U.S. Army Medical Research Institute Of Infectious Diseases Research Articles

Clinical characterization and placental pathology of mpox infection in hospitalized patients in the Democratic Republic of the Congo

We describe the results of a prospective observational study of the clinical natural history of human monkeypox (mpox) virus (MPXV) infections at the remote L'Hopital General de Reference de Kole (Kole hospital), the rainforest of the Congo River basin of the Democratic Republic of the Congo (DRC) from March 2007 until August 2011. The research was conducted jointly by the Institute National de Recherche Biomedical (INRB) and the US Army Medical Research Institute of Infectious Diseases (USAMRIID). The Kole hospital was one of the two previous WHO Mpox study sites (1981-1986). The hospital is staffed by a Spanish Order of Catholic Nuns from La Congregation Des Soeurs Missionnaires Du Christ Jesus including two Spanish physicians, who were members of the Order as well, were part of the WHO study on human mpox. Of 244 patients admitted with a clinical diagnosis of MPXV infection, 216 were positive in both the Pan-Orthopox and MPXV specific PCR. The cardinal observations of these 216 patients are summarized in this report. There were three deaths (3/216) among these hospitalized patients; fetal death occurred in 3 of 4 patients who were pregnant at admission, with the placenta of one fetus demonstrating prominent MPXV infection of the chorionic villi. The most common complaints were rash (96.8%), malaise (85.2%), sore throat (78.2%), and lymphadenopathy/adenopathy (57.4%). The most common physical exam findings were mpox rash (99.5%) and lymphadenopathy (98.6%). The single patient without the classic mpox rash had been previously vaccinated against smallpox. Age group of less than 5 years had the highest lesion count. Primary household cases tended to have higher lesion counts than secondary or later same household cases. Of the 216 patients, 200 were tested for IgM & IgG antibodies (Abs) to Orthopoxviruses. All 200 patients had anti-orthopoxvirus IgG Abs; whereas 189/200 were positive for IgM. Patients with hypoalbuminemia had a high risk of severe disease. Patients with fatal disease had higher maximum geometric mean values than survivors for the following variables, respectively: viral DNA in blood (DNAemia); maximum lesion count; day of admission mean AST and ALT.

Evaluation of 16 molecular assays for the detection of orthopox and mpox viruses

The current global mpox virus (MPXV) outbreak has been declared a Public Health Emergency of International Concern by WHO, with more than 80,000 cases confirmed across multiple continents. Diagnosis is confirmed by PCR of viral DNA from vesicle and other swabs. The aim of this study was to assess commercial RT PCR assays for Orthopoxvirus (OPX) and MPXV for analytical sensitivity, and percent agreements and compare them to primer/probe sets employed at the Victorian Infectious Diseases Reference Laboratory (VIDRL), Centers for Disease Control andPrevention (CDC) and US Army Medical Research Institute of Infectious Diseases (USAMRIID). Limits of detection (LOD), intra-run variability, cross-reactivity and performance on forty clinical samples was assessed on eleven commercial assays and five primer/probe combinations used at VIDRL, CDC and USAMRIID. All assays were able to detect OPX and MPXV (LOD 57 to 14,495 copies/mL) with intra-run coefficients of variation between Cycle thresholds of 0.58 and 3.44, and there was no unexpected cross-reactivity. All assays demonstrated 100% negative percent agreement with clinical samples and all but one yielded 100% positive percent agreement. Variations in LOD between assays may be dependent on the platform used and sample type. Despite the overall comparable performance of the assays assessed, it is important that routine laboratories perform in-house validations before implementing RT PCR for OPX and/or MPXV as reliable and accurate laboratory diagnosis of MPXV and isolation is crucial to containing the spread of this current outbreak and informing public health interventions and response.

