Aotus infulatus monkey is susceptible to Plasmodium falciparum infection and may constitute an alternative experimental model for malaria

Carvalho, Lidiane dos Santos; Oliveira, Salma Gomes de; Alves, Fábio; Brígido, Maria do Carmo de Oliveira; Muniz, José Augusto Pereira Carneiro; Daniel-Ribeiro, Cláudio Tadeu

doi:10.1590/s0074-02762000000300011

Cited by 19 publications

(24 citation statements)

References 7 publications

(10 reference statements)

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“…This means that only animals with low parasitemias remain parasitemic after approximately day 12, and this may account for the differences in incidence and intensity of anemia. Carvalho and others 18 also had a case of severe anemia among 5 Aotus infulatus infected with P. falciparum. Three of the animals 8 -* The first entry identifies the immunogen used in first 3 immunizations, and the second entry identifies immunogen or immunogens used in the fourth immunization.…”

Section: Discussionmentioning

confidence: 90%

Anemia in parasite- and recombinant protein-immunized aotus monkeys infected with Plasmodium falciparum.

Jones

Stroncek²,

Gozalo³

et al. 2002

The American Journal of Tropical Medicine and Hygiene

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Abstract. Plasmodium falciparum-induced anemia was characterized in Aotus monkeys repeatedly immunized by infection with P. falciparum (FVO strain) parasites, then cross-challenged with CAMP strain, or in monkeys receiving blood stage challenges as part of malaria vaccine trials. In 4 studies, 25 (30.5%) of 82 monkeys had at least a 50% reduction in hematocrit; mean day of maximum parasitemia was 12.5, whereas the mean day of minimum hematocrit was 18.8 (P < 0.0009). Decreased hematocrit levels were not associated with reticulocytosis until parasite densities decreased significantly from peak levels. Direct antibody tests to detect IgG and C3d on the surface of erythrocytes were negative. Nonantibody/noncomplement-mediated lysis of uninfected erythrocytes seems to be the principal cause of the anemia, and it also seems that bone marrow suppression and lysis of infected erythrocytes contributed to the anemia. Partial immunity-whether induced by repeated immunization with whole parasites or with vaccine-seems important to the development of anemia.

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Section: Discussionmentioning

confidence: 90%

Anemia in parasite- and recombinant protein-immunized aotus monkeys infected with Plasmodium falciparum.

Jones

Stroncek²,

Gozalo³

et al. 2002

The American Journal of Tropical Medicine and Hygiene

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“…Primate models have also had an important role in preclinical development by providing a model for the final evaluation of a drug candidate prior to human studies. As primates (particularly Aotus infulatus) are susceptible to P. falciparum infection, they can be used as an experimental model for the pre-clinical development of antimalarial drugs (Carvalho et al 2000(Carvalho et al , 2003. Infections caused by different strains of P. falciparum have been well characterized in both Aotus and Saimiri species, which has provided a clearer prediction of human efficacy and pharmacokinetics than rodent models.…”

Section: Antimalarial Drug Discovery: In Vivo Assaysmentioning

confidence: 99%

Plant-derived antimalarial agents: new leads and efficient phythomedicines. Part I. Alkaloids

Oliveira

Dolabela

Braga

et al. 2009

An. Acad. Bras. Ciênc.

124

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Malaria remains one of the most serious world health problem and the major cause of mortality and morbidity in the endemic regions. Brazil is among the 30 high-burden countries and most of the cases occur in the Legal Amazonian Region. New chemotherapeutical agents are needed for the treatment of malaria. Many plant species are used in traditional medicines of malarious countries and a relatively few number of these have been investigated for evaluation of their antimalarial effect. Still lower is the number of those that have had the active natural compounds isolated and the toxicity determined. This area is, then, of great research interest. A discovery project of antimalarial natural products from plants traditionally used to treat malaria must include in vitro and in vivo assays as well as bioguided isolation of active compounds. The final products would be antimalarial chemical entities, potential new drugs or templates for new drugs development, and/or standardized antimalarial extracts which are required for pre-clinical and clinical studies when the aim is the development of effective and safe phythomedicines. This review discusses these two approaches, presents briefly the screening methodologies for evaluation of antimalarial activity and focuses the activity of alkaloids belonging to different structural classes as well as its importance as new antimalarial drugs or leads and chemical markers for phytomedicines.

