Skip to Main Content

RTI uses cookies to offer you the best experience online. By clicking “accept” on this website, you opt in and you agree to the use of cookies. If you would like to know more about how RTI uses cookies and how to manage them please view our Privacy Policy here. You can “opt out” or change your mind by visiting: http://optout.aboutads.info/. Click “accept” to agree.

Accept
RTI International
  • About
    • Office Locations
    • Executive Leadership
    • Corporate Governance
    • Partner with Us
      • U.S. Government
      • Clients and Funding Agencies
      • Industry and Commercial Clients
      • Foundations and Associations
      • Bilateral Agencies and Multilateral Banks
      • Universities and Academic Research Institutions
      • Suppliers and Small Businesses
    • Commitment to Quality
      • RTI's Client Listening Program
    • Ethics and Human Research Protection
    • Living Our Mission
    • Open Science Initiative
    • Veteran Opportunities at RTI

    About

  • Practice Areas
    • Health
      • Public Health and Well-Being
      • Health Care Transformation
      • Behavioral Health
      • Health Behavior Change
      • Precision Medicine
      • RTI Health Solutions (RTI-HS)
      • Health Equity
      • Community & Workplace Health
      • Public Health Economics
      • Child and Adolescent Research and Evaluation Program
      • RTI Health Advance
    • Transformative Research Unit for Equity​
      • Equity Capacity Building Hub
      • Social and Economic Justice Research Collaborative
      • Narrative Research and Community Engagement Lab
    • Education and Workforce Development
      • Early Childhood
      • K-12 Education
      • Postsecondary Education
      • Career and Adult Education and Workforce Development
      • Education Policy, Systems, and Governance
      • Education Research Methodologies
      • Education Technologies
      • International Education
    • International Development
      • Climate Change
      • Energy for Development
      • Environment
      • Global Food Security, Agriculture, and Nutrition
      • Global Health
      • International Education
      • Monitoring, Evaluation, Research, Learning, and Adapting (MERLA)
      • Youth and Economic Opportunity
      • Water, Sanitation, and Hygiene (WASH)
      • RTI Center for Global Noncommunicable Diseases
      • RTI Center for Governance
      • RTI Center for Thriving Children
    • Climate Change
      • Clean Energy Technology and Renewables
      • Climate Finance
      • Climate Justice and Equity
      • Climate Planning, Preparedness and Resilience
      • Climate Policy
      • Climate Vulnerability, Adaptation, and Mitigation
      • Economic Impacts of Climate Change
    • Water
      • Food-Energy-Water Nexus
      • Water Quality
      • WASH (Water, Sanitation, Hygiene)
      • Water Resources Management
    • Energy Research
      • Carbon Capture and Utilization
      • Biomass Conversion
      • Natural Gas
      • Energy Efficiency
      • Industrial Water
      • Syngas Processing
    • Environmental Sciences
      • Air Quality
      • RTI Center for Water Resources
      • Urban Sustainability
      • Toxics
      • Building Resiliency in the FEW Nexus
      • Climate Change Sciences and Analysis
      • Environmental Policy
      • Environmental Justice
      • Sustainable Materials & Waste Management Solutions
    • Justice Research and Policy
      • RTI Center for Community Safety and Crime Prevention
      • RTI Center for Policing Research and Investigative Science
      • Child Well-Being and Family Strengthening
      • RTI Center for Forensic Sciences
      • Evidence-Based Strategies to Reduce Firearm Violence
    • Food Security and Agriculture
      • Food Security and Food Assistance
      • Nutrition, Physical Activity, & Obesity
      • Food Safety
      • Food Systems and Policy Analysis
      • Food Loss and Waste Research
      • Market Systems Strengthening
      • Global Food Security, Agriculture, and Nutrition
      • Climate-Smart Agriculture
      • Agricultural Innovation
    • Innovation Ecosystems
      • Innovation Advising
      • Innovation for Economic Growth
      • Innovation for Emerging and Developing Economies
      • Innovation for Organizations
      • Research, Technology, and Innovation Policy
      • Technology Acceleration
    • Military Support
      • Military Behavioral Health
      • Military Health and Human Performance
      • Military Sexual Assault, Harassment, and Domestic Violence Prevention
      • Wearable Sensor Technologies
      • Military Health System Transformation
      • North Carolina Center for Optimizing Military Performance

