Report

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

Office of Disease Prevention and Control Region 1 Department of Disease Control Ministry of Public Health

Evaluation Report

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

Office of Disease Prevention and Control Region 1 Chiang Mai Department of Disease Control Ministry of Public Health

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

Executive summary

Title: Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

Malaria is a mosquito-borne disease that needed a careful surveillance by the Act of Communicable Disease, 2015, and has been committed to eliminate under the International Pledge by the year 2024. Thailand steps forward into the phase of malaria elimination since 2017 and fights against drug resistant malaria, which is a regional and global serious health problem mainly in the border between Thailand and neighboring countries. Malaria is claimed as a deadly neglected disease, mainly found in the remote highlands along the country border, where 78.13% of all patients were poor in minority groups. At present, approximately 85% of malaria patients is Plasmodium vivax; which may be called as a chronic malaria due to its hypnozoite stage is embedded in the liver. Treatment of vivax malaria has to take primaquine for 14 days, that may cause side effects such as hemolysis of the red blood cells consequently affecting renal failure and dead in patients who have G6PD deficiency. Therefore, the objective of this initiative is to provide the underprivileged population in remote areas sustainably access to the precise, accurate, safe and complete diagnosis and treatment by using an innovative device/package, which is asimple, inexpensive and convenient method for both service providers and recipients. An innovative device/package was developed under the collaboration with many academic institutions, e.g. universities, local administrative units, malaria field workers, health volunteers and local people in the communities. The innovative device/package consists of: (1) A thick and thin film preparation box is a cozy innovative design for smearing blood films. The device helps local health care providers and health volunteers to prepare standard blood smears for malaria diagnosis; (2) Fluorescent Spot Test which is simplified in use by local health care providers to screen G6PD deficiency at a local level blood check before prescribing primaquine. Primaquine is a specific drug for radically curing malaria. Providing primaquine to a patient with G6PD deficiency leads to red blood cell hemolysis resulting in renal failure and life threat; and (3) “Drug package” labeled with a flow chart diagram of portraits of drug tablets showing how to take medicines correctly day by day. The package helps patients and relatives or caregivers to understand easily even they are unable to read

1

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

and write (e.g. a mother giving medicines to a child). The drug package is labeled in different local languages.

All malaria cases with normal G6PD enzyme were prescribed with the radical treatment plan. Treatment adherence increased from 26.8% in 2009 to 87.0 % in 2019, resulting in parasite clearance on the appointed follow-up date and the recovery rate was as high as 99.8%. Never was the evidence of drug resistance found in . The effectiveness of the implementation toward malaria cases dropped significantly from 1,180 cases in 2015 to 275 cases in 2019 (76.69% reduction rate). In Mae Hong Son province, the malaria morbidity rate decreased to 78% per 1000 population. Moreover, 4.59% of those malaria cases were detected with the G6PD deficiency according to the test. Those cases were referred to receive such treatment under the supervision of physicians to avoid renal failure and hemodialysis which burdens the patients with high expenditure at 3,500 baht/time; the treatment must be conducted twice a week for the lifetime.

In conclusion, the innovation has passed through all indicators. Most importantly, it was revealed that patients provided overall service satisfaction rate up to 95-100%. Based on the follow-up reports, there were no side effects from drugs, and all malaria cases were cured. As part of this initiative, not only the achievement of significant reduction of malaria cases and deaths, drug costs, and materials used, which is the broader early detection and treatment by using an innovative device/package. As a key strategy, the device/package is simple, inexpensive and convenient method for both service providers and clients. This initiative is ready to extend to other malaria transmission areas and should be applied to the regional countries for malaria elimination.

VDO Available on website: https://www.youtube.com/watch?v=3hl8iPSvaNs

2

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

Contents

Executive summary ...... 1 1. General Information of Mae Hong Son province ...... 4 1.1. Background and significance of malaria ...... 5 1.2. Burden of malaria in ...... 6 1.3. Organization structure ...... 8 1.3.1.National level ...... 8 1.3.2.Regional level ...... 11 2. Objective of this project ...... 12 3. Evolution of the Mae Hong Son Initiative ...... 13 4. Process and Implementation ...... 15 5. Results ...... 24 5.1.Innovative accomplishment ...... 24 5.2.Adaptability and Scaling up ...... 24 5.3.Prototype for National integrated the safety and efficacy surveillance scheme ...... 25 6. Discussion and conclusion ...... 26 6.1. Resource ...... 26 6.2. Evaluation ...... 27 6.3. Institutional Setup ...... 28 6.4. Stakeholder Engagement ...... 29 7. Lessons Learned ...... 29 8. Benefits and outcome ...... 30 9. Challenges...... 31 10. Acknowledgments ...... 32 Annex ...... 33 Annex 1 Awards ...... 33 Annex 2 Publications: ...... 35 Annex 3 News ...... 41 Annex 4 Standard Operational Procedures with Device/Package Materials ...... 44

3

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

1. General Information of Mae Hong Son province

Mae Hong Son Province is situated approximately 924 kilometers (574 mi) north of the city, . The province is situated in the border that ranged by mountainous forest attached to the Republic of Union of with many hard-to-reach areas. From the north to west border, it connects to three States in the Union of Myanmar, namely, the southern portion of , and Kawthoolei State, via the West ThanonThongchai Mountains, and the rivers, namely Salween and Moei - these formations serve as natural boundaries between the countries. From the south in Thailand side, it connects to Tha Song Yang and Tak Districts, via Yuam and Ngao rivers, which serve as a provincial boundary. To the east it connects to Wiang Haeng, Chiang Dao, Mae Taeng, Mae Chaem, Hot and Omkoi Districts in , via the Central and East sections of ThanonThongchai mountain ranges, which serve as a boundary line between the two provinces. Every district in Mae Hong Son Province shares a common border - measuring approximately 483 kilometers in total length - with the Republic of Union of Myanmar.

The common border line of approximately 326 kms (203 mi) is a forest land and 157 kms (98 mi) is of rivers (not included Salween, 127 kms (79 mi), and Moei, 30 kms (19 mi). Most of the areas of Mae Hong Son Province is the complex mountainous ranges of the , parts of which are still covered with rain forest. Of the approximately 6,976,650 rai of the national forest reserves, it is estimated that 88.02% is pristine virgin forest. The Daen Lao Range located on the northernmost portion of the province marks the northern boundary between Thailand and, while the in the west serves as the boundary between Thailand and R.U. Myanmar. The Thanon Thongchai Range in the east of the province serves as the boundary between the provinces of Mae Hong Son and Chiang Mai. The tallest peak of the Province is Doi Mae Ya, in in the northeast direction, as high as 2,005 meters (6,578 ft) above sea level. The population in the province

4

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

comprises hill tribes members (63%), including Hmong, Yao, Lahu, Lisu, Akha, Karen and Shan.

1.1. Background and significance of malaria

Malaria has been long for thousands of years and now is still a public health problem around the world including Thailand. In the tough remote areas in Thailand, particularly in the border areas have high transmission and population movement at all times, which is difficult to control the disease. Malaria is severe, it may cause death if the treatment is delayed or inappropriate. In 2018, WHO reported that 14 million people in Southeast Asia were contracted with malaria, which caused 26,000 fatal numbers. The figures of malaria fatality around the world were 438,000 people mainly living in Africa. The 10 highest malaria burden countries in Africa had estimated 3.5 million morbidity cases in 2017, which increased when compared to the previous year. WHO also reminded in 2017 that there approximately 219 million people were at risk of malaria contraction. A report from the Division of Vector Borne Diseases, Department of Disease Control, Ministry of Public Health revealed malaria situation in Thailand, fiscal year 2018, that the morbidity rate was 0.19 per 1,000 population (12,225 cases per 64,342,105 population). The fatal numbers were 43 persons or the rate of 0.022 per 100,000 population. Malaria in Thailand is spread in 30 provinces located along the country border where are precarious, inconvenient, cut off from towns, scarce of food and education. There are 11,079 malaria infected people in 30 provinces accounted for 90.6% of the whole country malaria cases. The morbidity rate in those 30 provinces is double higher than the rate of the country, which is 0.45 per 1,000 populations (11,097 from 24,620,000 population). It is found that the ratio of vivax malaria is higher than that of falciparum malaria (82.25:16.30, respectively). However, since the past ten years malaria cases in Thailand have dropped dramatically.

Thailand steps up to malaria elimination while drug resistant malaria is a worldwide health problem and is a main problem in 6 GMS countries particularly the borders between Thai- Cambodian, Thai-Lao, and Cambodian-Vietnam within the past 5 years. Drug resistance initially occurred in the western area of Cambodia and now is spread all over the country and crossed into Thailand through the provinces attached to the border, such as Sri Saket

5

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

and Ubon Ratchathani where malaria is found continuously. It is potentially the problem spread across to the west border of Thai-Myanmar and others accompanying the labor movement. The cause of drug resistance is from an improper treatment by the patients per se. From the research in 2009 found that vivax malaria patients took drugs incompletely and unfitted to the treatment plan up to 76.26%. Malaria online report found that vivax malaria ratio has increased up to 80% because Plasmodium vivax is able to embed in the liver for years.

Vivax malaria causes relapsing fever without any re-infection. Previously, it was believed that vivax malaria did not harmful to life as same as falciparum malaria, but nowadays, there are reports of deaths from vivax malaria in Indonesia, and Papua New Guinea and also the finding of absolute cure rates in vivax patients is possible after complete the medication on day 28. In the border areas between Thailand and Cambodia, the cure rate is 37% due to unavailable primaquine prescription in Cambodia. Other reason causing the patients to death is a high prevalence of G6PD deficiency, which the G6PD is important enzyme to protect red blood cell hemolysis otherwise a serious condition may occur such as acute red blood cells rupture, anemia, dark color urinate and may have the renal failure when the patient receives some stimulants. Persons having G6PD deficiency should avoid such stimulants for examples primaquine drug and broad bean consumption due to in the past there was no device to detect G6PD appropriately. Falciparum is a severe type of malaria and highly affects drug resistance that is challenging the use of drugs for treatment, which requires frequent new drug preparation. This problem causes high possibility for inefficiency of treatment, which is so dangerous to the patients.

1.2. Burden of malaria in Northern Thailand

The control of malaria in northern Thailand is under the responsibility of the Office of Disease Prevention and Control Region 1, Chiangmai, covering 5.76 million populations comprising mixed ethnic Thai and minority groups. In 2015, 1648 microscopically confirmed cases were reported, of which 21% were P. falciparum and 79% were P. vivax. The annual parasite incidences (API) per 1,000 population of the 8 provinces in the northern region (Maehongson, Chiangrai, Chiangmai, Lampang, Nan, Phrae, Lamphun and Phayoa

6

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

provinces) were 4.872, 0.188, 0.126, 0.009, 0.008, 0.006, 0.995 and 0.004, respectively in 2015, decreased consecutively to 1.071, 0.007, 0.006, 0.004, 0.002, 0.0, 0.0 and 0.0 in 2019, respectively. Noted that there are no malaria case report in Phrae, Lamphun and Phayoa provinces.

