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All sourcesNASA NTRSDOE OSTI
NASA NTRS2008

Incidence of Latent Virus Shedding during Space Flight

Measurements of immune parameters of both cellular and innate immunity indicate alterations in immune function in astronauts. Immune changes are due to stress and perhaps other factors associated with launch, flight, and landing phases. Medical relevance of observed changes is not known. The reactivation of latent viruses has been identified as an important in vivo indicator of clinically relevant immune changes. The polymerase chain reaction (PCR) was used to detect the presence of specific viral DNA in body fluids. Initial studies demonstrated Epstein-Barr virus (EBV) reactivation during all 3 mission phases. EBV is shed in saliva following reactivation from B-cells. Incidence of EBV in saliva was higher than control subjects during all 3 mission phases. However, quantitative PCR revealed 10-fold higher levels of EBV DNA present in saliva collected during flight than found in pre- and post flight specimens. To determine if other latent viruses showed similar effects, cytomegalovirus (CMV), another herpes virus, shed in urine following reactivation was studied. A very low incidence (less than 2%) of CMV in urine is found in healthy, lowstressed individuals. However, 25-50% of astronauts shed CMV in their urine before, during, or after flight. Our studies are now focused on varicella-zoster virus (VZV), the etiological agent of chicken-pox during childhood and shingles later in life. We demonstrated reactivation of VZV and shedding of the virus during and after spaceflight in saliva of astronauts with no sign of active infection or symptoms. The maximum shedding of VZV occurred during the flight phase and diminishes rapidly during the first five days after landing. We have utilized the same PCR assay for VZV in a clinical study of shingles patients. Generally, shingles patients shed much more VZV in saliva than astronauts. However, the VZV levels in astronauts overlap with the lower range of VZV numbers in shingles patients. Saliva from shingles patients and astronauts were cultured and infectious VZV was recovered from both groups. We have concluded that multiple latent viruses do reactivate before, during, and after spaceflight and serve as very sensitive indicators for diminished cellular immunity. Future plans will be focused on the clinical risks posed by the reactivation of these viruses. Initial efforts will determine the effect of longer missions on the International Space Station on the reactivation patterns of these viruses.

Mehta, Satish K.↗
NASA NTRS2010

Modeling Influenza Transmission Using Environmental Parameters

Influenza is an acute viral respiratory disease that has significant mortality, morbidity and economic burden worldwide. It infects approximately 5-15% of the world population, and causes 250,000 500,000 deaths each year. The role of environments on influenza is often drawn upon the latitude variability of influenza seasonality pattern. In regions with temperate climate, influenza epidemics exhibit clear seasonal pattern that peak during winter months, but it is not as evident in the tropics. Toward this end, we developed mathematical model and forecasting capabilities for influenza in regions characterized by warm climate Hong Kong (China) and Maricopa County (Arizona, USA). The best model for Hong Kong uses Land Surface Temperature (LST), precipitation and relative humidity as its covariates. Whereas for Maricopa County, we found that weekly influenza cases can be best modelled using mean air temperature as its covariates. Our forecasts can further guides public health organizations in targeting influenza prevention and control measures such as vaccination.

Soebiyanto, Radina P.↗
NASA NTRS2008

Using Light to Treat Mucositis and Help Wounds Heal

A continuing program of research and development is focusing on the use of controlled illumination by light-emitting diodes (LEDs) to treat mucositis and to accelerate healing of wounds. The basic idea is to illuminate the affected area of a patient with light of an intensity, duration, and wavelength (or combination of wavelengths) chosen to produce a therapeutic effect while generating only a minimal amount of heat. This method of treatment was originally intended for treating the mucositis that is a common complication of chemotherapy and radiation therapy for cancer. It is now also under consideration as a means to accelerate the healing of wounds and possibly also to treat exposure to chemical and radioactive warfare agents. Radiation therapy and many chemotherapeutic drugs often damage the mucosal linings of the mouth and gastrointestinal tract, leading to mouth ulcers (oral mucositis), nausea, and diarrhea. Hyperbaric-oxygen therapy is currently the standard of care for ischemic, hypoxic, infected, and otherwise slowlyhealing problem wounds, including those of oral mucositis. Hyperbaric-oxygen therapy increases such cellular activities as collagen production and angiogenesis, leading to an increased rate of healing. Biostimulation by use of laser light has also been found to be effective in treating mucositis. For hyperbaricoxygen treatment, a patient must remain inside a hyperbaric chamber for an extended time. Laser treatment is limited by laser-wavelength capabilities and by narrowness of laser beams, and usually entails the generation of significant amounts of heat.