    Practice Areas

  • Services + Capabilities
    • Surveys and Data Collection
      • Survey Design
      • Instrument Development
      • Survey Methodologies
      • Data Collection
      • Establishment Surveys
      • Health Registries
      • Data Analysis and Reporting
      • Research Operations Center
    • Statistics and Data Science
      • Survey Statistics
      • Environmental Statistics
      • Coordinating Centers for Multisite Studies
      • Analysis and Design of Complex Data
      • Biostatistics
      • RTI Center for Data Science
    • Evaluation, Assessment and Analysis
      • Evaluation Design and Execution
      • Advanced Qualitative, Quantitative, and Mixed Methods
      • Evaluation, Monitoring, and Assessment
      • Economic Analysis
      • Evaluating Communication Interventions and Campaigns
      • Evidence Synthesis for Policy and Practice
      • Risk Assessment and Prediction
    • Program Design and Implementation
      • Systems Strengthening and Scaling
      • Capacity Assessment and Building
      • Policy Reform Support
      • Curriculum and Teacher Professional Development
      • Interventions and Prevention Programs
      • Implementation Science
    • Digital Solutions for Social Impact
      • Human-Centered Design of Digital Solutions
      • Digital Product Development
      • Digital Communication Campaigns
      • Digital Data Analytics
    • Research Technologies
      • Survey Technologies
      • Data Management and Decision Support Systems
      • Geospatial Science, Technology, and Visualization
      • ICT for Limited-Resource Settings
      • Mobile Applications
      • Web Applications
      • Bioinformatics
      • Interactive Computing
    • Drug Discovery and Development
      • Medicinal Chemistry
      • Molecular Design and Cheminformatics
      • Behavioral Pharmacology
      • Drug Metabolism and Pharmacokinetics (DMPK)
      • In Vitro Pharmacology, Bioassay Development, and High-Throughput Screening (HTS)
      • Isotope Labeling
      • Regulatory Consulting and Support for Medical Products
    • Analytical Laboratory Sciences
      • Bioanalytical and Toxicology Research
      • Forensic Sciences
      • Physicochemical Characterizations
      • Metabolomics
      • Proficiency Testing and Reference Materials
      • Microbiology
      • Analytical Chemistry and Pharmaceutics
    • Engineering & Technology R&D
      • Biomedical Technologies
      • Decarbonization Sciences
      • Environmental Exposure & Protection
      • Materials & Environment
      • Sustainable Energy Solutions

    Services + Capabilities

  • Impact
    • Newsroom
    • Insights Blog
    • Events
    • Publications
    • RTI Press
      • About the RTI Press
      • Instructions for Authors
      • RTI Press Collections
    • Projects
    • Global Reach
      • Asia
      • Eastern Europe and Central Asia
      • RTI International India
      • Africa
      • Middle East and North Africa (MENA)
      • Latin America and the Caribbean (LAC)

    Impact

  • Experts
    • Our Experts
    • In-Depth With Our Experts
    • Related News
    • Experts In the Media
    • RTI Fellow Program

    Experts

  • Emerging Issues
    • COVID-19 Research
    • Artificial Intelligence
    • Global Health Security
    • Cannabis Research
    • Opioid Research
      • Interventions for Opioid Use Disorders
      • Preventing Opioid Misuse and Overdose
      • Treating Opioid Use Disorders
    • Policing Research and Investigative Science
    • Drone Research and Application
    • E-cigarette Research
    • Zika Virus Research
    • Integrated Governance

    Emerging Issues

  • Global Reach
  • Insights Blog
  • Newsroom
  • RTI Press
  • Publications
  • Partner With Us
  • Careers
  • Facebook IconTwitter IconInstagram IconYouTube IconLinkedin Icon
  • Home
  • Impact
  • Publications
  • Emerging implications of policies on malaria treatment

