Moroni M.,Armed forces Radiobiology Research Institute |
Ngudiankama B.F.,National Institute of Allergy and Infectious Diseases |
Christensen C.,Armed forces Radiobiology Research Institute |
Olsen C.H.,Uniformed Services University of the Health Sciences |
And 4 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2013
Purpose: We are characterizing the Gottingen minipig as an additional large animal model for advanced drug testing for the acute radiation syndrome (ARS) to enhance the discovery and development of novel radiation countermeasures. Among the advantages provided by this model, the similarities to human hematologic parameters and dynamics of cell loss/recovery after irradiation provide a convenient means to compare the efficacy of drugs known to affect bone marrow cellularity and hematopoiesis. Methods and Materials: Male Gottingen minipigs, 4 to 5 months old and weighing 9 to 11 kg, were used for this study. We tested the standard off-label treatment for ARS, rhG-CSF (Neupogen, 10 μg/kg/day for 17 days), at the estimated LD70/30 total-body γ-irradiation (TBI) radiation dose for the hematopoietic syndrome, starting 24 hours after irradiation. Results: The results indicated that granulocyte colony stimulating factor (G-CSF) enhanced survival, stimulated recovery from neutropenia, and induced mobilization of hematopoietic progenitor cells. In addition, the administration of G-CSF resulted in maturation of monocytes/macrophages. Conclusions: These results support continuing efforts toward validation of the minipig as a large animal model for advanced testing of radiation countermeasures and characterization of the pathophysiology of ARS, and they suggest that the efficacy of G-CSF in improving survival after total body irradiation may involve mechanisms other than increasing the numbers of circulating granulocytes. © 2013 Elsevier Inc.
Wangchuk S.,Ministry of Health |
Chinnawirotpisan P.,Armed Forces Research Institute of Medical science |
Dorji T.,Ministry of Health |
Tobgay T.,Ministry of Health |
And 2 more authors.
Emerging Infectious Diseases | Year: 2013
In 2012, chikungunya virus (CHIKV) was reported for the first time in Bhutan. IgM ELISA results were positive for 36/210 patient samples; PCR was positive for 32/81. Phylogenetic analyses confirmed that Bhutan CHIKV belongs to the East/Central/South African genotype. Appropriate responses to future outbreaks require a system of surveillance and improved laboratory capacity.
Nitayaphan S.,Armed Forces Research Institute of Medical science AFRIMS |
Ngauy V.,Armed Forces Research Institute of Medical science |
O'Connell R.,Us Military Hiv Research Program Mhrp |
Excler J.-L.,Foundation Medicine
Expert Review of Vaccines | Year: 2012
The recent evidence in Thailand for protection from acquisition of HIV through vaccination in a mostly heterosexual population has generated considerable hope. Building upon these results and the analysis of the correlates of risk remains among the highest priorities. Improved vaccine concepts including heterologous prime-boost regimens, improved proteins with potent adjuvants and new vectors expressing mosaic antigens may soon enter clinical development to assess vaccine efficacy in men who have sex with men. Identifying heterosexual populations with sufficient HIV incidence for the conduct of efficacy trials represents perhaps the main challenge in Asia. Fostering translational research efforts in Asian countries may benefit from the development of master strategic plans and program management processes. © 2012 Expert Reviews Ltd.
Paris R.M.,Armed Forces Research Institute of Medical science |
Kim J.H.,U.S. Army |
Robb M.L.,U.S. Army |
Robb M.L.,Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc |
Michael N.L.,U.S. Army
Expert Review of Vaccines | Year: 2010
Challenges in the development of an effective HIV-1 vaccine are myriad with significant hurdles posed by viral diversity, the lack of a human correlate of protection and difficulty in creating immunogens capable of eliciting broadly neutralizing antibodies. The implicit requirement for novel approaches to these problems has resulted in vaccine candidates designed to elicit cellular and/or humoral immune responses, to include recombinant DNA, viral and bacterial vectors, and subunit proteins. Here, we review data from clinical studies primarily of poxvirus and adenovirus vector vaccines, used in a heterologous prime-boost combination strategy. Currently, this strategy appears to hold the most promise for an effective vaccine based on results from immunogenicity testing and nonhuman primate challenge models, as well as the modest efficacy recently observed in the Thai prime-boost trial. © 2010 Expert Reviews Ltd.
