K M.Lwin - Academia.edu (original) (raw)

Papers by K M.Lwin

Research paper thumbnail of Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: a cross-sectional survey of the K13 molecular marker

The Lancet Infectious Diseases

Emergence of artemisinin resistance in southeast Asia poses a serious threat to the global contro... more Emergence of artemisinin resistance in southeast Asia poses a serious threat to the global control of Plasmodium falciparum malaria. Discovery of the K13 marker has transformed approaches to the monitoring of artemisinin resistance, allowing introduction of molecular surveillance in remote areas through analysis of DNA. We aimed to assess the spread of artemisinin-resistant P falciparum in Myanmar by determining the relative prevalence of P falciparum parasites carrying K13-propeller mutations. We did this cross-sectional survey at malaria treatment centres at 55 sites in ten administrative regions in Myanmar, and in relevant border regions in Thailand and Bangladesh, between January, 2013, and September, 2014. K13 sequences from P falciparum infections were obtained mainly by passive case detection. We entered data into two geostatistical models to produce predictive maps of the estimated prevalence of mutations of the K13 propeller region across Myanmar. Overall, 371 (39%) of 940 ...

Research paper thumbnail of Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: a cross-sectional survey of the K13 molecular marker

The Lancet Infectious Diseases, 2015

Background Emergence of artemisinin resistance in southeast Asia poses a serious threat to the gl... more Background Emergence of artemisinin resistance in southeast Asia poses a serious threat to the global control of Plasmodium falciparum malaria. Discovery of the K13 marker has transformed approaches to the monitoring of artemisinin resistance, allowing introduction of molecular surveillance in remote areas through analysis of DNA. We aimed to assess the spread of artemisinin-resistant P falciparum in Myanmar by determining the relative prevalence of P falciparum parasites carrying K13-propeller mutations.

Research paper thumbnail of The practicality and sustainability of a community advisory board at a large medical research unit on the Thai-Myanmar border

Health, 2013

Community engagement is increasingly promoted to strengthen the ethics of medical research in low... more Community engagement is increasingly promoted to strengthen the ethics of medical research in low-income countries. One strategy is to use community advisory boards (CABs): semi-independent groups that can potentially safeguard the rights of study participants and help improve research. However, there is little published on the experience of operating and sustaining CABs. The Shoklo Malaria Research Unit (SMRU) has been conducting research and providing healthcare in a population of refugees, migrant workers, and displaced people on the Thai-Myanmar border for over 25 years. In 2009 SMRU facilitated the establishment of the Tak Province Community Ethics Advisory Board (T-CAB) in an effort to formally engage with the local communities both to obtain advice and to establish a participatory framework within which studies and the provision of health care can take place. In this paper, we draw on our experience of community engagement in this unique setting, and on our interactions with the past and present CAB members to critically reflect upon the CAB's goals, structure and operations with a focus on the practicalities, what worked, what did not, and on its future directions.

Research paper thumbnail of Randomized, double-blind, placebo-controlled trial of monthly versus bimonthly dihydroartemisinin-piperaquine chemoprevention in adults at high risk of malaria

Antimicrobial agents and chemotherapy, 2012

Intermittent preventive treatment (IPT) is increasingly used to reduce malaria morbidity and mort... more Intermittent preventive treatment (IPT) is increasingly used to reduce malaria morbidity and mortality in children and pregnant women. The efficacy of IPT depends on the pharmacokinetic and pharmacodynamic properties of the antimalarial drugs used. Healthy adult male volunteers whose occupation put them at high risk of malaria on the Northwest border of Thailand were randomized to receive a 3-day-treatment dose of dihydroartemisinin-piperaquine monthly (DPm) or every 2 months (DPalt) or an identical placebo with or without fat (6.4 g/dose) over a 9-month period. All volunteers were monitored weekly. One thousand adults were recruited. Dihydroartemisinin-piperaquine was well tolerated. There were 114 episodes of malaria (49 Plasmodium falciparum, 63 P. vivax, and 2 P. ovale). The protective efficacy against all malaria at 36 weeks was 98% (95% confidence interval [CI], 96% to 99%) in the DPm group and 86% (95% CI, 81% to 90%) in the DPalt group (for both, P < 0.0001 compared to th...