Ignatius, Robert W.↗
NASA NTRS1996

Effect of space flight on cytokine production and other immunologic parameters of rhesus monkeys

During a recent flight of a Russian satellite (Cosmos #2229), initial experiments examining the effects of space flight on immunologic responses of rhesus monkeys were performed to gain insight into the effect of space flight on resistance to infection. Experiments were performed on tissue samples taken from the monkeys before and immediately after flight. Additional samples were obtained approximately 1 month after flight for a postflight restraint study. Two types of experiments were carried out throughout this study. The first experiment determined the ability of leukocytes to produce interleukin-1 and to express interleukin-2 receptors. The second experiment examined the responsiveness of rhesus bone marrow cells to recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). Human reagents that cross-reacted with monkey tissue were utilized for the bulk of the studies. Results from both studies indicated that there were changes in immunologic function attributable to space flight. Interleukin-1 production and the expression of interleukin-2 receptors was decreased after space flight. Bone marrow cells from flight monkeys showed a significant decrease in their response to GM-CSF compared with the response of bone marrow cells from nonflight control monkeys. These results suggest that the rhesus monkey may be a useful surrogate for humans in future studies that examine the effect of space flight on immune response, particularly when conditions do not readily permit human study.

unmanned↗
NASA NTRS2010

Particular Characterisation of an In-Vitro-DTH Test to Monitor Cellular Immunity - Applications for Patient Care and Space Flight

Goal:i) Characterization of the role of the main immune reactive cell types contributing to the cellular immune response in the in-vitro DTH and ii) Validation of the in-vitro DTH under different clinical and field conditions. Methods:As positive control whole blood was incubated in the in-vitro DTH, supernatants were gathered after 12, 24 and 48h. Readout parameters of this test are cytokines in the assay's supernatant. To determine the role of T-cells, monocytes and natural killer (NK), these cell populations were depleted using magnetic beads prior to in-vitro-DTH incubation. Validation of the test has occurred under clinical (HIV-patients, ICU) and field-conditions (parabolic/space-flights, confinement). Results:T-cell depletion abandoned almost any IL-2 production and reduced IFN-gamma production irrespective of the type of antigen, whereas CD56 depleted cultures tended to lower IL-2 secretion and IFN-gamma and to parallel a IL-10-increase after viral challenge. This IL-10-increase was seen also in CD14-depleted setups. DTH read-out was significantly different under acute stress (parabolic flight) or chronic stress (ISS), respectively. Preliminary data of HIV infected patients demonstrate that this test can display the contemporary immune status during an antiviral therapy. Conclusion:The in-vitro DTH mirrors adaptive and innate immune activation and may serve as tool also for longitudinal follow up of Th1/Th2 weighed immune response under adverse life conditions on earth and in space. It is planned to implement the assay in the on the ISS (MoCISS).

Feurecker, M.↗
NASA NTRS2003

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.↗
NASA NTRS2018

Gene Expression of Pathogens in Simulated Microgravity

Extended exposure to radiation and microgravity in space has been linked to astronauts developing chronic diseases upon returning to Earth. The Gram-negative pathogen Serratia marcescens has been shown to potentially cause significant infections in humans and in insect models on Earth. Our recent findings also showed that S. marcescens shows an increase in virulence after a short period of growth in the spaceflight environment, which raises initiatives to find the correlation between space environment and the increased virulence. Because we know that the health of astronauts is immunocompromised in space, it is possible that the combination of increased bacterial virulence and the weakened immune system will cause astronauts to be more susceptible to chronic diseases in extended spaceflight. With 75% of human disease genes being conserved in the fruit fly Drosophila melanogaster, these insects act as an ideal model organism to study the human immune system. The high accessibility, low cost, high rate of reproductivity, and short lifespans of D. melanogaster facilitate efficient, high-quality research that seeks to understand altered virulence of this opportunistic pathogen. In this ground-based study, we will use a rotating wall vessel apparatus to simulate microgravity and determine how pathogenicity changes by evaluating differences in gene expression for S. marcescens between bacteria grown in simulated microgravity conditions and controls. We will compare the results of our findings to gene expression patterns in actual spaceflight samples of S. marcescens grown on the ISS (International Space Station) during a recent validation mission, to see if there are common mechanisms across our simulated microgravity and actual spaceflight microgravity samples that both show increased virulence in the fruit fly. With extended space travel in the foreseeable future, understanding how human physiology will be affected by these different factors will help mitigate risks and deaths.

