Efficacy of Focal Primaquine Mass Administration for Eliminating Plasmodium Vivax Malaria in Northern Myanmar

G6PD Deficiency Prevalence and Targeted Elimination of Residual Plasmodium Vivax Hypnozoites in Community: Township Level Implementation in Banmauk and Moe Mauk, Myanmar

Plasmodium vivax has become the predominant species in the Greater Mekong Subregion and is a major challenge for regional malaria elimination. Mass primaquine administration has played a decisive role in malaria elimination in many temperate zone countries, but its efficacy in tropical areas remains to be evaluated. This study aims to assess the efficacy of targeted primaquine mass treatment (TPT) for eliminating P. vivax malaria in northern Myanmar.

Study Overview

• Status: Active, not recruiting
• Conditions: Malaria; Plasmodium Vivax; Myanmar; Mass Drug Administration; Primaquine
• Intervention / Treatment: Drug: Focal Mass Drug Administration with Primaquine

Detailed Description

This study employed a cluster-randomized crossover design in which two groups of villages received TPT at different times. In August-September 2019, Group 1 received TPT (0.25 mg/kg/day primaquine base for 14 days), while Group 2 was the control. In June-July 2020, Group 2 received TPT, while Group 1 served as the control. To evaluate the effectiveness of TPT for preventing relapses of vivax malaria, two indicators were utilized: infection prevalence at 3-month intervals estimated through cross-sectional surveys and monthly malaria incidence by passive case detection. The data were analyzed using descriptive statistics, chi-squared test, cumulative hazard function, and mixed model logistic regression.

• Study Type: Interventional
• Enrollment (Actual): 1208
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Myanmar
  • Yangon, Myanmar, 11091
    • Myanmar Health Network Organization

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Residents in study villages
• Male/ female
• Consent to participate

Exclusion Criteria:

• Low Hb%
• G6PD deficiency
• pregnant women,
• breastfeeding mothers and
• children under 7 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TPT Group; Based on the WHO malaria treatment guidelines, a standard PQ regimen of 0.25 mg PQ base/kg body weight daily for 14 days was administered to eligible individuals through directly observed treatment (DOT) to ensure drug intake and monitor potential adverse effects during August-September 2019. The safety of each participant was monitored by follow-up blood testing using Hemocue's hemoglobin photometers to track changes in hemoglobin levels.	Drug: Focal Mass Drug Administration with Primaquine; A population census was conducted in each village in August 2019 to record the demographic information and malaria histories of the villagers. Vulnerable groups such as pregnant women, breastfeeding mothers, and children under 7 years were excluded from PQ administration. Both Group 1 &2 underwent a preliminary clinical assessment to exclude individuals with G6PD deficiency and low hemoglobin levels. Based on the WHO malaria treatment guidelines, a standard PQ regimen of 0.25 mg PQ base/kg body weight daily for 14 days was administered through directly observed treatment (DOT) to ensure drug intake and monitor potential adverse effects. The safety of each participant was monitored by follow-up blood testing using Hemocue's hemoglobin photometers to track changes in hemoglobin levels. As per cross-over design, eligible individulas from Group-1 received PQ-MDA in year 1 and Group-2 received PR-MDA in the following year.; Other Names: Focal MDA with PQ
No Intervention: Non-TPT; To mitigate potential season effects, we included a crossover design to switch the two groups after nine months, when Group 2 (non-TPT) received focal PQ MDA in June-July 2020, while Group 1 served as control during this period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infection prevalence at 3-month intervals estimated through cross-sectional surveys	The primary outcome of the study was the reduction in the prevalence of infection in the study population in 3 and 6 months after the PQ MDA. Malaria prevalence was determined through cross-sectional surveys (CSSs) of the village populations one week before MDA to assess baseline infection prevalence and three and six months after the MDA. For each CSS, finger-prick blood was obtained from each participant to prepare two dried filter-paper blood spots (DBSs). DNA was extracted from the DBSs, and Plasmodium DNA was detected by nested PCR using species-specific primers. Per recommendations from the National Malaria Treatment Guidelines and because molecular detection was performed after the completion of the field studies, PCR-positive asymptomatic infections were not treated. Therefore, to determine malaria prevalence, six cross-sectional surveys were conducted, collecting blood samples from both groups at 3-month intervals between each round.	upto 24 months
Monthly malaria incidence by passive case detection	The another outcome of the study was the incidence of clinical malaria within 6 months of PQ MDA. Clinical malaria cases were diagnosed using an RDT (SD BIOLINETM Malaria Ag P.f/P.v test) and recorded at either the villages by the Integrated Community Malaria Volunteers or the township hospital.	upto 24 months

Collaborators and Investigators

• Sponsor: Pyae Linn Aung
• Collaborators: University of South Florida; Mahidol University
• Investigators: Principal Investigator: Myat Phone Kyaw, PhD, Myanmar Health Network Organization

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Actual): March 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: April 24, 2024
• First Submitted That Met QC Criteria: April 26, 2024
• First Posted (Actual): April 30, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 26, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Mosquito-Borne Diseases; Malaria; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Primaquine
• Other Study ID Numbers: MHNO-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No