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R Edelman

Publications and source records attributed to R Edelman.

At least 19 recordsLinked to original sources
PubMed2005

Epidemiology of capsular and surface polysaccharide in Staphylococcus aureus infections complicated by bacteraemia.

Staphylococcus aureus is a leading cause of serious hospital- and community-acquired infections. The discovery of serologically distinct capsular polysaccharides on the surface of clinical isolates has allowed the development of vaccines and passive protective immunity. We have studied patient characteristics, infection characteristics and the surface and capsular polysaccharide serotype distribution in patients with S. aureus infections complicated by bacteraemia admitted to VA hospitals in Maryland between 1995 and 2000. Nine hundred and ninety-three blood cultures from 331 patients were positive for S. aureus. Thirty-eight percent of patients had diabetes, 11% had end-stage renal failure, and 23% were injection drug users. Forty-two percent of infections were caused by methicillin-resistant strains (MRSA), and 60% were acquired during hospitalization. Serotyping of the first available isolate per patient (N=234 isolates) using polyclonal antibodies showed three major phenotypes--42%, type 8 (T8) capsule; 50%, type 5 (T5) capsule; and 8%, 336 polysaccharide. MRSA isolates were significantly more likely to be T5 than methicillin-susceptible isolates (66% vs. 39%, P<0.001). The proportion of T5 MRSA increased significantly (years 1-2: 41%; years 3-4: 65%; years 5-6: 90%, P<0.001). This large sample of patients with serious S. aureus infection confirms that capsular polysaccharides T5 and T8 cause most human infections, and together with serotype 336, account for nearly all those with bacteraemia.

Bacteremia↗
PubMed2003

Active surveillance for respiratory virus infections in adults who have undergone bone marrow and peripheral blood stem cell transplantation.

Community-acquired respiratory virus (RV) infections are an important cause of disease in immunocompromised adults with cancer. To investigate the viral etiology, incidence, clinical presentation, and outcome of RV infections in an outpatient cohort of adult bone marrow or peripheral blood stem cell transplant (SCT) recipients, we monitored 62 outpatient volunteers from January 1 to April 30, 2001. A nasopharyngeal aspirate was collected from subjects when they reported new respiratory symptoms and tested for RV (influenza A, influenza B, human parainfluenza 1-3, adenovirus, and respiratory syncytial virus) by culture and reverse transcription polymerase chain reaction (RT-PCR) assay. Of 62 subjects enrolled, 27% had received allogeneic SCT and 45% were within 1 year of their transplant. In all, 35 participants (56%) reported 37 episodes of respiratory symptoms. Of the 37 specimens tested, five (14%) were positive for RV by culture and 20 (54%) were positive by RT-PCR. Only six patients with RV infections developed lower respiratory tract illnesses; these patients had received either autologous or allogeneic transplants and developed illnesses between 41 and 2666 days post transplant. Although RV infections were common in SCT outpatients during the RV season, most participants had upper respiratory tract infections, which resolved without the need for hospitalization.

Adenoviridae↗
PubMed2003

Phase 1 studies of Walter Reed Army Institute of Research candidate attenuated dengue vaccines: selection of safe and immunogenic monovalent vaccines.

We describe the results of initial safety testing of 10 live-attenuated dengue virus (DENV) vaccine candidates modified by serial passage in primary dog kidney (PDK) cells at the Walter Reed Army Institute of Research. The Phase 1 studies, conducted in 65 volunteers, were designed to select an attenuated vaccine candidate for each DENV serotype. No recipient of the DENV candidate vaccines sustained serious injury or required treatment. Three vaccine candidates were associated with transient idiosyncratic reactions in one volunteer each, resulting in their withdrawal from further clinical development. Increasing PDK cell passage of DENV-1, DENV-2, and DENV-3 candidate vaccines increased attenuation for volunteers, yet also decreased infectivity and immunogenicity. This effect was less clear for DENV-4 candidate vaccines following 15 and 20 PDK cell passages. Only one passage level each of the tested DENV-2, -3, and -4 vaccine candidates was judged acceptably reactogenic and suitable for expanded clinical study. Subsequent studies with more recipients will further establish safety and immunogenicity of the four selected vaccine candidates: DENV-1 45AZ5 PDK 20, DENV-2 S16803 PDK 50, DENV-3 CH53489 PDK 20, and DENV-4 341750 PDK 20.