Mae Hong Son was one of the top ten highest malaria incidence provinces. Population growth, human settlements in forested and forest-fringed areas, and socio-political and economic dynamics are driving forces that exert increased interconnectedness among the border populations. Border crossings of local people and migrations of workers result in increased malaria transmission, limiting public health efforts to control malaria along the border region. Annual income for a typical border resident is 1,085 USD compared to a Thai national average of 4,650 USD. Distance from a pocket border village to a nearest malaria unit can be 50 kilometers. requiring up to 7 hours of walking through mountainous forest terrain without access to public road. The situation is worse during the rainy season, the peak malaria season (figure 4). The low household income status, frequent border crossings of local people and migrant workers, and limited public health services were the main obstacles to prevention of malaria deaths. Most at-risk populations spent significant proportions of their income on direct and indirect costs of treatment. Cost associated with time off from work and transportation to seek treatment further reduced household income. Poor school performance due to malaria illness and absenteeism reduced children‟s chances of escaping from poverty. Malaria thus locked people in poverty trap.

7

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

1.3. Organization structure

1.3.1. National level

Thailand‟s malaria control programme, established since the 1950s, has developed its own sophisticated malaria surveillance system, and coupled with a marked decline in malaria incidence from its successful programme. Thailand is striving for malaria elimination while drug-resistant malaria is a worldwide serious health problem. However, Plasmodium falciparum malaria resistant to artemisinin has been reported in Thailand. Malaria is claimed as a neglected disease, mainly found in the remote highlands along the country border where 78.13% of all patients were poor people among the minority groups. Malaria is the cause of death if they take improper or delayed treatment.

8

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

Figure 1 Endemic villages Figure 2 District stratification

Most of the malaria cases in Thailand are contracted with P. vivax infectionor mixed infections by P. vivax and P. falciparum. These increasing trends of P. vivax malaria incidence and the emergence of drug-resistant strains of the P. vivax parasite are a major concern for future malaria control (WHO, 2015). In 2018, the country‟s annual parasite incidence rate was 0.11/10,000 population. There were 15 deaths, resulting in a mortality rate of 0.022 deaths/100,000 population (Bureau of Vector Borne Disease, 2018). The successful control of P. vivax transmission in larger malaria-endemic areas depends on a precise definition of local epidemiology and consistent government support.

9

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

10

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

1.3.2. Regional level

Office of Disease Prevention and Control Region 1 (ODPC1), Chiang Mai, is a regional academic agency which is responsible for eight provinces in Northern Thailand including Mar Hon Son province. There are 12 ODPC offices distributed in all regions of the country which most are under administratation by the Department of Disease Control (DDC), Ministry of Public Health (MOPH). Our mission mainly respond to the disease surveillance, prevention and control through the health policy, partnerships and networks, IT, research and operational units. There are Vector-Borne Disease Control Center 1.1 (VBDC 1.1), which is an operational center, and seven Vector-Borne Disease Control Units (VBDU 1.1.1 – 1.1.7) in Mae Hon Son province under the ODPC1 which provides malaria clinics and serves malaria patients in the endemic areas.

Organization Chart and Reporting System of Malaria and Vector Borne Disease Control in Thailand

11

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

2. Objective of this project

The objective of this initiative is to provide the underprivileged population in remote areas to access the precise, accurate, safe and complete treatment with sustainability by using an innovative device/package, which is simple, inexpensive and convenient methods for both service providers and clients in the distant areas where have tough communication and transportation.

We confidence both service providers and clients will obtain equity of services coverage with same quality as that in the town and to reduce cost of travel to reach the health service units.

The innovative device/package consists of the following: (1) A thick and thin film preparation block is a simple innovation for smearing blood films. The device helps local health care providers and health volunteers to prepare standard blood smears for malaria diagnosis; (2) Fluorescent Spot Test which is simplified in use by local health care providers to screen G6PD deficiency at a local level to prevent complication from taking primaquine. Primaquine is a specific drug for radically curing malaria. Providing primaquine to the patient with G6PD deficiency leads to red blood cell hemolysis resulting in renal failure and death; and (3) “Drug package” labeled with a flow chart diagram of tablet portraits showing how to take medicines correctly day by day. The package helps patients and relatives who are caregivers to understand easily even they are unable to read and write (e.g. a child with malaria having a mother who is a caregiver to give medicines correctly).

These packages are developed into different local languages. This innovative device/package is able to eliminate malaria effectively and sustainably due to an increase in the surveillance coverage on drug resistance by participating people and health volunteers in the curative measure.

12

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

3. Evolution of the Mae Hong Son Initiative

This initiative aligns with the category 1 to deliver inclusive and equitable services as malaria is a neglected disease. Most of the patients are ethnic groups having destitute backgrounds and living in remote areas along the country border. With innovational services provided in the package, the local health care providers in outreach areas are able to render effective services to the deprived people, including expanding service channels to deliver the accurate and precise screening test prior to treatment prescription. Patients must be safe during taking anti-malarial drugs for treatment and adhere to the treatment completely without any cost.

The implementation of providing the precision medicine in the outreach areas mutually correlates with the Sustainable Development Goals (SDGs) 3: Good Health and Wellbeing under assurance to live healthy and good socially for everyone and every age as the initiative reduced malaria incidence rate to 1.07 person per 1000 population. According to the KPI 3.3, the initiative contributes to ensure the healthy living and well-being of malaria cases and eliminate malaria transmission by the end of 2030 to achieve the scheme of health for all. Everyone, even staying in the tough areas, can simply access to malaria services effectively and safely.

The device/package is practically applied from local and economical materials and developed for mass production as in-house tools. As these instruments can lower the costs, shorten the time of services, and increase channels to access quality services, all patients can obtain convenient, prompt and safe services as well as a reduction in travel expenses. These also include access to the same quality of care and services as urban patients have. Moreover, they have an opportunity to receive medical consultation via telephone calls, online applications, and telemedicine system to sustain the management of public services.

Mae Hong Son province is the eighth largest province in Thailand, sharing a common border, measuring 483 kilometers in length, with Myanmar. The province covers with mountainous terrain and is surrounded by tropical forest and creeks which are considered as

13

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

suitable sites for mosquitoes to keep cycle and breed. Various ethnic groups in Mae Hong Son, such as mobile migrants and stateless groups, frequently cross back and forth between the neighboring country to find new jobs due to impoverishment in their areas while the transportation is difficult and limited to access to health care services, especially in the rainy season. It is also found that the language barrier and cultural differences are the great challenges which enable them to receive primary healthcare services. Therefore, public health officers and healthcare volunteers are required to provide such services on behalf of physicians, nurses, pharmacists, and medical technologists. The invention of the innovation does not only allow these practitioners to enhance their capability to work effectively, but also reduce the unnecessary cost that may occur. The patients can look after themselves by applying an appropriate approach and the health volunteers can track patient‟s symptoms and provide measures to prevent malaria transmission in the area.

This initiative provides precision of malaria diagnosis and treatment in remote and inaccessible areas. The government concentrates on the management of the coverage for all in equity services without any cost. Due to the basic human rights and welfare, all people living in remote communities, including persons living in the neighboring country, shall equally receive effective malaria care such as diagnosis, treatment, and monitoring regardless of genders, nationality, ethnicity, and religions.

The target group is all malaria cases. This initiative is beneficial to all clients to receive 100% accurate malaria diagnosis and have a precision of G6PD deficiency test prior to taking for the proper treatment. All malaria cases with normal G6PD enzyme were prescribed with the radical treatment plan. Treatment adherence increased from 26.8% in 2009 to 87.0 % in 2019, resulting in parasite clearance on the appointed follow-up date and the recovery rate was as high as 99.8%. No evidence of drug resistance found in Mae Hong Son province. The effectiveness of the implementation toward malaria achieved the cases dropped significantly from 1,180 cases in 2015 to 275 cases in 2019 (76.69% reduction rate). In Mae Hong Son province, the malaria morbidity rate decreased to 78 per 1,000 population. Moreover, 4.59% of those malaria cases were detected with the G6PD deficiency according to results of the test. Those cases were referred to receive such

14

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

treatment under the supervision of physicians to avoid renal failure and to prevent hemodialysis, which burdens the patients with high expenditure at 3,500 baht/time; the dialysis must be conducted twice a week for lifetime.

4. Process and Implementation

This innovation is established for the local healthcare providers and clients to utilize this innovation to enhance efficacy of providing accurate, precision and safe treatment toward malaria patients.

In 2010, a first device was initiated to highlight efficacy of diagnosis by developing an online quality control system by using webcam connected microscope (Webscope). It was aimed to shorten waiting time of the diagnosis results. Together with development of “drug package” aimed to assist patients to obtain the medical treatment and act appropriately according to the instructions received. The result clearly showed the average time of diagnosis reduced from 21 days to 24 hours. Additionally, the webcam could visually display the malaria parasites via VDO conference simultaneously.

From 2011 to present, the Webscopes have been supplied to other areas. The results from the online assessment toward the quality control system for malaria diagnosis and treatment revealed that preparation of standardized blood film was significant for diagnosis. Owing to the challenges on malaria drug-resistance in several areas of the country, an integrated system for treatment follow-up is necessary to have participation from all public health facilities and health volunteers to prepare blood films. Therefore, the innovation to prepare blood films and G6PD deficiency screening test implemented by health care providers was developed for treatment safety.

To ensure drug adherence, the “drug package” was enhanced from an envelope to a durable ziplock plastic pack with labels. Each bag is filled with tablets. Due to language barrier, the labels on packs are illustrated with a diagram showing drug tablets flow from day 1 to the end. Four different languages (Thai, Tai Yai, Karen and English) are also printed on the pack.

15

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

The adherence measure is based on the patients self-reporting that they followed the course of the drug prescription as instructed on the “drug package”. Patients are also inquired with questions to see whether they remember the color, packaging, duration of treatment, and their understanding of the prescription label and instructions.

According to the 2019 assessment report, it was found that 95–100 % of the users were satisfied with this innovation, overall.

Please see Timeline with key development steps, monitoring and evaluation activities since 2010.