Development of an o-pthalaldehyde (OPA) assay to measure protein content in Ricin Vaccine E. coli (RVEc™)

A recombinant ricin vaccine from E. coli (RVEc™), was developed at the US Army Medical Research Institute of Infectious Diseases (USAMRIID) and assessed in an FDA sponsored Phase 1a clinical trial. At the maximum dosage, two of the study participants developed physiological responses that were elevated to the level of severe adverse reactions. To stay within safe dosing guidelines, the FDA recommended that an assay be developed to accurately quantify the recombinant protein content in the vaccine. The RVEc™ vaccine Final Drug Product (FDP) contains the adjuvant Alhydrogel®, which by its colloidal nature interferes with most conventional protein assay methods. We decided to develop an assay measuring RVEc™ FDP using o-pthalaldehyde (OPA) reagent. The OPA reagent reacts to the primary amines and lysine side chains of proteins in the presence of a thiol under alkaline conditions with a quantifiable fluorescent signature, but does not react with Alhydrogel®. Protein content in the RVEc™ FDP can be determined by comparing the fluorescence of the test sample to the fluorescence of a standard curve of defined concentration. Each phase of the assay was tested to optimize and simplify the assay procedure. The accuracy, specificity, reproducibility, and stability of the assay were evaluated. Results indicated that the optimized and modified OPA assay was simple and able to quantify antigen concentration from a standard curve in the 25 µg/mL–600 µg/mL range. The assay accuracy and coefficient of variation (CV) was 95% and less than 8%, respectively, when determining the ricin protein content in the 200 µg/mL vialed RVEc™ FDP. The assay was simple to perform and used conventional laboratory equipment. This assay could be adapted to measure the protein content in the FDP of other vaccines, but with the proviso that each step of the assay would need to be optimized for each antigen.

Epidemiological Review of Francisella Tularensis: A Case Study in the Complications of Dual Diagnoses.

Introduction:Tularemia is a rare but potentially fatal disease that develops in numerous wild and domestic animals, including lagomorphs, rodents, cats, and humans. Francisella tularensis bacterium, the causative agent of tularemia, was identified by veterinary personnel at Fort Riley, Kansas during a routine post-mortum evaluation of a domestic feline. However, before formal diagnosis was confirmed, the sample was sent and prepared for rabies testing at the Department of Defense (DoD) U.S. Army Public Health Command Central (PHC-C), Food Analysis and Diagnostic Laboratory (FADL). This case report provides insight on how veterinarian staff and laboratory personnel can clinically manage esoteric, unexplained, or post-mortum examinations. The epidemiologic characteristics of tularemia, F. tularensis as an organism of military interest, potential laboratory management of F. tularensis, and clinical findings on a case of feline tularemia are discussed. It further raises questions as to whether or not dead animals should be treated as sentinels and be pre-screened for select agents, especially in instances of dual diagnoses.Methods:A necropsy was performed on the cat by the Fort Riley veterinarian, DNA extraction and PCR analyses were conducted by FADL microbiologists, histology and immunohistology analyses were conducted by the Kansas State Veterinary Diagnostic Laboratory, and feline tissue and blood were sent to the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) for confirmatory testing and strain identification of tularemia.Results:Tularemia was identified in the spleen of the cat by the Fort Riley veterinarian and during the histological sampling of the spleen by the Kansas State Veterinary Diagnostic Laboratory. A specific subsequent real-time polymerase chain reaction (RT-PCR) in vitro diagnostic detection of target DNA sequences of F. tularensis was conducted by the FADL microbiologists using a Joint Biological Agent Identification and Diagnostic System (JBAIDS) Tularemia Detection Kit to detect a presumptive qualitative result to detect tularemia in feline and blood samples. USAMRIID also performed RT-PCR and identified genomic DNA from F. tularensis Type A, (SPL15.013.02), thus confirming the FADL’s initial presumptive result of F. tularensis. USAMRIID attempted to culture F. tularensis from three samples (swab, feline tissue, and transfer pipette tip), but no growth consistent with F. tularensis was observed on the cysteine heart agar with sheep blood and antibiotics (CHAB) and chocolate (CHOC) plates. Discussions:Our case study of a dual diagnosis of presumptive F. tularensis and possible rabies exposure transmission from a pet cat to its owner provides insight on how veterinarian staff and laboratory personnel can clinically manage esoteric, unexplained, or post-mortum examinations. Our case study also demonstrates the obligation for cooperation between animal health, human health, and public health professionals in the management of zoonotic diseases.

