timika, Papua Province. Tel No.: +628 1149 0738; E-mail: didot2266@yahoo.com. Dr Din Syafrudin, Eijkman Institute for Molecular Biology,Jl. P. Diponegoro No.69,Kompleks Rumah Sakit Cipto Mangunkusumo, Daerah Khusus Ibukota 10430 Jakarta. Tel No.:+62 21 3917131, E-mail: dinkarim@yahoo.com; din@eijkman.go.id. LAO PEOPLE'S DEMOCRATIC REPUBLIC Dr Viengxay Vanisaveth, Deputy Director, Center of Malariology, Parasitology and Entomology, Ministry of Health, Vientiane, Lao PDR. Tel No.: (856 21) 214040, 252673, Email: v.viengxay@gmail.com Dr Maniphone Khanthavong; Technical staff of Laboratory and Treatment Unit; Center of Malariology, Parasitology and Entomology, Ministry of Health, Vientiane, Lao PDR. Tel No.: (856 21) 214040, 252673, E-mail: kv.maniphone@gmail.com. MALAYSIA Dr Ummi Kalthom Shamsudin, Public Health Physician, Senior Principal Assistant Director (Malaria Elimination Program),Vector Borne Disease Section, Disease Control Division, Ministry of Health Malaysia, Level 4, Block E10, Complex E, Federal Government Administrative Centre, 62590 Putrajaya, Malaysia. Tel No.: +603-8883 4261 / +6019-662 5885,E-mail:drummi@moh.gov.my; mmishamsudinmd@gmail.com. Dr Raden Shamilah Binti Raden Hisham, Medical Research Specialist Officer, Institute for Medical Research,Jalan Pahang,50588 Kuala Lumpur, Malaysia. Tel No.: +603-2616 2682/+6019-283 9795, E-mail: shamilah@imr.gov.my MYANMAR Dr Aung Thi, Deputy Director (Malaria), Department of Public Health, Naypyitaw. Tel No.: +9595600129, E-mail: aungthi08@gmail.com. Dr Khin Lin, Deputy Director General (Retired), Department of Medical Research, Pyinoolwin Branch, Tel.: +958550251, E-mail: dr.khinlin.dir@gmail.com. Dr Myat Phone Kyaw, Deputy Director General (Retired), Department of Medical Research, Yangon, Tel No.: +959 7955 26206,E-mail: kyaw606@gmail.com. Dr Than Naing Soe, Assistant Director (Malaria),Department of Public Health, Naypyitaw. Tel No.: 09 594 5420 6210, E-mail: drsoe.thannaing@gmail.com. PAPUA NEW GUINEA Mr Leo Makita, Program Manager, Department of Health, P.O. Box 807, Waigani, NCD, Papua New Guinea. Tel No: +675 3013774, E-mail: leo.makita@gmail.com. Dr Leonard Nawara, Medical Officer,Malaria and Vectorborne Diseases, Department of Health, P.O. Box 807’Waigani, NCD. Tel No: +675 301 3760,E-mail: leonardnawara@gmail.com.

PHILIPPINES Mr Sherwin A. Galit, Senior Science Research Specialist, Research Institute for Tropical Medicine - Department of Health, 9002 Research Drive, Filinvest Corporate City, Alabang, Muntinlupa City 1781. Tel No: (632) 807-2628 (to 30) loc. 254 or 227, E-mail: s_galit12@yahoo.com SOLOMON ISLANDS Mr Albino Bobogare, Director, National Vector Borne Disease Control Programme, Ministry of Health and Medical Services, P.O. Box 349, Honiara. Tel No: (677) 30655 / (677) 7779131, E-mail: a47bobogare@gmail.com. SRI LANKA Dr Hettikankanamalage Priyani Ranjanaprabha Dharmawardena, Medical Officer, Anti - Malaria Campaign, 555/5, Elvitigala Mawatha, Colombo 5. Tel No.: +94-716830161, Email: drpriyanid@gmail.com. TIMOR-LESTE Ms Maria do Rosiaro de Fatima Mota, Programme Manager, National Malaria Control Programme, Timor-Leste. Tel No.: +67 0 7732 4403,E-mail: mariadordef.mota@gmail.com. Mr Virgilio Mendonca, Laboratory Analyst, Co‐Investigator Therapeutic Efficacy Study, National Health Laboratory, Timor-Leste. Tel.: + +670 7742 2763. THAILAND Dr Nipon Chinanonwait, Director, Bureau of Vector-borne Diseases, Department of Diseases Control, Ministry of Public Health, Nonthaburi 11000. Tel No.: +66 2590 3121, Email: chinnipon2011@gmail.com. Mr Theerayot Kobasa, Public Health Technical Officer, Professional level, Bureau of Vector Borne Diseases, Department of Disease Control , Ministry of Public Health, Nonthaburi, 11000. Tel No.: +66 2590 3128, E-mail: ktheerayot@gmail.com. VIETNAM Dr Ho Dinh Trung, Vice Director, National Institute for Malariology, Parasitology, and Entomology (NIMPE), Ministry of Health, 35 Trung Van Road, Nam Tu Liem district, Hanoi. Tel no.: +849 1220 5758, E-mail: hodinhtrung@fpt.vn Dr Bui Quang Phuc, Head of Department of Malaria Research and Treatment National Institute of Malarialogy, Parasitology & Entomology 245 Luong The Vinh Str, Ha Noi, Vietnam. Tel No.: +844 3854 0099, E-mail: phucnimpe@yahoo.com. Dr Huynh Hong Quang, Vice Director, Institute of Malariology, Parasitology and Entomology of Quy Nhon 483 Nguyen Thai Hoc street, Quy Nhon City, Binh Dinh Province, Vietnam. Tel No.: +84 905 103496, E-mail: huynhquangimpe@yahoo.com.

