Molecular Surveillance of Artemisinin Resistance Malaria in Myanmar

A Multi-site Cohort Observational Study for Molecular Assessment of Artemisinin Resistance Falciparum Malaria in Myanmar

Efficacy and safety of the artemisinin combination therapy (ACT) in uncomplicated falciparum malaria patients in Myanmar and artemisinin molecular markers analysis

Study Overview

• Status: Completed
• Conditions: Plasmodium Falciparum Malaria; Drug Resistance
• Intervention / Treatment: Drug: First line antimalarial in Myanmar (artemether-lumefrantrine, dihydroartemisinin-piperaquine, and artesunate-mefloquine)

Detailed Description

The investigators assessed the efficacy and safety of the ACT in uncomplicated falciparum malaria in different sentinel sites in Myanmar. The recruited patients were follow-up until day 28 or day-42 based on the ACTs. Day-0 samples were analysed for artemisinin molecular markers, (K13 kelch propeller, Pfmdr2, Pffd and Pfarps10).

• Study Type: Observational
• Enrollment (Actual): 550

Contacts and Locations

Study Locations

• Myanmar
  • Yangon, Myanmar, 11191
    • Dr. Myat Phone Kyaw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Study populations were selected purposely based on the previous evidence of the drug resistance in Myanmar

Description

Inclusion Criteria:

• Plasmodium falciparum mono infection by microscopy
• Presence of axillary equal to or more than 37.5 degrees centigrade or history of fever during the past 24 hours
• Ability to swallow oral medication
• Ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule
• Informed consent from the patient or from a parent or guardian in the case of children

Exclusion Criteria:

• Presence of signs of severe falciparum malaria according to the definitions of World Health Organisation (WHO)
• Mixed or mono-infection with another Plasmodium species detected by microscopy
• Presence of severe malnutrition (defined as a child whose growth standard is below 3 z-score, has symmetrical oedema involving at least the feet or has a mid-upper arm circumference below 110 mm)
• Presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, Human Immune Deficiency Virus (HIV)/Acquired Immune Deficiency Syndrom (AIDS)
• Regular medication, which may interfere with antimalarial pharmacokinetics
• History of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s)
• A positive pregnancy test or breastfeeding
• Unable to or unwilling to take a pregnancy test or contraceptives

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Kawthaung Site; The efficacy and safety of the ACT in different sentinel sites will be assessed. The administrated anti-malarial were same and all will be administrated under direct observation. The dosage will be calculated by weight of the patients. Kawthaung is one of the sentinel site and located at the Southern Myanmar.	Drug: First line antimalarial in Myanmar (artemether-lumefrantrine, dihydroartemisinin-piperaquine, and artesunate-mefloquine); Being a observational cohort study, one of the ACT was selected in each study site to assess the efficacy and safety.
Myawaddy Site; The efficacy and safety of the ACT in different sentinel sites will be assessed. The administrated anti-malarial were same and all will be administrated under direct observation. The dosage will be calculated by weight of the patients. Myawaddy is one of the sentinel site and located at the northern part of the Southern Myanmar.	Drug: First line antimalarial in Myanmar (artemether-lumefrantrine, dihydroartemisinin-piperaquine, and artesunate-mefloquine); Being a observational cohort study, one of the ACT was selected in each study site to assess the efficacy and safety.
Thanbyuzayat Site; The efficacy and safety of the ACT in different sentinel sites will be assessed. The administrated anti-malarial were same and all will be administrated under direct observation. The dosage will be calculated by weight of the patients. Thanbyuzayat is one of the sentinel site and located at the northern part of the Southern Myanmar.	Drug: First line antimalarial in Myanmar (artemether-lumefrantrine, dihydroartemisinin-piperaquine, and artesunate-mefloquine); Being a observational cohort study, one of the ACT was selected in each study site to assess the efficacy and safety.
Shwegyin Site; The efficacy and safety of the ACT in different sentinel sites will be assessed. The administrated anti-malarial were same and all will be administrated under direct observation. The dosage will be calculated by weight of the patients. Shwegyin is one of the sentinel site and located at the southern part of the central Myanmar.	Drug: First line antimalarial in Myanmar (artemether-lumefrantrine, dihydroartemisinin-piperaquine, and artesunate-mefloquine); Being a observational cohort study, one of the ACT was selected in each study site to assess the efficacy and safety.
Magway Site; The efficacy and safety of the ACT in different sentinel sites will be assessed. The administrated anti-malarial were same and all will be administrated under direct observation. The dosage will be calculated by weight of the patients. Magway is one of the sentinel site and located at the middle part of the central Myanmar.	Drug: First line antimalarial in Myanmar (artemether-lumefrantrine, dihydroartemisinin-piperaquine, and artesunate-mefloquine); Being a observational cohort study, one of the ACT was selected in each study site to assess the efficacy and safety.
Rakhine Site; The efficacy and safety of the ACT in different sentinel sites will be assessed. The administrated anti-malarial were same and all will be administrated under direct observation. The dosage will be calculated by weight of the patients. Rakhine is one of the sentinel site and located at the western Myanmar.	Drug: First line antimalarial in Myanmar (artemether-lumefrantrine, dihydroartemisinin-piperaquine, and artesunate-mefloquine); Being a observational cohort study, one of the ACT was selected in each study site to assess the efficacy and safety.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of adequate clinical and parasitological response (ACPR)	For artesunate-mefloquine or dihydroartemisinin-piperaquine, 42 days follow-ups and for artemether-lumefrantrine combinations, 28 days followe-ups	day 28 or day 42 after initial dose of ACT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of the day-3 parasite positivity after ACT by microscopy	72 hr after ACT is one of the indicator for delayed clearance of parasitaemia in falciparum malaria	3rd day after initial dose of ACT
Treatment failure rate	Early Treatment Failure (ETF), Late Clinical Failure (LCF), Late Parasitological Failure (LPF) based on the WHO standard protocol and definitions	anytime within observation period (28/42 days after treatment with one of ACTs)
Mutant rate	Day-0 samples were used to amplify the artemisinin resistance molecular markers to know the mutant rate in each study sites	Day-0 samples

Collaborators and Investigators

• Sponsor: Department of Medical Research, Lower Myanmar
• Collaborators: Kangwon National University

Publications and helpful links

General Publications

• Nyunt MH, Soe MT, Myint HW, Oo HW, Aye MM, Han SS, Zaw NN, Cho C, Aung PZ, Kyaw KT, Aye TT, San NA, Ortega L, Thimasarn K, Bustos MDG, Galit S, Hoque MR, Ringwald P, Han ET, Kyaw MP. Clinical and molecular surveillance of artemisinin resistant falciparum malaria in Myanmar (2009-2013). Malar J. 2017 Aug 14;16(1):333. doi: 10.1186/s12936-017-1983-9.

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: May 31, 2016
• First Submitted That Met QC Criteria: June 7, 2016
• First Posted (Estimate): June 8, 2016

Study Record Updates

• Last Update Posted (Estimate): June 8, 2016
• Last Update Submitted That Met QC Criteria: June 7, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Falciparum; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Antiprotozoal Agents; Antiparasitic Agents; Anthelmintics; Schistosomicides; Antiplatyhelmintic Agents; Artemether; Artesunate; Piperaquine; Artenimol; Antimalarials; Mefloquine
• Other Study ID Numbers: KMRL_2016_02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: We may share the data on request after publication.