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“…Aotus or Saimiri monkeys are World Health Organizationrecommended primate species for studies of human malaria, and they can both be infected with P. falciparum (3). Healthy and splenectomized animals are susceptible to infection (19); the intact ones are able to keep parasitemia at lower levels for several days as a nonlethal pattern, but they develop complications such as severe anemia.…”

mentioning

confidence: 99%

“…The therapeutic time window for intact or splenectomized monkey models of P. falciparum (4,29) infection is 0.4 to 3 days, with an average of about 2 days. However, the monkey model is not optimal for severe human malaria research because of the low level of parasitemia (Ͻ3%) in intact monkeys, and neither major complications nor immunoreactions are seen in the splenectomized monkeys (3). Although the splenectomized monkey model is often used in severe malaria research, the therapeutic time window is usually too short to treat the animals before they die from hyperparasitemia.…”

mentioning

confidence: 99%

New Potential Antimalarial Agents: Therapeutic-Index Evaluation of Pyrroloquinazolinediamine and Its Prodrugs in a Rat Model of Severe Malaria

Xie

Lin

et al. 2006

Antimicrob Agents Chemother

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Tetra-acetamide pyrroloquinazolinediamine (PQD-A4) and bis-ethylcarbamyl pyrroloquinazolinediamine (PQD-BE) are new derivatives of pyrroloquinazolinediamine (PQD) and are being investigated as potential chemotherapeutic agents for the treatment of malaria. Comparative studies to assess the therapeutic indices of PQD-A4, PQD-BE, and PQD were conducted in Plasmodium berghei-infected rats following daily intragastric dosing for three consecutive days. Artesunate (AS), a standard drug for treatment of severe malaria, was used as a comparator. The minimum doses required to clear malaria parasitemia were 156 mol/kg of body weight for AS and 2.4 mol/kg for PQD, PQD-4A, and PQD-BE. The maximum tolerated dose (MTD) of AS was 625 mol/kg, and its therapeutic index was calculated to be 4. The MTDs of PQD-A4, PQD-BE, and PQD were found to be 190, 77, and 24 mol/kg, respectively, yielding therapeutic indices of 80, 32, and 10, respectively. Although PQD-A4 and PQD-BE are only half as potent as PQD based on their curative effects, the two new derivatives, PQD-4A and PQD-BE, are 8.0-fold and 3.2-fold safer, respectively, than their parent compound when they are dosed for three consecutive days. Oral PQD-A4 and PQD-BE are 44 to 70 times more potent on an mg basis than intravenous AS. As assessed from the therapeutic index over 3 days, PQD-A4, PQD-BE, and PQD administered orally are 20.0, 8.0, and 2.5 times safer than AS given intravenously. The results indicate that PQD-4A is a promising candidate for antimalarial treatment.

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Aotus infulatus monkey is susceptible to Plasmodium falciparum infection and may constitute an alternative experimental model for malaria

Cited by 19 publications

References 7 publications

Anemia in parasite- and recombinant protein-immunized aotus monkeys infected with Plasmodium falciparum.

Anemia in parasite- and recombinant protein-immunized aotus monkeys infected with Plasmodium falciparum.

Plant-derived antimalarial agents: new leads and efficient phythomedicines. Part I. Alkaloids

New Potential Antimalarial Agents: Therapeutic-Index Evaluation of Pyrroloquinazolinediamine and Its Prodrugs in a Rat Model of Severe Malaria

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