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Plasmodium vivax infection
Image by Mae Melvin
Researchers say they have developed a human-chimeric mouse model that can advance the study of the malaria parasite Plasmodium vivax.
The model is engineered to grow human livers that can be infected with P vivax and used for investigations into parasite development, dormancy, and activation, as well as the effect certain drugs have on each aspect of the infection.
The researchers described this model in Cell Host & Microbe.
Stefan Kappe, PhD, of Seattle Biomedical Research Institute in Washington, and his colleagues noted that P vivax malaria parasites are more resistant to control and elimination than other malaria parasites because, after infection, they fall dormant within the liver for months to years.
When these dormant parasites eventually become activated, they replicate, infect the bloodstream, and cause relapsing malaria.
The lack of tractable P vivax animal models has made it difficult to examine P vivax liver-stage infection, but Dr Kappe and his colleagues found a solution in a model known as FRG KO huHep.
To create the FRG KO huHep model, the team transplanted human hepatocytes in the severely immunocompromised FRG KO mouse, which has deletions in fumarylacetoacetate hydrolase (FAH), recombinationactivating gene 2 (Rag2), and interleukin-2 receptor subunit gamma (Il2rg).
The researchers found that FRG KO huHep mice support P vivax sporozoite infection, liver-stage development, and the formation and persistence of dormant liver-stage parasites.
In addition, experiments with this model revealed that the antimalarial drug primaquine could prevent and eliminate liver-stage infection.
The researchers therefore concluded that P vivax-infected FRG KO huHep mice are a suitable model for studying liver-stage development and dormancy and may facilitate the discovery of drugs targeting relapsing malaria.
“This model is a real game-changer,” said Ivo Mueller, PhD, a malaria expert at the Walter and Eliza Hall Institute in Melbourne, Victoria, Australia, who was not involved in this research.
“For the first time, we now have a realistic opportunity that not only allows us to directly study this normally hidden P vivax life-stage, but also to test new drugs and vaccines. This new model is an essential resource in our quest to develop the new anti-vivax interventions that we will need to eliminate P vivax malaria.” 
Plasmodium vivax infection
Image by Mae Melvin
Researchers say they have developed a human-chimeric mouse model that can advance the study of the malaria parasite Plasmodium vivax.
The model is engineered to grow human livers that can be infected with P vivax and used for investigations into parasite development, dormancy, and activation, as well as the effect certain drugs have on each aspect of the infection.
The researchers described this model in Cell Host & Microbe.
Stefan Kappe, PhD, of Seattle Biomedical Research Institute in Washington, and his colleagues noted that P vivax malaria parasites are more resistant to control and elimination than other malaria parasites because, after infection, they fall dormant within the liver for months to years.
When these dormant parasites eventually become activated, they replicate, infect the bloodstream, and cause relapsing malaria.
The lack of tractable P vivax animal models has made it difficult to examine P vivax liver-stage infection, but Dr Kappe and his colleagues found a solution in a model known as FRG KO huHep.
To create the FRG KO huHep model, the team transplanted human hepatocytes in the severely immunocompromised FRG KO mouse, which has deletions in fumarylacetoacetate hydrolase (FAH), recombinationactivating gene 2 (Rag2), and interleukin-2 receptor subunit gamma (Il2rg).
The researchers found that FRG KO huHep mice support P vivax sporozoite infection, liver-stage development, and the formation and persistence of dormant liver-stage parasites.
In addition, experiments with this model revealed that the antimalarial drug primaquine could prevent and eliminate liver-stage infection.
The researchers therefore concluded that P vivax-infected FRG KO huHep mice are a suitable model for studying liver-stage development and dormancy and may facilitate the discovery of drugs targeting relapsing malaria.
“This model is a real game-changer,” said Ivo Mueller, PhD, a malaria expert at the Walter and Eliza Hall Institute in Melbourne, Victoria, Australia, who was not involved in this research.
“For the first time, we now have a realistic opportunity that not only allows us to directly study this normally hidden P vivax life-stage, but also to test new drugs and vaccines. This new model is an essential resource in our quest to develop the new anti-vivax interventions that we will need to eliminate P vivax malaria.”
Plasmodium vivax infection
Image by Mae Melvin
Researchers say they have developed a human-chimeric mouse model that can advance the study of the malaria parasite Plasmodium vivax.
The model is engineered to grow human livers that can be infected with P vivax and used for investigations into parasite development, dormancy, and activation, as well as the effect certain drugs have on each aspect of the infection.
The researchers described this model in Cell Host & Microbe.
Stefan Kappe, PhD, of Seattle Biomedical Research Institute in Washington, and his colleagues noted that P vivax malaria parasites are more resistant to control and elimination than other malaria parasites because, after infection, they fall dormant within the liver for months to years.
When these dormant parasites eventually become activated, they replicate, infect the bloodstream, and cause relapsing malaria.
The lack of tractable P vivax animal models has made it difficult to examine P vivax liver-stage infection, but Dr Kappe and his colleagues found a solution in a model known as FRG KO huHep.
To create the FRG KO huHep model, the team transplanted human hepatocytes in the severely immunocompromised FRG KO mouse, which has deletions in fumarylacetoacetate hydrolase (FAH), recombinationactivating gene 2 (Rag2), and interleukin-2 receptor subunit gamma (Il2rg).
The researchers found that FRG KO huHep mice support P vivax sporozoite infection, liver-stage development, and the formation and persistence of dormant liver-stage parasites.
In addition, experiments with this model revealed that the antimalarial drug primaquine could prevent and eliminate liver-stage infection.
The researchers therefore concluded that P vivax-infected FRG KO huHep mice are a suitable model for studying liver-stage development and dormancy and may facilitate the discovery of drugs targeting relapsing malaria.
“This model is a real game-changer,” said Ivo Mueller, PhD, a malaria expert at the Walter and Eliza Hall Institute in Melbourne, Victoria, Australia, who was not involved in this research.
“For the first time, we now have a realistic opportunity that not only allows us to directly study this normally hidden P vivax life-stage, but also to test new drugs and vaccines. This new model is an essential resource in our quest to develop the new anti-vivax interventions that we will need to eliminate P vivax malaria.”