A Brief History of Biocontainment.

Opinion statementThe concept of clinical biocontainment, otherwise known as high-level containment care (HLCC), had its birth among a confluence of near-simultaneous events in 1969. The U.S. Army’s Medical Research Institute of Infectious Diseases (USAMRIID) began construction of the first modern biocontainment unit that year, and opened the two-bed facility, often referred to as “the Slammer” in 1971. Over its 41-year existence, 21 persons exposed to highly hazardous infectious diseases were admitted to the Slammer, but none ever contracted the disease to which they had been exposed. Owing, in part, to this underutilization, some questioned the utility of HLCC units. This concern notwithstanding, Emory University and the University of Nebraska opened HLCC units in civilian academic medical centers in 2004 and 2005, respectively. These units, distinct from conventional infectious disease isolation wards found in most major medical centers, proved their worth during the West African Ebola Virus Disease (EVD) outbreak of 2014–2015. It is our opinion that such units, as well as the parallel high-level containment transport systems necessary to move patients to them, will continue to play an important role in the global response to emerging and highly hazardous contagious pathogens. Moreover, we feel that the lessons derived from their successful operation will lead to improvements in infection control procedures and practices throughout the healthcare system.

Hard Lessons In Ebola Research

Last year, at the height of the Ebola outbreak, Sina Bavari and Travis Warren found their labs at the U.S. Army Medical Research Institute of Infectious Diseases ( USAMRIID) flooded with compounds for testing against the Ebola virus. Well-meaning drug companies hoping to help stem the crisis were offering anything that might have activity against Ebola to the government lab, which is one of only a handful of places in the country with a containment facility for screening molecules against the deadly virus. Bavari and Warren were happy for the help but also overwhelmed as well as uncertain whether anything they were getting would actually work. Most of the compounds were developed for other diseases. Bavari, who is chief scientific officer of USAMRIID, compared the screening effort to trying to catch apples by holding a basket under a peach tree. Fortunately, at least one apple seems to have fallen. In ...

Mutations in Ebola Not Disrupting Drug Binding Sites—So Far

The mechanisms of the experimental therapeutics used during the 2014–2015 West African Ebola epidemic were developed to target strains that caused the 1976 and 1995 outbreaks. However, some 600 mutations appear in circulating strains of Ebola that postdate those earlier strains, and 10 of those changes might affect the efficacy of these therapeutics, according to Gustavo F. Palacios of the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) at Fort Detrick in Frederick, Md., and his collaborators. Details appeared 20 January 2015 in mBio (doi:10.1128/mBio.02227–14).

