Martin Kabongo - Academia.edu (original) (raw)
Papers by Martin Kabongo
Vaccine, Nov 1, 2013
The currently licensed hepatitis B vaccines have limitations including hyporesponsiveness in olde... more The currently licensed hepatitis B vaccines have limitations including hyporesponsiveness in older adults, poor compliance, and the extended time for most persons to develop seroprotection (e.g. >6months). A vaccine containing HBsAg combined with a Toll-like receptor 9 agonist adjuvant (HBsAg-1018) has been developed to overcome these limitations. A Phase 3, multicenter, randomized, subject- and observer-blinded, active-controlled trial was conducted among healthy subjects 40-70years of age comparing the immunogenicity and safety of two doses of HBsAg-1018 at 0 and 4weeks to three doses of licensed hepatitis B vaccine, HBsAg-Eng, at 0, 4, and 24weeks. The primary immunogenicity endpoint was noninferiority of the seroprotection rate (SPR; % with anti-HBs≥10mIU/mL) of HBsAg-1018 compared to the SPR of HBsAg-Eng at 8 weeks following the last dose of vaccine. Conditional upon meeting noninferiority, superiority of HBsAg-1018 over HBsAg-Eng was assessed. Safety was compared between the two vaccines. At the primary endpoint, the SPR for the HBsAg-1018 group (90.0%) was superior to the SPR for the HBsAg-Eng group (70.5%) with an SPR difference of 19.5% (95% CI, 14.7%, 24.7%). At week 28 when the SPR peaked in the HBsAg-Eng group (72.8%), the SPR in the HBsAg-1018 group (94.8%) was significantly higher than in the HBsAg-Eng group. The SPR in the HBsAg-1018 group was significantly higher than in the HBsAg-Eng group at each study visit from week 4 through week 52. The safety profiles for the two vaccines were similar. When compared to the HBsAg-Eng three-dose regimen given at 0, 1, and 6months, HBsAg-1018 demonstrated superior seroprotection with only two doses at 0 and 1month. The safety profile of HBsAg-1018 was comparable to that of the licensed vaccine, HBsAg-Eng. HBsAg-1018 would provide a significant public health contribution toward the prevention of hepatitis B infection.
Background: Missed or delayed diagnoses are a common but understudied area in patient safety rese... more Background: Missed or delayed diagnoses are a common but understudied area in patient safety research. To better understand the types, causes, and prevention of such errors, we surveyed clinicians to solicit perceived cases of missed and delayed diagnoses. Methods: A 6-item written survey was administered at 20 grand rounds presentations across the United States and by mail at 2 collaborating institutions. Respondents were asked to report 3 cases of diagnostic errors and to describe their perceived causes, seriousness, and frequency. Results: A total of 669 cases were reported by 310 clinicians from 22 institutions. After cases without diagnostic errors or lacking sufficient details were excluded, 583 remained. Of these, 162 errors (28%) were rated as major, 241 (41%) as moderate, and 180 (31%) as minor or insignificant. The most common missed or delayed diagnoses were pulmonary embolism (26 cases [4.5% of total]), drug
The Journal of Infectious Diseases, Nov 1, 2010
Background. When the novel H1N1 influenza A strain appeared in April of 2009, development of nove... more Background. When the novel H1N1 influenza A strain appeared in April of 2009, development of novel H1N1 vaccines became a public health priority. Methods. We conducted a phase-2, multicenter, randomized, placebo-controlled, observer-blind clinical trial of a 2009 H1N1 vaccine in 1313 young (age, 18-64 years) and older (age, у65 years) adults. Participants were randomized 1:4:4:4 to receive 2 doses of placebo or 7.5, 15, or 30 mg of H1N1 hemagglutinin administered 21 days apart. In post hoc analyses, hemagglutination inhibition (HI) titers measured at baseline and after vaccination were analyzed for young adults (age, 18-64 years), "younger elderly" adults (age, 65-74 years), and "very elderly" adults (age, у75 years). Results. At baseline, 28.8% of young adults, 43.9% of younger elderly adults, and 62.9% of very elderly adults had HI titers to A/2009 H1N1 of у1:40. A single 7.5-mg dose induced HI titers у1:40 in 94.5% (95% confidence interval [CI], 91.8%-96.3%) of all adults. After one 7.5-mg dose, the geometric mean titers achieved were 326.4 (95% CI, 275.9-386.0) in young adults, 155.4 (95% CI, 123.4-195.8) in "younger elderly" adults, and 243.9 (95% CI, 167.1-356.0) in "very elderly" adults. Conclusions. This large phase-2 trial demonstrated that a single 7.5-mg dose of a monovalent unadjuvanted H1N1 vaccine induced protective HI antibody levels in adults of all ages, including very elderly adults. Trial registration. Clinicaltrials.gov identifier NCT00958126 The rapid spread of a novel influenza A 2009 virus (2009 H1N1) led to the declaration of a pandemic in June 2009 [1]. As of May 2010, this virus had spread to 1200 countries and caused 118,000 deaths [2], underscoring the need to develop and deploy safe and effective H1N1 vaccines. Clinical trials of 2009 H1N1 vaccines were initiated during July and August 2009 [3-5]. Preliminary data from these studies suggested that one dose of unadjuvanted vaccine containing 15 mg of hemagglutinin antigen (HA) was sufficient for immunization of adults.