16

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

Table Initiative Implementation, Monitoring and Evaluation Year Activities Monitoring and Evaluation 2010 Development of the innovation Implementation, began in Mae Hong Son, confirmed malaria diagnosis by according to the objective were 1) to Webcam microscope: Webscope in increase malaria diagnostic accuracy; and starving remote areas. All malaria 2) to reduce malaria treatment delay by patients received precise diagnosis, improving the Malaria QA system and confirmed accuracy, and prompt training of malaria field staffs. treatment. Thus the prevention of The first application of Webscope is to death and spread of malaria was our enable real-time microscopic consultation main focus. of difficult or equivocal diagnostic cases. The second application of Webscope is to save video files of blood films. The files are uploaded onto a centralized computer system at the end of each day. A microscopist at a reference laboratory re- examines the videos of blood films in accordance with established malaria QA protocol (e.g. 10% negative and 100% positive). Initiation of Webscope project reduced the time used for confirming blood film from an average of 21 days before implementation to less than 24 hours after implementation. All the blood films that had been discussed online are re-examined again by an expert microscopist to ensure diagnostic accuracy. The malaria field staffs were confidently relied on lab diagnosis. Including on the job training online, the system also improved blood film

17

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

Year Activities Monitoring and Evaluation preparation after learning from trainer‟s instruction. The number of malaria morbidity in Mae Hong Son decreased continuously from 1,414cases in 2011 to 275 in 2019. There has no evidence of death since 2011 until present (fatality rate is zero) due to our progressive activities. 2010 Innovation of paper drug envelops The patients adhere with drug treatment labeled with a flow chart guiding to correctly increased from 26.8% to 71.1%. take drugs prescribed day by day for Patients and villagers gave comments to vivax malaria treatment. Clinic staff redesign the envelope for their living prepared drugs in a small plastic bag status. The helpful adaptation to life was per dose before put them together in the user friendly tailor health package. paper drug envelop. The label of flow chart on one side suggested patients to comply with the drugs all 14 days and suggested to return for follow-up blood check. 2012- The Webcam cameras were supplied The number of malaria patients in 30 2014 more after 14 places in MHS and provinces along the country border Chiang Mai provinces in 2012 up to decreased 53.38% ( since 36,003 cases in 39 places in 2013 and then to 64 2014 to 17,594 cases in 2016) places in 2014. All available supplies covered 30 provinces in long distant communities accounted as high endemic areas of malaria. 2015 Due to Webscope project result Outputs of activities suggested that there is some 1. The health personnel and health difficulty in blood film preparation volunteers were able to prepare standard

18

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

Year Activities Monitoring and Evaluation among malarial filed workers and thick and thin blood smears correctly up health volunteers. Consequently we to 90-100%. developed Assistant Blood Smear 2. They had satisfaction with ABSP up to Preparation: ABSP to improve the 95-100%. quality of blood film preparation. It 3. At present, an application to use ABSP was not only for routine malaria is 95%. microscope diagnosis by malaria staffs but also for health volunteers to make standard blood smears for monitoring and evaluation of drug efficacy. Therefore, using ABSP for health personnel and health volunteers was added on the agenda for Workshop training on integrated drug efficacy surveillance. 2015 Development of G6PD deficiency 1. Results from G6PD deficiency test by test kit. modified FST found patients without 1. Review of literatures and G6PD G6Pd deficiency were 104 persons or test method for distant population. 95.41%, patients with complete deficiency The Committee for Standardization 4 persons or 3.64%, and one patient had in Haematology (ICSH) suggests to partial deficiency as 0.92%. Values of carry out FST in this task for specificity, correctness, positive screening G6PD deficiency due to prediction, and negative prediction were this test has fewer parts, is 100%. The prevalence of G6PD convenient to transport, and is able to deficiency patients with malaria was find out either partial or fully 4.59% (5/109). deficiency levels. 2. Outcome from the workshops on 2. Build the G6PD deficiency test kit training of health personnel to practice by a method of Fluorescent Spot Test with the same test kit. (FST) to precisely screen the malaria 3. The health personnel had confidence

19

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

Year Activities Monitoring and Evaluation patients before prescribing radical and satisfaction with the test kit up to 95- malaria drugs in Mae Hong Son 100%. province. The test result is easily interpreted, uncomplicated, and high precision. Normally, this test is used in the lab, initiatively, the test is a first time for this portable FST kit applied in the field where it is a first place in long distant area in Mae Hong Son. 3. A pretest was tried for quality check. 4. Training the health staff. 5. Monitoring of results observed through Line system and by site visit. 2015- Thailand has adjusted drug regimens 1. Drug adherence monitoring revealed 2019 for malaria treatment then it is that all patients compiled with drug necessary to change the design of prescription up to 87% and there were drug envelop from paper to zipped clearance of parasites in the blood after plastic bag. The bag is labeled with a the follow up blood check. diagram instructing how to take 2. The patients up to 95% understood how drugs 14 days for vivax malaria and 3 to take drug correctly and satisfied the days for falciparum malaria, drug bag labeled with instruction. respectively. The instructions are 3. The drug bags were distributed into 30 different 4 groups according to body provinces along the country border. weight of patients. The implementation performs in Mae Hong Son, Chang Mai, and Chiang Rai provinces with different linguistics then we print out in 4

20

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

Year Activities Monitoring and Evaluation different languages in Thai, Thai Yai, Karen, and English. 2019- Procedure of diagnosis and treatment 1. ODPC 1 evaluated the application of a present of malaria in health sectors in distant standard G6PD screening test in the areas along the country border. malaria clinics in remote areas of Mae 1. After arrival, the patient is required Hong Son to record the history of sickness, drug See annex 4. publication: Modified allergy, chronic illness, and present Fluorescent Spot Test for screening G6PD symptoms. If suspected with malaria deficiency among malaria patients in contraction, thick and thin films (in a remote health care services, Northern single glass slide) will be made at the Thailand malaria clinic. At the hospital for sub 2. Chiangmai University conducted district health promotion, the method assessment of G6PD screening fluorescent of blood check will use a rapid test spot test comparing with the registered taking time for 30 minutes. G6PD RDT test kit 2. If the blood exam is positive with See annex 4. publication: Assessment of malaria, formerly the G6PD screened CareStartTM G6PD RDT for G6PD by a verbal history of the patient, at deficiency screening in newborns and present use accuracy FST-G6PD malaria diagnosed subjects in the screening test for 15 minutes. If Northern Thailand. found G6PD deficiency the patient will be referred to the hospital. In the case of normal, the patient will receive treatment at a malaria clinic and get through a health education program in self-care and drug adherence. This strategy is for quality control both the last of reagent that needed to change every 3 months and the

21

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

Year Activities Monitoring and Evaluation malaria diagnosis method. The quality control of malaria diagnosis relies on an existing procedure such as blood film transportation, rechecking blood slide, and online exam using Webscope. 3. In case of malaria positive, the patient with his relatives will receive health education and suggestion using learning materials. The learning stuff for vivax malaria comprise 4 different groups of:1) aged 14 years and above about 50 kgs of weight, 2) aged 8-13 years and weight between 25-30 kgs, 3) aged 3- 7 years at weight between 15-24 kgs, and 4) aged 1-2 years. Cases of falciparum malaria have 8 groups according to body weight as follows: 1) above 80 kgs, 2) 60-80 kgs, 3) 50-<60 kgs, 4) 36-50 kgs, 5) 25-<36kgs, 6) 17-<25kgs, 7) 15- <17kgs,and 8) 11-14kgs. The learning materials are given to patients and their relatives concerning teaching with a flip chart of knowledge about malaria and drugs to cure, disease transmission, diagnosis, treatment with drugs under standard from the Department of

22

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

Year Activities Monitoring and Evaluation Disease Control, observation of side effects, appointment dates and malaria prevention and control. The health staff explains how to take drugs by follow the diagram labeled on the drug bag. The pharmacist arranges and explains about drugs before put them into the drug bag also concerns on the appointment date for blood check- up which is noted on the drug bag. The health personnel monitor patients whether there are drug resistant cases.

23

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

5. Results

5.1. Innovative accomplishment

Drug resistance in malaria is a major health problem worldwide, particularly the underprivileged populations in outreach areas. This device/package is the world‟s first innovation for the people in remote areas. According to the complexity of accuracy malaria microscope diagnosis, G6PD deficiency screening test and complication of antimalarial prescription, the device/package was launched to precise malaria services and treatment. In addition the device/package was also served network health sectors as a tool to specify the date for a follow up visit. This innovation has been widely accepted from both health providers and clients that benefit to people in remote areas. Based on the research and development and the periodical feedback from the clients and the healthcare providers, the morbidity and fatality rates of malaria dropped to zero in Mae Hong Son province. The past operations performed of each device and package was combined so that the people in remote areas would receive prompt, precise, and safe medical operations. More importantly, integrated drug efficacy surveillance system was successfully established in Mae Hong Son initiative

5.2. Adaptability and Scaling up

The initiative invention was presented at the ASTMH 67th Annual Meeting in 2018, New Orleans, Louisiana, USA. In 2018, this innovation was widely implemented in 43 provinces in Thailand where malaria transmission occurred. There were different geographical conditions, human, and social which were complicated. Even though it was a beginning phase and involved many health care providers and health sectors, it was highly accepted that some devices such as the “blood film preparation block”, which assisted the preparation of standardized thick and thin blood films in a single slide in a faster and easier manner. The “Webscopes” were also used in many areas to capture photos in the microscope either malaria or parasitic worms, which were required diagnoses by a microscope. It was useful in training programs for malaria diagnosis, parasitological study, and efficacy measurement of insecticide sprayers in vector control. Moreover, the G6PD deficiency screening test was

24

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

applied to the newborns in hospitals, and the test gave results with better efficiency when compared to other methods.

G6PD deficiency screening test is not only used for malaria patients, but it can also be applied in the ordinary people. Rather than primaquine, which is applied to treat malaria, the other drugs have affected to patients with G6PD deficiency are antibiotics agent groups: chloramphenicol, co-trimoxazole, furazolidone, furmethonol, nalidixic acid, neoarsphenamine, nitrofurantoin, nitrofurazone, para-amino salicylic acid (PAS), sulfa group: co-trimoxazole, sulfacetamide, sulfamethoxypyrimidine, dapsoneand chemical, other medicines: (naphthalene), alpha-methyldopa, methylene blue, and pyridium. However, this initiative kit has limited use according to budget and manufacturing issues. The development plan is set for knowledge transfer, quality control system for reagent preparation in production and uses. The “labeled plastic drug packs”, only needs illustration of malaria tablets that can help patients to understand and to remind themselves and their relatives to comply with the prescribed medicines. These initiatives still require support to develop in mass production. The national control also scale up the use of IEC package in 43 provinces throughout Thailand.

5.3. Prototype for National integrated the safety and efficacy surveillance scheme

The surveillance of drug effectiveness and safety for malaria treatment needs an implementation of coverage, correctness, and continuation systematically, which is very important towards provision of efficient curative guideline for patients with high care. The point is to protect fatality and to prevent the disease transmission by implementing with the surveillance and effectiveness scheme. At the same time, the people seek for malaria diagnosis in several health sectors. Most importance to all health sectors are giving diagnosis and treatment must comprehensively implement safety and efficacy of drugs for curative surveillance.

It is, therefore, the Division of Vector Borne Diseases has adopted our initiative; Integrated Drug Efficacy Surveillance (iDES) scheme for curative drugs among all cases of malaria with all health service units to be as a routine job. This is to focus on the follow up of treatment covering all health service units in order for managing and suggesting for the drug compliance.