Tempering the risk: Rift Valley fever and bioterrorism

Rift Valley fever virus (RVFV) is an arthropod-borne pathogen that primarily affects ruminants in eastern and sub-Saharan Africa first described following an outbreak on a farm in Kenya in 1931. Periodic outbreaks of RVFV since that time have resulted in significant losses to the African livestock industry as well as large numbers of infections in some of the most impoverished human populations. In one 2006/2007 outbreak across Kenya, Somalia and Tanzania alone, there were an estimated 145 000 human cases, and the ban imposed on imports after the 1997/1998 outbreak in Somalia led to a collapse of the vital livestock industry. Previously ignored, it is only in the past decade that the international community has started to take an increased interest in the disease. This followed the recognition of its potential to spread beyond the confines of the African continent after a large outbreak in Saudi Arabia in 2000. There has also been acknowledgement of the widespread presence of arthropod vectors capable of transmitting RVFV in many nonendemic regions of the world. This has led to a range of increased efforts in better understanding the virus and developing tools to predict outbreaks, combat the disease and limit its spread (Anyamba et al. 2010; Pepin et al. 2010). However, a more longstanding, parallel interest in the disease has also developed internationally; one centred around the biosecurity implications of the virus. The United States for instance, included RVFV as a candidate pathogen in its offensive biological weapons programme; a programme officially closed in 1969 (Borio et al. 2002). In more recent times, the classification of the virus as a potential bioterrorism agent has spurred investment and activity, particularly in the area of vaccine development and diagnostics (Borio et al. 2002; Sidwell & Smee 2003). While biosecurity interest has contributed to this increased funding over the past few decades, most notably from military sources such as the US Army Medical Research Institute of Infectious Diseases (USAMRIID), it may have acted as an impediment to international collaboration, with research being restricted to fewer, more expensive laboratories. After the signing of the US Patriot Act of 2002 and the classification of RVFV as a ‘select agent’, visiting experts and scientific collaborators are, for instance, now required to provide fingerprints, signed affidavits and be registered with intelligence services before working with the pathogen. Such measures are likely to act as a disincentive amongst scientists wanting to study the virus and could ultimately serve to drive experts to dedicate their efforts to other pathogens with fewer working restrictions (Animal & Plant Health Inspection Service, Centre for Disease Control & Prevention 2005, 2011). These restrictions have also been applied in parts of Europe as well, with national legislation such as the Anti-terrorism, Crime and Security Act 2001 of the UK, which also includes RVFV as a potential bioterrorism agent. For comparison and contrast, we include the current lists of biological agents and toxins around which bioterrorism legislation has been passed in the US and UK in Table 1. Focus on US policy internationally stems from its greater leadership role within the global community and the influence and impact its decisions have on people and institutions far beyond its borders. With large numbers of laboratories worldwide affected by US policy either directly through funding or indirectly as a result of political influence, restrictions have also resulted in the transfer between laboratories of RVFV samples for culture also becoming constrained and increasingly expensive. This undermines efforts to lower the industrial production costs of existing vaccines and of commercial kits for virus neutralisation and ELISA diagnostic tests (currently the prescribed tests for international livestock trade) (World Organization for Animal Health 2008). Expertise and experience thus tends to remain confined to a limited number of laboratories and companies by and large located in high income countries where investigation of the disease is neither a significant economic or health priority nor considered sufficiently profitable for drug companies. The resulting monopolies on expert technical knowledge and skills not only delays progress in developing new therapies

The Need for Professional Society Advocacy for a Laboratory-acquired Illness/Incident Reporting and Analysis System

Biosafety professionals have long recognized the value of information derived from the reporting and analysis of laboratory-acquired illnesses (LAIs). Analysis of events surrounding an exposure event which resulted in an LAI has been used to identify equipment and facility design issues and flaws in operational procedures, as well as the hazardous characteristics of biological agents that are being studied or manipulated. Information obtained from the investigation and analysis of LAIs is a valuable resource for assessing risks posed by proposed work with pathogens, designing and selecting protective equipment and facilities, and developing agent-specific occupational health and surveillance programs. Lessons learned from analyzing LAIs also can provide a basis for developing educational tools in the form of case studies and utilized for training laboratory workers, principal investigators, and biosafety professionals. Some institutions such as the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) have a good track record of reporting and publishing exposure events that have resulted in LAIs and continue to look for new ways to present this information to the life-sciences community and their stakeholders (CDC, 2000; Mabeus, 2012; Rusnak, 2004). Unfortunately, institutions that routinely report and share lessons learned from LAIs remain the exception rather than the rule. All institutions that have experienced LAIs should be encouraged to share with the larger life-science community, via publication in scientific journals or reporting in another accessible resource LAIrelated information and analysis of the event. Sharing the nature of the incident, the probable cause, and lessons learned with relevant stakeholders would allow many individuals and facilities to benefit from an unfortunate event (Kozlovac, 2011). One hallmark of an organization that incorporates safety as an institutional value within its organizational culture is encouraging employee participation in reporting accidents, near misses, and unsafe conditions. Another hallmark is that the organization’s leadership has established a mechanism to investigate reported issues and ensure corrective actions are identified, documented, and communicated to relevant staff in a timely manner. Although most organizations have developed internal reporting mechanisms, perhaps one of the disincentives for an organization to report and share information on LAIs and incidents with the broader community is the absence of an easy, voluntary mechanism for sharing LAI information. Indeed, a central theme common to published LAI research within the scientific literature—beginning with the first surveys conducted by Kisskalt (1915), continuing with the collective work of Sulkin and Pike (1951, 1979), and the more recent reviews by Sewell (1995), Harding and Byers (2000), and Weinstein and Singh (2009)—is that LAI risk determination is hampered by the lack of a systematic reporting mechanism at the regional, national, or international level. Indeed, biosafety professionals have intermittently discussed the need and recommended the establishment of such a system for many years. Unfortunately, establishing such a system has been beset with many challenges and obstacles, including a lack of sustained advocacy from professional biosafety organizations.

