Genetic studies of malaria parasites, especially in relation to drug resistance

• Main Author: Rosario, Virgilio
• Published: University of Edinburgh 1976
• Subjects: 616.9883
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.661373

1. A chloroquine-resistant parasite line of Plasmodium chabaudi was obtained by submitting a sensitive line to a continuous and gradually increasing level of drug pressure. The line 411AS survived treatment of 3 mg/kg given for 6 days which eliminates the original drug sensitive line. 2. Cyclical transmission of 411AS as well as stability studies carried out showed that resistance was stable and transmissable through mosquitoes in the absence of drug pressure. 3. The genetic basis of chloroquine resistance was studied by making a cross between 411AS and a sensitive line of different origin, 96AJ, which differed additionally in 3 characters. Seventy clones from this cross were classified. Various recombinant classes were obtained and the results showed that chloroquine resistance in P. chabaudi is a stable character which undergoes genetic recombination with other markers. 4. Another line, 524AJ, resistant to 3 mg of chloroquine/kg administered for 6 days, was obtained by similar low drug pressure method. 5. Cyclical transmission of 524AJ and from clones established from this population showed that this line exhibited two types of resistance: (a) a stable, heritable form detectable after mosquito transmission, and (b) an unstable form which could not be detected after mosquito transmission. 6. Competition studies between chloroquine-resistant and chloroquine-sensitive parasites were made by mixing different proportions of blood forms in mice and by establishing and testing clones at different stages of the infection. Sporozoites from mosquitoes which fed on each mixture were also used to establish new infections in mice and clones were established and tested in a similar way. All the experiments showed an apparent selective advantage of the resistant over the sensitive forms in the absence of chloroquine pressure. 7. A discussion of the selection experiments, crossing experiments and competition studies is included and further research suggested by this work is considered.