Research paper thumbnail of Modeling Motion Control System for Motorized Robot Arm using MATLAB

... Ea(s)=Ra Ia(s)+ Las Ia(s)+Vb(s) (3) This may also be written as: Modeling Motion Control Syst... more ... Ea(s)=Ra Ia(s)+ Las Ia(s)+Vb(s) (3) This may also be written as: Modeling Motion Control System for Motorized Robot Arm using MATLAB Chun Htoo Aung, Khin Thandar Lwin, and Yin Mon Myint M World Academy of Science, Engineering and Technology 42 2008 372 Page 2. ...

Research paper thumbnail of Characterization of an in vivo concentration-effect relationship for piperaquine in malaria chemoprevention

Science translational medicine, Jan 29, 2014

A randomized, placebo-controlled trial conducted on the northwest border of Thailand compared mal... more A randomized, placebo-controlled trial conducted on the northwest border of Thailand compared malaria chemoprevention with monthly or bimonthly standard 3-day treatment regimens of dihydroartemisinin-piperaquine. Healthy adult male subjects (N = 1000) were followed weekly during 9 months of treatment. Using nonlinear mixed-effects modeling, the concentration-effect relationship for the malaria-preventive effect of piperaquine was best characterized with a sigmoidal Emax relationship, where plasma concentrations of 6.7 ng/ml [relative standard error (RSE), 23%] and 20 ng/ml were found to reduce the hazard of acquiring a malaria infection by 50% [that is, median inhibitory concentration (IC50)] and 95% (IC95), respectively. Simulations of monthly dosing, based on the final model and published pharmacokinetic data, suggested that the incidence of malaria infections over 1 year could be reduced by 70% with a recently suggested dosing regimen compared to the current manufacturer's re...

Research paper thumbnail of Linking international clinical research with stateless populations to justice in global health

BMC Medical Ethics, 2014

Background: In response to calls to expand the scope of research ethics to address justice in glo... more Background: In response to calls to expand the scope of research ethics to address justice in global health, recent scholarship has sought to clarify how external research actors from high-income countries might discharge their obligation to reduce health disparities between and within countries. An ethical framework-'research for health justice'-was derived from a theory of justice (the health capability paradigm) and specifies how international clinical research might contribute to improved health and research capacity in host communities. This paper examines whether and how external funders, sponsors, and researchers can fulfill their obligations under the framework.

Research paper thumbnail of An open label randomized comparison of mefloquine?artesunate as separate tablets vs. a new co-formulated combination for the treatment of uncomplicated multidrug-resistant falciparum malaria in Thailand

Tropical Medicine and International Health, 2006

background Delivering drugs in a fixed combination is essential to the success of the strategy of... more background Delivering drugs in a fixed combination is essential to the success of the strategy of artemisinin-based combination therapy. This prevents one drug being taken without the protection of the other, reducing the chance of emergence and spread of drug resistant strains of Plasmodium falciparum. A lower tablet burden should also facilitate adherence to treatment. A new fixed combination of mefloquine plus artesunate has been developed. This was compared with the conventional regimen of separate tablets for the treatment of uncomplicated multidrug-resistant falciparum malaria.

Research paper thumbnail of Ancillary Care: From Theory to Practice in International Clinical Research

Public Health Ethics, 2013

How international research might contribute to justice in global health has not been substantivel... more How international research might contribute to justice in global health has not been substantively addressed by bioethics. This article describes how the provision of ancillary care can link international clinical research to the reduction of global health disparities. It identifies the ancillary care obligations supported by a theory of global justice, showing that Jennifer Ruger's health capability paradigm requires the delivery of ancillary care to trial participants for a limited subset of conditions that cause severe morbidity and mortality. Empirical research on the Shoklo Malaria Research Unit's (SMRU) vivax malaria treatment trial was then undertaken to demonstrate whether and how these obligations might be upheld in a resource-poor setting. Our findings show that fulfilment of the ancillary care obligations is feasible where there is commitment from chief investigators and funders and is strongly facilitated by SMRU's dual role as a research unit and medical non-governmental organization.

