Analyses of cytochrome b mutations in Plasmodium falciparum isolates in Thai-Myanmar border.
BACKGROUND
The combination of atovaquone and proguanil (Malarone) has been established as a drug of choice to prevent and treat multi-drug resistant Plasmodium (P.) falciparum malaria in travelers. However, several cases of resistance against Malarone have been reported in some parts of Africa, and many of the cases are believed to be associated with mutations at the codon 268 of cytochrome b gene in mitochondria of P. falciparum. The aim of the study was to estimate the effectiveness of Malarone in treatment and prophylaxis for the travelers to Thai-Myanmar border where multi-drug resistant malaria is highly endemic.


METHODS
Seventy P. falciparum samples obtained from patients from Thai-Myanmar border were sequenced to detect mutations around the codon 268. The same samples were also sequenced to detect P. falciparum chloroquine resistance transporter mutation (PfCRT K76T).


RESULTS
All the 70 samples showed no mutations at the codon 268 of cytochrome b gene. Whereas, 50 samples, whose pfcrt genes were sequenced successfully, had an identical genotype for K76T mutation.


CONCLUSIONS
In Asian countries, even in the multi-drug resistant areas in the great Mekong region, no case of Malarone resistance has been reported clinically or genetically thus far. In this study, all the P. falciparum parasites tested successfully were shown to be chloroquine resistant but atovaquone susceptible genetically. The more the usefulness of Malarone increases for both treatment and prophylaxis, the wider the drug-resistance against Malarone may spread in the region. Although the total number of samples examined is not large, it is concluded from these findings that Malarone should be recommended for prophylaxis of malaria for travelers to the Mekong region.
Naoshima-Ishibashi
Yasuko
Y
Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku, Tokyo 162-8665, Japan.
Iwagami
Moritoshi
M
Kawazu
Shin-Ichiro
S
Looareesuwan
Sornchai
S
Kano
Shigeyuki
S
D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use; D053626:Atovaquone / Q000627:therapeutic use; D045303:Cytochromes b / Q000235:genetics*; D017931:DNA Primers; D016054:DNA, Protozoan / Q000032:analysis; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics*; D004359:Drug Therapy, Combination; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology*; D009154:Mutation; D010963:Plasmodium falciparum / Q000235:genetics*; D016133:Polymerase Chain Reaction; D002727:Proguanil / Q000627:therapeutic use; D013785:Thailand; D014195:Travel
D000962:Antimalarials; D017931:DNA Primers; D016054:DNA, Protozoan; D004338:Drug Combinations; C109496:atovaquone, proguanil drug combination; D045303:Cytochromes b; D002727:Proguanil; D053626:Atovaquone