Vaccine, Mar 1, 2010
Background: Development of vaccines against highly pathogenic avian influenza virus H5N1 subtypes... more Background: Development of vaccines against highly pathogenic avian influenza virus H5N1 subtypes posing a pandemic threat remains a priority. Limitations in manufacturing capacity and production time of conventional inactivated vaccines highlight the need for additional approaches. Methods: We conducted two double-blind, placebo-controlled phase 1 studies involving a total of 103 healthy adults who received two intramuscular injections of Vaxfectin ®-adjuvanted plasmid DNA vaccine or placebo 21 days apart. Vaccine cohorts received either a monovalent vaccine containing an A/Vietnam/1203/04 H5 hemagglutinin-encoding plasmid or a trivalent vaccine with plasmids encoding H5, NP, and M2 proteins in doses from 0.1 to 1 mg of DNA/injection. Results: All doses were well tolerated without vaccine-related serious adverse events or discontinuations. In the monovalent cohorts, hemagglutination inhibition (HI) titers of ≥40 and 4-fold rises from baseline were achieved in 47-67% of subjects and H5-specific T-cell responses in 75-100%. Trivalent cohorts had lower HI response rates (≤20%), but 72% of subjects achieved T-cell and/or antibody responses to one or more antigens. Conclusions: Vaxfectin ®-adjuvanted monovalent H5 DNA vaccines were well tolerated and induced HI response rates and titers in the reported range of inactivated protein-based H5 vaccines, suggesting that adjuvanted DNA vaccines with rapid vaccine production could be useful for pandemic control.
PubMed, Jul 1, 1997
Group A streptococci are responsible for much of the morbidity associated with skin infections. N... more Group A streptococci are responsible for much of the morbidity associated with skin infections. Necrotizing fasciitis, the most extreme form of these infections, may be life-threatening. Consequently, physicians need to know how to diagnose and effectively treat this deep infection of the subcutaneous tissues. The diagnosis of necrotizing fasciitis is based on the history (i.e., predisposing factors to infection), gram staining and culture, radiography and, ultimately, surgical exploration. The infection is treated with antibiotics, hyperbaric oxygenation and surgical debridement.
American family physician, Jan 15, 1993
Microbiologica, 1982
Thirty strains of Propionibacterium acnes were assayed to detect the effect of lecithin on their ... more Thirty strains of Propionibacterium acnes were assayed to detect the effect of lecithin on their growth and to test the nutritional requirement of this bacterium for this phospholipid. The liquid lecithin medium (LLM) and solid lecithin medium (SLM), containing purified bovine lecithin (PBL) supported the growth of P. acnes strains assayed. Two percent PBL, which was an optimal concentration of lecithin (w/v in LLM and SLM) for the normal growth of P. acnes, was found to be inhibitory for the growth of a strain of Staphylococcus aureus tested. the growth of P. acnes in lecithin media was consistently comparable to the growth patterns of P. acnes in complex media. These results indicated that lecithin in lower concentrations than 2% stimulated the growth of P. acnes. There was an indication that this bacterium may produce enzymes capable of hydrolyzing this phosphoglyceride, incorporated in a defined basal medium, to use it as a source of carbon, energy and fatty acids.
American family physician, 1989
Branhamella (Moraxella) catarrhalis is responsible for a significant number of bronchopulmonary i... more Branhamella (Moraxella) catarrhalis is responsible for a significant number of bronchopulmonary infections in adults, as well as otitis media and sinusitis in children. This gram-negative diplococcus is indistinguishable from Neisseria gonorrhoeae on gram-stained smear. Many strains of the organism produce beta-lactamase and are resistant to the penicillins and other beta-lactam antibiotics. When B. catarrhalis is the probable pathogen, a beta-lactamase-resistant antibiotic is the initial drug of choice in both adults and children.