25

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

The management of drug quality control aims to rely on the same standard. It is needed to follow-up the patient‟s symptoms in coordination with monitoring and evaluation of malaria parasites responding to drugs and diagnosis by improving biomolecular diagnosis method. Steps of follow-up for malaria patient‟s curative have developed from the research of Division of Vector-borne Diseases and the Office of Disease Prevention and Control 1, Chiang Mai, which have been done in an integration with the routine work since 2016.

The organizers extremely wish this standard operating procedure (SOP) manual of malaria patient‟s treatment monitor is helpful for health providers who are aware of the needs of treatment follow-up and able to perform correctly in the same standard. This manual received support for printing from the World Health Organization.

6. Discussion and conclusion

6.1. Resource

This innovation is funded by the Global Fund for malaria disease. The funds cover expenditures on materials, trainings, handouts and other mass publications. Budget assistance is also from the Department of Disease Control, health sectors, and other local administrative organizations to spend for human resources, infrastructures, utility expenses,

26

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

and wages. Moreover, the innovation receives support of electronic software, social media channels/facilities to be used by local health care providers. The significant dedication is the user‟s support for their time to learn and use this innovation and answer the evaluation forms.

To achieve the declaration which 6 GMS countries jointly endorsed the agreement in moving forward to eliminate malaria at the 9th ASEAN Summit Meeting in 2014, Thailand endorsed the policy to eliminate malaria by 2024. Form Communicable Diseases Act B.E. 2558, requires the integration of all government sectors to join the mission. The health volunteers enter refreshment literacy training annually to raise incremental awareness of malaria drug resistance impacts, including requirement of the monitoring efficacy of treatment which is subject to run as routine and mandatory work for all public health facilities. This model demonstrates the cost effectiveness innovation obviously.

6.2. Evaluation

The national monitoring and evaluation committee for the midterm strategic plan of malaria elimination program, which consisted of malaria expertise from various sectors, monitored and evaluated this initiative. Also, an ad hoc evaluated team from the Innovation and Research Division, Department of Disease Control, in classification of Business Process Management Innovation, conceded an excellent level award. Moreover, Office of the Public Sector Development Commission conducted the evaluation and officially granted an award for this innovation for “Thailand Service Award 2018” category. Several monitoring and assessment by the experts from WHO headquarters and WHO Thailand were also made.

The indicators of this initiative were 100% malaria patients received precise services, accuracy diagnosis, safety treatment, completed prescription of malaria drug courses. 100% of primary diagnosis was accurate. All malaria cases are tested for G6PD deficiency before providing a prescription. 70% of malaria cases followed their appointment schedule. 80% of the cases had punctual drug adherence completely and accurately. According to questionnaires and online interviews, it was revealed that patients provided overall service

27

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

satisfaction rate increased up to 95-100%. Based on the follow-up reports, there were no side effects from drugs, and all malaria cases were cured.

The outcome of this initiative was approved as a guidance policy for the national surveillance malaria drug resistance. Public health facility in Mae Hong Son province gained knowledge and understood awareness as well as importance of treatment and follow- up procedures by using the innovation package as a device, which produced credible data and information to modify the national drug policy. Especially, this innovation helped ensure the completion and accuracy of treatment in distant areas without a chance to return for follow-up visit. Additionally, the local implementations facilitated integration at the local level to share human resources, budget, and materials. Another challenge was an expansion of the innovation to other areas where different contexts of social, culture, life style, living conditions, including the risk in conflict areas, were identified for the acceptance, utilization, monitoring and evaluation, the collaboration from all sectors and stakeholders was required. Moreover, quality control system of the innovation was necessary to provide confidence of services to all users and patients.

6.3. Institutional Setup

The Office of Prevention and Disease Control 1, Chiang Mai province, plays the major role in research, development of literacy for surveillance, disease prevention and control, and health threats in 8 provinces in the northern region. The Office supports several operations such as prescribing medicines and non-medicine commodities and provides malaria health training to the public health officers at the health promotion hospitals, community hospitals and provincial hospitals in order to facilitate the integration of service system. Division of Vector-Borne Disease monitors and evaluates the operations. Then the results will be publicized and can be raised as a policy at the national level. Local government organizations and provincial health offices provide the budget and human resources to support utilization of the innovation effectively. Faculty of Associated Medical Technology, Chiang Mai University, provides technical supports and knowledge on G6PD deficiency test. Health volunteers and population in the target areas are able to take care of themselves to completely adhere to the treatment and to remind the check-up schedule of the patient.

28

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

Otherwise, the patient may passively wait at home for the service or the relatives are accountable for reminding the patients to perform according to the instructions.

6.4. Stakeholder Engagement

The key objectives of the network collaboration for comprehensive implementation between public health sectors and other local sectors that have a mutual goal, are to improve quality of life among the outreach population; and to provide same standard of services. New malaria cases will be reported immediately within 24 hours while case investigation will be completed within 3 days, and the control of disease transmission shall be implemented within 7 days. In addition, there is a patient referral system from both local units to a hospital and after discharge from the hospital. Hospital shares information to local health care providers to follow up the case who resides remotely and cannot return for the future check-up appointment at the hospital. Faculty of Associated Medical Sciences, Chiang Mai University coordinates the monitoring and evaluation of the use of innovation for G6PD deficiency test.

7. Lessons Learned

It is understood that medical services that are provided to raise the quality of life of the locals by government sectors are necessary to understand different contexts of the rural people so that they can receive quality of services as same as that of the services in urban areas. The officers shall comprehend and accept those differences. Not only does the success of the initiative come from recommendations and suggestions from the involving groups, but it also derives from the mutual understanding between service providers and the local people. Utilizing the innovation correctly will be beneficial for the officers to disseminate knowledge to prevent malaria transmission to ordinary people and officers from different functions in case the disease occurs in their areas

29

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

8. Benefits and outcome

This project demonstrates the success of the public services under standard methods to all as equally as we can do, even people are living in remote areas. The implementation has expanded into 43 provinces of malaria endemic areas. We expected malaria will be eliminated in 2021, 3 years prior to the elimination commitment plan target. Implementation result in Mae Hong Son is on the track to achieve this target for the elimination as per Annual Parasite Incident data from 2015 to 2019 (on 2nd October 2019)

In addition to the benefit in malaria case reduction and increase radical curative rate, the initiative helps increase the number of patients received the screening procedure for G6PD deficiency test with impressive result from the measure of friendly-tailored teaching package and the use of drug pack. Malaria health providers were able to develop their capability in the services. Patients and care-takers were appreciated and satisfied with this implementation especially the communication package can help improve patient‟s understanding and adherence to malaria treatment.

30

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

9. Challenges

The challenges of this innovation are acceptability of the users and sustainable use of the innovation package without feelings of burden. The problems were resolved by providing regular training, user manual, and demonstration video to which the users can access at all times. The online tracking and field supervision were applied so that the users can see how valuable their tasks were. The innovation is progressively improved by the user's recommendations and observations.

This innovation should be integrated into the regular services and expanded into all remote areas which need support for the highest political level both from DDC and General Health Services to utilize and expand this initiative effectively. To maximize the benefit of using this initiative at health facility, raising awareness of availability and provision of freely access to this initiative services should be done continuously.

Periodically evaluate for improvement is a must to ensure effectiveness and a socio- culturally accepted the environment of implementation.

31

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

10. Acknowledgments

We would like to acknowledge contributions of the following persons for kind support,assistance and guidance; Dr.Suwannachai Wattanayingcharoenchai Director - General, Department of Disease Control (DDC) Dr. Tanarak Plipat Deputy Director - General, DDC Dr. Sombat Thanphasertsuk Senior Expert in Prevention Medicine, DDC Dr. Cheewanan Lertpiriyasuwat Director of Division of Vector Borne Diseases, DDC Dr. Jatuchai Maneerat Director of Mae Hong Son Provincial Health Office Prof.Sakorn Pornprasert Dean, Faculty of Associated Medical Technology, Chiang Mai University Assoc. Prof.Piyarat Butraporn Faculty of Tropical Medicine, Mahidol University Dr. Sumet Ongwandee Director, Office of Disease Prevention and Control Region 1, Chiang Mai, Mrs.Benjamaporn Pinyopornpanit, Director, Public Sector Development Group, DDC. For conducting this initiative, collecting statistic data related to this initiative results and writing the report.

All staff from Vector Borne Disease Center 1.1 Mae Hong Son and Vector Borne Disease Center 1.4 Chiang Mai for collaborating, supporting, sharing resource and offering the important data for the initiative and report. We would also like to thank the district and sub-district malaria field workers teams, including regional administrative staff, village health volunteers in Mae Hong Son Province, for supporting this initiative. Last but not least, patients and all people who contributed time and actively participated in the project.

32

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

Annex

Annex 1 Awards

The OPDC Annual Seminar on „Good Governance for Better Life‟ and the Public Sector Excellence Award (Lert-Rat) Ceremony of 2018 Available from: URL:https://www.opdc.go.th/content/ODAy/?lang=en This project received Public Service Award on September 14th, 2018 at IMPACT Forum, Muang Thong Thani, Bangkok from The Office of The Public Sector Development Commision: ODPC Annual Seminar on „Good Governance for Better Life‟ and the Public Sector Excellence Award (Lert-Rat) Ceremony of 2018.

33

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

Public Service Award, Office of the Public Sector Development Commission, 2019

The outstanding of Business Process Management Innovation, DDC INNOVATION AWARD 2019

34

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

Annex 2 Publication:

2.1 Poster Presentation. The 67th Annual Meeting of the American Society of Tropical Medicine and Hygiene (ASTMH). New Orleans, Louisiana, USA. October 28 - November 1, 2018.

ABSTRACT

A HEALTH COMMUNICATION PACKAGE TO INCREASE DRUG ADHERENCE AMONG VIVAX MALARIA PATIENTS WITHOUT G6PD DEFICIENCY ON THE INTERNATIONAL BORDER OF NORTHERN THAILAND Author: Nardlada Khantikul1, Aungkana Saejeng1, Prayuth Sudathip2, Jintana Chaiwan1, Rungrawee Tipmontree2, Suravadee Kitchakarn2, ,Surachet Arunothong1 1 Office of Disease Prevention and Control Region 1, Department of Disease Control, Ministry of Public Health, Chiang Mai, Thailand, 2 Bureau of Vector Borne Disease, Ministry of Public Health, Nonthaburi, Thailand.