Research paper thumbnail of Changes in the Treatment Responses to Artesunate-Mefloquine on the Northwestern Border of Thailand during 13 Years of Continuous Deployment

PLoS ONE, 2009

Background: Artemisinin combination treatments (ACT) are recommended as first line treatment for ... more Background: Artemisinin combination treatments (ACT) are recommended as first line treatment for falciparum malaria throughout the malaria affected world. We reviewed the efficacy of a 3-day regimen of mefloquine and artesunate regimen (MAS 3 ), over a 13 year period of continuous deployment as first-line treatment in camps for displaced persons and in clinics for migrant population along the Thai-Myanmar border.

Research paper thumbnail of Clinically uncomplicated Plasmodium falciparum malaria with high schizontaemia: A case report

Malaria Journal, 2008

The treatment options for acute Plasmodium falciparum malaria are based on the clinician classify... more The treatment options for acute Plasmodium falciparum malaria are based on the clinician classifying the patient as uncomplicated or severe according to the clinical and parasitological findings. This process is not always straightforward.

Research paper thumbnail of Triangular test design to evaluate tinidazole in the prevention of Plasmodium vivax relapse

Malaria Journal, 2013

Background: There are very few drugs that prevent the relapse of Plasmodium vivax malaria in man.... more Background: There are very few drugs that prevent the relapse of Plasmodium vivax malaria in man. Tinidazole is a 5-nitroimidazole approved in the USA for the treatment of indications including amoebiasis and giardiasis. In the non-human primate relapsing Plasmodium cynomolgi/macaque malaria model, tinidazole cured one of six macaques studied with an apparent mild delay to relapse in the other five of 14-28 days compared to 11-12 days in controls. One study has demonstrated activity against P. vivax in man. Presented here are the results of a pilot phase II, randomized, open-label study conducted along the Thai-Myanmar border designed to evaluate the efficacy of tinidazole to prevent relapse of P. vivax when administered with chloroquine. Methods: This study utilized a modified triangular test sequential analysis which allows repeated statistical evaluation during the course of enrolment while maintaining a specified power and type 1 error and minimizing recruitment of subjects. Enrolment was to be halted when a pre-specified success/failure ratio was surpassed. The study was designed to have a 5% type 1 error and 90% power to show whether tinidazole would produce a relapse rate of less than 20% or greater than 45% through Day 63 of weekly follow-up after initiation of treatment and initial parasite clearance with 3 days of an oral weight based dosing of chloroquine and five days of 2 grams/ day of tinidazole.

Research paper thumbnail of Closing the translation gap for justice requirements in international research

Abstract Bioethicists have long debated the content of sponsors and researchers' obligations of j... more Abstract Bioethicists have long debated the content of sponsors and researchers' obligations of justice in international clinical research. However, there has been little empirical investigation as to whether and how obligations of responsiveness, ancillary care, post-trial benefits and research capacity strengthening are upheld in low-and middle-income country settings. In this paper, the authors argue that research ethics guidelines need to be more informed by international research practice.

Research paper thumbnail of Community engagement on the Thai-Burmese border: rationale, experience and lessons learnt

International Health, 2010

Community engagement is increasingly promoted in developing countries, especially in internationa... more Community engagement is increasingly promoted in developing countries, especially in international health research, but there is little published experience. The Shoklo Malaria Research Unit (SMRU) conducts research with refugees, migrant workers, displaced people, and day migrants on the Thai-Burmese border, and has recently facilitated the set up of the Tak Province Border Community Ethics Advisory Board (T-CAB). Valuable lessons have been learnt from consultation with the T-CAB especially in the area of participant recruitment and the informed consent process. A lot of new research questions have emerged from consultation with the T-CAB. This paper describes our experience, lessons learnt and the unique challenges faced working with the T-CAB from its initial conception to date. We conclude that consultation with the T-CAB has made improvements in our research in particular operational and ethical aspects of our studies.

Research paper thumbnail of Exploitation and community engagement: Can Community Advisory Boards successfully assume a role minimising exploitation in international research?