Adolescent↗
PubMed2003

Atypical antibody responses in dengue vaccine recipients.

Eight of 69 (12%) healthy adult volunteers vaccinated with monovalent live-attenuated dengue virus (DENV) vaccine candidates had atypical antibody responses, with depressed IgM:IgG antibody ratios and induction of high-titer hemagglutination-inhibiting and neutralizing (NT) antibodies to all four DENV serotypes. These features suggested flavivirus exposure prior to DENV vaccination, yet no volunteer had a history of previous flavivirus infection, flavivirus vaccination, or antibody to flaviviruses evident before DENV vaccination. Moreover, production of antibody to DENV by atypical responders (AR) was not accelerated compared with antibody responses in the 61 flavivirus-naive responders (NR). Further evaluation revealed no differences in sex, age, race, DENV vaccine candidate received, or clinical signs and symptoms following vaccination between AR and NR. However, viremia was delayed at the onset in AR compared with NR. A comparative panel of all AR and five randomly selected NR found flavivirus cross-reactive antibody after vaccination only in AR. Unexpectedly, six of eight AR had NT antibodies to yellow fever virus (YFV) > 1:10 before vaccination while NR had none (P = 0.04). The AR also universally demonstrated YFV NT antibody titers > or = 1:160 after DENV vaccination, whereas four of five NR failed to seroconvert (P = 0.02). Yellow fever virus priming broadens the antibody response to monovalent DENV vaccination. The effect of flavivirus priming on the clinical and immunologic response to tetravalent DENV vaccine remains to be determined.

Adolescent↗
PubMed2002

[Sports in children and adolescents].

The current conditions in Belgium are paradoxical. Indeed, adequate measures are now in place to allow sports activities in a favorable environment: increase in leisure time, widespread availability of indoor and outdoor facilities. However, there has been a significant increase in obesity among young people as well as a gradual erosion in physical fitness of young Belgians. Therefore, physical activity is mandated, not only as a general personal health issue, but also as a public health issue. It should be encouraged, taking into account psychological and physiological growth parameters of teenagers.

Adolescent↗
PubMed2001

Infections at high altitude.

Every year, thousands of outdoor trekkers worldwide visit high-altitude (>2500 m) destinations. Although high-altitude areas per se do not harbor any specific agents, it is important to know the pathogens encountered in the mountains to be better able to help the ill sojourner at high altitude. These are the same pathogens prevalent in the surrounding lowlands, but various factors such as immunomodulation, hypoxia, physiological adaptation, and harsh environmental stressors at high altitude may enhance susceptibility to these pathogens. Against this background, various gastrointestinal, respiratory, dermatological, neurological, and other infections encountered at high altitude are discussed. Because there are few published data on infections at high altitude, this review is largely anecdotal and based on personal experience.

Altitude↗
PubMed2001

Three double-blind, randomized trials evaluating the safety and tolerance of different formulations of the saponin adjuvant QS-21.

The effects of the adjuvant QS-21 in various formulations on immediate pain on injection after intramuscular injection were evaluated in three Phase I clinical trials in healthy adults. Each trial was designed as a double-blind, randomized, four-way or five-way cross-over study with each subject acting as his/her own control. In the first trial, four formulations designed to evaluate the effect of QS-21 or pH (over a range of 6--7.2) were evaluated: phosphate-buffered saline at pH 6.0 or 7.2, and 50 microg of QS-21 in phosphate-buffered saline at pH 6.0 or 7.2. Thirty-three volunteers received each of the four intramuscular injections in random order separated by approximately 1 week. The volunteers assessed the immediate injection pain from 0 to 10 (none to most pain). The data indicate that the presence of QS-21, but not pH, is associated with transient injection site pain. The second trial, which utilized the same design as the first trial, evaluated formulations of QS-21 in various excipients. Fifteen volunteers received phosphate-buffered saline, QS-21/PBS, QS-21/aluminum hydroxide, and QS-21/4 mg/ml of polysorbate 80. Polysorbate 80, but not aluminum hydroxide, reduced the mean pain score compared to QS-21/PBS. The third trial evaluated formulations of QS-21 in additional excipients. Fifteen volunteers received aluminum hydroxide (without QS-21), QS-21/PBS, QS-21/0.72% benzyl alcohol, QS-21/30 mg/ml of hydroxypropyl-beta-cyclodextrin, and QS-21/8-mg/ml of polysorbate 80. Benzyl alcohol, cyclodextrin, and the higher concentration of polysorbate 80 reduced the pain scores associated with QS-21. Hence, QS-21 is associated with injection pain in simple buffer formulations, but it is possible to improve the acceptability of QS-21-containing formulations through reformulation with certain excipients.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed2001

Dissemination of antibiotic-resistant bacteria across geographic borders.