spaceflight analogue↗
NASA NTRS2007

Surveillance and Control of Malaria Transmission in Thailand using Remotely Sensed Meteorological and Environmental Parameters

These slides address the use of remote sensing in a public health application. Specifically, this discussion focuses on the of remote sensing to detect larval habitats to predict current and future endemicity and identify key factors that sustain or promote transmission of malaria in a targeted geographic area (Thailand). In the Malaria Modeling and Surveillance Project, which is part of the NASA Applied Sciences Public Health Applications Program, we have been developing techniques to enhance public health's decision capability for malaria risk assessments and controls. The main objectives are: 1) identification of the potential breeding sites for major vector species; 2) implementation of a risk algorithm to predict the occurrence of malaria and its transmission intensity; 3) implementation of a dynamic transmission model to identify the key factors that sustain or intensify malaria transmission. The potential benefits are: 1) increased warning time for public health organizations to respond to malaria outbreaks; 2) optimized utilization of pesticide and chemoprophylaxis; 3) reduced likelihood of pesticide and drug resistance; and 4) reduced damage to environment. !> Environmental parameters important to malaria transmission include temperature, relative humidity, precipitation, and vegetation conditions. The NASA Earth science data sets that have been used for malaria surveillance and risk assessment include AVHRR Pathfinder, TRMM, MODIS, NSIPP, and SIESIP. Textural-contextual classifications are used to identify small larval habitats. Neural network methods are used to model malaria cases as a function of the remotely sensed parameters. Hindcastings based on these environmental parameters have shown good agreement to epidemiological records. Discrete event simulations are used for modeling the detailed interactions among the vector life cycle, sporogonic cycle and human infection cycle, under the explicit influences of selected extrinsic and intrinsic factors. The output of the model includes the individual infection status and the quantities normally observed in field studies, such as mosquito biting rates, sporozoite infection rates, gametocyte prevalence and incidence. Results are in good agreement with mosquito vector and human malaria data acquired by Coleman et al. over 4.5 years in Kong Mong Tha, a remote village in western Thailand. Application of our models is not restricted to the Greater Mekong Subregion. Our models have been applied to malaria in Indonesia, Korea, and other regions in the world with similar success.

Kiang, Richard K.↗
NASA NTRS1997

Seedborne fungal contamination: consequences in space-grown wheat

Plants grown in microgravity are subject to many environmental stresses that may promote microbial growth and result in disease symptoms. Wheat (cv. Super Dwarf) recovered from an 8-day mission aboard a NASA (National Aeronautics and Space Administration) space shuttle showed disease symptoms, including girdling of leaf sheaths and chlorosis and necrosis of leaf and root tissues. A Neotyphodium species was isolated from the seed and leaf sheaths of symptomatic wheat used in the spaceflight mission. Certain isozymes of a peroxidase unique to extracts from the microgravity-grown plants were observed in extracts from earth-grown Neotyphodium-infected plants but were not present in noninfected wheat. The endophytic fungus was eliminated from the wheat seed by prolonged heat treatment at 50 degrees C followed by washes with water at 50 degrees C. Plants from wheat seed infected with the Neotyphodium endophyte were symptomless when grown under greenhouse conditions, whereas symptoms appeared after only 4 days of growth in closed containers. Disease spread from an infected plant to noninfected plants in closed containers. Dispersion via spores was found on asymptomatic plants at distances of 7 to 18 cm from infected plants. The size and shape of the conidia, mycelia, and phialide-bearing structures and the ability to grow rapidly on carbohydrates, especially xylose, resembled the characteristics of N. chilense, which is pathogenic on orchard grass, Doctylis glomerati. The Neotyphodium wheat isolate caused disease symptoms on other cereals (wheat cv. Malcolm, orchard grass, barley, and maize) grown in closed containers.