Developing World Bioethics, 2013

It has been suggested that community advisory boards (CABs) can play a role in minimising exploit... more It has been suggested that community advisory boards (CABs) can play a role in minimising exploitation in international research. To get a better idea of what this requires and whether it might be achievable, the paper first describes core elements that we suggest must be in place for a CAB to reduce the potential for exploitation. The paper then examines a CAB established by the Shoklo Malaria Research Unit under conditions common in resource-poor settings -namely, where individuals join with a very limited understanding of disease and medical research and where an existing organisational structure is not relied upon to serve as the CAB. Using the Tak Province Border Community Ethics Advisory Board (T-CAB) as a case study, we assess the extent to which it might be able to take on a role minimising exploitation were it to decide to do so. We investigate whether, after two years in operation, T-CAB is capable of assessing clinical trials for exploitative features and addressing those found to have them. The findings show that, although T-CAB members have gained knowledge and developed capacities that are foundational for one-day taking on a role to reduce exploitation, their ability to critically evaluate studies for the presence of exploitative elements has not yet been strongly demonstrated. In light of this example, we argue that CABs may not be able to perform such a role for a number of years after initial formation, making it an unsuitable responsibility for many short-term CABs. We recognise that a lack of responsiveness, appropriate standard of care, and post-trial benefits are not the only features associated with exploitative research and that consensus on the association of these features with exploitation may not be universal. 7 A.

Research paper thumbnail of Motivations and perceptions of community advisory boards in the ethics of medical research: the case of the Thai-Myanmar border

BMC Medical Ethics, 2014

Background: Community engagement is increasingly promoted as a marker of good, ethical practice i... more Background: Community engagement is increasingly promoted as a marker of good, ethical practice in the context of international collaborative research in low-income countries. There is, however, no widely agreed definition of community engagement or of approaches adopted. Justifications given for its use also vary. Community engagement is, for example, variously seen to be of value in: the development of more effective and appropriate consent processes; improved understanding of the aims and forms of research; higher recruitment rates; the identification of important ethical issues; the building of better relationships between the community and researchers; the obtaining of community permission to approach potential research participants; and, the provision of better health care. Despite these diverse and potentially competing claims made for the importance of community engagement, there is very little published evidence on effective models of engagement or their evaluation. Methods: In this paper, drawing upon interviews with the members of a Community Advisory Board on the Thai-Myanmar border, we describe and critically reflect upon an approach to community engagement which was developed in the context of international collaborative research in the border region.

Research paper thumbnail of Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription

Research paper thumbnail of Exploring the Contribution of Candidate Genes to Artemisinin Resistance in Plasmodium falciparum

Antimicrobial Agents and Chemotherapy, 2010

The reduced in vivo sensitivity of Plasmodium falciparum has recently been confirmed in western C... more The reduced in vivo sensitivity of Plasmodium falciparum has recently been confirmed in western Cambodia. Identifying molecular markers for artemisinin resistance is essential for monitoring the spread of the resistant phenotype and identifying the mechanisms of resistance. Four candidate genes, including the P. falciparum mdr1 (pfmdr1) gene, the P. falciparum ATPase6 (pfATPase6) gene, the 6-kb mitochondrial genome, and ubp-1, encoding a deubiquitinating enzyme, of artemisinin-resistant P. falciparum strains from western Cambodia were examined and compared to those of sensitive strains from northwestern Thailand, where the artemisinins are still very effective. The artemisinin-resistant phenotype did not correlate with pfmdr1 amplification or mutations (full-length sequencing), mutations in pfATPase6 (full-length sequencing) or the 6-kb mitochondrial genome (full-length sequencing), or ubp-1 mutations at positions 739 and 770. The P. falciparum CRT K76T mutation was present in all isolates from both study sites. The pfmdr1 copy numbers in western Cambodia were significantly lower in parasite samples obtained in 2007 than in those obtained in 2005, coinciding with a local change in drug policy replacing artesunate-mefloquine with dihydroartemisinin-piperaquine. Artemisinin resistance in western Cambodia is not linked to candidate genes, as was suggested by earlier studies.

Research paper thumbnail of Refugee and Migrant Women's Views of Antenatal Ultrasound on the Thai Burmese Border: A Mixed Methods Study

PLoS ONE, 2012

Background: Antenatal ultrasound suits developing countries by virtue of its versatility, relativ... more Background: Antenatal ultrasound suits developing countries by virtue of its versatility, relatively low cost and safety, but little is known about women's or local provider's perspectives of this upcoming technology in such settings. This study was undertaken to better understand how routine obstetric ultrasound is experienced in a displaced Burmese population and identify barriers to its acceptance by local patients and providers.