2. SPECIAL INVITEES CAMBODIA Dr Didier Menard, Malaria Molecular Epidemiology Unit, Institut Pasteur Cambodia, 5 Boulevard Monivong - PO Box 983, Phnom Penh 12201- Cambodia. Tel No: +855 23 426 009 poste 219, E-mail: dmenard@pasteur-kh.org; dmenard@pasteur.fr INDIA Dr Neeru Singh, Scientist G and Director, National Institute for Research in Tribal Health, Medical College Campus, Nagpur Road, Jabalpur 482003. Tel No:0761-2672239, 2672973, E-mail: nsmrc@hotmail.com; neeru.singh@gmail Dr Neelina Mishra, Scientist E, National Institute of Malaria Research, Dwarka, Sector- 8, New Delhi-110077. Tel No:011- 25307333, E-mail: nm@icmr.org.in; neelima.nimr@gmail.com. 3. PARTNERS Ms Cecilia Hugo, Malaria Microscopy Training Coordinator/Consultant, ACTMalaria Foundation, Inc., 11th floor Ramon Magsaysay Center, 1680 Roxas Boulevard, Malate, Manila 1004, PHILIPPINES. Tel No.: +63(2)5360971), E-mail: cecil_hugo@actmalaria.net. Dr Richard Lee, Regional Program Manager, Regional Programs – Department of Foreign Affairs and Trade, Australian Embassy, 37 South Sathorn Rd, Bangkok, Thailand 10120. Tel No.: +66 (0)2 344 6477, E-mail: Richard.Lee@dfat.gov.au. Professor Arjen Dondorp, Deputy Director and Head of Malaria Research at the MahidolOxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Email: arjen@tropmedres.ac. Dr Attila Molnar, Programme Coordinator, Principal Recipient for the Global Fund to Fight AIDS, Tuberculosis and Malaria, UNOPS Myanmar. Tel No.: (95-1) 657281 – 17, E-mail: AttilaM@unops.org. Dr Gunawardena Dissanayake, Resident Malaria Advisor-U.S. President Malaria Initiative, Office of Public Health and Education, US Agency for International Development, American Embassy, #1, St. 96, Sangkat Wat Phnom, Phnom Penh, Cambodia. Tel No.: +855-23728383, E-mail: gdissanayake@usaid.gov. Dr Feliciano Monti, Senior Malaria Advisor, President’s Malaria Initiative (PMI), U.S.Agency for International Development (USAID), American Embassy, Yangon, Myanmar. Tel No.: +95 (0)1- 536 509 ext. 4877, E-mail: fmonti@usaid.gov. Dr David Sintasath, Regional Malaria Advisor, President's Malaria Initiative, USAID / Regional Development Mission for Asia, Athenee Tower, 25th Floor, 63 Wireless Road, Bangkok 10330, Thailand. Tel No.: +66-2-257-3249, E-mail: dsintasath@usaid.gov.

