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Mehta, Satish K.

Publications and source records attributed to Mehta, Satish K..

27 records · Page 2

Varicella Zoster Virus in Saliva of Patients With Herpes Zoster

Background. VZV DNA is present in saliva of healthy astronauts and patients with Ramsay Hunt syndrome (geniculate zoster). We hypothesized that a prospective analysis of patients with zoster would detect VZV in saliva independent of zoster location. Methods. We treated 54 patients with valacyclovir. On the first treatment day, 7- and 14-days later, pain was scored and saliva examined for VZV DNA. Saliva from six subjects with chronic pain and 14 healthy subjects was similarly studied. Results. Follow-up data was available for 50/54 patients. Pain decreased in 43/50 (86 percent), disappeared in 37 (74 percent), recurred after disappearing in three (6 percent) and increased in four (8 percent). VZV DNA was found in every patient the day treatment was started, decreased in 47/50 (94 percent), transiently increased in three (6 percent) before decreasing, increased in two (4 percent) and disappeared in 41 (82 percent). There was a positive correlation between the presence of VZV DNA and pain, as well as between the VZV DNA copy number and pain (P<0.0005). Saliva of two patients was cultured, and infectious VZV was isolated from one. VZV DNA was present in one patient before rash and in four patients after pain resolved, and not in any control subjects. Conclusion. VZV DNA is present in saliva of zoster patients.

Mehta, Satish K.↗

Monitoring Immune System Function and Reactivation of Latent Viruses in the Artificial Gravity Pilot Study

Numerous studies have indicated that dysregulation of the immune system occurs during or after spaceflight. Using 21 day -6 degrees head-down tilt bed rest as a spaceflight analog, this study describes the effects of artificial gravity (AG) as a daily countermeasure on immunity, stress and reactivation of clinically important latent herpes viruses. The specific aims were to evaluate psychological and physiological stress, to determine the status of the immune system, and to quantify reactivation of latent herpes viruses. Blood, saliva, and urine samples were collected from each participating subject at different times throughout the study. An immune assessment was performed on all treatment and control subjects that consisted of a comprehensive peripheral immunophenotype analysis, intracellular cytokine profiles and a measurement of T cell function. The treatment group displayed no differences throughout the course of the study with regards to peripheral leukocyte distribution, cytokine production or T cell function. Shedding of Epstein barr virus (EBV), Cytomegalovirus (CMV), and Varicella zoster virus (VZV) was quantified by real time PCR in saliva and urine samples, respectively. There was no significant difference in CMV DNA in the treatment group as compared to the control group. EBV and VZV on the other hand showed a mild reactivation during the study. There were no significant differences in cortisol between the control and treatment groups. In addition, no significant differences between antiviral antibody titers (EBV-VCA, -EA, -EBNA, CMV) or tetramer-positive (EBV, CMV) were found between the two groups. EBV DNA copies in blood were typically undetectable but never exceeded 1,500 copies per 106 PBMCs. Overall, these data indicate that the artificial gravity countermeasure and the 21 day head-down tilt bed rest regimen had no observable adverse effect on immune function.