Living Weapons: Biological Weapons and International Security

In the summer of 1996, as a (much younger) Army infectious disease physician, I headed off to a new assignment with the US Army Medical Research Institute of Infectious Diseases (USAMRIID) at Fort Detrick, Maryland. It was a heady time to be entering the niche field of biodefense. Five years before the events of 9/11 and the subsequent “Amerithrax” attacks would become an integral part of the world’s consciousness, USAMRIID was (with the exception of a few veterinary laboratories studying anthrax, brucellosis, Q fever, and similar zoonotic diseases) the “only game in town.” The institute had quietly wrestled with issues of medical biodefense since the United States shuttered its old offensive biowarfare program in 1969. As an assignee to its division of operational medicine, I was enamored of my ability to master the sparse literature and science of the field and soon became an “expert.” Such luxurious self-confidence is no longer warranted (if it ever was) or even possible. The field has, for better or worse, burgeoned in the decade since 9/11. Hundreds of texts and thousands of scientific articles now address every aspect of the daunting problems of biowarfare and bioterrorism defense, and mastery of such material is beyond the grasp of any one scientist, diplomat, or arms-control expert. Fortunately, several good reviews exist to guide those wishing to gain a basic understanding of these complex issues. Was yet another treatise thus necessary? My initial reaction was an emphatic “no,” until I read Gregory Koblentz’s book, Living Weapons. Koblentz, deputy director of a graduate degree program in biodefense at George Mason University, tackles the myriad issues surrounding biodefense from a policy perspective. In so doing, however, he puts forth a readable, succinct, yet thorough review of the field. After a crisp introduction to the history of biowarfare, he focuses on the seemingly insurmountable obstacles to nonproliferation efforts aimed at state-sponsored weapons programs: treaty compliance verification, program oversight, and intelligence. He then addresses the parallel problems posed by nonstate actors and terrorists and closes with a prescription for reducing the dangers of uncontrolled biology. A tour de force of bureaucratic hurdles and treaty-compliance issues would hardly seem compelling reading for all but a few die-hard policy wonks. Not so in the case of Koblentz’s text. Even though his penchant for frequent summary makes for some redundancy, he provides an extremely readable, yet comprehensive, compendium of the implications for national security posed by wayward biology. Moreover, he does so without the ideological bias often found in other treatises on this subject. Specifically, Koblentz delivers a detailed review of the United Nations Special Commission inspections in Iraq and the lessons they provide. He similarly deals with the now-discredited 2002 National Intelligence Estimate, which provided much of the impetus for President George Bush’s decision to invade Iraq. Yet, he analyzes these efforts and their implications for diplomats, policymakers, and arms-control experts without descending into partisan politics or anti-US demagoguery. In summary, Living Weapons is a thoroughly readable book, filled with enough anecdotes to capture the reader’s interest. But, more importantly, it provides a disturbing yet refreshing look at the myriad obstacles confronting those who would play a role—whether political, diplomatic, or scientific—in attempting to rein in the use of biology in war and terror. It is a must read for graduate students and experts alike.

Questions Linger over Science behind Anthrax Letters

Despite the outcome in mid-2008 of the Federal Bureau of Investigation (FBI) probe into the deadly and disruptive anthrax attacks of 2001, the FBI in May arranged for the National Academy of Sciences (NAS) to review the microbial and other forensic efforts that bureau officials coordinated as part of its broader investigation. It led FBI officials to conclude that microbiologist Bruce Ivins of the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) at Fort Detrick in Frederick, Md., was the sole culprit behind the letter-based attacks (Microbe, October 2008, p. 453).

