Plasmodium falciparum Resistance to Sulfadoxine in Cambodia (Scientist)

Plasmodium falciparum is the agent that causes malaria in humans, the pathogen is well distributed in developing countries and has a high mortality rate.  In Africa alone there are hundreds of strains of falciparum malaria making it impossible to sequence the genome.  Malaria is a medical, social and economic burden in endemic population, over the years more drug resistant malaria have been reported¹. 

Chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) are the least expensive and widely available antimalarial drugs.  The synergetic effects between SP and antifolate is used to treat CQ resistant or uncomplicated falciparum malaria.  Sulfadoxine works by inhibiting the enzyme dihydropteroate synthase (dhps) of the folate biosynthesis pathway².  Mutations in Plasmodium falciparum crt, dhfr and dhps genes have lead to resistance in CQ and SP antimalarial drugs². 

In Sumiti Vinayak investigation, they study the origins of dhps alleles resistant in Cambodia.  Blood was collected from five sites in Cambodia, DNA was extracted using QIAmp Mini kit, and a total of 234 P. falciparum were isolated and amplified.  The dhps genotypes were analyzed for eight neutral microsatellite loci on chromosome 2, ten microsatellite loci of the dhps gene were found.  Microsatellites were used to determine genetic differentiation and origin of the dhps alleles.  In Cambodia, ancestral wild type dhps alleles SAKAA were present in 11% of the isolated DNA, wild type dhps is resistant to sulfadoxine.  Mutants of dhps were as followed: single mutant were at 10%, double mutant at 7.5%.  and triple mutants at 51%.  It is believed that from the ancestral wild type the single mutant evolved followed by the double and then the triple mutant. 

Sulfadoxine resistant falciparum malaria has evolved because of sulfadoxine-pyrimethamine pressure.  Countries that use sulfadoxine-pyrimethamine as antimalarial drug will experience an increase in malaria resistance to SP.  It is also likely that cross resistance to related drugs like cotrimoxazole (trimethoprim plus sulfamethoxazole), may have a role in selection of this allele³.  With more strains of Plasmodium falciparum resistance antimalarial drug, the task to control and treat malaria is becoming impossible, there for new methods or treatment must be created to treat or cure malaria.

            Genetic techniques are a useful tool to detect mutations in pathogenic organisms that can lead to resistance in drug treatment.  Although no new treatment was proposed for Sulfadoxine resistant falciparum malaria, genetic sequencing can provide information on developing specific drug treatments for these resistant strains.

References:

1.       CDC. Malaria.  Retrieved from: http://www.cdc.gov/malaria/about/disease.html

2.       Global report on antimalarial efficacy and drug resistance: 2000-2010.  2010.  World Health Organization.  WHO Press.

3.       Sumiti Vinayak and et al.  Origin and Evolution of Sulfadoxine Resistant Plasmodium falciparum.  2010.  PLoS Pathogens.  6(3)