The development of antibiotic-resistant (AR) bacteria in any country is of global importance. After their initial selection and local dissemination, AR bacteria can be transferred across international borders by human travelers, animal and insect vectors, agricultural products, and surface water. The sources and routes of importation of strains of AR bacteria are most often unknown or undetected, because many bacteria carrying resistance genes do not cause disease, and routine surveillance often does not detect them. Control of international dissemination of AR bacteria depends on methods to reduce selection pressure for the development of such bacteria and improved surveillance to detect their subsequent spread.

Animals↗
PubMed2001

Unusual persistence in healthy volunteers and ill patients of hyperimmune immunoglobulin directed against multiple Pseudomonas O-chain and Klebsiella serotypes after intravenous infusion.

Persistence of intravenous (i.v.) hyperimmune immunoglobulin (100 mg/kg) directed against clinically predominant serotypes of Pseudomonas and Klebsiella in ill, febrile patients was compared to healthy volunteers to determine if ill patients have a decreased Ig half-life resulting in an increased immunoglobulin requirement. Type-specific antibodies were measured by ELISA for 83 days in eight healthy volunteers and for 35 days in eight ill patients with surgical complications or hematologic malignancy. Mean values and fold rises of antibody concentrations for the two groups were above preinfusion values at 35 days. The antibody fold rises in patients and in healthy volunteers were similar. Type-specific antibody levels in some patients increased after illness coincident with elevation of total immunoglobulins. We conclude that the duration of potentially therapeutic levels of infused type-specific hyperimmune immunoglobulin may persist for a longer period of time than what has been measured for total immunoglobulin. While the mechanism of this persistence remains to be characterized, the possibility of type-specific antibody synthesis induced by immunoglobulin administration must be considered.

Adult↗
PubMed2001

Determination of regional pulmonary parenchymal strain during normal respiration using spin inversion tagged magnetization MRI.

In clinical practice, the assessment of lung mechanics is limited to a global physiological evaluation, which measures, in the aggregate, the contributions of the pulmonary parenchyma, pleura, and chest wall. In this study, we used an MR imaging methodology which applies two-dimensional bands of inverted magnetization directly onto the pulmonary parenchyma, thus allowing for the quantification of local pulmonary tissue deformation, or strain, throughout inhalation. Our results showed that the magnitude of strain was maximal at the base and apex of the lung, but was curtailed at the hilum, the anatomical site of the poorly mobile bronchial and vascular insertions. In-plane shear strain mapping showed mostly positive shear strain, predominant at the apex throughout inhalation, and increasing with expanding lung volume. Anisotropy mapping showed that superior-inferior axial strain was greater than medial-lateral axial strain at the apex and base, while the opposite was true for the middle lung field. This study demonstrates that localized pulmonary deformation can be measured in vivo with tagging MRI, and quantified by applying finite strain definitions from continuum mechanics.

Adult↗
PubMed2001

Safety and immunogenicity of increasing doses of a Clostridium difficile toxoid vaccine administered to healthy adults.

Clostridium difficile is a major cause of nosocomial diarrhea in industrialized countries. Although most illnesses respond to available therapy, infection can increase morbidity, prolong hospitalization, and produce life-threatening colitis. Vaccines are being explored as an alternative means for protecting high-risk individuals. We assessed the safety, immunogenicity, and dose response of a parenteral vaccine containing C. difficile toxoids A and B. Thirty healthy adults were assigned to receive four spaced inoculations on days 1, 8, 30, and 60 with one of three doses of vaccine (6.25, 25, or 100 microg). At each dose level, subjects were randomized, in a double-blind fashion, to receive either the soluble toxoids (n = 5) or toxoids adsorbed to alum (n = 5). Subjects were monitored for clinical and immunologic responses to vaccination. Vaccination was generally well tolerated, with occasional, usually mild, systemic reactions (abdominal pain, arthralgia, and diarrhea). The most common local reaction, mild arm pain, was reported by all recipients of the toxoid-alum formulation. Nearly all subjects (> or = 90%) developed vigorous serum antibody responses to both toxins, as measured by immunoglobulin G (IgG) enzyme-linked immunosorbent assay and neutralization of cytotoxicity, whereas fecal IgA increases occurred in approximately 50%. Statistically significant effects of dose and formulation on immunogenicity were not seen, although antibody levels tended to be higher with the alum-adjuvanted formulations and with increasing doses of soluble toxoid. Serum antibody responses among the toxoid-alum group appeared to plateau at 25 microg. We concluded that the C. difficile toxoid vaccine is safe and immunogenic in healthy volunteers. Further development as a prophylactic vaccine or for producing C. difficile hyperimmune globulin is justified.