NASA Discipline Plant Biology↗
NASA NTRS2004

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↗
NASA NTRS2001

The Effect of Regional Climate Variability on Outbreak of Bartonellosis Epidemics in Peru

Bartonellosis is a vector-borne, highly fatal, emerging infectious disease, which has been known in the Peruvian Andes since the early 1600s and has continued to be a problem in many mountain valleys in Peru and other Andean South American countries. The causative bacterium, Bartonella bacilliformis (Bb), is believed to be transmitted to humans by bites of the sand fly Lutzomyia verrucarum. According to available medical records, the transmission of infection often occurs in river valleys of the Andes Mountains at an altitude between 800 and 3500 meters above sea level. It shows a seasonal pattern, which usually begins to rise in December, peaks in February and March, and is at its lowest from July until November. The epidemics of bartonellosis also vary interannually, occurring every four to eight years, and appear to be associated with the El Nino cycle. In response to the National Oceanic and Atmospheric Administration (NOAA) announcement on climate variability and human health, which was constructed to stimulate integrated multidisciplinary research in the area of climate variability and health interactions, we have conducted a study to investigate the relationship between the El Nino induced regional climate variation and the outbreak of bartonellosis epidemics in Peru. Two test sites, Caraz and Cusco, were selected for this study. According to reports, Caraz has a long-standing history of endemic transmission and Cusco, which is located about five degrees poleward of Caraz, had no recorded epidemics until the most recent 1997/1998 El Nino event. The goal of this study is to clarify the relative importance of climatic risk factors for each area that could be predicted in advance, thus allowing implementation of cost-effective control measures, which would reduce disease morbidity and mortality.

Zhou, Jia-Yu↗
NASA NTRS2000

Reactivation and shedding of cytomegalovirus in astronauts during spaceflight

The reactivation of cytomegalovirus (CMV) in 71 astronauts was investigated, using polymerase chain reaction. A significantly greater (P<.0001) shedding frequency was found in urine samples from astronauts before spaceflight (10.6%) than in urine from the healthy control subject group (1.2%). Two of 4 astronauts studied during spaceflight shed CMV in urine. A significant increase (P<.0001) in CMV antibody titer, compared with baseline values, was also found 10 days before spaceflight. CMV antibody titer was further increased (P<.001) 3 days after landing, compared with 10 days before the mission. Significant increases in stress hormones were also found after landing. These results demonstrate that CMV reactivation occurred in astronauts before spaceflight and indicate that CMV may further reactivate during spaceflight.

NASA Center JSC↗
NASA NTRS2004

Teleoperation from Mars Orbit: A proposal for Human Exploration

For a human expedition to Mars, a case can be made that the best strategy for initial exploration is not to actually land the humans on Mars, but to put the humans into Mars orbit and operate on the surface by the technology of teleoperation. This will provide the results of human exploration, but at greatly reduced risk and cost. Teleoperation of Mars surface robots from a Mars-orbital habitat will operation near real time operation with minimum time delay, giving a virtual presence on the surface. By use of teleoperation, it is possible to vastly simplify the surface exploration mission. We now have no need to develop a human-rated Mars Lander and Mars Ascent Vehicle, and we can send geologists & biologists on the mission; not VTOL pilots. It is a cheaper, simpler, and safer way to explore, and hence it will be a faster way to explore. It has the excitement of being there, at a fraction of the price. Tele-exploration from Mars orbit also allows human (virtual) presence at a wide variety of locations. With an orbital base controlling surface telerobotics, human explorers are not stuck with one base location, but can explore all over Mars. They can explore the polar caps and also near-equatorial canyon regions, from the same orbiting base. This frees the mission from landing site constraints. With no need to select a "grab bag" site that contains a large number of geologically diverse features at or near a single location; it is now possible go to all the best sites-- paleolake sites, river beds, volcanic calderas, lava tube sites, layered terrain, canyons, possible shoreline features, the North and South poles. A near-polar inclination 24-hr 39-minute period Mars orbit, for example, will put the orbital station in line-of-sight of a given region for about 8 hours per day-- one teleoperation shift. Since present day life could exist on Mars, planetary protection is also needed to preserve the (possible) fragile Mars biosphere from competition from ferocious Earth life. Isolated biospheres on Earth have been devastated when they have been exposed to alien life forms introduced-accidentally or deliberately-- from another continent. If there is life on Mars, we will wish to protect it from having to compete with introduced Earth biota. Reverse planetary protection-protecting the Earth biosphere from exposure to Mars microorganisms-is also an important consideration. Exploring from orbit will reduce biological risk by keeping humans from exposure to possible Mars microbes. A telerobotic mission will need no quarantine on return to Earth, and avoids the difficult human question of how to isolate Mars mission astronauts infected by Martian microorganisms.

Landis, Geoffrey A.↗