Molecular Surveyor updated to include 418 publications

WWARN’s Molecular Surveyors are interactive mapping tools that summarise the location and prevalence of the molecular markers associated with resistance to particular drugs throughout the world. This tool allows researchers and policy makers to visualise these data by providing a map presentation of the prevalence of molecular markers of resistance in the malaria parasites. Changes over time in the prevalence can act as an early warning of reduced susceptibility of those parasites to a particular antimalarial.

Mutations on the pfmdr1 and pfcrt genes in the genome of the P. falciparum malaria parasite act as indicators of reduced parasite susceptibility to the former frontline antimalarial treatment, chloroquine, and artemisinin partner drugs: lumefantrine, mefloquine and amodiaquine.

With the emergence of artemisinin drug resistance across many parts of Southeast Asia, this Surveyor tool is becoming increasingly important to observe trends and changes in the prevalence of the pfmdr1 and pfcrt molecular markers known to be associated with reduced antimalarial susceptibility across regions where malaria is endemic.

“As the efficacy of artemisinin derivatives is decreasing in many parts of Southeast Asia, it is essential that we monitor any changes in efficacy of the partner drugs,” says Prof Carol Sibley, WWARN’s Scientific Director. “Researchers and policy makers can use this tool to select further locations for strategically placed molecular studies and identify the optimal ACT partner drug in each location. ”

These latest updates include two prominent studies from Myanmar, where previously, little information was available on these molecular markers. The new studies provide insight in to the resistance pattern in Myanmar. A low prevalence of the pfmdr1 mutation was observed in Myanmar, which indicates that the drugs mefloquine and lumefantrine, when partnered with an artemisinin derivative, should be effective across the country.

Surprisingly the latest data on pfcrt 76T – a mutation associated with chloroquine resistance – showed that the mutation was absent from a site in northern Myanmar. This result suggests that the P. falciparum malaria parasite in the region could once again be susceptible to chloroquine, the former first line antimalarial treatment heavily affected by drug resistance. (See Related studies below for publication details)

“For certain countries, we know little about the efficacy of malaria drugs or about the prevalence of markers of antimalarial resistance. It is extremely useful to have an easy point of access to the molecular information that is being generated on these complicated molecular markers and see where the gaps in information lie,’ adds Prof Mallika Imwong from Mahidol University, Bangkok.  

Previous research from the WWARN AS-AQ/AL Molecular Marker Study Group showed that the artemisinin combination therapies, artesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AL), exerted opposing selective effects on mutations in pfcrt and pfmdr1 genes. From these results, the group recommended that prevalence of these molecular markers should be determined routinely to track any changes in their prevalence, as an indicator of changes in efficacy of the lumefantrine and amodiaquine partners of the artemisinin combination therapies.

The Molecular Surveyor pfmdr1 & pfcrt builds on this study to both easily track the prevalence of these markers across time and location, as well as highlight regions where little information on these markers has been gathered.

Two other Molecular Surveyors display resistance markers for sulphadoxine pyrimethamine found on genes, dhfr and dhps, and the prominent K13 resistance markers associated with artemisinin drug resistance in many parts of Southeast Asia.

Did you know? Access to the code that powers some of our interactive mapping tools - such as the WWARN Molecular Surveyor, Antimalarial Quality Surveyor and the WWARN Explorer  is now open source. Please email our Informatics Team for more information on how to access this open source code: informatics@wwarn.org

Related studies:

• Venkatesan M, et al. Polymorphisms in Plasmodium falciparum Chloroquine Resistance Transporter and Multidrug Resistance 1 Genes: Parasite Risk Factors that Affect Treatment Outcomes for P. falciparum Malaria after Artemether Lumefantrine and Artesunate-Amodiaquine. American Journal of Tropical Medicine, 2014; 91(4): 833-43 Doi: 10.4269/ajtmh.14-0031  PMID: 25048375
• Win AA, et al. K13 mutations and pfmdr1 copy number variation in Plasmodium falciparum malaria in Myanmar. Malaria Journal. 2016 Feb 24;15(1):110. Doi: 10.1186/s12936-016-1147-3
• Lo E, et al. Examining Plasmodium falciparum and P. vivax clearance subsequent to antimalarial drug treatment in the Myanmar-China border area based on quantitative real-time polymerase chain reaction. BMC Infectious Diseases. 2016 Apr 16;16(1):154. Doi: 10.1186/s12879-016-1482-6. PMID: 27084511