Adolescent↗
PubMed2000

Synthetic malaria peptide vaccine elicits high levels of antibodies in vaccinees of defined HLA genotypes.

A multiple antigen peptide (MAP) malaria vaccine containing minimal Plasmodium falciparum circumsporozoite protein repeat epitopes was assessed for safety and immunogenicity in volunteers of known class II genotypes. The MAP/alum/QS-21 vaccine formulation elicited high levels of parasite-specific antibodies in 10 of 12 volunteers expressing DQB1*0603, DRB1*0401, or DRB1*1101 class II molecules. In contrast, volunteers of other HLA genotypes were low responders or nonresponders. A second study of 7 volunteers confirmed the correlation of class II genotype and high responder phenotype. This is the first demonstration in humans that a peptide vaccine containing minimal T and B cell epitopes composed of only 5 amino acids (N, A, V, D, and P) can elicit antibody titers comparable to multiple exposures to irradiated P. falciparum-infected mosquitoes. Moreover, the high-responder phenotypes were predicted by analysis of peptide/HLA interactions in vitro, thus facilitating the rational design of epitope-based peptide vaccines for malaria, as well as for other pathogens.

Adult↗
PubMed2000

Safety and immune responses to attenuated Salmonella enterica serovar typhi oral live vector vaccines expressing tetanus toxin fragment C.

Attenuated Salmonella enterica serovar Typhi vaccine strain CVD 908-htrA was used as a vector to deliver fragment C of tetanus toxin as a single-dose oral tetanus vaccine candidate to elicit protective levels of serum tetanus antitoxin. Twenty-one healthy adult volunteers received doses of 1.6 x 10(7) to 8.2 x 10(9) CFU of one of two strains, CVD 908-htrA(pTETnir15) or CVD 908-htrA(pTETlpp), which contained plasmid-encoded fragment C, with sodium bicarbonate, and the safety and immune responses to serovar Typhi antigens and tetanus toxin were assessed. No volunteer had fever or positive blood cultures after vaccination, although diarrhea occurred in 3 volunteers and vomiting in 2 volunteers within 3 weeks after vaccination. Most volunteers excreted the vaccine strain in the first 72 h after vaccination. Three of nine volunteers who received 10(8) CFU or higher doses of the CVD 908-htrA(pTETlpp) construct developed rises in serum antitoxin antibodies. The serum and cellular immune responses to serovar Typhi antigens were less frequent than those previously observed in volunteers who ingested the parent strain CVD 908-htrA. This study demonstrates that fragment C of tetanus toxin delivered orally to volunteers in an S. Typhi vector can elicit protective levels of serum antitoxin.

Adolescent↗
PubMed2000

Acute medical problems in the Himalayas outside the setting of altitude sickness.

Well-recognized medical threats at high altitude (>2,500 m) include acute mountain sickness (AMS), high altitude pulmonary edema (HAPE), and high altitude cerebral edema (HACE). Thousands of travelers in the Himalayas are exposed annually to these often life-threatening syndromes. Their recognition and treatment has advanced considerably in recent years. In the Himalayas, we frequently see acute medical problems outside the setting of AMS and the two types of altitude edemas. Many of these other conditions are also hypoxia related and sometimes may mimic the classic high altitude illnesses of AMS, HAPE, and HACE. Although the vast majority of these medical problems are neurological, pulmonary and other organ system dysfunction also occur. These "non-high altitude sickness" disease entities in persons who sojourn to remote mountainous environments are reviewed in this paper to enhance their recognition, diagnosis, and treatment.