Thailand‟s national guideline for treatment of complicated vivax malaria is 3-day chloroquine (blood schizontocide) and 14 day primaquine (tissue schizontocide). Previous retrospective study of patients in Mae Sariang and Muang districts in Mae Hong Son Province, showed up to 76% of 206 vivax patients reported varying degrees of non- adherence to the treatment guideline (Khantikul et al., 2009). More recent clinical trials along the western border of Thailand showed the P.vivax patients who self-administered treatment showed higher non-adherence rate and compared to patients who received directly observed treatment (DOT) (Cheoymang et al, 2015). We developed a new health communication package aimed to improve treatment adherence in vivax malaria patients with normal glucose-6-phophate dehydrogenase enzyme (G6PD) in Northern Thailand. Information from previous studies on patient‟s drug adherence behaviors and participation from the local malaria clinical staff were incorporated in the development of the health communication package. The format and contents were tailored to target the communities in northern Thailand, including hill tribe communities and cross-border migrants from a neighboring country. Thirty-six vivax patients diagnosed in malaria clinics in Mae Hong Son Province from January to March 2015 provided interviews before and after introduction of the communication package. Patients were given a G6PD fluorescent spot test (FST) prior to receiving treatments according to the national guidelines along with health communication package. Exit interview were conducted during the follow-up visit to determine patient‟s treatment adherence behaviors. The majority of patients 83.3% (30 out of 36) complied with drug correctly and followed the guideline of treatment program of the clinics. The average scores on knowledge and perception of malaria and malaria treatment were significantly higher than the scores before the implementation (p<0.05). Our results showed targeted health communication package can help improve patient‟s understanding and adherence to vivax malaria treatment.

35

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

36

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

2.2 Oral Presentation. The 67th Annual Meeting of the American Society of Tropical Medicine and Hygiene. New Orleans, Louisiana, USA. October 28 - November 1, 2018.

ABSTRACT

INTEGRATED DRUG EFFICACY SURVEILLANCE (iDES): THE FEASIBILITY OF USING ROUTINE CASE MANAGEMENT AND FOLLOW-UP ACTIVITIES TO MONITOR DRUG EFFICACY AND RESISTANCE IN THAILAND.

Author: Aungkana Saejeng1, Nardlada Khantikul1, Prayuth Sudathip2, Suravadee Kitchakarn2, Preecha Prempree2, David Sintasath3, Surasak Sawang4, Richard Reithinger4, Darin Kongkasuriyachai4, Deyer Gopinath5

1 Office of Disease Control and Prevention Region 1, Department of Disease Control, Ministry of Public Health, Thailand 2 Bureau of Vector Borne Diseases, Department of Disease Control, Ministry of Public Health, Thailand 3 U.S. President‟s Malaria Initiative, Regional Development Mission for Asia, United States Agency for International Development, Bangkok, Thailand 4 Inform Asia: USAID‟s Health Research Program, RTI International, Research Park Triangle, NC, USA 5 World Health Organization, Thailand Country Office, Nonthaburi, Thailand

Therapeutic efficacy studies (TES) are the World Health Organization‟s (WHO) recommended approach for national malaria programs to monitor the efficacy of antimalarial drugs. With declining malaria transmission, TES case enrollment has become challenging. In 2017, WHO and the Thai Ministry of Public Health recommended piloting integrated Drug Efficacy Surveillance (iDES) to ensure complete treatment of all cases in the context of malaria elimination. iDES integrates patient follow-up for all species with microscopy and dried blood spots (for molecular testing) as part of routine case surveillance to ensure compliance and adequate treatment outcomes. The approach included supervised radical treatment according to the national guidelines (dihydroartemisinin-piperaquine + primaquine for P. falciparum and mixed infection; chloroquine + primaquine for P. vivax and monitoring of parasite clearance during follow-up visits. Blood films were confirmed by an expert microscopist via the routine laboratory quality assurance system. Dried blood spots were collected at the time of diagnosis for detection of drug resistance markers and during each follow-up for confirmation of positive microscopic results. From May- December 2017, a total of 270 malaria cases were registered. Approximately 25% of the 88 migrant cases completed three or more follow-up visits. Among the 182 Thai cases, 78% of 25 Pf cases (78% on day 7, 87% on day 28, 65% on day 42, and 74% on day 60) and 63% of the 156 Pv cases (72% on day 14, 63% on day 28, 63% on day 60, and 62% on day 90) completed three or more follow-up visits. None of the patients exhibited delayed parasite clearance. While we are currently assessing what infrastructure and resources are needed to implement iDES in a malaria elimination context, as compared to TES, our results suggest that iDES can be used to monitor radical cure of cases and drug resistance through adequate routine case management.

37

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

2.3 Saejeng A, Khantikul N, Boonin P, Anantasuk, Srithep S, Pornprasert. (2018). Modified Fluorescent Spot Test for screening G6PD deficiency among malaria patients in remote health care services, Northern Thailand. Lanna Public Health Journal, 14(2), 12- 20.Available from: URL: https://www.tci-thaijo.org/index.php/LPHJ/article/view/163063

ABSTRACT The objective of this study was to apply a standard G6PD screening test in the malaria clinics in remote areas of Mae Hong Son province. Primaquine is now the only one antimalarial drug available in Thailand for radical treatment in P.vivax and kills gametocytes of all malaria parasite species However, severe hemolytic anemia might occur in some patients with G6PD deficiency. Therefore, all malaria patients should be screened for G6PD before taking the drug. Fluorescent Spot Test (FST) for G6PD was a method recommended by the International Committee of Standardization in Hematology (ICSH) as the most acceptable and reliable screening test for G6PD deficiency. But, it needed tools and skills in diagnosis and interpretation of the results. There were 109 malaria patients tested for G6PD by the modified FST G6PD and CareStartTmG6PD RDT. The efficacy and side effects of antimalarial drug were observed carefully. If any evidence of the side effect found, the patient must be referred to the hospital immediately. The result showed that the modified FST G6PD had 100% sensitivity and specificity compared with Methylene blue Oxidation and observation of any side effect of primaquine in malaria patients. There were 109 (95.41%) patients normal G6PD, 4 (3.67%) patients with G6PD deficiency, and 1 (0.91%) patient with partial G6PD deficiency. In contrast, CareStartTmG6PD RDT had 35.78% (39 cases) of invalid results which was unusual as rapid diagnosis test normally simply to use. There were several reasons, one of them was a blood sample might have high hematocrit which resulted in a difficulty to flow through the RDT strip and also the temperature was high. In conclusion, the result of this study clearly indicated that modified FSTG6PD can be used as screening test in remote areas by health worker.

38

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

2.4 Khantikul N, Saejeng A, Chaiwan J, Boon-in P, Arunothong S, Sudathip P. (2018). The communication package to improve drug adherence behavior among vivax malaria patients without G6PD deficiency for malaria elimination along international borders, Northern Thailand. Disease Control Journal, 44(4): 363-73. Available from: URL: https://www.tci-thaijo.org/index.php/DCJ/article/view/162729

ABSTRACT

A communication package for malaria Plasmodium vivax patient‟s treatment is urgently needed at the first step in malaria elimination program. The objectives of this quasi experimental research were to compare knowledge and perception before and after implementation of a novel tool package, a vivax malaria education program toward the patients and, secondly, to measure levels of patients‟ ability of drug adherence, behaviors of taking drugs and satisfaction after receiving this intervention. The research was conducted in public health service units in Mae Hong Son, Chiang Mai and Chiang Rai provinces between January and March 2015. Vivax Malaria patients were screened for G6PD deficiency using Fluorescence spot test (FST), only 36 normal G6PD patients were enrolled after a written informed consent had been obtained for voluntary participation and completion of research procedures. Results showed that the majority of the patients 83.3% (30 out of 36) presented their drug taking behavior with correction, completion and adherence to malaria treatment according to the National Malaria Treatment Guidelines. After the implementation, average scores of knowledge and perception were significantly higher than those before the implementation (p<0.05). Following the implementation, the participants became acutely aware of their ability to comply with drug adherence. Besides that the participants had a high level of satisfaction from malaria clinic services units. The overall feedback from this study is beneficial for public health officers as it could help them be cognizant of socio-cultural factors in developing an innovative intervention program for vivax malaria patients concerning adherence to the drug prescriptions.

39

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

2.5 Pienthai, N., Ruengdit, C., Manowong, S., Kongthai, K., Maneewong, K., Pongmorn, K., ... & Pornprasert, S. (2019). Assessment of CareStartTM G6PD RDT for G6PD deficiency screening in newborns and malaria diagnosed subjects in the Northern Thailand. Journal of Associated Medical Sciences, 52(1), 78-82. Available from: URL: https://www.tci-thaijo.org/index.php/bulletinAMS/article/view/145589/113719

ABSTRACT

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited enzymatic disorder associated with severe neonatal hyperbilirubinemia and acute hemolysis after exposure to certain drugs or infections. The most common test for screening G6PD deficiency is fluorescent spot test which is rapid and convenient. However, fluorescent spot test needs tools and skills in diagnosis and interpretation of the results. CareStartTM G6PD Rapid Diagnosis Test (RDT) is an enzyme chromatographic strip test based on reduction of colorless nitro blue tetrazolium into formazan which gives purple color and the results could be read within 10 minutes. Objective: This study aimed to analyze the sensitivity, specificity and accuracy of CareStartTM G6PD RDT for screening of G6PD deficiency in newborn and subjects with malaria diagnosis. Materials and methods: This study was conducted from December 2017 to February 2018. G6PD diagnostic tests including fluorescent spot test and CarestartTMG6PD RDT were performed in 196 newborns aged varied from 1 day to 12 years and 48 subjects with malaria diagnosis. The efficiency of CareStartTMG6PD RDT was analyzed by comparing with the reference method, fluorescent spot test. Results: CareStartTMG6PD RDT demonstrated 100% sensitivity, 100% specificity and 100% accuracy for screening of G6PD deficiency in malarial diagnosed samples. However, it presented invalid results up to 27.04% in newborns. Therefore, sensitivity, specificity and accuracy were not applicable in this group. Conclusion: CareStartTMG6PD RDT could be used for preliminary screening of G6PD deficiency in malarial diagnosed samples. However, it should be improved to reduce the invalid results in newborns.

40

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

Annex 3 News

3.1 News from National Broadcasting Services of Thailand, Chiang Mai Province Available from: URL: http://region3.prd.go.th/chiangmai/detail_new.php?id=25189 October 11, 2019

Office of Diseases Prevention and Control 1 Chiang Mai received an award from the National Government Service of the year 2019, level “the Best Service Award” raising efficiency of governmental sector services to develop an innovative intervention.

Dr. Sumet Ongwandee, Director of ODPC 1 Chiang Mai unveiled receiving Thailand Public Services awards from the Office of the Public Sector Development (OPDC) of the year 2019 in the title “An Innovation of Malaria Precision Treatment in Remote Border Areas in Thailand”. The award was categorized as “the best innovative service”, which has been under an investigation of Dr. Nardlada Khantikul, Senior Public Health Technical Officer, and Ms. Sarinee Srithep, Medical Technologist. This innovative research concept is to raise an efficiency of governmental function in services to search for a new invention, accessible to health service, and economic cost. It aims to prevent and control diseases for the people living in remote settings, safe and rapid access in a low cost of expenses. Under the theme about the health services are equal for all.