The Pediatric Infectious Disease Journal, 2011
Background Meningococcal serogroup B disease disproportionately aff ects infants. We assessed lot... more Background Meningococcal serogroup B disease disproportionately aff ects infants. We assessed lot-to-lot consistency, safety and immunogenicity, and the eff ect of concomitant vaccination on responses to routine vaccines of an investigational multicomponent vaccine (4CMenB) in this population. Methods We did primary and booster phase 3 studies between March 31, 2008, and Aug 16, 2010, in 70 sites in Europe. We used two series of sponsor-supplied, computer-generated randomisation envelopes to allocate healthy 2 month-old infants to receive routine vaccinations (diphtheria-tetanus-acellular pertussis, inactivated poliovirus, hepatitis B plus Haemophilus infl uenzae type b, and seven-valent pneumococcal vaccine) wat 2, 4, and 6 months of age alone, or concomitantly with 4CMenB or serogroup C conjugate vaccine (MenC) in: 1) an open-label, lot-to-lot immunogenicity and safety substudy of three 4CMenB lots compared with routine vaccines alone (1:1:1:1, block size eight); or 2) an observer-blind, lot-to-lot safety substudy of three 4CMenB lots compared with MenC (1:1:1:3, block size six). At 12 months, 4CMenB-primed children from either substudy were randomised (1:1, block size two) to receive 4CMenB booster, with or without measles-mumps-rubella-varicella (MMRV) vaccine. Immunogenicity was assessed by serum bactericidal assay with human complement (hSBA) against serogroup B test strains, and on randomly selected subsets of serum samples for routine vaccines; laboratory personnel were masked to assignment. The fi rst coprimary outcome was lot-to-lot consistency (hSBA geometric mean ratio of all lots between 0•5 and 2•0), and the second was an immune response (hSBA titre ≥5) for each of the three strains. The primary outcome for the booster study was immune response to booster dose. Immunogenicity data for 4CMenB were for the modifi ed intention-totreat population, including all infants from the open-label substudy who provided serum samples. The safety population included all participants who contributed safety data after at least one dose of study vaccine. These trials are registered with ClinicalTrials.gov, numbers NCT00657709 and NCT00847145. Findings We enrolled 2627 infants in the open-label phase, 1003 in the observer-blind phase, and 1555 in the booster study. Lot-to-lot consistency was shown for the three 4CMenB lots, with the lowest 95% lower confi dence limit being 0•74 and the highest upper limit being 1•33. Of 1181-1184 infants tested 1 month after three 4CMenB doses (all lots pooled), 100% (95% CI 99−100) had hSBA titres of 5 or more against strains selective for factor H binding protein and neisserial adhesin A, and 84% (82−86) for New Zealand outer-membrane vesicle. In a subset (n=100), 84% (75−91) of infants had hSBA titres of 5 or more against neisseria heparin binding antigen. At 12 months of age, waning titres were boosted by a fourth dose, such that 95−100% of children had hSBA titres of 5 or more for all antigens, with or without concomitant MMRV. Immune responses to routine vaccines were much the same with or without concomitant 4CMenB, but concomitant vaccination was associated with increased reactogenicity. 77% (1912 of 2478) of infants had fever of 38•5°C or higher after any 4CMenB dose, compared with 45% (295 of 659) after routine vaccines alone and 47% (228 of 490) with MenC, but only two febrile seizures were deemed probably related to 4CMenB. Interpretation 4CMenB is immunogenic in infants and children aged 12 months with no clinically relevant interference with routine vaccines, but increases reactogenicity when administered concomitantly with routine vaccines. This breakthrough vaccine off ers an innovative solution to the major remaining cause of bacterial meningitis in infant and toddlers. Funding Novartis Vaccines and Diagnostics.
The Journal of Infectious Diseases, 2010
Background. When the novel H1N1 influenza A strain appeared in April of 2009, development of nove... more Background. When the novel H1N1 influenza A strain appeared in April of 2009, development of novel H1N1 vaccines became a public health priority. Methods. We conducted a phase-2, multicenter, randomized, placebo-controlled, observer-blind clinical trial of a 2009 H1N1 vaccine in 1313 young (age, 18-64 years) and older (age, у65 years) adults. Participants were randomized 1:4:4:4 to receive 2 doses of placebo or 7.5, 15, or 30 mg of H1N1 hemagglutinin administered 21 days apart. In post hoc analyses, hemagglutination inhibition (HI) titers measured at baseline and after vaccination were analyzed for young adults (age, 18-64 years), "younger elderly" adults (age, 65-74 years), and "very elderly" adults (age, у75 years). Results. At baseline, 28.8% of young adults, 43.9% of younger elderly adults, and 62.9% of very elderly adults had HI titers to A/2009 H1N1 of у1:40. A single 7.5-mg dose induced HI titers у1:40 in 94.5% (95% confidence interval [CI], 91.8%-96.3%) of all adults. After one 7.5-mg dose, the geometric mean titers achieved were 326.4 (95% CI, 275.9-386.0) in young adults, 155.4 (95% CI, 123.4-195.8) in "younger elderly" adults, and 243.9 (95% CI, 167.1-356.0) in "very elderly" adults. Conclusions. This large phase-2 trial demonstrated that a single 7.5-mg dose of a monovalent unadjuvanted H1N1 vaccine induced protective HI antibody levels in adults of all ages, including very elderly adults. Trial registration. Clinicaltrials.gov identifier NCT00958126 The rapid spread of a novel influenza A 2009 virus (2009 H1N1) led to the declaration of a pandemic in June 2009 [1]. As of May 2010, this virus had spread to 1200 countries and caused 118,000 deaths [2], underscoring the need to develop and deploy safe and effective H1N1 vaccines. Clinical trials of 2009 H1N1 vaccines were initiated during July and August 2009 [3-5]. Preliminary data from these studies suggested that one dose of unadjuvanted vaccine containing 15 mg of hemagglutinin antigen (HA) was sufficient for immunization of adults.