FBI’S ANTHRAX ANALYSIS

FBI OFFICIALS and scientific experts revealed more information about the scientific experiments used to study anthrax spores disseminated in 2001 mailings at a briefing held on Aug 18. The briefing aimed to ease speculation about the bureau’s conclusions. “After nearly seven years of investigation, we have developed a body of powerful evidence that allows us to conclude that we have identified the origin and the perpetrator of the 2001 Bacillus anthracis mailings,” said Vahid Majidi of the FBI’s Weapons of Mass Destruction Directorate. Last month, FBI officials identified Bruce E. Ivins, a longtime anthrax investigator at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), based in Fort Detrick, Md., as the primary suspect in the case. Ivins’ death on July 29 from an apparent suicide spurred controversy and speculation about the FBI investigation. Although the FBI does not typically disclose evidence against suspects who have not been officially charged, the circumstances surroundi...

Spores, Plagues, and History: The Story of Anthrax (review)

Reviewed by: Spores, Plagues, and History: The Story of Anthrax Michael B. A. Oldstone Chris Holmes . Spores, Plagues, and History: The Story of Anthrax. Dallas: Durban House, 2003. 227 pp. Ill. $15.95 (paperbound, 1-930754-45-0). Spores, Plagues, and History contains a mix of topics: the medical identification and treatment of anthrax, the history of the recent anthrax bioterror attack in the United States, the history of presumed anthrax use as a weapon of terror, and the influence of anthrax through history. These subjects are coupled with a discussion of past biowarfare programs, primarily of Japan, the United States, and Russia. The book is an enjoyable and overall informative read, although some [End Page 381] parts are superficially presented, lacking detail, while others, especially the history sections, provide more questions than answers. The clear strength of the volume is Chris Holmes's discussion of the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), the Army Dugway testing program, and the account of the anthrax bioterror attack in the United States in 2001. The reader is transported into the events occurring in Florida, post offices, the U.S. Senate, and NBC/CBS news networks. Holmes emphasizes that this investigation is still not complete four years later, and he relates the costs of surveillance and investigating hoaxes. Chapters on biowarfare experiments done by the Japanese in Manchuria and China in the 1930s and 1940s are chilling, as is the author's discussion of the agreements regarding the fate of Japan's biological weapons between Japan and the United States, and Japan and Russia, after World War II—and the effect of these bargains on the Cold War. Unfortunately, there are a number of weaknesses that lessen the value of this book. For one, there are overt errors. For example, the statement "Anthrax was diagnosed by Polymerase Chain Reaction (PCR) testing, a technique which produces large amounts of bacteria from a single cell" (p. 13) is incorrect: PCR amplifies the DNA of a sample, and does not enhance organisms' growth. Second, there are also a number of omissions. For example, although there is detail as to the clinical diagnosis of anthrax and the treatment of the disease, there is minimal information as to why anthrax is virulent: mention is made of "protective antigens," "lethal factor," and "edema factor"—but what they are, and how they work, is given short shrift. This is unfortunate, given the enormous knowledge on the structure and function of these toxins that has accumulated over the last several years. Similarly, there is no information on either how the antibiotics work against anthrax, or how the vaccine works. Other omissions that lessened the value of the book to this reader were the lack of discussion on host susceptibility, or why certain people got sick and others did not, and what separates sickness from death. Later in the book (p. 133), Table 2 lists the advantages of various biological weapons in terms of influencing a population of 500,000 to become predictably ill or to die. Its source is listed as only WHO: there is no bulletin, volume, page, or year listed, in either the text or the references, to allow the interested reader to further explore this issue. Similarly, the outbreak of anthrax in Sverdlovsk, Russia, in the 1970s is presented in a way that the reader is unable to satisfactorily evaluate because the total number of those exposed is not given—just the numbers of those who died, entered hospital, or were ill. Lastly, although it is interesting for discussion, there is little evidence to support the author's claim that anthrax was probably one (the fifth and sixth) of the ten plagues visited on the pharaoh of Egypt through God's messenger, Moses; or that anthrax killed Alexander the Great; or that it caused the Plague of Athens; or that it was involved in the Great Plague of the thirteenth century. However, the discussion of woolsorter's disease in England and of Pasteur's anthrax vaccine study in Pouilly-le-Fort, and the association of anthrax as a bioterror weapon with the Iraqis in the Gulf War and the period leading up to the...