The ODPC 1 Chiang Mai has malaria staff work at malaria clinics, who are skillful to provide blood examination service and can prescribe medicines for treatment under the regimens of DDC, MOPH. So far, the patients with G6PD deficiency and having malaria infection who have prescribed with radical treatment may have hemolysis of red blood cells, pallor, renal failure and dead. The ODPC 1 Chiang Mai has collaboration with Chiang Mai University, Faculty of Medical Technology to develop a test kit called “Fluorescent Spot Test” to be used to examine and screen for G6PD deficiency in malaria infected patients before the prescription. If the patient found G6PD deficiency, the patient will be referred to the hospital to receive treatment under care of the physician, but if found normal blood, the patient will receive a radical treatment at the malaria clinic. Medicines are prescribed and put in a zipped envelop showing flowchart of tablets to be taken day by day in order to warn the patient to take drug correctly. On one side of the envelop, it appears a follow-up date to remind the patient to go back to the clinic for re-checking the blood. There is a monitoring

41

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

system to evaluate drug efficacy for treating malaria in 8 provinces in the most northern region until drug resistant malaria is scoured. Any further information please contacts ODPC 1 Chiang Mai, Tel: 0 5327 6364 in official hours or an urgent line call DDC 1422.

42

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

3.2 News from Bureau of Risk Communication and Health Behavior Development, Department of Disease Control, Ministry of Public Health, Thailand. Available from: URL: https://ddc.moph.go.th/riskcomthai/news.php?news=10371&deptcode=riskcomthai&news_views=15

43

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

Annex 4 Standard Operational Procedures and Device/Package Materials

1. Standard Operational Procedures (SOP) For malaria case follow up in Thailand 2019 2. Device/Package Materials Available composed of: 2.1. ASBP Instruction Manual 2.2. Simple Fluorescent Spot Test (FST) for G6PD Screening Instruction Manual 2.3. Labeled malaria drug packaging 2.4. Video clip: How to use the simple assistant blood slide preparation (ASBP) for thick and thin blood slide film to investigate and look for malaria parasites. Available from URL: Available from URL: http://gg.gg/fuwi7 2.5. Video clip: How to prepare Webscope Available from URL: https://www.youtube.com/watch?v=oJ25JonIA2w 2.6. Video clip: Preparation of specimen for malaria and G6PD fluorescent screening test Available from URL: https://www.youtube.com/watch?v=A5HSGqCkQAA

44

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

STANDARD OPERATING PROCEDURES (SOP)

FOR MALARIA CASE FOLLOW UP IN THAILAND 2019 1. Definition of terms Malaria patients are persons with symptomatic or asymptomatic fever with appearance of malaria parasites in the blood from diagnosis with a microscope or biomolecular technique in the laboratory. All infected cases must receive prompt treatment. Supervised treatment is a follow-up procedure for all malaria cases take drugs completely and correctly by using “direct observed therapy” technique as a treatment policy assisting health providers, health volunteers, village headman, neighbors, or relatives are able to supervise how the uncomplicated falciparum malaria patients can take drugs completely within 3 days or vivax malaria patients can do the same for 14 days. Supervision of treatment for uncomplicated malaria patients Treatment regimen for falciparum malaria without complication is a first line drugs that is Artemisinin-based CombinationTherapy: ACT which is containing several formulas. In Thailand‟s regimen recommends the formula that combined 2 types of drug in one tablet, which are Dihydro-artimisinin and Piperaquine in divided doses for three consecutive days. Some areas may prescribe different types depending on the national policy, however, the drug is still being artimisinin-based to use for killing non-sexual stage of malaria parasites in the blood. Primaquine is necessary to be prescribed on first day or others under conditions of sickness. Recommended that, the health providers should observe the patients to take drugs completely, to follow appointment for recheck the blood and to be sure that the patients are cured. Treatment for uncomplicated vivax or ovale malaria. The therapy is by prescribing chloroquine for three consecutive days and primaquine for 14 days in the purpose of eliminating merozoites in the liver that cause relapsing fever. Exceptedly, cases of pregnancy, children below five years, and G6PD deficiency who must be refered to treat by the physician in hospital. Treatment of uncomplicated malariae malaria provides chloroquine in divided doses for 3 consecutive days without primaquine because malariae does not cause a relapse. Treatment of uncomplicated mixed infection (falciparum type is included) provides drugs as same as that of falciparum infection and plus primaquine, depending on the species.

45

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

Treatment for uncomplicated knowlesi malaria. In case of suspected, refer the case to visit the physician in the hospital due to this type of malaria cannot be diagnosed by a microscope or a rapid test. It needs a biomolecular test from the community hospital level or above. Generally, falciparum malaria develops to severe symptoms as same as vivax and knowlesi malaria. It needs to observe symptoms of patients with care. Treatment for failure cases who receive the first line drug regimen. Suggestion is made to refer the patients to the hospital. Treatment for complicated malaria or severe malaria or risk group who have potentially complication or severity should be proceeded to treat in the hospital. Follow up all patients must be performed according to diagnosis and treatment guideline 2015, under consciderated species of malaria parasites. Observe the result of treatment on the schedule for sure there is parasite clearance from the blood. The data from blood check at any point of time is useful for analysis the effectiveness and efficacy of drugs to be deserved for “Integrated Drug Efficacy Surveillance”. - Patients have Pf. malaria, Pm., Pk. or mixed infection with Pf must be followed up on days 3, 7, 28, and 42. - Patients have Pv. and Po. malaria must be followed up on days 14, 28, 60, and 90. The assigned health providers should make appointment dates with patients to return to the clinic or to make home visit schedules. Blood is collected on glass slide and on filter paper slip every time. 2. Objectives 1. To assign guidelines for patient follow-up by malaria health providers. 2. To develop the Integrated Drug Efficacy Surveillance.

46

Mae Hong Son Initiative Report: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

3. Implementation for follow up treated malaria patients in Thailand

All malaria cases need to be monitored using the guideline for diagnosis and treatment in Thailand, year 2015.

3.1 Day0 1. Collect blood onto a filter paper slip for 3 spots. 2. Collect blood for thin and thick films onto glass slides. 3. G6PD screening test. In case finding G6PD deficiency patients, they have to be referred to the hospital. If the test is not available at the malaria clinic, patient‟s history should be recruited and if suspected, such as history of dark color urinated after eating broad beans, the patient is sent to treat by the physician promptly. 4. “Direct observe therapy” should be done at the time of drug prescription, which is from guideline of treatment‟s rule 2015, and the patient waits for 30 minutes whether the patient show any signs of drug allergy, such as vomiting. If in case of allergic signs are happened after repeating the drugs, the patient should be going to see the physician. 5. It is to recommend the relatives or persons accompany the patients have to receive health education that how the patient takes drugs completely and follows 2015 guidelines. The drugs is packed in small plastic bags for daily consume, and put all in the zipped labeled package telling how to take drugs day by day. Repeat the instruction to the relatives to be sure they understand clearly. 6. Note an appointment date on the drug package and on OPD card for return back for blood check. - For patients with Pf, Pm, Pk, or mixed infection with Pf on days 3, 7, 28, and 42. - For patients with Pv or Po must be followed up on days 14, 28, 60, and 90. 7. Record the information of the patient‟s treatment follow-up in the forms. 8. Record every patient‟s data to the malaria online forms.

------Page 1 of 51 Mae Hong Son Initiative Report: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

3.2 Follow-up malaria patients with Pf, Pm, Pk or other than one species with Pf. On days 3, 7, 28 and 42 1. Collect blood onto filter paper slip 3 spots 2. Collect blood for thin and thick smears onto glass slides 3. In case of taking drugs at home, follow the day 3, collect the drug package back, and inquire for drug taking instruction or sign the name or stamp a fingerprint on the drug package

4. Record patient‟s data in reporting forms when the treatment is complete. 5. Record the follow up data every time in the malaria online system. 3.2 Follow-up malaria patients with Pv, Po or other than one species without Pf. On days14, 28, 60, 90. 1. Collect blood onto filter paper slip 3 spots 2. Collect blood for thin and thick smears onto glass slides 3. In case of taking drugs at home, follow the day 3, collect the drug package back, and inquire for drug taking instruction or sign the name or stamp a fingerprint on the drug package 4. Record patient‟s data in the report form when the treatment is complete.

5. Record the follow up data every time in the malaria online system.

In case of finding malaria parasites on an appointment date or other reason of patient’s visit, the health provider performs as follows: Condition 1 Finding the same parasite species (relapsing species) as previous “count it as an old case”. Record it in the surveillance form as done before and note it in a new treatment follow up form and make a note underneath its code as “relapsed species found”. Use the same the patient‟s code and count it as day “0” and then start the treatment follow up until the end. Submit the blood slides, filter papers and all forms into the usual system, also send the patient to be treated at the hospital immediately. Condition 2. Finding different species “count as a new case”. Record the malaria species in the surveillance form and note it in a new treatment follow-up form by using a new patient‟s code and count it as Day “0” and then start the treatment follow up until the end. Submit the blood slides, filter papers and all forms into the usual system, also send the patient to be treated at the hospital immediately. ------Page 2 of 51 Mae Hong Son Initiative Report: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

4. Samples delivery To monitor the efficacy of drugs to treat malaria, the samples to be submitted are blood films, filter papers, and report forms. Consider an appropriate method for delivering the samples to prevent damage and loss during transportation should be done in steps as follow: 1. Blood films and filter papers for quality control and recheck are delivered every 10 days from the Vector Borne Disease Unit (VBDU) to the Vector Borne Disease Center (VBDC) and then to the lab in the Office of Disease Prevention and Control (ODPC), consecutively. 2. The ODPC collects the samples and transports them to VBD Division in Bangkok. 3. The surveillance forms of malaria patients are delivered when: 3.1 The follow up is complete as follows: 3.1.1 Patients with Pf, Pm, Pk or mixed infection with Pf all 4 days of 3, 7, 28 and 42. 3.1.2 Patients with Pv, Po, must receive follow-up all 4 days of 14, 28, 60 and 90. If unable to follow the patients or terminate the follow up due to moved, return to the place of origin. 5. Finding the relapsing species. 1. If parasites are found the same species as previous, count it as an old case and record it in the same surveillance form. Note in the new follow up form underneath the patient‟s code (relapsing species) and then send the patient to the hospital promptly. 2. Finding parasites but different species, count it as a new case and record it in the same surveillance form. Note it in the new follow up form underneath the patient‟s code and then send the patient to the hospital promptly 3. Finding mixed infection with Pf on the day “0”

------Page 3 of 51 Mae Hong Son Initiative Report: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

------Page 4 of 51 Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

2.1 Assistant Slide Blood Preparation: ASBP Instruction Manual

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

2.1 Preparation of blood spot on filter paper and collection of finger-prick blood for preparation of thick and thin blood films.

1. Label the slide with the patient’s details and record in the register.

2. Wearing protective latex gloves, select the third finger from the thumb of the nondominant hand. Hold the patient’s hand, palm facing upwards, and clean the selected finger with a piece of cotton soaked lightly in 70% ethanol or alcohol swab. Use firm strokes to remove dirt and oil from the ball of the finger and to stimulate blood circulation. Make sure the finger is warm by applying gentle massage if required. Let the alcohol dry from the finger.