Canadian Journal of Microbiology, 1982
Thirty strains of Propionibacterium acnes were grown in basal salt medium containing lecithin as ... more Thirty strains of Propionibacterium acnes were grown in basal salt medium containing lecithin as a lipid substrate and in other media. The cultures were assayed for production of lipase (measured as fatty acid esterase) and other exoenzymes. Lipase was assayed spectrophotometrically; other enzymes were assayed using the API ZYM system (Analytab Products Inc., Plainview, NY). Substrates for lipase were α- and β-naphthol esters of propionic, butyric, valeric, caprylic, lauric, myristic, and oleic acids. All strains showed fatty acid esterase activity. Using the API ZYM system 19 enzymes were detected, 8 of which were found frequently and had high activity in most strains. Acid and alkaline phosphatases, phosphoamidase, ester lipase, trypsin–chymotrypsin-like proteases, β-glucuronidase (80%),β-galactosidase (80%), and N-acetyl-β-glucosaminidase were found. Many enzymes of P. acnes appear to be adaptive, dependent on the culture subtrate.
American Family Physician, 1997
Use of Radiotherapy in Graves' Orbitopathy. The inflammatory changes of the orbit in some ca... more Use of Radiotherapy in Graves' Orbitopathy. The inflammatory changes of the orbit in some cases of Graves' disease are believed to be autoimmune reactions. Many cases are mild and self-limiting, but some produce significant ...
Background: Missed or delayed diagnoses are a common but understudied area in patient safety rese... more Background: Missed or delayed diagnoses are a common but understudied area in patient safety research. To better understand the types, causes, and prevention of such errors, we surveyed clinicians to solicit perceived cases of missed and delayed diagnoses. Methods: A 6-item written survey was administered at 20 grand rounds presentations across the United States and by mail at 2 collaborating institutions. Respondents were asked to report 3 cases of diagnostic errors and to describe their perceived causes, seriousness, and frequency. Results: A total of 669 cases were reported by 310 clinicians from 22 institutions. After cases without diagnostic errors or lacking sufficient details were excluded, 583 remained. Of these, 162 errors (28%) were rated as major, 241 (41%) as moderate, and 180 (31%) as minor or insignificant. The most common missed or delayed diagnoses werepulmonaryembolism(26cases[4.5%oftotal]),drug reactions or overdose (26 cases [4.5%]), lung cancer (23 cases [3.9%]),...
The Journal of family practice
Journal of the Pediatric Infectious Diseases Society, Jan 8, 2018
Reduced-antigen-content tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommende... more Reduced-antigen-content tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended in many countries for boosting immunity in adolescents and adults. Although immunity to these antigens wanes with time, currently available Tdap products are not labeled for repeat administration in the United States. We performed an observer-blinded, randomized controlled trial in 1330 adults aged 18 to <65 years who received either the Tdap (n = 1002) or tetanus-diphtheria (Td) (n = 328) vaccine 8 to 12 years after a dose of Tdap vaccine administered previously. Solicited adverse events following immunization were documented for 7 days after vaccination, and serious adverse events and adverse events of medical significance were documented for 6 months after vaccination. Levels of antibodies against component vaccine antigens were measured before and 1 month after vaccination. A solicited adverse event was reported by 87.7% of Tdap and 88.0% of Td vaccine recipients. We found no si...
American family physician, 1987
A systematic examination of the nails provides clues to many vascular, nutritional, endocrine and... more A systematic examination of the nails provides clues to many vascular, nutritional, endocrine and infectious diseases, connective tissue disorders and intrinsic skin diseases. Variations in color and shape, swelling, abnormal blood vessels, bands, indentations and ridges, as well as separation of the nail plate, may be signs of systemic disease.
Development of vaccines against highly pathogenic avian influenza virus H5N1 subtypes posing a pa... more Development of vaccines against highly pathogenic avian influenza virus H5N1 subtypes posing a pandemic threat remains a priority. Limitations in manufacturing capacity and production time of conventional inactivated vaccines highlight the need for additional approaches. We conducted two double-blind, placebo-controlled phase 1 studies involving a total of 103 healthy adults who received two intramuscular injections of Vaxfectin-adjuvanted plasmid DNA vaccine or placebo 21 days apart. Vaccine cohorts received either a monovalent vaccine containing an A/Vietnam/1203/04 H5 hemagglutinin-encoding plasmid or a trivalent vaccine with plasmids encoding H5, NP, and M2 proteins in doses from 0.1 to 1mg of DNA/injection. All doses were well tolerated without vaccine-related serious adverse events or discontinuations. In the monovalent cohorts, hemagglutination inhibition (HI) titers of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =40 and 4-fold rises from baseline were achieved in 47-67% of subjects and H5-specific T-cell responses in 75-100%. Trivalent cohorts had lower HI response rates (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or = 20%), but 72% of subjects achieved T-cell and/or antibody responses to one or more antigens. Vaxfectin-adjuvanted monovalent H5 DNA vaccines were well tolerated and induced HI response rates and titers in the reported range of inactivated protein-based H5 vaccines, suggesting that adjuvanted DNA vaccines with rapid vaccine production could be useful for pandemic control.
