South American monkeys in the development and testing of malarial vaccines - a review

Collins, William E.

doi:10.1590/s0074-02761992000700068

Cited by 28 publications

(19 citation statements)

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“…vivax readily infects a number of other primates including chimpanzee, gibbon, owl monkey, squirrel monkey, spider monkey, some tamarins, and white-faced monkey (51). The owl and squirrel monkeys have emerged as the favored model by virtue of availability and ease of care and infection (54). Infections by chloroquine-sensitive strains of P. vivax have been treated using these models, including the Chesson, Palo Alto, and Achiote strains (58,186,194).…”

Section: Diagnosismentioning

confidence: 99%

Resistance to Therapies for Infection by Plasmodium vivax

2009

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SUMMARY The gravity of the threat posed by vivax malaria to public health has been poorly appreciated. The widely held misperception of Plasmodium vivax as being relatively infrequent, benign, and easily treated explains its nearly complete neglect across the range of biological and clinical research. Recent evidence suggests a far higher and more-severe disease burden imposed by increasingly drug-resistant parasites. The two frontline therapies against vivax malaria, chloroquine and primaquine, may be failing. Despite 60 years of nearly continuous use of these drugs, their respective mechanisms of activity, resistance, and toxicity remain unknown. Although standardized means of assessing therapeutic efficacy against blood and liver stages have not been developed, this review examines the provisional in vivo, ex vivo, and animal model systems for doing so. The rationale, design, and interpretation of clinical trials of therapies for vivax malaria are discussed in the context of the nuance and ambiguity imposed by the hypnozoite. Fielding new drug therapies against real-world vivax malaria may require a reworking of the strategic framework of drug development, namely, the conception, testing, and evaluation of sets of drugs designed for the cure of both blood and liver asexual stages as well as the sexual blood stages within a single therapeutic regimen.

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Section: Diagnosismentioning

confidence: 99%

Resistance to Therapies for Infection by Plasmodium vivax

2009

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“…With the discovery in the early 90's that the owl monkey (Aotus trivirgatus) is susceptible to infection with the human parasites P. falciparum and P. vivax, the simian models of malaria have regained interest. Infection with P. falciparum is now well characterized in both Aotus and Saimiri monkeys (Collins, 1992), and primate models, because they provide a clear prediction of drug efficacy and pharmacokinetics in humans, are a logical transition to clinical studies. However, there are obvious limitations to their use, and any primary screen dependent upon monkeys appears both wasteful in terms of animal conservation, drug consumption, and ethics.…”

Section: In Vivo Antimalarial Drug Evaluationmentioning

confidence: 99%

Advances in Antimalarial Drug Evaluation and New Targets for Antimalarials

Grellier¹,

Deregnaucourt²,

Isabelle³

2012

Malaria Parasites

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“…Infection of Aotus and Saimiri monkeys from the New World is important as it to some extent mimics the course of natural infections. However, the monkeys are often resistant to reinfection and difficult to acquire (6,7,14,22). The more recent use of SCID mice combined with transplanted human tissue has verified important mechanisms in real-time interaction between iRBC and the endothelium (16).…”

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confidence: 99%

Whole-Body Imaging of Sequestration of Plasmodium falciparum in the Rat

et al. 2005

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The occlusion of vessels by packed Plasmodium falciparum-infected (iRBC) and uninfected erythrocytes is a characteristic postmortem finding in the microvasculature of patients with severe malaria. Here we have employed immunocompetent Sprague-Dawley rats to establish sequestration in vivo. Human iRBC cultivated in vitro and purified in a single step over a magnet were labeled with 99m technetium, injected into the tail vein of the rat, and monitored dynamically for adhesion in the microvasculature using whole-body imaging or imaging of the lungs subsequent to surgical removal. iRBC of different lines and clones sequester avidly in vivo while uninfected erythrocytes did not. Histological examination revealed that a multiadhesive parasite adhered in the larger microvasculature, inducing extensive intravascular changes while CD36-and chondroitin sulfate A-specific parasites predominantly sequester in capillaries, inducing no or minor pathology. Removal of the adhesive ligand Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), preincubation of the iRBC with sera to PfEMP1 or preincubation with soluble PfEMP1-receptors prior to injection significantly reduced the sequestration. The specificity of iRBC binding to the heterologous murine receptors was confirmed in vitro, using primary rat lung endothelial cells and rat lung cryosections. In offering flow dynamics, nonmanipulated endothelial cells, and an intact immune system, we believe this syngeneic animal model to be an important complement to existing in vitro systems for the screening of vaccines and adjunct therapies aiming at the prevention and treatment of severe malaria.Cerebral malaria, respiratory distress, and anemia, or combinations thereof, are the major clinical syndromes associated with severe Plasmodium falciparum malaria. These disease states are in part attributable to the blockage of the microvasculature (9) with a reduction of the blood flow and an induction of inflammatory processes in the surrounding tissues. This is generally accepted to depend on the unique ability of the P. falciparum-infected erythrocyte (iRBC) to sequester away from the peripheral circulation during the intraerythrocytic cycle (23), confirmed by iRBC found adherent to the endothelial lining and to RBC in autopsy material (20,25,26,34). The sequestration is in part attributable to the relatively high rigidity of the iRBC (35), but also to expression of the adhesive ligand Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) at the iRBC surface. PfEMP1 interacts with receptors on host cells, mediating adhesion to the endothelial lining of the microvasculature (cytoadhesion) and to uninfected erythrocytes (RBC) and to iRBC (rosetting and autoagglutination, respectively) (1,8,19,37).While iRBC of patients with uncomplicated malaria predominantly adhere to CD36 at the endothelial cell surface (24), iRBC of children with severe malaria are frequently found to also bind to other endothelial receptors (multiadhesive) and to form rosettes and autoagglutinates (2,1...

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South American monkeys in the development and testing of malarial vaccines - a review

Cited by 28 publications

References 0 publications

Resistance to Therapies for Infection by Plasmodium vivax

Resistance to Therapies for Infection by Plasmodium vivax

Advances in Antimalarial Drug Evaluation and New Targets for Antimalarials

Whole-Body Imaging of Sequestration of Plasmodium falciparum in the Rat

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