3. Using a new, sterile lancet and a quick rolling action, puncture the center of the ball of the finger or toe.

4. Apply gentle pressure to the finger (or toe), and express the first drop of blood. Wipe the first drop of blood off with dry cotton, making sure that no cotton strands remain on the finger that might stick to the blood.

2.1-1

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

5. Drop blood in a concentric circular motion onto the center printed circle area on the card, with at least two circle areas for each patient. Avoid “puddling” the liquid sample, as it will overload chemicals onto the card. Also, do not rub or smear the blood onto the card.

6. The samples applied to filter paper are ready for immediate storage at room temperature. Allow the sample to dry for at least 1 h at room temperature before placing it in a plastic zip lock bag.

7. Express and touch the blood with the slide to collect a small drop of blood, and use it to make the thin film. Collect 2 - 3 more small drops of blood, and use them to make the thick film.

8. Wipe the remaining blood from the finger.

2.1-2

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

spreader 9. To prepare the thin film, place the edge of a clean “spreader” slide at 45o in front of the blood drop intended for the thin film. Slowly pull the “spreader” back until it touches the drop of blood and the blood spreads along the edge of the “spreader”. Rapidly push the “spreader” forwards (away from the center) in a smooth, continuous motion, until the spreader leaves a “feathery” end for the thin film.

10. With the corner of the same “spreader” used for making the thin film, make the thick film by swirling the three drops of blood together forming a circle of about 1 cm in diameter size. Do not stir the blood. A circular or rectangular film can be made by three to six quick strokes with the corner of the spreader.

11. After preparing the thin and thick blood films, allow them to dry in air in a horizontal position on a slide tray. If rapid drying is required, dry the films with low heat from a hair-dryer for 5 s, at a distance of 30 cm. Do not place the slides too close to the dryer, as the films might become heat fixed.

12. Allow blood in filter paper to dry for at least 1 hr. at room temperature before placing it in a plastic zip lock bag. Ensure completely dry storage conditions (check the desiccants regularly for any color change indicating exposure to moisture, and change if necessary). Sending with one of stained malaria slide and iDES form.

2.1-3

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

2.2 Simple Fluorescent Spot Test (FST) for G6PD Screening Instruction Manual

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

2.3 Screening G6PD Deficiency by using simple Fluorescent Spot Test (FST) in Malaria Elimination Program

 Screening with G6PD Fluorescence spot test

Procedure 1. 10L collect finger- prick blood with 10 L loop into control tube and mix

2. 10uL collect finger- prick blood with 10 L loop into Test tube and mix

3. Incubate 5 mins. Pipette out 5-10 L. of solution into filter paper as below position.

4. Continue incubate 10 mins until 15 mins. Pipette out 5-10 L. of solution into filter paper as below position.

2.2-1

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

Interpretation result of G6PD

Control spot at 5 mins and 15 mins.  No Fluoresce Test spot at 5 mins and 15 mins.  Fluoresce

“Normal” or “No G6PD Deficiency”

Control spot at 5 mins and 15 mins.  No Fluoresce Test spot at 5 mins  No Fluoresce Test spot at 15 mins.  Fluoresce

“Partial G6PD Deficiency”

Control spot at 5 mins and 15 mins.  No Fluoresce Test spot at 5 mins and 15 mins.  Fluoresce

“G6PD Deficiency”

2.2-2

Mae Hong Son Initiative: The Innovation of Precise Malaria Services and Treatment in Remote Border Areas

2.3. Labeled malaria drug packaging

ODPC 1 Chiang Mai 1 Sticker contains instruction for vivax and falciparum malaria treatment

for different body weight groups posted on ziplock bag.

Front side of the packaging is for labeling the name of the patient, the date

of take drug, G6PD result, and state of the follow-up appointment date.

Back side show the instruction for the time of day and specified medication

to be taken during the 3 day for Pf. and 14 days for Pv.

Produced in 4 languages; Thai, Tai Yai, Karen, and English

2 English language

Antimalarial drug treatment for Pv. (Chloroquine & Primaquine)

3

4

5

Antimalarial drug treatment for Pv. (Chloroquine & Primaquine)

6 ลืมกินยามื้อใด ให้กินทันทีที่นึกขึ้นได้ ลืมกินยามื้อใด ให้กินทันทีที่นึกขึ้นได้ ยารักษาไข้มาลาเรียไวแวกซ์ (พีวี) ยารักษาไข้มาลาเรียไวแวกซ์ (พีวี) สถานที่ตรวจรักษา...... ล าดับผู้ป่วย...... สถานที่ตรวจรักษา...... ล าดับผู้ป่วย...... ชื่อผู้ป่วย...... อายุ...... ปี ชื่อผู้ป่วย...... อายุ...... ปี วันที่เริ่มกินยา (d0)...... ลงนาม...... วันที่เริ่มกินยา (d0)...... ลงนาม...... วันที่กินยาครบ...... วันที่กินยาครบ...... ผลการตรวจ G6PD □ Normal □ Deficiency □ Partial Deficiency ผลการตรวจ G6PD □ Normal □ Deficiency □ Partial Deficiency วันที่ตรวจตามนัด/ติดตามครั้งที่ 1 (d14)...... ลงนาม...... วันที่ตรวจตามนัด/ติดตามครั้งที่ 1 (d14)...... ลงนาม...... วันที่ติดตามครั้งที่ 2 (d28)...... ลงนาม...... วันที่ติดตามครั้งที่ 2 (d28)...... ลงนาม...... วันที่ติดตามครั้งที่ 3 (d60)...... ลงนาม...... วันที่ติดตามครั้งที่ 3 (d60)...... ลงนาม...... วันที่ติดตามครั้งที่ 4 (d90)...... ลงนาม...... วันที่ติดตามครั้งที่ 4 (d90)...... ลงนาม......

สิ่งที่ส่งมาด้วย □ แบบรายงานติดตามผู้ป่วย □ สไลด์ □ กระดาษกรอง สิ่งที่ส่งมาด้วย □ แบบรายงานติดตามผู้ป่วย □ สไลด์ □ กระดาษกรอง ส านักงานป้องกันควบคุมโรคที่ 1 เชียงใหม่ กรมควบคุมโรค กระทรวงสาธารณสุข ส านักงานป้องกันควบคุมโรคที่ 1 เชียงใหม่ กรมควบคุมโรค กระทรวงสาธารณสุข

ลืมกินยามื้อใด ให้กินทันทีที่นึกขึ้นได้ ลืมกินยามื้อใด ให้กินทันทีที่นึกขึ้นได้ ยารักษาไข้มาลาเรียไวแวกซ์ (พีวี) ยารักษาไข้มาลาเรียไวแวกซ์ (พีวี) สถานที่ตรวจรักษา...... ล าดับผู้ป่วย...... สถานที่ตรวจรักษา...... ล าดับผู้ป่วย...... ชื่อผู้ป่วย...... อายุ...... ปี ชื่อผู้ป่วย...... อายุ...... ปี วันที่เริ่มกินยา (d0)...... ลงนาม...... วันที่เริ่มกินยา (d0)...... ลงนาม...... วันที่กินยาครบ...... วันที่กินยาครบ...... ผลการตรวจ G6PD □ Normal □ Deficiency □ Partial Deficiency ผลการตรวจ G6PD □ Normal □ Deficiency □ Partial Deficiency วันที่ตรวจตามนัด/ติดตามครั้งที่ 1 (d14)...... ลงนาม...... วันที่ตรวจตามนัด/ติดตามครั้งที่ 1 (d14)...... ลงนาม...... วันที่ติดตามครั้งที่ 2 (d28)...... ลงนาม...... วันที่ติดตามครั้งที่ 2 (d28)...... ลงนาม...... วันที่ติดตามครั้งที่ 3 (d60)...... ลงนาม...... วันที่ติดตามครั้งที่ 3 (d60)...... ลงนาม...... วันที่ติดตามครั้งที่ 4 (d90)...... ลงนาม...... วันที่ติดตามครั้งที่ 4 (d90)...... ลงนาม......

สิ่งที่ส่งมาด้วย □ แบบรายงานติดตามผู้ป่วย □ สไลด์ □ กระดาษกรอง สิ่งที่ส่งมาด้วย □ แบบรายงานติดตามผู้ป่วย □ สไลด์ □ กระดาษกรอง 7 ส านักงานป้องกันควบคุมโรคที่ 1 เชียงใหม่ กรมควบคุมโรค กระทรวงสาธารณสุข ส านักงานป้องกันควบคุมโรคที่ 1 เชียงใหม่ กรมควบคุมโรค กระทรวงสาธารณสุข ส าหรับผู้ป่วยน้ าหนัก 50 กิโลกรัม ขึ้นไป ส าหรับผู้ป่วยน้ าหนัก 25 - 50 กิโลกรัม C = 10 เม็ด, P (15 mg) = 14 เม็ด C = 6 เม็ด, P (5 mg) = 28 เม็ด)

ส าหรับผู้ป่วยน้ าหนัก 15 - 24 กิโลกรัม ส าหรับผู้ป่วยน้ าหนัก 11 - 14 กิโลกรัม C = 5 เม็ด, P (5 mg) = 14 เม็ด) C = 4 เม็ด

ผู้ป่วยที่อายุน้อยกว่า 1 ปี หรือน้ าหนักน้อยกว่า 11 กก. ให้ท าการรักษาโดยแพทย์เท่านั้น

8 Karen language

Antimalarial drug treatment for Pv. (Chloroquine & Primaquine)

9 สิ่งที่ส่งมาด้วย □ แบบรายงานติดตามผู้ป่วย □ สไลด์ □ กระดาษกรอง สิ่งที่ส่งมาด้วย □ แบบรายงานติดตามผู้ป่วย □ สไลด์ □ กระดาษกรอง ส านักงานป้องกันควบคุมโรคที่ 1 เชียงใหม่ กรมควบคุมโรค กระทรวงสาธารณสุข ส านักงานป้องกันควบคุมโรคที่ 1 เชียงใหม่ กรมควบคุมโรค กระทรวงสาธารณสุข

สิ่งที่ส่งมาด้วย □ แบบรายงานติดตามผู้ป่วย □ สไลด์ □ กระดาษกรอง สิ่งที่ส่งมาด้วย □ แบบรายงานติดตามผู้ป่วย □ สไลด์ □ กระดาษกรอง ส านักงานป้องกันควบคุมโรคที่ 1 เชียงใหม่ กรมควบคุมโรค กระทรวงสาธารณสุข ส านักงานป้องกันควบคุมโรคที่ 1 เชียงใหม่ กรมควบคุมโรค กระทรวงสาธารณสุข10

11 Tai Yai Language

Antimalarial drug treatment for Pv. (Chloroquine & Primaquine)

12

13

14 Thai language

Antimalarial drug treatment for Pf without complications. (Dihydroartemisinin-Piperaquine & Primaquine)