Vaccine, Nov 1, 2013
The currently licensed hepatitis B vaccines have limitations including hyporesponsiveness in olde... more The currently licensed hepatitis B vaccines have limitations including hyporesponsiveness in older adults, poor compliance, and the extended time for most persons to develop seroprotection (e.g. &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;6months). A vaccine containing HBsAg combined with a Toll-like receptor 9 agonist adjuvant (HBsAg-1018) has been developed to overcome these limitations. A Phase 3, multicenter, randomized, subject- and observer-blinded, active-controlled trial was conducted among healthy subjects 40-70years of age comparing the immunogenicity and safety of two doses of HBsAg-1018 at 0 and 4weeks to three doses of licensed hepatitis B vaccine, HBsAg-Eng, at 0, 4, and 24weeks. The primary immunogenicity endpoint was noninferiority of the seroprotection rate (SPR; % with anti-HBs≥10mIU/mL) of HBsAg-1018 compared to the SPR of HBsAg-Eng at 8 weeks following the last dose of vaccine. Conditional upon meeting noninferiority, superiority of HBsAg-1018 over HBsAg-Eng was assessed. Safety was compared between the two vaccines. At the primary endpoint, the SPR for the HBsAg-1018 group (90.0%) was superior to the SPR for the HBsAg-Eng group (70.5%) with an SPR difference of 19.5% (95% CI, 14.7%, 24.7%). At week 28 when the SPR peaked in the HBsAg-Eng group (72.8%), the SPR in the HBsAg-1018 group (94.8%) was significantly higher than in the HBsAg-Eng group. The SPR in the HBsAg-1018 group was significantly higher than in the HBsAg-Eng group at each study visit from week 4 through week 52. The safety profiles for the two vaccines were similar. When compared to the HBsAg-Eng three-dose regimen given at 0, 1, and 6months, HBsAg-1018 demonstrated superior seroprotection with only two doses at 0 and 1month. The safety profile of HBsAg-1018 was comparable to that of the licensed vaccine, HBsAg-Eng. HBsAg-1018 would provide a significant public health contribution toward the prevention of hepatitis B infection.
Background: Missed or delayed diagnoses are a common but understudied area in patient safety rese... more Background: Missed or delayed diagnoses are a common but understudied area in patient safety research. To better understand the types, causes, and prevention of such errors, we surveyed clinicians to solicit perceived cases of missed and delayed diagnoses. Methods: A 6-item written survey was administered at 20 grand rounds presentations across the United States and by mail at 2 collaborating institutions. Respondents were asked to report 3 cases of diagnostic errors and to describe their perceived causes, seriousness, and frequency. Results: A total of 669 cases were reported by 310 clinicians from 22 institutions. After cases without diagnostic errors or lacking sufficient details were excluded, 583 remained. Of these, 162 errors (28%) were rated as major, 241 (41%) as moderate, and 180 (31%) as minor or insignificant. The most common missed or delayed diagnoses were pulmonary embolism (26 cases [4.5% of total]), drug
The Journal of Infectious Diseases, Nov 1, 2010
Background. When the novel H1N1 influenza A strain appeared in April of 2009, development of nove... more Background. When the novel H1N1 influenza A strain appeared in April of 2009, development of novel H1N1 vaccines became a public health priority. Methods. We conducted a phase-2, multicenter, randomized, placebo-controlled, observer-blind clinical trial of a 2009 H1N1 vaccine in 1313 young (age, 18-64 years) and older (age, у65 years) adults. Participants were randomized 1:4:4:4 to receive 2 doses of placebo or 7.5, 15, or 30 mg of H1N1 hemagglutinin administered 21 days apart. In post hoc analyses, hemagglutination inhibition (HI) titers measured at baseline and after vaccination were analyzed for young adults (age, 18-64 years), "younger elderly" adults (age, 65-74 years), and "very elderly" adults (age, у75 years). Results. At baseline, 28.8% of young adults, 43.9% of younger elderly adults, and 62.9% of very elderly adults had HI titers to A/2009 H1N1 of у1:40. A single 7.5-mg dose induced HI titers у1:40 in 94.5% (95% confidence interval [CI], 91.8%-96.3%) of all adults. After one 7.5-mg dose, the geometric mean titers achieved were 326.4 (95% CI, 275.9-386.0) in young adults, 155.4 (95% CI, 123.4-195.8) in "younger elderly" adults, and 243.9 (95% CI, 167.1-356.0) in "very elderly" adults. Conclusions. This large phase-2 trial demonstrated that a single 7.5-mg dose of a monovalent unadjuvanted H1N1 vaccine induced protective HI antibody levels in adults of all ages, including very elderly adults. Trial registration. Clinicaltrials.gov identifier NCT00958126 The rapid spread of a novel influenza A 2009 virus (2009 H1N1) led to the declaration of a pandemic in June 2009 [1]. As of May 2010, this virus had spread to 1200 countries and caused 118,000 deaths [2], underscoring the need to develop and deploy safe and effective H1N1 vaccines. Clinical trials of 2009 H1N1 vaccines were initiated during July and August 2009 [3-5]. Preliminary data from these studies suggested that one dose of unadjuvanted vaccine containing 15 mg of hemagglutinin antigen (HA) was sufficient for immunization of adults.
