Chronic immune stimulation accelerates SIV‐induced disease progression

Villinger, François; Rowe, Thomas; Parekh, Bharat; Green, Timothy A.; Mayne, Ann E.; Grimm, Bennett D.; McClure, Harold M.; Lackner, Andrew A.; Dailey, Peter J.; Ansari, Aftab A.; Folks, Thomas M.

doi:10.1034/j.1600-0684.2001.d01-57.x

Cited by 25 publications

(16 citation statements)

References 13 publications

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“…The use of antibiotics, fluids, blood transfusions, analgesics, and nutrition is the standard of care for treating severe myelosuppression in the clinic and in the treatment of radiation accident victims (Waselenko et al 2004; Ricks and Fry 1990; Villinger et al 2001; Baranov et al 1994; Timmer-Bonte et al 2005a; Liu et al 2008; Browne et al 1990a; Gourmelon et al 2010; Hirama et al 2003). This will not change in the large casualty situation for personnel exposed to high-dose radiation (Waselenko et al 2004; Meineke and Fliedner 2005; Gourmelon et al 2010).…”

Section: Discussionmentioning

confidence: 99%

A Nonhuman Primate Model of the Hematopoietic Acute Radiation Syndrome Plus Medical Management

Farese¹,

Cohen²,

Katz³

et al. 2012

Health Physics

121

171

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The development of medical countermeasures against the hematopoietic sub-syndrome of the acute radiation syndrome requires well characterized and validated animal models. The model must define the radiation dose- and time-dependent relationships for mortality and major signs of morbidity to include other organ damage that may contribute to the morbidity and mortality. Herein, we define these parameters for the nonhuman primate exposed to total-body radiation and administered medical management. A blinded, randomized study (n=48 rhesus macaques) determined the lethal dose response relationship using bilateral, 6 MV linear accelerator photon radiation to doses in the range of 7.20 to 8.90Gy at 0.80Gy minute−1. Following irradiation animals were monitored for complete blood counts, body weight, temperature, diarrhea, and hydration status for 60 days. Animals were administered medical management consisting of intravenous fluids, prophylactic antibiotics, blood transfusions, anti-diarrheals, analgesics and nutrition. The primary endpoint was survival at 60 days post irradiation; secondary endpoints included hematopoietic-related parameters, number of transfusions, incidence of documented infection, febrile neutropenia, severity of diarrhea, mean survival time of decedents and tissue histology. The study defined an LD30/60 of 7.06Gy, LD50/60 of 7.52Gy, and an LD70/60 of 7.99Gy with a relatively steep slope of 1.13 probits per linear dose. This study establishes a rhesus macaque model of the hematopoietic acute radiation syndrome and shows the marked effect of medical management on increased survival and overall mean survival time for decedents. Furthermore, following a nuclear terrorist event, medical management may be the only treatment administered at its optimal schedule.

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Section: Discussionmentioning

confidence: 99%

A Nonhuman Primate Model of the Hematopoietic Acute Radiation Syndrome Plus Medical Management

Farese¹,

Cohen²,

Katz³

et al. 2012

Health Physics

121

171

View full text Add to dashboard Cite

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“…We do not know whether the lack of SHIV-specifi antibody responses was driven by tenofovir or host/genetic-related factors. It is known that ∼25% of rhesus macaques do not seroconvert after SIV infection and progress to death with high virus loads [31][32][33].…”

