Safety and immunogenicity of a mutagenized, live attenuated Rift Valley fever vaccine, MP-12, in a Phase 1 dose escalation and route comparison study in humans.

Rift Valley fever (RVF) poses a risk as a potential agent in bioterrorism or agroterrorism. A live attenuated RVF vaccine (RVF MP-12) has been shown to be safe and protective in animals and showed promise in two initial clinical trials. In the present study, healthy adult human volunteers (N=56) received a single injection of (a) RVF MP-12, administered subcutaneously (SQ) at a concentration of 10(4.7) plaque-forming units (pfu) (SQ Group); (b) RVF MP-12, administered intramuscularly (IM) at 10(3.4)pfu (IM Group 1); (c) RVF MP-12, administered IM at 10(4.4)pfu (IM Group 2); or (d) saline (Placebo Group). The vaccine was well tolerated by volunteers in all dose and route groups. Infrequent and minor adverse events were seen among recipients of both placebo and RVF MP-12. One subject had viremia detectable by direct plaque assay, and six subjects from IM Group 2 had transient low-titer viremia detectable only by nucleic acid amplification. Of the 43 vaccine recipients, 40 (93%) achieved neutralizing antibodies (measured as an 80% plaque reduction neutralization titer [PRNT80]) as well as RVF-specific IgM and IgG. The highest peak geometric mean PRNT80 titers were observed in IM Group 2. Of 34 RVF MP-12 recipients available for testing 1 year following inoculation, 28 (82%) remained seropositive (PRNT80≥1:20); this included 20 of 23 vaccinees (87%) from IM Group 2. The live attenuated RVF MP-12 vaccine was safe and immunogenic at the doses and routes studied. Given the need for an effective vaccine against RVF virus, further evaluation in humans is warranted.

An assessment of health status among medical research volunteers who served in the Project Whitecoat program at Fort Detrick, Maryland.

Between 1954 and 1973, more than 2000 men entering military service as conscientious objectors participated in Project Whitecoat as medical research volunteers for the Army's biological warfare defense program. An assessment of self-reported, current health status among 358 "exposed" individuals and 164 unexposed control subjects found no conclusive evidence that receipt of investigational agents was related to adverse health outcomes. No differences in current overall health, current exercise levels, self-reported symptoms, and self-reported medical conditions were seen between the study groups. Possible associations were seen between exposure to antibiotics or other biological agents and self-reported asthma (13.0% vs. 2.4%, relative risk [RR] = 6.00, 95% confidence interval [CI] = 1.03-34.90, p = 0.050), as well as between receipt of tularemia vaccine(s) and self-reported asthma (13.3% vs. 2.4%, RR = 6.15, 95% CI = 1.03-36.70, p = 0.049) and increased frequency/severity of headaches (35.6% vs. 18.3%, RR = 2.46, 95% CI = 0.99-6.15, p = 0.074). However, the size of the population under study was insufficient to assert with confidence that these statistical associations are real.

Long-term health effects of repeated exposure to multiple vaccines.

The health of 155 former workers in a US military research program who had received multiple vaccines and 265 matched community controls was assessed. The study population was mostly male (83%) and elderly (median age, 69 years). Multiply immunized (MIP) subjects received vaccines and/or skin tests (median = 154) over a median of 17.3 years; interval from start of immunizations to survey completion was 15-55 years (mean = 43.1 years). MIP subjects characterized themselves as slightly less healthy than controls (P = 0.057). Fatigue (but no other symptom) was reported more frequently in the MIP group (P = 0.011), but was not associated with number of injections, number of vaccines, or time in program. No differences between MIP and control groups were seen for numerous self-reported medical conditions. Several statistically significant abnormalities were seen in clinical laboratory tests among MIP subjects, but none appeared to be clinically significant. A significant difference in frequency of monoclonal spikes and/or paraprotein peaks between MIP (12.5%) and control (4.5%) groups (RR = 2.7, P < 0.003) was observed; no associations with lifestyle, vaccine exposure, or medical conditions were found.

Medical informatics standards applicable to emergency department information systems: making sense of the jumble.

The adoption of medical informatics standards by emergency department information systems (EDISs) is not universal, despite obvious benefits. Clinicians and administrators looking to obtain an EDIS need to know exactly what the various standards can do for them and how the systems they depend on can be integrated and extended. In addition to the standard methods for systems to communicate (chiefly Health Level 7 [HL7]) and those required for submission of claims (Current Procedural Terminology [CPT]-4, International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM], and X12N), there are several other available standards that are clinically useful and can greatly improve the ability to access and exchange patient information. Major advances in the Unified Medical Language System of the National Library of Medicine have made the patient medical record information standards (Systematized Nomenclature of Medicine [SNOMED], Logical Observation Identifiers, Names, and Codes [LOINC], RxNorm) easily accessible. Detailed knowledge of the arcana associated with the technical aspects of the standards is not needed (or desired) by clinicians to use standards-based systems. However, some knowledge about the commonly used standards is helpful in choosing an EDIS, interfacing the EDIS with the other hospital information systems, extending or upgrading systems, and adopting decision support technologies.