Rodriguez-Barraquer I.,Johns Hopkins University |
Buathong R.,Ministry of Public Health |
Iamsirithaworn S.,Ministry of Public Health |
Nisalak A.,Armed Forces Research Institute of Medical science |
And 5 more authors.
American Journal of Epidemiology | Year: 2014
Dengue virus has traditionally caused substantial morbidity and mortality among children less than 15 years of age in Southeast Asia. Over the last 2 decades, a significant increase in the mean age of cases has been reported, and a once pediatric disease now causes substantial burden among the adult population. An age-stratified serological study (n = 1,736) was conducted in 2010 among schoolchildren in the Mueang Rayong district of Thailand, where a similar study had been conducted in 1980/1981. Serotype-specific forces of infection (λ(t)) and basic reproductive numbers (R0) of dengue were estimated for the periods 1969-1980 and 1993-2010. Despite a significant increase in the age at exposure and a decrease in λ(t) from 0.038/year to 0.019/year, R0 changed only from 3.3 to 3.2. Significant heterogeneity was observed across subdistricts and schools, with R0 ranging between 1.7 and 6.8. These findings are consistent with the idea that the observed age shift might be a consequence of the demographic transition in Thailand. Changes in critical vaccination fractions, estimated by using R 0, have not accompanied the increase in age at exposure. These results have implications for dengue control interventions because multiple countries in Southeast Asia are undergoing similar demographic transitions. It is likely that dengue will never again be a disease exclusively of children. © 2013 The Author.
Lombardini E.D.,Armed Forces Research Institute of Medical science |
Harshbarger J.C.,George Washington University
Veterinary Pathology | Year: 2014
The veterinary literature contains scattered reports of primary tumors of the urinary tract of fish, dating back to 1906. Many of the more recent reports have been described in association with the Registry of Tumors in Lower Animals, and most of the spontaneous neoplasms of the kidney and urinary bladder are single case reports. In rare instances, such as described in nephroblastomas of Japanese eels and tubular adenomas/adenocarcinomas of Oscars, there is suggestion of a genetic predisposition of certain populations to specific renal neoplasms, environmental carcinogenesis, or potentially an unknown infectious etiology acting as a promoter. Hematopoeitic neoplasms have been infrequently described as primary to the kidney of a variety of fish species, and therefore those case reports of renal lymphoma and plasmacytic leukemia are addressed within the context of this review. © The Author(s) 2013.
Gibbons R.V.,Armed Forces Research Institute of Medical Science |
Streitz M.,Uniformed Services University of the Health Sciences |
Babina T.,Uniformed Services University of the Health Sciences |
Fried J.R.,Mahidol Oxford Tropical Medicine Research Unit
Emerging Infectious Diseases | Year: 2012
Dengue is a major cause of illness among travelers and a threat to military troops operating in areas to which it is endemic. Before and during World War II, dengue frequently occurred in US military personnel in Asia and the South Pacific. From the 1960s into the 1990s, dengue often occurred in US troops in Vietnam, the Philippines, Somalia, and Haiti. We found attack rates as high as 80% and periods of convalescence up to 3-1/2 weeks beyond the acute illness. The increase in dengue throughout the world suggests that it will remain a problem for military personnel until an effective vaccine is licensed.
Rodkvamtook W.,Armed Forces Research Institute of Medical Science
Journal of the Medical Association of Thailand = Chotmaihet thangphaet | Year: 2012
Scrub typhus caused by the Orientia tsutsugamushi. Rodents, particularly rats, serve as principal reservoir hosts. Infection in man is transmitted by the, chigger bite. Repellents provide an effective agent of protecting individuals from chigger. In the present study 6 plant essential oils were tested for evaluation of their repellent activity against the chigger, Leptotrombidium imphalum. The results showed that Clove oil was significantly more effective than others with ED50 and EC50 of 0.420 mg and 2.3%, followed by Zingiber oil (8.458 mg and 42.3%), Vetiver oil (19.582 mg and 97.9%), Turmeric oil (24.343 mg and 121.7%), Orange oil (27.310 mg and 136.6%) and Boesenbergia oil (30.486 mg and 152.4%). These results suggested that Clove oil was the most efficient repellent against chigger which is the vector for scrub typhus.