Vaccine, Mar 1, 2010
Background: Development of vaccines against highly pathogenic avian influenza virus H5N1 subtypes... more Background: Development of vaccines against highly pathogenic avian influenza virus H5N1 subtypes posing a pandemic threat remains a priority. Limitations in manufacturing capacity and production time of conventional inactivated vaccines highlight the need for additional approaches. Methods: We conducted two double-blind, placebo-controlled phase 1 studies involving a total of 103 healthy adults who received two intramuscular injections of Vaxfectin ®-adjuvanted plasmid DNA vaccine or placebo 21 days apart. Vaccine cohorts received either a monovalent vaccine containing an A/Vietnam/1203/04 H5 hemagglutinin-encoding plasmid or a trivalent vaccine with plasmids encoding H5, NP, and M2 proteins in doses from 0.1 to 1 mg of DNA/injection. Results: All doses were well tolerated without vaccine-related serious adverse events or discontinuations. In the monovalent cohorts, hemagglutination inhibition (HI) titers of ≥40 and 4-fold rises from baseline were achieved in 47-67% of subjects and H5-specific T-cell responses in 75-100%. Trivalent cohorts had lower HI response rates (≤20%), but 72% of subjects achieved T-cell and/or antibody responses to one or more antigens. Conclusions: Vaxfectin ®-adjuvanted monovalent H5 DNA vaccines were well tolerated and induced HI response rates and titers in the reported range of inactivated protein-based H5 vaccines, suggesting that adjuvanted DNA vaccines with rapid vaccine production could be useful for pandemic control.
PubMed, Jul 1, 1997
Group A streptococci are responsible for much of the morbidity associated with skin infections. N... more Group A streptococci are responsible for much of the morbidity associated with skin infections. Necrotizing fasciitis, the most extreme form of these infections, may be life-threatening. Consequently, physicians need to know how to diagnose and effectively treat this deep infection of the subcutaneous tissues. The diagnosis of necrotizing fasciitis is based on the history (i.e., predisposing factors to infection), gram staining and culture, radiography and, ultimately, surgical exploration. The infection is treated with antibiotics, hyperbaric oxygenation and surgical debridement.
American family physician, Jan 15, 1993
Microbiologica, 1982
Thirty strains of Propionibacterium acnes were assayed to detect the effect of lecithin on their ... more Thirty strains of Propionibacterium acnes were assayed to detect the effect of lecithin on their growth and to test the nutritional requirement of this bacterium for this phospholipid. The liquid lecithin medium (LLM) and solid lecithin medium (SLM), containing purified bovine lecithin (PBL) supported the growth of P. acnes strains assayed. Two percent PBL, which was an optimal concentration of lecithin (w/v in LLM and SLM) for the normal growth of P. acnes, was found to be inhibitory for the growth of a strain of Staphylococcus aureus tested. the growth of P. acnes in lecithin media was consistently comparable to the growth patterns of P. acnes in complex media. These results indicated that lecithin in lower concentrations than 2% stimulated the growth of P. acnes. There was an indication that this bacterium may produce enzymes capable of hydrolyzing this phosphoglyceride, incorporated in a defined basal medium, to use it as a source of carbon, energy and fatty acids.
American family physician, 1989
Branhamella (Moraxella) catarrhalis is responsible for a significant number of bronchopulmonary i... more Branhamella (Moraxella) catarrhalis is responsible for a significant number of bronchopulmonary infections in adults, as well as otitis media and sinusitis in children. This gram-negative diplococcus is indistinguishable from Neisseria gonorrhoeae on gram-stained smear. Many strains of the organism produce beta-lactamase and are resistant to the penicillins and other beta-lactam antibiotics. When B. catarrhalis is the probable pathogen, a beta-lactamase-resistant antibiotic is the initial drug of choice in both adults and children.
