Genetic control of malaria parasite transmission: threshold levels for infection in an avian model system.
Genetic strategies for controlling malaria transmission based on engineering pathogen resistance in Anopheles mosquitoes are being tested in a number of animal models. A key component is the effector molecule and the efficiency with which it reduces parasite transmission. Single-chain antibodies (scFvs) that bind the circumsporozoite protein of the avian parasite, Plasmodium gallinaceum, can reduce mean intensities of sporozoite infection of salivary glands by two to four orders of magnitude in transgenic Aedes aegypti. Significantly, mosquitoes with as few as 20 sporozoites in their salivary glands are infectious for a vertebrate host, Gallus gallus. Although scFvs hold promise as effector molecules, they will have to reduce mean intensities of infection to zero to prevent parasite transmission and disease. We conclude that similar endpoints must be reached with human pathogens if we are to expect an effect on disease transmission.
Jasinskiene
Nijole
N
Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697-3900, USA.
Coleman
Judy
J
Ashikyan
Aurora
A
Salampessy
Michael
M
Marinotti
Osvaldo
O
James
Anthony A
AA
D000330:Aedes / Q000235:genetics* / Q000469:parasitology*; D000818:Animals; D002645:Chickens; D004195:Disease Models, Animal; D005260:Female; D007303:Insect Vectors / Q000235:genetics* / Q000469:parasitology*; D008289:Malaria, Avian / Q000469:parasitology / Q000517:prevention & control / Q000635:transmission*; D008297:Male; D030781:Organisms, Genetically Modified / Q000469:parasitology; D010964:Plasmodium gallinaceum / Q000254:growth & development*; D011201:Poultry Diseases / Q000469:parasitology* / Q000635:transmission; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D016053:RNA, Protozoan / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012469:Salivary Glands / Q000469:parasitology
D015800:Protozoan Proteins; D016053:RNA, Protozoan; C041595:circumsporozoite protein, Protozoan