Emerging implications of policies on malaria treatment

Genetic changes in the Pfmdr-1 gene affecting susceptibility to artemether-lumefantrine and artesunate-amodiaquine in Africa

Okell, L. C., Reiter, L. M., Ebbe, L. S., Baraka, V., Bisanzio, D., Watson, O. J., Bennett, A., Verity, R., Gething, P., Roper, C., & Alifrangis, M. (2018). Emerging implications of policies on malaria treatment: Genetic changes in the Pfmdr-1 gene affecting susceptibility to artemether-lumefantrine and artesunate-amodiaquine in Africa. BMJ Global Health, 3(5), e000999. [000999]. https://doi.org/10.1136/bmjgh-2018-000999

Copy citation

Abstract

Artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ) are the most commonly used artemisinin-based combination therapies (ACT) for treatment of Plasmodium falciparum in Africa. Both treatments remain efficacious, but single nucleotide polymorphisms (SNPs) in the Plasmodium falciparum multidrug resistance 1 (Pfmdr1) gene may compromise sensitivity. AL and AS-AQ exert opposing selective pressures: parasites with genotype 86Y, Y184 and 1246Y are partially resistant to AS-AQ treatment, while N86, 184 F and D1246 are favoured by AL treatment. Through a systematic review, we identified 397 surveys measuring the prevalence of Pfmdr1 polymorphisms at positions 86 184 or 1246 in 30 countries in Africa. Temporal trends in SNP frequencies after introduction of AL or AS-AQ as first-line treatment were analysed in 32 locations, and selection coefficients estimated. We examined associations between antimalarial policies, consumption, transmission intensity and rate of SNP selection. 1246Y frequency decreased on average more rapidly in locations where national policy recommended AL (median selection coefficient(s) of -0.083), compared with policies of AS-AQ or both AL and AS-AQ (median s=-0.035 and 0.021, p<0.001 respectively). 86Y frequency declined markedly after ACT policy introduction, with a borderline significant trend for a more rapid decline in countries with AL policies (p=0.055). However, these trends could also be explained by a difference in initial SNP frequencies at the time of ACT introduction. There were non-significant trends for faster selection of N86 and D1246 in areas with higher AL consumption and no trend with transmission intensity. Recorded consumption of AS-AQ was low in the locations and times Pfmdr1 data were collected. SNP trends in countries with AL policies suggest a broad increase in sensitivity of parasites to AS-AQ, by 7-10 years after AL introduction. Observed rates of selection have implications for planning strategies to cycle drugs or use multiple first-line therapies to maintain drug efficacy.

Share
  • Share on Facebook
  • Share on Twitter
  • Share on Linkedin
  • Email

Publications Info

To contact an RTI author, request a report, or for additional information about publications by our experts, send us your request.

  • +1 919 541 8787
  • publications@rti.org

Meet the Experts

View All Experts
Donal Bisanzio

Donal Bisanzio

Recent Publications

Article

Multifaceted risk for non-suicidal self-injury only versus suicide attempt in a population-based cohort of adults

Article

Long-term effects of a diet supplement containing Cannabis sativa oil and Boswellia serrata in dogs with osteoarthritis following physiotherapy treatments

Article

Epigenetic biomarkers for smoking cessation

Article

A pilot PT scheme for external assessment of laboratory performance in testing synthetic opioid compounds in urine, plasma, and whole blood

65 Years
Partner With Us
  • US Government
  • Commercial
  • Foundations & Associations
  • Multilateral Donors
  • Universities
  • Suppliers
Site
  • Privacy Policy
  • Security Policy
  • Site Map
  • Terms of Use
  • Accessibility
  • Contact Us
Contact Us
Facebook Icon Twitter Icon Instagram Icon YouTube Icon Linkedin Icon
delivering the promise of science
for global good
RTI International Logo
RTI Health Solutions RTI Innovation Advisors RTI Health Advance

© 2023 RTI International. RTI International is a trade name of Research Triangle Institute. RTI and the RTI logo are U.S. registered trademarks of Research Triangle Institute.