15 ส านักงานป้องกันควบคุมโรคที่ 1 เชียงใหม่ กรมควบคุมโรค กระทรวงสาธารณสุข ส านักงานป้องกันควบคุมโรคที่ 1 เชียงใหม่ กรมควบคุมโรค กระทรวงสาธารณสุข ยารักษาไข้มาลาเรียฟัลซิปารัม (พีเอฟ) ยารักษาไข้มาลาเรียฟัลซิปารัม (พีเอฟ) สถานที่ตรวจรักษา...... ล าดับผู้ป่วย...... สถานที่ตรวจรักษา...... ล าดับผู้ป่วย...... ชื่อผู้ป่วย...... อายุ...... ชื่อผู้ป่วย...... อายุ...... ปีวันที่เริ่มกินยา (d0)...... ลงนาม...... ปีวันที่เริ่มกินยา (d0)...... ลงนาม...... วันที่กินยาครบ...... น้าหนักผู้ป่วย ...... กิโลกรัม วันที่กินยาครบ...... น้าหนักผู้ป่วย ...... กิโลกรัม ผลการตรวจ G6PD □ Normal □ Deficiency □ Partial Deficiency ผลการตรวจ G6PD □ Normal □ Deficiency □ Partial Deficiency วันที่ตรวจตามนัด/ติดตามครั้งที่ 1 (d3)...... ลงนาม...... วันที่ตรวจตามนัด/ติดตามครั้งที่ 1 (d3)...... ลงนาม...... วันที่ติดตามครั้งที่ 2 (d7)...... ลงนาม...... วันที่ติดตามครั้งที่ 2 (d7)...... ลงนาม...... วันที่ติดตามครั้งที่ 3 (d28)...... ลงนาม ...... วันที่ติดตามครั้งที่ 3 (d28)...... ลงนาม ...... วันที่ติดตามครั้งที่ 4 (d42)...... ลงนาม ...... วันที่ติดตามครั้งที่ 4 (d42)...... ลงนาม ...... วันที่ติดตามครั้งที่ 5 (d60)...... ลงนาม ...... วันที่ติดตามครั้งที่ 5 (d60)...... ลงนาม ......

สิ่งที่ส่งมาด้วย □ แบบรายงานติดตามผู้ป่วย □ สไลด์ □ กระดาษกรอง สิ่งที่ส่งมาด้วย □ แบบรายงานติดตามผู้ป่วย □ สไลด์ □ กระดาษกรอง

ส านักงานป้องกันควบคุมโรคที่ 1 เชียงใหม่ กรมควบคุมโรค กระทรวงสาธารณสุข ส านักงานป้องกันควบคุมโรคที่ 1 เชียงใหม่ กรมควบคุมโรค กระทรวงสาธารณสุข ยารักษาไข้มาลาเรียฟัลซิปารัม (พีเอฟ) ยารักษาไข้มาลาเรียฟัลซิปารัม (พีเอฟ) สถานที่ตรวจรักษา...... ล าดับผู้ป่วย...... สถานที่ตรวจรักษา...... ล าดับผู้ป่วย...... ชื่อผู้ป่วย...... อายุ...... ชื่อผู้ป่วย...... อายุ...... ปีวันที่เริ่มกินยา (d0)...... ลงนาม...... ปีวันที่เริ่มกินยา (d0)...... ลงนาม...... วันที่กินยาครบ...... น้าหนักผู้ป่วย ...... กิโลกรัม วันที่กินยาครบ...... น้าหนักผู้ป่วย ...... กิโลกรัม ผลการตรวจ G6PD □ Normal □ Deficiency □ Partial Deficiency ผลการตรวจ G6PD □ Normal □ Deficiency □ Partial Deficiency วันที่ตรวจตามนัด/ติดตามครั้งที่ 1 (d3)...... ลงนาม...... วันที่ตรวจตามนัด/ติดตามครั้งที่ 1 (d3)...... ลงนาม...... วันที่ติดตามครั้งที่ 2 (d7)...... ลงนาม...... วันที่ติดตามครั้งที่ 2 (d7)...... ลงนาม...... วันที่ติดตามครั้งที่ 3 (d28)...... ลงนาม ...... วันที่ติดตามครั้งที่ 3 (d28)...... ลงนาม ...... วันที่ติดตามครั้งที่ 4 (d42)...... ลงนาม ...... วันที่ติดตามครั้งที่ 4 (d42)...... ลงนาม ...... วันที่ติดตามครั้งที่ 5 (d60)...... ลงนาม ...... วันที่ติดตามครั้งที่ 5 (d60)...... ลงนาม ...... 16 สิ่งที่ส่งมาด้วย □ แบบรายงานติดตามผู้ป่วย □ สไลด์ □ กระดาษกรอง สิ่งที่ส่งมาด้วย □ แบบรายงานติดตามผู้ป่วย □ สไลด์ □ กระดาษกรอง โปรดอ่านให้เข้าใจก่อนกินยา โปรดอ่านให้เข้าใจก่อนกินยา วิธีการกินยารักษามาลาเรียฟัลซิปารัม วิธีการกินยารักษามาลาเรียฟัลซิปารัม ส าหรับผู้ป่วยน้ าหนัก 60 ถึง 80 กิโลกรัม ส าหรับผู้ป่วยน้ าหนักมากกว่า 80 กิโลกรัม

 กินยาหลังอาหารตามจ านวนที่ก าหนดให้ครบ 3 วัน  กินยาหลังอาหารตามจ านวนที่ก าหนดให้ครบ 3 วัน  ยาชุดนี้ส าหรับรักษาผู้ป่วย 1 คนเท่านั้น  ยาชุดนี้ส าหรับรักษาผู้ป่วย 1 คนเท่านั้น  ห้ามน ายานี้ไปให้ผู้อื่นกิน 15 mg  ห้ามน ายานี้ไปให้ผู้อื่นกิน 15 mg

โปรดอ่านให้เข้าใจก่อนกินยา โปรดอ่านให้เข้าใจก่อนกินยา วิธีการกินยารักษามาลาเรียฟัลซิปารัม วิธีการกินยารักษามาลาเรียฟัลซิปารัม ส าหรับผู้ป่วยน้ าหนัก มากกว่า 50 ถึง < 60 กิโลกรัม ส าหรับผู้ป่วยน้ าหนัก 36 - 50 กิโลกรัม

 กินยาหลังอาหารตามจ านวนที่ก าหนดให้ครบ 3 วัน  กินยาหลังอาหารตามจ านวนที่ก าหนดให้ครบ 3 วัน  ยาชุดนี้ส าหรับรักษาผู้ป่วย 1 คนเท่านั้น  ยาชุดนี้ส าหรับรักษาผู้ป่วย 1 คนเท่านั้น 17  ห้ามน ายานี้ไปให้ผู้อื่นกิน 15 mg  ห้ามน ายานี้ไปให้ผู้อื่นกิน 15 mg โปรดอ่านให้เข้าใจก่อนกินยา โปรดอ่านให้เข้าใจก่อนกินยา วิธีการกินยารักษามาลาเรียฟัลซิปารัม วิธีการกินยารักษามาลาเรียฟัลซิปารัม ส าหรับผู้ป่วยน้ าหนัก 17 ถึง < 25 กิโลกรัม ส าหรับผู้ป่วยน้ าหนัก 15 ถึง < 17 กิโลกรัม

 กินยาหลังอาหารตามจ านวนที่ก าหนดให้ครบ 3 วัน  กินยาหลังอาหารตามจ านวนที่ก าหนดให้ครบ 3 วัน  ยาชุดนี้ส าหรับรักษาผู้ป่วย 1 คนเท่านั้น  ยาชุดนี้ส าหรับรักษาผู้ป่วย 1 คนเท่านั้น 5 mg  ห้ามน ายานี้ไปให้ผู้อื่นกิน 5 mg  ห้ามน ายานี้ไปให้ผู้อื่นกิน

โปรดอ่านให้เข้าใจก่อนกินยา โปรดอ่านให้เข้าใจก่อนกินยา วิธีการกินยารักษามาลาเรียฟัลซิปารัม วิธีการกินยารักษามาลาเรียฟัลซิปารัม ส าหรับผู้ป่วยน้ าหนัก 11 - 14 กิโลกรัม ส าหรับผู้ป่วยน้ าหนัก 25 ถึง < 36 กิโลกรัม

 กินยาหลังอาหารตามจ านวนที่ก าหนดให้ครบ 3 วัน  กินยาหลังอาหารตามจ านวนที่ก าหนดให้ครบ 3 วัน  ยาชุดนี้ส าหรับรักษาผู้ป่วย 1 คนเท่านั้น  ยาชุดนี้ส าหรับรักษาผู้ป่วย 1 คนเท่านั้น 18  ห้ามน ายานี้ไปให้ผู้อื่นกิน 5 mg  ห้ามน ายานี้ไปให้ผู้อื่นกิน 15 mg โปรดอ่านให้เข้าใจก่อนกินยา โปรดอ่านให้เข้าใจก่อนกินยา วิธีการกินยารักษามาลาเรียฟัลซิปารัม วิธีการกินยารักษามาลาเรียฟัลซิปารัม ส าหรับผู้ป่วยน้ าหนัก 60 ถึง 80 กิโลกรัม ส าหรับผู้ป่วยน้ าหนักมากกว่า 80 กิโลกรัม

 กินยาหลังอาหารตามจ านวนที่ก าหนดให้ครบ 3 วัน  กินยาหลังอาหารตามจ านวนที่ก าหนดให้ครบ 3 วัน  ยาชุดนี้ส าหรับรักษาผู้ป่วย 1 คนเท่านั้น  ยาชุดนี้ส าหรับรักษาผู้ป่วย 1 คนเท่านั้น  ห้ามน ายานี้ไปให้ผู้อื่นกิน 15 mg  ห้ามน ายานี้ไปให้ผู้อื่นกิน 15 mg

โปรดอ่านให้เข้าใจก่อนกินยา โปรดอ่านให้เข้าใจก่อนกินยา วิธีการกินยารักษามาลาเรียฟัลซิปารัม วิธีการกินยารักษามาลาเรียฟัลซิปารัม ส าหรับผู้ป่วยน้ าหนัก มากกว่า 50 ถึง < 60 กิโลกรัม ส าหรับผู้ป่วยน้ าหนัก 36 - 50 กิโลกรัม

 กินยาหลังอาหารตามจ านวนที่ก าหนดให้ครบ 3 วัน  กินยาหลังอาหารตามจ านวนที่ก าหนดให้ครบ 3 วัน  ยาชุดนี้ส าหรับรักษาผู้ป่วย 1 คนเท่านั้น  ยาชุดนี้ส าหรับรักษาผู้ป่วย 1 คนเท่านั้น 19  ห้ามน ายานี้ไปให้ผู้อื่นกิน 15 mg  ห้ามน ายานี้ไปให้ผู้อื่นกิน 15 mg