The Pediatric Infectious Disease Journal, 2011
Background Meningococcal serogroup B disease disproportionately aff ects infants. We assessed lot... more Background Meningococcal serogroup B disease disproportionately aff ects infants. We assessed lot-to-lot consistency, safety and immunogenicity, and the eff ect of concomitant vaccination on responses to routine vaccines of an investigational multicomponent vaccine (4CMenB) in this population. Methods We did primary and booster phase 3 studies between March 31, 2008, and Aug 16, 2010, in 70 sites in Europe. We used two series of sponsor-supplied, computer-generated randomisation envelopes to allocate healthy 2 month-old infants to receive routine vaccinations (diphtheria-tetanus-acellular pertussis, inactivated poliovirus, hepatitis B plus Haemophilus infl uenzae type b, and seven-valent pneumococcal vaccine) wat 2, 4, and 6 months of age alone, or concomitantly with 4CMenB or serogroup C conjugate vaccine (MenC) in: 1) an open-label, lot-to-lot immunogenicity and safety substudy of three 4CMenB lots compared with routine vaccines alone (1:1:1:1, block size eight); or 2) an observer-blind, lot-to-lot safety substudy of three 4CMenB lots compared with MenC (1:1:1:3, block size six). At 12 months, 4CMenB-primed children from either substudy were randomised (1:1, block size two) to receive 4CMenB booster, with or without measles-mumps-rubella-varicella (MMRV) vaccine. Immunogenicity was assessed by serum bactericidal assay with human complement (hSBA) against serogroup B test strains, and on randomly selected subsets of serum samples for routine vaccines; laboratory personnel were masked to assignment. The fi rst coprimary outcome was lot-to-lot consistency (hSBA geometric mean ratio of all lots between 0•5 and 2•0), and the second was an immune response (hSBA titre ≥5) for each of the three strains. The primary outcome for the booster study was immune response to booster dose. Immunogenicity data for 4CMenB were for the modifi ed intention-totreat population, including all infants from the open-label substudy who provided serum samples. The safety population included all participants who contributed safety data after at least one dose of study vaccine. These trials are registered with ClinicalTrials.gov, numbers NCT00657709 and NCT00847145. Findings We enrolled 2627 infants in the open-label phase, 1003 in the observer-blind phase, and 1555 in the booster study. Lot-to-lot consistency was shown for the three 4CMenB lots, with the lowest 95% lower confi dence limit being 0•74 and the highest upper limit being 1•33. Of 1181-1184 infants tested 1 month after three 4CMenB doses (all lots pooled), 100% (95% CI 99−100) had hSBA titres of 5 or more against strains selective for factor H binding protein and neisserial adhesin A, and 84% (82−86) for New Zealand outer-membrane vesicle. In a subset (n=100), 84% (75−91) of infants had hSBA titres of 5 or more against neisseria heparin binding antigen. At 12 months of age, waning titres were boosted by a fourth dose, such that 95−100% of children had hSBA titres of 5 or more for all antigens, with or without concomitant MMRV. Immune responses to routine vaccines were much the same with or without concomitant 4CMenB, but concomitant vaccination was associated with increased reactogenicity. 77% (1912 of 2478) of infants had fever of 38•5°C or higher after any 4CMenB dose, compared with 45% (295 of 659) after routine vaccines alone and 47% (228 of 490) with MenC, but only two febrile seizures were deemed probably related to 4CMenB. Interpretation 4CMenB is immunogenic in infants and children aged 12 months with no clinically relevant interference with routine vaccines, but increases reactogenicity when administered concomitantly with routine vaccines. This breakthrough vaccine off ers an innovative solution to the major remaining cause of bacterial meningitis in infant and toddlers. Funding Novartis Vaccines and Diagnostics.
The Journal of Infectious Diseases, 2010
Background. When the novel H1N1 influenza A strain appeared in April of 2009, development of nove... more Background. When the novel H1N1 influenza A strain appeared in April of 2009, development of novel H1N1 vaccines became a public health priority. Methods. We conducted a phase-2, multicenter, randomized, placebo-controlled, observer-blind clinical trial of a 2009 H1N1 vaccine in 1313 young (age, 18-64 years) and older (age, у65 years) adults. Participants were randomized 1:4:4:4 to receive 2 doses of placebo or 7.5, 15, or 30 mg of H1N1 hemagglutinin administered 21 days apart. In post hoc analyses, hemagglutination inhibition (HI) titers measured at baseline and after vaccination were analyzed for young adults (age, 18-64 years), "younger elderly" adults (age, 65-74 years), and "very elderly" adults (age, у75 years). Results. At baseline, 28.8% of young adults, 43.9% of younger elderly adults, and 62.9% of very elderly adults had HI titers to A/2009 H1N1 of у1:40. A single 7.5-mg dose induced HI titers у1:40 in 94.5% (95% confidence interval [CI], 91.8%-96.3%) of all adults. After one 7.5-mg dose, the geometric mean titers achieved were 326.4 (95% CI, 275.9-386.0) in young adults, 155.4 (95% CI, 123.4-195.8) in "younger elderly" adults, and 243.9 (95% CI, 167.1-356.0) in "very elderly" adults. Conclusions. This large phase-2 trial demonstrated that a single 7.5-mg dose of a monovalent unadjuvanted H1N1 vaccine induced protective HI antibody levels in adults of all ages, including very elderly adults. Trial registration. Clinicaltrials.gov identifier NCT00958126 The rapid spread of a novel influenza A 2009 virus (2009 H1N1) led to the declaration of a pandemic in June 2009 [1]. As of May 2010, this virus had spread to 1200 countries and caused 118,000 deaths [2], underscoring the need to develop and deploy safe and effective H1N1 vaccines. Clinical trials of 2009 H1N1 vaccines were initiated during July and August 2009 [3-5]. Preliminary data from these studies suggested that one dose of unadjuvanted vaccine containing 15 mg of hemagglutinin antigen (HA) was sufficient for immunization of adults.