Acute Disease↗
PubMed2000

Phase 2 clinical trial of attenuated Salmonella enterica serovar typhi oral live vector vaccine CVD 908-htrA in U.S. volunteers.

Salmonella enterica serovar Typhi strain CVD 908-htrA is a live attenuated strain which may be useful as an improved oral typhoid vaccine and as a vector for cloned genes of other pathogens. We conducted a phase 2 trial in which 80 healthy adults received one of two dosage levels of CVD 908-htrA in a double-blind, placebo-controlled, crossover study. There were no differences in the rates of side effects among volunteers who received high-dose vaccine (4.5 x 10(8) CFU), lower-dose vaccine (5 x 10(7) CFU), or placebo in the 21 days after vaccination, although recipients of high-dose vaccine (8%) had more frequent diarrhea than placebo recipients (0%) in the first 7 days. Seventy-seven percent and 46% of recipients of high- and lower-dose vaccines, respectively, briefly excreted vaccine organisms in their stools. All blood cultures were negative. Antibody-secreting cells producing antilipopolysaccharide (LPS) immunoglobulin A (IgA) were detected in 100 and 92% of recipients of high- and lower-dose vaccines, respectively. Almost half the volunteers developed serum anti-LPS IgG. Lymphocyte proliferation and gamma interferon production against serovar Typhi antigens occurred in a significant proportion of vaccinees. This phase 2 study supports the further development of CVD 908-htrA as a single-dose vaccine against typhoid fever and as a possible live vector for oral delivery of other vaccine antigens.

Administration, Oral↗
PubMed2000

Phase II safety and immunogenicity study of live chikungunya virus vaccine TSI-GSD-218.

We conducted a phase II, randomized, double-blind, placebo-controlled, safety and immunogenicity study of a serially passaged, plaque-purified live chikungunya (CHIK) vaccine in 73 healthy adult volunteers. Fifty-nine volunteers were immunized one time subcutaneously with the CHIK vaccine and 14 were immunized with placebo (tissue culture fluid). Vaccinees were clinically evaluated intensively for one month, and had repeated blood draws for serological assays (50% plaque-reduction neutralization test) for one year. Except for transient arthralgia in five CHIK vaccinees, the number and severity of local and systemic reactions and abnormal laboratory tests after immunization were similar in CHIK vaccinees and placebo recipients. Fifty-seven (98%) of 58 evaluable CHIK vaccinees developed CHIK neutralizing antibody by day 28, and 85% of vaccinees remained seropositive at one year after immunization. No placebo recipients seroconverted. This promising live vaccine was safe, produced well-tolerated side effects, and was highly immunogenic.

Adult↗
PubMed2000

Limited potential for transmission of live dengue virus vaccine candidates by Aedes aegypti and Aedes albopictus.

To evaluate the transmission risk of four live dengue (DEN) vaccine candidates developed by the U.S. Army (DEN-1, 45AZ5 PDK 20; DEN-2, S16803 PDK 50; DEN-3, CH53489 PDK 20; and DEN-4, 341750 PDK 20), we tested 3,010 Aedes aegypti and 1,576 Aedes albopictus mosquitoes blood-fed on 21 volunteers who had been administered one of the four vaccine candidates or the licensed yellow fever (YF) vaccine (17D). We used an indirect immunofluorescence assay (IFA) to detect DEN or YF viral antigen in the heads of mosquitoes. Corresponding to the lack of a detectable viremia among volunteers inoculated 8-13 days previously with live DEN-1 or DEN-2 vaccine candidates, only six mosquitoes developed disseminated infections after feeding on these volunteers. These six mosquitoes included 4 of 247 Ae. albopictus fed on volunteers inoculated with the DEN-1 vaccine candidate and 2 of 528 Ae. aegypti fed on volunteers inoculated with the DEN-2 vaccine candidate. Infection was confirmed in each of these IFA-positive mosquitoes by isolating infectious virus from the mosquito's body in Vero-cell culture. None of the 1,252 or the 969 mosquitoes fed on DEN-3 or DEN-4 recipients, respectively, were infected. Overall, dissemination rates in Ae. albopictus and Ae. aegypti were low. Dissemination rates were 0.5%, 0.3%, < 0.1%, and < 0.1% for the DEN-1 through DEN-4 vaccine candidates, respectively. Because of the observed low dissemination rates, it is unlikely that these vaccine viruses would be transmitted under natural conditions.

Aedes↗