Mehta, Satish K.↗

Spacecraft Environment May Reduce Resistance To Infection

Living and working in a spacecraft exposes the crew to a unique environment. This environment includes microgravity, increased radiation, chemical and biological contamination, and a variety of stressors. Disturbances in this balance are often manifested by diminished immunity in astronauts/cosmonauts. Reactivation of Epstein- Barr virus (EBV), cytomegalovirus (CMV), and varicella-zoster virus (VZV) has been used as an indicator of immune status. Reactivation of EBV and VZV were detected and quantified in saliva. CMV was measured in urine. The DNA was extracted using a Qiagen Inc. kit and viral DNA was detected by real time polymerase chain reaction (PCR) based assay with Taqman 7700 (PE Biosystems). Patterns of Epstein-Barr virus (EBV) reactivation in 32 astronauts and 18 healthy age-matched control subjects were characterized by quantifying EBV shedding. Saliva samples were collected before, during, and after 10 space shuttle missions of 5 to 14 d duration. Of 1398 saliva specimens from 32 astronauts, 314 (23%) were positive for EBV DNA. Examination by flight phase showed that 29% of the saliva specimens collected from 28 astronauts before flight were positive for EBV DNA, as were 16% of those collected from 25 astronauts during flight and 16% of those collected after flight from 23 astronauts. The mean number of EBV copies/mL from samples taken during the flights was 417, ten-fold greater (p < 0.05) than the copies from the preflight (40) and post flight (44) phases. In contrast, the control subjects shed EBV DNA with a frequency of 3.7% and mean EBV copies of 40 per mL of saliva. Ten days before flight and on landing day, titers of antibody to EBV viral capsid antigen were significantly (p < 0.05) greater than baseline levels. Increases in the number of viral copies and in the amount of EBV-specific antibody were consistent with EBV reactivation before, during, and after space flight. Similarly, CMV and VZV reactivation increased in response to space flight conditions. Data indicates that space flight is a unique stress environment that may produce stress-induced changes in the host-microbe relationship resulting in increased risk of infection.

Pierson, Duane L.↗

Stress-induced subclinical reactivation of varicella zoster virus in astronauts

Varicella zoster virus (VZV) becomes latent in human ganglia after primary infection. VZV reactivation occurs primarily in elderly individuals, organ transplant recipients, and patients with cancer and AIDS, correlating with a specific decline in cell-mediated immunity to the virus. VZV can also reactivate after surgical stress. The unexpected occurrence of thoracic zoster 2 days before space flight in a 47-year-old healthy astronaut from a pool of 81 physically fit astronauts prompted our search for VZV reactivation during times of stress to determine whether VZV can also reactivate after non-surgical stress. We examined total DNA extracted from 312 saliva samples of eight astronauts before, during, and after space flight for VZV DNA by polymerase chain reaction: 112 samples were obtained 234-265 days before flight, 84 samples on days 2 through 13 of space flight, and 116 samples on days 1 through 15 after flight. Before space flight, only one of the 112 saliva samples from a single astronaut was positive for VZV DNA. In contrast, during and after space flight, 61 of 200 (30%) saliva samples were positive in all eight astronauts. No VZV DNA was detected in any of 88 saliva samples from 10 healthy control subjects. These results indicate that VZV can reactivate subclinically in healthy individuals after non-surgical stress. Copyright 2004 Wiley-Liss, Inc.

Astronauts↗

The dynamics of herpesvirus and polyomavirus reactivation and shedding in healthy adults: a 14-month longitudinal study

Humans are infected with viruses that establish long-term persistent infections. To address whether immunocompetent individuals control virus reactivation globally or independently and to identify patterns of sporadic reactivation, we monitored herpesviruses and polyomaviruses in 30 adults, over 14 months. Epstein-Barr virus (EBV) DNA was quantitated in saliva and peripheral blood mononuclear cells (PBMCs), cytomegalovirus (CMV) was assayed in urine, and JC virus (JCV) and BK virus (BKV) DNAs were assayed in urine and PBMCs. All individuals shed EBV in saliva, whereas 67% had >or=1 blood sample positive for EBV. Levels of EBV varied widely. CMV shedding occurred infrequently but occurred more commonly in younger individuals (P<.03). JCV and BKV virurias were 46.7% and 0%, respectively. JCV shedding was age dependent and occurred commonly in individuals >or=40 years old (P<.03). Seasonal variation was observed in shedding of EBV and JCV, but there was no correlation among shedding of EBV, CMV, and JCV (P>.50). Thus, adults independently control persistent viruses, which display discordant, sporadic reactivations.

Non-NASA Center↗

Stress-Induced Subclinical Reactivation of Varicella Zoster Virus in Astronauts

After primary infection, varicella-zoster virus (VZV) becomes latent in ganglia. VZV reactivation occurs primarily in elderly individuals, organ transplant recipients, and patients with cancer and AIDS, correlating with a specific decline in cell-mediated immunity to VZV. VZV can also reactivate after surgical stress. To determine whether VZV can also reactivate after acute non-surgical stress, we examined total DNA extracted from 312 saliva samples of eight astronauts before, during and after space flight for VZV DNA by PCR: 112 samples were obtained 234 to 265 days before flight, 84 samples on days 2 through 13 of space flight, and 116 samples on days 1 through 15 after flight. Before space flight only one of the 112 saliva samples from a single astronaut was positive for VZV DNA. In contrast, during and after space flight, 61 of 200 (30%) saliva samples were positive in all 8 astronauts. No VZV DNA was detected in any of 88 saliva samples from 10 healthy control subjects. These data indicate that VZV can reactivate subclinically in healthy individuals after acute stress.