Research paper thumbnail of Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: a cross-sectional survey of the K13 molecular marker

The Lancet Infectious Diseases

Emergence of artemisinin resistance in southeast Asia poses a serious threat to the global contro... more Emergence of artemisinin resistance in southeast Asia poses a serious threat to the global control of Plasmodium falciparum malaria. Discovery of the K13 marker has transformed approaches to the monitoring of artemisinin resistance, allowing introduction of molecular surveillance in remote areas through analysis of DNA. We aimed to assess the spread of artemisinin-resistant P falciparum in Myanmar by determining the relative prevalence of P falciparum parasites carrying K13-propeller mutations. We did this cross-sectional survey at malaria treatment centres at 55 sites in ten administrative regions in Myanmar, and in relevant border regions in Thailand and Bangladesh, between January, 2013, and September, 2014. K13 sequences from P falciparum infections were obtained mainly by passive case detection. We entered data into two geostatistical models to produce predictive maps of the estimated prevalence of mutations of the K13 propeller region across Myanmar. Overall, 371 (39%) of 940 ...

Research paper thumbnail of Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: a cross-sectional survey of the K13 molecular marker

The Lancet Infectious Diseases, 2015

Background Emergence of artemisinin resistance in southeast Asia poses a serious threat to the gl... more Background Emergence of artemisinin resistance in southeast Asia poses a serious threat to the global control of Plasmodium falciparum malaria. Discovery of the K13 marker has transformed approaches to the monitoring of artemisinin resistance, allowing introduction of molecular surveillance in remote areas through analysis of DNA. We aimed to assess the spread of artemisinin-resistant P falciparum in Myanmar by determining the relative prevalence of P falciparum parasites carrying K13-propeller mutations.

Research paper thumbnail of The practicality and sustainability of a community advisory board at a large medical research unit on the Thai-Myanmar border

Health, 2013

Community engagement is increasingly promoted to strengthen the ethics of medical research in low... more Community engagement is increasingly promoted to strengthen the ethics of medical research in low-income countries. One strategy is to use community advisory boards (CABs): semi-independent groups that can potentially safeguard the rights of study participants and help improve research. However, there is little published on the experience of operating and sustaining CABs. The Shoklo Malaria Research Unit (SMRU) has been conducting research and providing healthcare in a population of refugees, migrant workers, and displaced people on the Thai-Myanmar border for over 25 years. In 2009 SMRU facilitated the establishment of the Tak Province Community Ethics Advisory Board (T-CAB) in an effort to formally engage with the local communities both to obtain advice and to establish a participatory framework within which studies and the provision of health care can take place. In this paper, we draw on our experience of community engagement in this unique setting, and on our interactions with the past and present CAB members to critically reflect upon the CAB's goals, structure and operations with a focus on the practicalities, what worked, what did not, and on its future directions.

Research paper thumbnail of Randomized, double-blind, placebo-controlled trial of monthly versus bimonthly dihydroartemisinin-piperaquine chemoprevention in adults at high risk of malaria

Antimicrobial agents and chemotherapy, 2012

Intermittent preventive treatment (IPT) is increasingly used to reduce malaria morbidity and mort... more Intermittent preventive treatment (IPT) is increasingly used to reduce malaria morbidity and mortality in children and pregnant women. The efficacy of IPT depends on the pharmacokinetic and pharmacodynamic properties of the antimalarial drugs used. Healthy adult male volunteers whose occupation put them at high risk of malaria on the Northwest border of Thailand were randomized to receive a 3-day-treatment dose of dihydroartemisinin-piperaquine monthly (DPm) or every 2 months (DPalt) or an identical placebo with or without fat (6.4 g/dose) over a 9-month period. All volunteers were monitored weekly. One thousand adults were recruited. Dihydroartemisinin-piperaquine was well tolerated. There were 114 episodes of malaria (49 Plasmodium falciparum, 63 P. vivax, and 2 P. ovale). The protective efficacy against all malaria at 36 weeks was 98% (95% confidence interval [CI], 96% to 99%) in the DPm group and 86% (95% CI, 81% to 90%) in the DPalt group (for both, P < 0.0001 compared to th...