TOXIN FOUND IN SENATE MAIL ROOM

THE ANTHRAX ATTACKS OF October 2001 have had one salutary effect: Congress was better prepared for the recent ricin scare that harmed no one and only temporarily closed three Senate office buildings. On Feb. 2, a white powder was discovered in Senate Majority Leader Bill Frist's Dirksen building mail room. Analyses of the powder identified the potentially lethal poison ricin, aplant protein. Officials have not released information on the purity, formulation—whether other chemicals were added—or particle size of the ricin used, says Jonathan B. Tucker, abioweapons expert with the Monterey Institute. The fact that no one has become ill suggests that the material was crude and not particularly dangerous. Unlike anthrax, ricin not infectious and is not a good mass casualty agent, says David R. Franz, a senior biological scientist at Midwest Research Institute and former commander of the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID). It makes a good terror weapon, ...

Hopkins Dean criticizes smallpox research

Bioterrorism research appears to be the hottest lab activity in the US at the moment, and virtually every university website carries a special focus on the field. But not everyone is enamored of the types of investigation taking place. Alfred Sommer, Dean of the Johns Hopkins Bloomberg School of Public Health, has broken ranks and gone public with criticism of smallpox studies at the US Army Medical Research Institute of Infectious Diseases (USAMRIID) in Fort Detrick, Maryland.

Role of the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) as a Component of the Military Public Health Laboratory System: A Historical Perspective (Abstract No. 7)

Role of the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) as a Component of the Military Public Health Laboratory System: A Historical Perspective (Abstract No. 7)

Antibodies that protect mice against ebola virus hold promise of vaccine and therapy for disease

Researchers in the virology division of the US Army Medical Research Institute of Infectious Diseases (USAMRID) have identified several antibodies that protect mice from infection with the deadly Ebola virus ( Science 2000;287:1664–1666). In fact, the team led by Julie Wilson, PhD, said that the antibodies protected the mice whether …

Immunogenicity of an inactivated Rift Valley fever vaccine in humans: a 12-year experience

Rift Valley fever (RVF) virus causes serious and fatal disease in animals and man. To protect personnel who work with RVF virus in the laboratory, or troops who may be exposed to this virus, the US Army successfully developed an improved version of inactivated RVF vaccine, TSI-GSD-200. From early 1986 to late 1997, 598 at-risk workers at the US Army Medical Research Institute of Infectious Diseases (USAMRIID) were vaccinated as part of an occupational safety and health program. The subjects of this study received three subcutaneous doses (0, 7 and 28 days) of 0.5 ml of TSI-GSD-200. A total of 540 vaccinees (90.3%) initially responded (group A) with an 80% plaque-reduction neutralization antibody titer (PRNT 80) of ≥1:40; whereas 58 subjects (9.7%) were initial nonresponders (group B) failing to achieve this titer. Volunteers who either failed to respond or who achieved a titer of ≥1:40 but whose titer waned below 1:40 were boosted 1–4 times with the same vaccine. Among 247 group A subjects who received the first recall injection, 242 (98%) were successfully boosted, achieving a PRNT 80 ≥1:40. Thirty-three of 44 (75%) initial nonresponders were converted to responder status after the first booster, which is a lower rate than that of group A ( P<0.001). After the primary series and the first booster, Kaplan–Meier analysis showed 50% probability of group A members maintaining a titer of ≥1:40 for approximately eight years; whereas group B had a 50% probability of maintaining a titer for only 204 days. Group A immune response rates to boosts 1–4 ranged from 87 to 100% with geometric mean titers (GMTs) ranging from 80 to 916. Boosts 1–4 immune response rates of group B volunteers ranged from 67 to 79% with GMTs ranging from 90 to 177. Minor side effects to TSI-GSD-200 were noted in 2.7% of all vaccinees after primaries and 3.5% of all vaccinees who had primaries and up to four boosters. We conclude that the use of TSI-GSD-200 is safe and provides good long-term immunity in humans when the primary series and one boost are administered.