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Silver Spring, MD, United States

Richards A.L.,Naval Medical Research Center
FEMS Immunology and Medical Microbiology | Year: 2012

To determine the prevalence and distribution of rickettsial pathogens around the world, scientists have relied more and more upon molecular techniques in addition to serological and culture methods. The ease of use and sensitivity/specificity of molecular techniques such as quantitative real-time PCR assays and multilocus sequence typing have lead to an increase in reports of the detection and identification of new and old rickettsiae in previously known and in new endemic regions. These assays have been successfully used with clinical samples such as serum, blood, and tissue biopsies and with environmental samples such as arthropod vectors including ticks, fleas, lice, and mites, and blood and tissue specimens from small mammal collections and from wild and domestic large animals. These methods have lead to the detection of new and old rickettsial pathogens often in new locations leading investigators to suggest new regions of risk of these rickettsioses. © 2011.

Verdu E.F.,McMaster University | Riddle M.S.,Naval Medical Research Center
American Journal of Gastroenterology | Year: 2012

Acute infectious diarrhea is a frequent occurrence both in the developing world, where it results in considerable mortality, and in developed countries, where it accounts for a significant number of health visits, hospitalizations, and medical and non-medical losses. Recent evidence in basic, clinical, and epidemiological science domains has emerged that suggest that the burden caused by these infections is not limited to the acute illness, but may result in triggering or contributing to the pathogenesis of a number of chronic health problems. This review considers the breadth of this information for the purpose of consolidating what is currently known, identifying gaps in knowledge, and describing future directions and policy implications related to the chronic consequences of acute infectious diarrhea. A unifying hypothesis of this review is that infections may trigger a number of long-lasting changes in gut physiology and immunity that can increase the risk to a variety of chronic gastrointestinal diseases, particularly in genetically susceptible individuals.

Bevevino A.J.,Naval Medical Research Center
Clinical orthopaedics and related research | Year: 2014

Open calcaneus fractures can be limb threatening and almost universally result in some measure of long-term disability. A major goal of initial management in patients with these injuries is setting appropriate expectations and discussing the likelihood of limb salvage, yet there are few tools that assist in predicting the outcome of this difficult fracture pattern. We developed two decision support tools, an artificial neural network and a logistic regression model, based on presenting data from severe combat-related open calcaneus fractures. We then determined which model more accurately estimated the likelihood of amputation and which was better suited for clinical use. Injury-specific data were collected from wounded active-duty service members who sustained combat-related open calcaneus fractures between 2003 and 2012. One-hundred fifty-five open calcaneus fractures met inclusion criteria. Median followup was 3.5 years (interquartile range: 1.5, 5.1 years), and amputation rate was 44%. We developed an artificial neural network designed to estimate the likelihood of amputation, using information available on presentation. For comparison, a conventional logistic regression model was developed with variables identified on univariate analysis. We determined which model more accurately estimated the likelihood of amputation using receiver operating characteristic analysis. Decision curve analysis was then performed to determine each model's clinical utility. An artificial neural network that contained eight presenting features resulted in smaller error. The eight features that contributed to the most predictive model were American Society of Anesthesiologist grade, plantar sensation, fracture treatment before arrival, Gustilo-Anderson fracture type, Sanders fracture classification, vascular injury, male sex, and dismounted blast mechanism. The artificial neural network was 30% more accurate, with an area under the curve of 0.8 (compared to 0.65 for logistic regression). Decision curve analysis indicated the artificial neural network resulted in higher benefit across the broadest range of threshold probabilities compared to the logistic regression model and is perhaps better suited for clinical use. This report demonstrates an artificial neural network was capable of accurately estimating the likelihood of amputation. Furthermore, decision curve analysis suggested the artificial neural network is better suited for clinical use than logistic regression. Once properly validated, this may provide a tool for surgeons and patients faced with combat-related open calcaneus fractures in which decisions between limb salvage and amputation remain difficult.

Connor B.A.,Cornell University | Riddle M.S.,Naval Medical Research Center
Journal of Travel Medicine | Year: 2013

Background Travelers' diarrhea (TD) has generally been considered a self-limited disorder which resolves more quickly with expeditious and appropriate antibiotic therapy given bacteria are the most frequently identified cause. However, epidemiological, clinical, and basic science evidence identifying a number of chronic health conditions related to these infections has recently emerged which challenges this current paradigm. These include serious and potentially disabling enteric and extra-intestinal long-term complications. Among these are rheumatologic, neurologic, gastrointestinal, renal, and endocrine disorders. This review aims to examine and summarize the current literature pertaining to three of these post-infectious disorders: reactive arthritis, Guillain-Barré syndrome, and post-infectious irritable bowel syndrome and the relationship of these conditions to diarrhea associated with travel as well as to diarrhea associated with gastroenteritis which may not be specifically travel related but relevant by shared microbial pathogens. It is hoped this review will allow clinicians who see travelers to be aware of these post-infectious sequelae thus adding to our body of knowledge in travel medicine. Methods Data for this article were identified by searches of PubMed and MEDLINE, and references from relevant articles using search terms "travelers' diarrhea" "reactive arthritis" "Guillain-Barré syndrome" "Post-Infectious Irritable Bowel Syndrome." Abstracts were included when related to previously published work. Results and Conclusions A review of the published literature reveals that potential consequences of travelers' diarrhea may extend beyond the acute illness and these post-infectious complications may be more common than currently recognized. In addition since TD is such a common occurrence it would be helpful to be able to identify those who might be at greater risk of post-infectious sequelae in order to target more aggressive prophylactic or therapeutic approaches to such individuals. It is hoped this review will allow clinicians who see travelers to be aware of these post-infectious sequelae thus adding to our body of knowledge in travel medicine. © 2013 International Society of Travel Medicine.

Weiss W.R.,Naval Medical Research Center | Jiang C.G.,Naval Medical Research Center | Jiang C.G.,Booz Allen Hamilton
PLoS ONE | Year: 2012

Live attenuated malaria vaccines are more potent than the recombinant protein, bacterial or viral platform vaccines that have been tested, and an attenuated sporozoite vaccine against falciparum malaria is being developed for humans. In mice, attenuated malaria sporozoite vaccines induce CD8 + T cells that kill parasites developing in the liver. We were curious to know if CD8 + T cells were also important in protecting primates against malaria. We immunized 9 rhesus monkeys with radiation attenuated Plasmodium knowlesi sporozoites, and found that 5 did not develop blood stage infections after challenge with live sporozoites. We then injected 4 of these protected monkeys with cM-T807, a monoclonal antibody to the CD8 molecule which depletes T cells. The fifth monkey received equivalent doses of normal IgG. In 3 of the 4 monkeys receiving cM-T807 circulating CD8 + T cells were profoundly depleted. When re-challenged with live sporozoites all 3 of these depleted animals developed blood stage malaria. The fourth monkey receiving cM-T807 retained many circulating CD8 + T cells. This monkey, and the vaccinated monkey receiving normal IgG, did not develop blood stage malaria at re-challenge with live sporozoites. Animals were treated with antimalarial drugs and rested for 4 months. During this interval CD8 + T cells re-appeared in the circulation of the depleted monkeys. When all vaccinated animals received a third challenge with live sporozoites, all 5 monkeys were once again protected and did not develop blood stage malaria infections. These data indicate that CD8 + T cells are important effector cells protecting monkeys against malaria sporozoite infection. We believe that malaria vaccines which induce effector CD8+ T cells in humans will have the best chance of protecting against malaria.

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