Research paper thumbnail of Modeling Motion Control System for Motorized Robot Arm using MATLAB

... Ea(s)=Ra Ia(s)+ Las Ia(s)+Vb(s) (3) This may also be written as: Modeling Motion Control Syst... more ... Ea(s)=Ra Ia(s)+ Las Ia(s)+Vb(s) (3) This may also be written as: Modeling Motion Control System for Motorized Robot Arm using MATLAB Chun Htoo Aung, Khin Thandar Lwin, and Yin Mon Myint M World Academy of Science, Engineering and Technology 42 2008 372 Page 2. ...

Research paper thumbnail of Characterization of an in vivo concentration-effect relationship for piperaquine in malaria chemoprevention

Science translational medicine, Jan 29, 2014

A randomized, placebo-controlled trial conducted on the northwest border of Thailand compared mal... more A randomized, placebo-controlled trial conducted on the northwest border of Thailand compared malaria chemoprevention with monthly or bimonthly standard 3-day treatment regimens of dihydroartemisinin-piperaquine. Healthy adult male subjects (N = 1000) were followed weekly during 9 months of treatment. Using nonlinear mixed-effects modeling, the concentration-effect relationship for the malaria-preventive effect of piperaquine was best characterized with a sigmoidal Emax relationship, where plasma concentrations of 6.7 ng/ml [relative standard error (RSE), 23%] and 20 ng/ml were found to reduce the hazard of acquiring a malaria infection by 50% [that is, median inhibitory concentration (IC50)] and 95% (IC95), respectively. Simulations of monthly dosing, based on the final model and published pharmacokinetic data, suggested that the incidence of malaria infections over 1 year could be reduced by 70% with a recently suggested dosing regimen compared to the current manufacturer's re...

Research paper thumbnail of Linking international clinical research with stateless populations to justice in global health

BMC Medical Ethics, 2014

Background: In response to calls to expand the scope of research ethics to address justice in glo... more Background: In response to calls to expand the scope of research ethics to address justice in global health, recent scholarship has sought to clarify how external research actors from high-income countries might discharge their obligation to reduce health disparities between and within countries. An ethical framework-'research for health justice'-was derived from a theory of justice (the health capability paradigm) and specifies how international clinical research might contribute to improved health and research capacity in host communities. This paper examines whether and how external funders, sponsors, and researchers can fulfill their obligations under the framework.

Research paper thumbnail of An open label randomized comparison of mefloquine?artesunate as separate tablets vs. a new co-formulated combination for the treatment of uncomplicated multidrug-resistant falciparum malaria in Thailand

Tropical Medicine and International Health, 2006

background Delivering drugs in a fixed combination is essential to the success of the strategy of... more background Delivering drugs in a fixed combination is essential to the success of the strategy of artemisinin-based combination therapy. This prevents one drug being taken without the protection of the other, reducing the chance of emergence and spread of drug resistant strains of Plasmodium falciparum. A lower tablet burden should also facilitate adherence to treatment. A new fixed combination of mefloquine plus artesunate has been developed. This was compared with the conventional regimen of separate tablets for the treatment of uncomplicated multidrug-resistant falciparum malaria.

Research paper thumbnail of Ancillary Care: From Theory to Practice in International Clinical Research

Public Health Ethics, 2013

How international research might contribute to justice in global health has not been substantivel... more How international research might contribute to justice in global health has not been substantively addressed by bioethics. This article describes how the provision of ancillary care can link international clinical research to the reduction of global health disparities. It identifies the ancillary care obligations supported by a theory of global justice, showing that Jennifer Ruger's health capability paradigm requires the delivery of ancillary care to trial participants for a limited subset of conditions that cause severe morbidity and mortality. Empirical research on the Shoklo Malaria Research Unit's (SMRU) vivax malaria treatment trial was then undertaken to demonstrate whether and how these obligations might be upheld in a resource-poor setting. Our findings show that fulfilment of the ancillary care obligations is feasible where there is commitment from chief investigators and funders and is strongly facilitated by SMRU's dual role as a research unit and medical non-governmental organization.