Mehta, Satish K.↗

Decreased NK-Cell Cytotoxicity after Short Flights on the Space Shuttle

Cytotoxic activity of natural killer (NK) cells and cell surface marker expression of peripheral blood mononuclear cells (PBMCs) isolated from 11 U.S. astronauts on two different missions were determined before and after 9 or 10 days of spaceflight aboard the space shuttle. Blood samples were collected 10 and 3 days before launch, within 3 hours after landing, and 3 days after landing. All PBMC preparations were cryopreserved and analyzed simultaneously in a 4-hour cytotoxicity "Cr-release assay using NK-sensitive K-562 target cells. Compared to preflight values, NK-cell cytotoxicity (corrected for lymphopenia observed on landing day) was significantly decreased at landing (P < 0.0125). It then apparently began to recover and approached preflight values by 3 days after landing. Consistent with decreased NK-cell cytotoxicity, significant increases from preflight values were found in plasma adrenocorticotropic hormone at landing. Plasma and urinary cortisol levels did not change significantly from preflight values. Expression of major lymphocyte surface markers (CD3, CD4, CD8, CD14, CD16, CD56), determined by flow cytometric analysis, revealed no consistent phenotypic changes in relative percent of NK or other lymphoid cells after 10 days of spaceflight.

Mehta, Satish K.↗

Epstein-Barr Virus Reactivation Associated with Diminished Cell-Mediated Immunity in Antarctic Expeditioners

Reactivation of Epstein-Barr virus (EBV) and cell-mediated immune (CMI) responses were followed in 16 Antarctic expeditioners during winter-over isolation at two Australian National Antarctic Research Expedition stations. Delayed-type hypersensitivity skin testing was used as an indicator of the CMI response, which was evaluated two times before winter isolation and three times during isolation. At all five evaluation times, 8 or more of the 16 subjects had a diminished. CMI response. Diminished CMI was observed on every test occasion in 4/16 subjects; only 2/16 subjects exhibited normal CMI responses for all five tests. A polymerase chain reaction (PCR) assay was used to detect EBV DNA in saliva specimens collected before, after, and during the winter isolation. EBV DNA was present in 17% (111/642) of the saliva specimens; all 16 subjects shed EBV in their saliva on at least one occasion. The probability of EBV shedding increased (p=0.013) from 6% before or after winter isolation to 13% during the winter period. EBV appeared in saliva during the winter isolation more frequently (p<0.0005) when CMI responsiveness was diminished than when CMI status was normal. The findings indicate that the psychosocial, physical, and other stresses associated with working and living in physical isolation during the Antarctic winter results in diminished CMI and an accompanying increased reactivation and shedding of latent viruses.

Pierson, Duane L.↗

Incidence of Epstein-Barr Virus in Astronaut Saliva During Spaceflight

Astronauts experience psychological and physical stresses that may result in re-activation of latent viruses during spaceflight, potentially increasing the risk of disease among crew members. The shedding of Epstein-Barr virus (EBV) in the saliva of astronauts will increase during spaceflight. A total of 534 saliva specimens were collected from 11 EBV-seropositive astronauts before, during, and after four space shuttle missions. The presence of EBV DNA in saliva, assessed by polymerase chain reaction (PCR), was used to determine shedding patterns before, during, and after spaceflight. EBV DNA was detected more frequently before flight than during (p less than 0.001) or after (p less than 0.01) flight. No significant difference between the in-flight and postflight periods was detected in the frequency of occurrence of EBV DNA. The increased frequency of shedding of EBV before flight suggests that stress levels may be greater before launch than during or after spaceflight.

Payne, Deborah A.↗