Dr Pratin Dharmarak, Project Management Specialist (Malaria), USAID / Regional Development Mission for Asia, Athenee Tower, 25th Floor, 63 Wireless Road, Bangkok 10330, Thailand. Tel No.: +66-2-2573255, E-mail: pdharmarak@usaid.gov. Ms Teresita Prombuth, BVBD TES Monitor, Research Triangle Institute (RTI), Bangkok, Thailand. Tel No.: +66 81 689 1419, E-mail: tlprombuth@yahoo.com. 4. SECRETARIAT Dr Pascal Ringwald, Coordinator, Drug Efficacy and Response (DER), Global Malaria Programme, World Health Organization, 20 Avenue Appia, 1211 Geneva 27. Tel No. :+41 22 791 3469, E-mail: ringwaldp@who.int. Dr Fred Newton Binka, Technical Officer, Emergency Response to Artemisinin Resistance (ERAR) in the Greater Mekong subregion, Office of the WHO Representative in Cambodia, Phnom Penh, Cambodia. Tel No.: 855 23 216610, E-mail: binkaf@who.int. Ms Abigail Gines, Programme Officer, Emergency Response to Artemisinin Resistance (ERAR) in the Greater Mekong subregion, WHO Country Office in Cambodia, P.O. box 1217, Phnom Penh, Cambodia. Tel No.: +855 92236992, E-mail: ginesa@who.int. Dr Lin Aung, Coordinator, Department of Communicable Diseases, South East Asia Regional Office, IP Estate, Mahatama Gandhi Marg, New Delhi 110002, India. Tel No.: +9111-43040409, E-mail: Linaung@who.int. Dr Rabindra Abeyasinghe, Coordinator, Malaria, Other Vectorborne and Parasitic Diseases, Regional Office for the Western Pacific, P.O. Box 2932, 1000 Manila, Philippines. Tel No.: +632 528 9725, E-mail: abeyasingher@wpro.who.int. Dr Roop Kumari, National Professional Officer (Malaria), Rooms 533-537, 'A' Wing, Nirman Bhawan, Maulana Azad Road, New Delhi 110011.E-mail: kumarir@who.int. Dr Badri Thapa, Scientist (Malaria Control), WHO Country Office, Myanmar, No. 2, Pyay Road, (7 Mile), Mayangone Township, Yangon 11061, Myanmar. Tel No.: +959 650 405406, 650 416, E-mail: thapab@who.int. Dr Md Mushfiqur Rahman, Technical Officer (Malaria), WHO Country Office, Myanmar, No. 2, Pyay Road, (7 Mile), Mayangone Township, Yangon 11061, Myanmar. Tel No.: +959 4306 4739, E-mail: rahmanmdr@who.int. Dr Daniel Kertesz, WHO Representative to Thailand, WHO Country Office for Thailand, Permanent Secretary Building 3, 4th floor, Ministry of Public Health, Tiwanon Rd, 11000, Nonthaburi, Thailand. Tel No.: +66 2 547 0100, E-mail: kerteszd@who.int. Dr Deyer Gopinath, Medical Officer (Malaria and Border Health), WHO Country Office for Thailand, Permanent Secretary Building 3, 4th floor,Ministry of Public Health, Tiwanon Rd, 11000, Nonthaburi, Thailand. Tel No.: +66 2 547 0131, E-mail: gopinathd@who.int.

Dr Maria Dorina Bustos, Malaria Technical Officer for Drug Resistance Monitoring, Emergency Response to Artemisinin Resistance (ERAR-GMS), WHO Country Office for Thailand, Permanent Secretary Building 3, 4th floor, Ministry of Public Health, Tiwanon Rd, 11000, Nonthaburi, Thailand. Tel No.: +66 2 547 0132, E-mail: bustosm@who.int. Ms Kallayanee Laempoo, Programme Associate, WHO Country Office for Thailand, Permanent Secretary Building 3, 4th floor, Ministry of Public Health, Tiwanon Rd, 11000, Nonthaburi, Thailand. Tel No.: +662 547 0133, E-mail: laempook@who.int. Dr Amarakoon Mudiyanselage Girty Manel Yapabandara, Technical Officer (Malaria), WHO Country Office for Timor-Leste, United Nations House, Caicoli street, Dili, TimorLeste. Tel No.: +670 3310 968, E-mail: yapabandaraa@who.int. 5. CONTRACTOR Ms Teresa O’Shannassy, Consultant, Bangkok, Thailand. Tel No.: +66 (0) 871643130, Email: teresajaneo@gmail.com.

www.wpro.who.int

Informations clés

Organisation Organisation mondiale de la santé (OMS)

Type de document Technical Documents

Date d'adoption 31 décembre 2016

Source Organisation mondiale de la santé