Research paper thumbnail of Changes in the Treatment Responses to Artesunate-Mefloquine on the Northwestern Border of Thailand during 13 Years of Continuous Deployment

PLoS ONE, 2009

Background: Artemisinin combination treatments (ACT) are recommended as first line treatment for ... more Background: Artemisinin combination treatments (ACT) are recommended as first line treatment for falciparum malaria throughout the malaria affected world. We reviewed the efficacy of a 3-day regimen of mefloquine and artesunate regimen (MAS 3 ), over a 13 year period of continuous deployment as first-line treatment in camps for displaced persons and in clinics for migrant population along the Thai-Myanmar border.

Research paper thumbnail of Clinically uncomplicated Plasmodium falciparum malaria with high schizontaemia: A case report

Malaria Journal, 2008

The treatment options for acute Plasmodium falciparum malaria are based on the clinician classify... more The treatment options for acute Plasmodium falciparum malaria are based on the clinician classifying the patient as uncomplicated or severe according to the clinical and parasitological findings. This process is not always straightforward.

Research paper thumbnail of Triangular test design to evaluate tinidazole in the prevention of Plasmodium vivax relapse

Malaria Journal, 2013

Background: There are very few drugs that prevent the relapse of Plasmodium vivax malaria in man.... more Background: There are very few drugs that prevent the relapse of Plasmodium vivax malaria in man. Tinidazole is a 5-nitroimidazole approved in the USA for the treatment of indications including amoebiasis and giardiasis. In the non-human primate relapsing Plasmodium cynomolgi/macaque malaria model, tinidazole cured one of six macaques studied with an apparent mild delay to relapse in the other five of 14-28 days compared to 11-12 days in controls. One study has demonstrated activity against P. vivax in man. Presented here are the results of a pilot phase II, randomized, open-label study conducted along the Thai-Myanmar border designed to evaluate the efficacy of tinidazole to prevent relapse of P. vivax when administered with chloroquine. Methods: This study utilized a modified triangular test sequential analysis which allows repeated statistical evaluation during the course of enrolment while maintaining a specified power and type 1 error and minimizing recruitment of subjects. Enrolment was to be halted when a pre-specified success/failure ratio was surpassed. The study was designed to have a 5% type 1 error and 90% power to show whether tinidazole would produce a relapse rate of less than 20% or greater than 45% through Day 63 of weekly follow-up after initiation of treatment and initial parasite clearance with 3 days of an oral weight based dosing of chloroquine and five days of 2 grams/ day of tinidazole.

Research paper thumbnail of Closing the translation gap for justice requirements in international research

Abstract Bioethicists have long debated the content of sponsors and researchers' obligations of j... more Abstract Bioethicists have long debated the content of sponsors and researchers' obligations of justice in international clinical research. However, there has been little empirical investigation as to whether and how obligations of responsiveness, ancillary care, post-trial benefits and research capacity strengthening are upheld in low-and middle-income country settings. In this paper, the authors argue that research ethics guidelines need to be more informed by international research practice.

Research paper thumbnail of Community engagement on the Thai-Burmese border: rationale, experience and lessons learnt

International Health, 2010

Community engagement is increasingly promoted in developing countries, especially in internationa... more Community engagement is increasingly promoted in developing countries, especially in international health research, but there is little published experience. The Shoklo Malaria Research Unit (SMRU) conducts research with refugees, migrant workers, displaced people, and day migrants on the Thai-Burmese border, and has recently facilitated the set up of the Tak Province Border Community Ethics Advisory Board (T-CAB). Valuable lessons have been learnt from consultation with the T-CAB especially in the area of participant recruitment and the informed consent process. A lot of new research questions have emerged from consultation with the T-CAB. This paper describes our experience, lessons learnt and the unique challenges faced working with the T-CAB from its initial conception to date. We conclude that consultation with the T-CAB has made improvements in our research in particular operational and ethical aspects of our studies.

Research paper thumbnail of Exploitation and community engagement: Can Community Advisory Boards successfully assume a role minimising exploitation in international research?