Chuenchitra T.,Armed Forces Research Institute of Medical science
Journal of the Medical Association of Thailand = Chotmaihet thangphaet | Year: 2012
Cytokines play an important role in controlling the homeostasis of the immune system and contribute to the pathogenesis of HIV infection. The measurement soluble cytokines in plasma of HIV-1 infected individuals with different rates of disease progression may provide additional information to complement prognostic markers and understand disease process. The aim of the present study was to determine the cytokine profiles in plasma of Thai HIV-1 CRFO1_AE infected individuals with different rates of disease progression by using a multiplex system for simultaneous detection of 7 cytokines. The authors used a multiplex immunoassay method to measure 7 cytokines (IL-2, IL-4, IL-6, IL-7, IL-10, IL-15 and IFN-gamma) in plasma of 23 progressors (PRs; symptomatic or AIDS within 5 years and CD4+ < 200/mm3), 23 slower progressors (SPs; asymptomatic more than 5 years and CD4+ > 350/mm3) and 23 normal healthy individuals. Both PRs and SPs demonstrated significantly higher levels of IL-7, IL-10 and IFN-gamma than healthy controls (p < 0.05). No significant difference in IL-6 between SPs and healthy controls but significant difference between RPs and controls were found. Furthermore, PRs showed significantly higher levels of plasma IL-6 (p = 0.001), IL-7 (p = 0.016), IL-10 (p < 0.001) and IFN-gamma (p = 0.026) than SPs. No significant difference in IL-2, IL-4 and IL-15 was found among 3 groups (PRs, SPs and healthy control). These results suggested that a Th1 to Th2 cytokine switch did not occur. However, the measurements of plasma levels of cytokines could be used for predicting disease progression.
Blagborough A.M.,Imperial College London |
Yoshida S.,Jichi Medical University |
Sattabongkot J.,Armed Forces Research Institute of Medical science |
Tsuboi T.,Ehime University |
Sinden R.E.,Imperial College London
Vaccine | Year: 2010
We have recently developed a new experimental vaccine vector system based on Autographa californica nucleopolyhedrosis virus (AcNPV) termed the "Baculovirus Dual Expression System", which drives expression of vaccine candidate antigens by a dual promoter that consists of tandemly arranged baculovirus-derived polyhedrin and mammalian-derived CMV promoters. The present study used this system to generate a Plasmodium vivax transmission-blocking immunogen (AcNPV-Dual-Pvs25). AcNPV-Dual-Pvs25 not only displayed Pvs25 on the AcNPV envelope, exhibiting aspects of its native three-dimensional structure, but also expressed appropriately immunogenic protein upon transduction of mammalian cells. Both intranasal and intramuscular immunization of mice with AcNPV-Dual-Pvs25 induced high Pvs25-specific antibody titres, notably of IgG1, IgG2a and IgG2b isotypes, indicating a mixed Th1/Th2 response. Importantly, sera obtained from subcutaneously immunized rabbits exhibited a significant transmission-blocking effect (96% reduction in infection intensity, 24% reduction in prevalence) when challenged with human blood infected with P. vivax gametocytes using the standard membrane feeding assay. Additionally, active immunization (both intranasal and intramuscular routes) of mice followed by challenge using a transgenic P. berghei line expressing Pvs25 in place of native Pbs25 and Pbs28 (clone Pvs25DR3) demonstrates a strong transmission-blocking response, with a 92.1% (intranasal) and 83.8% (intramuscular) reduction in oocyst intensity. Corresponding reductions in prevalence of infection were observed (88.4% and 75.5% respectively). This study offers a novel tool for the development of malarial transmission-blocking vaccines against the sexual stages of the parasite, using the Baculovirus Dual Expression System that functions as both a subunit, and DNA based vaccine. © 2010 Elsevier Ltd.