777. A Novel Mouse Model of Cerebral Malaria and HIV Coinfection
Session: Oral Abstract Session: Travel/Tropical Medicine and Parasitology
Friday, October 21, 2011: 2:15 PM
Room: 204AB
Background: Although there are nearly 1 million annual deaths due to cerebral malaria (CM) and the majority of these occur in areas of high HIV-1 prevalence, the effects of HIV/malaria coinfection on disease pathogenesis and outcome remain virtually unknown.  We have developed a mouse model to study the pathophysiology of coinfection by infecting mice transgenic for an infectious HIV-1 provirus and for the human cyclin T1 gene [1] with Plasmodium berghei ANKA. 

Methods: 24 mice (12 transgenic “HIVJR-CSF”, 12 littermate controls) age 6 weeks-4 months were infected IV with 105 P. berghei ANKA.  Parasitemia was counted daily by blood smear.  Behavioral assessment by the Rapid Murine Coma and Behavioral Scale [2] was performed  daily until a decline was noted, then twice daily until death.  Mice were sacrificed when they displayed severe impairment, indicated by a RMCBS score ≤ 5. 

Results: All mice developed peripheral parasitemia.  Ten out of 12 HIVJR-CSF mice (83.3%) developed CM on day 6-10 post-infection (p.i.), and 7 out of 12 controls (58.3%) developed CM on day 6-9 p.i.  HIVJR-CSF mice that developed CM (N=10) had a mean parasitemia prior to sacrifice/death of 5.34% (SD=0.977), compared with 4.76% (SD=0.958) in control mice that developed CM (N=7), a non-significant difference.  Mice that did not develop CM were sacrificed when they became less active and severely anemic on day 16-17 p.i., with mean parasitemia of 48.23% (SD=12.120) for HIVJR-CSF mice (N=2) and 45.31% (SD=8.925) for controls (N=5).

Conclusion: We have developed a novel mouse model of CM in the setting of HIV coinfection. HIV increases the incidence of CM in P. berghei ANKA experimental cerebral malaria, as more HIVJR-CSF mice developed CM than did controls.  We are now doing histopathology on murine brain and spleen tissue to examine the mechanisms by which HIV influences CM.

1.            Sun, J., et al., CD4-specific transgenic expression of human cyclin T1 markedly increases human immunodeficiency virus type 1 (HIV-1) production by CD4+ T lymphocytes and myeloid cells in mice transgenic for a provirus encoding a monocyte-tropic HIV-1 isolate. J Virol, 2006. 80(4): p. 1850-62.

2.            Carroll, R.W., et al., A rapid murine coma and behavior scale for quantitative assessment of murine cerebral malaria. PLoS One. 5(10).


Subject Category: T. Travel/tropical medicine and parasitology

Sarah Hochman, MD, Monica Dutta, Harris Goldstein, MD and Kami Kim, MD, FIDSA, Albert Einstein College of Medicine, Bronx, NY

Disclosures:

S. Hochman, None

M. Dutta, None

H. Goldstein, None

K. Kim, None

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