Section: Discussionmentioning

confidence: 99%

Chemoprophylaxis with Tenofovir Disoproxil Fumarate Provided Partial Protection against Infection with Simian Human Immunodeficiency Virus in Macaques Given Multiple Virus Challenges

et al. 2006

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We examined the efficacy of tenofovir disoproxil fumarate (TDF) in blocking simian human immunodeficiency virus (SHIV) infection in Chinese rhesus macaques. Once weekly for 14 weeks or until a macaque became infected, 12 male macaques were inoculated intrarectally with amounts of SHIV(SF162P3) (10 median tissue culture infective doses; 3.8 x 10(5) virus particles) that were approximately 5-fold higher than the human immunodeficiency virus type 1 RNA levels noted in human semen during an acute infection. Of the 12 macaques, 4 received oral TDF daily, 4 received oral TDF once weekly, and 4 (control animals) received no TDF. The control animals became infected after receiving a median of 1.5 virus inoculations; macaques receiving TDF daily (1 macaque remained uninfected after 14 inoculations) and those receiving TDF weekly became infected after a median duration of 6.0 and 7.0 weeks, respectively. Although infection was delayed in treated macaques, compared with control macaques, the differences were not statistically significant (P=.315); however, the study was limited by the small numbers of animals evaluated and the variability in blood levels of TDF that resulted from oral dosing. These data demonstrate that treatment with oral TDF provided partial protection against SHIV infection but ultimately did not protect all TDF treated animals against multiple virus challenges.

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“…Until the recent past, many primate research institutions, including TNPRC, withheld instituting a prophylactic vaccination program due to concerns that an immunized population of nonhuman primates would be unsuitable candidates for infectious disease research studies. For example, tetanus antigen has been used as a T-cell dependent immunogen for both in vivo and in vitro tests to assess the changes in the humoral and cellular immune responses associated with simian immunodeficiency virus (SIV) infection in rhesus macaques, the principal model for human immunodeficiency virus (HIV) 1,5,8,15,17,28,31,37. In humans, tetanus antigen is used as a recall antigen where responses to delayed hypersensitivity testing (DTH) and in vitro cell proliferation assays predicts time to progression to AIDS, survival time and progressive HIV illness 1,8,11,31.…”

Section: Discussionmentioning

confidence: 99%

Retrospective Analysis of Wound Characteristics and Tetanus Development in Captive Macaques

Springer

Phillippi-Falkenstein²,

Smith³

2009

Journal of Zoo and Wildlife Medicine

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Traumatic wounds and access to outdoor enclosures containing soil contribute to development of tetanus in non-human primates. A retrospective matched case-control study was conducted at a primate center to evaluate these factors by analysis of medical records of animals sustaining traumatic injuries during a three year study period: 31 macaques with traumatic injuries and a clinical diagnosis of tetanus were selected as cases and 62 macaques with traumatic injuries and no diagnosis of tetanus were selected as controls. For an animal with injuries to the digits, the odds of developing tetanus were 9.6 times those of a similar animal without injuries to the digits (OR = 9.55, 95% CI = 1.56 – 58.59); with injuries to the tail, the odds of developing tetanus were 8.0 times those of a similar animal without injuries to the tail (OR = 7.95, 95% CI = 0.82 – 77.04); and with injuries in more than one location, the odds of developing tetanus were 8.5 times those for a similar animal with injuries in just one location (OR = 8.45, 95% CI = 1.01 – 70.46). A non-human primate with injuries to the leg was less likely to develop tetanus than a similar non-human primate without injuries to the leg (OR = 0.19, 95% CI = 0.03 – 1.2). Results indicated that wound location is associated with development of tetanus infection in rhesus macaques. Identification of high risk trauma cases will allow better allocation of wound management and tetanus prophylaxis in institutions, especially those housing non-human primates outdoors.

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Chronic immune stimulation accelerates SIV‐induced disease progression

Cited by 25 publications

References 13 publications

A Nonhuman Primate Model of the Hematopoietic Acute Radiation Syndrome Plus Medical Management

A Nonhuman Primate Model of the Hematopoietic Acute Radiation Syndrome Plus Medical Management

Chemoprophylaxis with Tenofovir Disoproxil Fumarate Provided Partial Protection against Infection with Simian Human Immunodeficiency Virus in Macaques Given Multiple Virus Challenges

Retrospective Analysis of Wound Characteristics and Tetanus Development in Captive Macaques

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