Developing World Bioethics, 2013

It has been suggested that community advisory boards (CABs) can play a role in minimising exploit... more It has been suggested that community advisory boards (CABs) can play a role in minimising exploitation in international research. To get a better idea of what this requires and whether it might be achievable, the paper first describes core elements that we suggest must be in place for a CAB to reduce the potential for exploitation. The paper then examines a CAB established by the Shoklo Malaria Research Unit under conditions common in resource-poor settings -namely, where individuals join with a very limited understanding of disease and medical research and where an existing organisational structure is not relied upon to serve as the CAB. Using the Tak Province Border Community Ethics Advisory Board (T-CAB) as a case study, we assess the extent to which it might be able to take on a role minimising exploitation were it to decide to do so. We investigate whether, after two years in operation, T-CAB is capable of assessing clinical trials for exploitative features and addressing those found to have them. The findings show that, although T-CAB members have gained knowledge and developed capacities that are foundational for one-day taking on a role to reduce exploitation, their ability to critically evaluate studies for the presence of exploitative elements has not yet been strongly demonstrated. In light of this example, we argue that CABs may not be able to perform such a role for a number of years after initial formation, making it an unsuitable responsibility for many short-term CABs. We recognise that a lack of responsiveness, appropriate standard of care, and post-trial benefits are not the only features associated with exploitative research and that consensus on the association of these features with exploitation may not be universal. 7 A.

Research paper thumbnail of Motivations and perceptions of community advisory boards in the ethics of medical research: the case of the Thai-Myanmar border

BMC Medical Ethics, 2014

Background: Community engagement is increasingly promoted as a marker of good, ethical practice i... more Background: Community engagement is increasingly promoted as a marker of good, ethical practice in the context of international collaborative research in low-income countries. There is, however, no widely agreed definition of community engagement or of approaches adopted. Justifications given for its use also vary. Community engagement is, for example, variously seen to be of value in: the development of more effective and appropriate consent processes; improved understanding of the aims and forms of research; higher recruitment rates; the identification of important ethical issues; the building of better relationships between the community and researchers; the obtaining of community permission to approach potential research participants; and, the provision of better health care. Despite these diverse and potentially competing claims made for the importance of community engagement, there is very little published evidence on effective models of engagement or their evaluation. Methods: In this paper, drawing upon interviews with the members of a Community Advisory Board on the Thai-Myanmar border, we describe and critically reflect upon an approach to community engagement which was developed in the context of international collaborative research in the border region.

Research paper thumbnail of Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription

Research paper thumbnail of Exploring the Contribution of Candidate Genes to Artemisinin Resistance in Plasmodium falciparum

Antimicrobial Agents and Chemotherapy, 2010

The reduced in vivo sensitivity of Plasmodium falciparum has recently been confirmed in western C... more The reduced in vivo sensitivity of Plasmodium falciparum has recently been confirmed in western Cambodia. Identifying molecular markers for artemisinin resistance is essential for monitoring the spread of the resistant phenotype and identifying the mechanisms of resistance. Four candidate genes, including the P. falciparum mdr1 (pfmdr1) gene, the P. falciparum ATPase6 (pfATPase6) gene, the 6-kb mitochondrial genome, and ubp-1, encoding a deubiquitinating enzyme, of artemisinin-resistant P. falciparum strains from western Cambodia were examined and compared to those of sensitive strains from northwestern Thailand, where the artemisinins are still very effective. The artemisinin-resistant phenotype did not correlate with pfmdr1 amplification or mutations (full-length sequencing), mutations in pfATPase6 (full-length sequencing) or the 6-kb mitochondrial genome (full-length sequencing), or ubp-1 mutations at positions 739 and 770. The P. falciparum CRT K76T mutation was present in all isolates from both study sites. The pfmdr1 copy numbers in western Cambodia were significantly lower in parasite samples obtained in 2007 than in those obtained in 2005, coinciding with a local change in drug policy replacing artesunate-mefloquine with dihydroartemisinin-piperaquine. Artemisinin resistance in western Cambodia is not linked to candidate genes, as was suggested by earlier studies.

Research paper thumbnail of Refugee and Migrant Women's Views of Antenatal Ultrasound on the Thai Burmese Border: A Mixed Methods Study

PLoS ONE, 2012

Background: Antenatal ultrasound suits developing countries by virtue of its versatility, relativ... more Background: Antenatal ultrasound suits developing countries by virtue of its versatility, relatively low cost and safety, but little is known about women's or local provider's perspectives of this upcoming technology in such settings. This study was undertaken to better understand how routine obstetric ultrasound is experienced in a displaced Burmese population and identify barriers to its acceptance by local patients and providers.