Canadian Journal of Microbiology, 1982
Thirty strains of Propionibacterium acnes were grown in basal salt medium containing lecithin as ... more Thirty strains of Propionibacterium acnes were grown in basal salt medium containing lecithin as a lipid substrate and in other media. The cultures were assayed for production of lipase (measured as fatty acid esterase) and other exoenzymes. Lipase was assayed spectrophotometrically; other enzymes were assayed using the API ZYM system (Analytab Products Inc., Plainview, NY). Substrates for lipase were α- and β-naphthol esters of propionic, butyric, valeric, caprylic, lauric, myristic, and oleic acids. All strains showed fatty acid esterase activity. Using the API ZYM system 19 enzymes were detected, 8 of which were found frequently and had high activity in most strains. Acid and alkaline phosphatases, phosphoamidase, ester lipase, trypsin–chymotrypsin-like proteases, β-glucuronidase (80%),β-galactosidase (80%), and N-acetyl-β-glucosaminidase were found. Many enzymes of P. acnes appear to be adaptive, dependent on the culture subtrate.
American Family Physician, 1997
Use of Radiotherapy in Graves' Orbitopathy. The inflammatory changes of the orbit in some ca... more Use of Radiotherapy in Graves' Orbitopathy. The inflammatory changes of the orbit in some cases of Graves' disease are believed to be autoimmune reactions. Many cases are mild and self-limiting, but some produce significant ...
Background: Missed or delayed diagnoses are a common but understudied area in patient safety rese... more Background: Missed or delayed diagnoses are a common but understudied area in patient safety research. To better understand the types, causes, and prevention of such errors, we surveyed clinicians to solicit perceived cases of missed and delayed diagnoses. Methods: A 6-item written survey was administered at 20 grand rounds presentations across the United States and by mail at 2 collaborating institutions. Respondents were asked to report 3 cases of diagnostic errors and to describe their perceived causes, seriousness, and frequency. Results: A total of 669 cases were reported by 310 clinicians from 22 institutions. After cases without diagnostic errors or lacking sufficient details were excluded, 583 remained. Of these, 162 errors (28%) were rated as major, 241 (41%) as moderate, and 180 (31%) as minor or insignificant. The most common missed or delayed diagnoses werepulmonaryembolism(26cases[4.5%oftotal]),drug reactions or overdose (26 cases [4.5%]), lung cancer (23 cases [3.9%]),...
The Journal of family practice
Journal of the Pediatric Infectious Diseases Society, Jan 8, 2018
Reduced-antigen-content tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommende... more Reduced-antigen-content tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended in many countries for boosting immunity in adolescents and adults. Although immunity to these antigens wanes with time, currently available Tdap products are not labeled for repeat administration in the United States. We performed an observer-blinded, randomized controlled trial in 1330 adults aged 18 to <65 years who received either the Tdap (n = 1002) or tetanus-diphtheria (Td) (n = 328) vaccine 8 to 12 years after a dose of Tdap vaccine administered previously. Solicited adverse events following immunization were documented for 7 days after vaccination, and serious adverse events and adverse events of medical significance were documented for 6 months after vaccination. Levels of antibodies against component vaccine antigens were measured before and 1 month after vaccination. A solicited adverse event was reported by 87.7% of Tdap and 88.0% of Td vaccine recipients. We found no si...
American family physician, 1987
A systematic examination of the nails provides clues to many vascular, nutritional, endocrine and... more A systematic examination of the nails provides clues to many vascular, nutritional, endocrine and infectious diseases, connective tissue disorders and intrinsic skin diseases. Variations in color and shape, swelling, abnormal blood vessels, bands, indentations and ridges, as well as separation of the nail plate, may be signs of systemic disease.
Development of vaccines against highly pathogenic avian influenza virus H5N1 subtypes posing a pa... more Development of vaccines against highly pathogenic avian influenza virus H5N1 subtypes posing a pandemic threat remains a priority. Limitations in manufacturing capacity and production time of conventional inactivated vaccines highlight the need for additional approaches. We conducted two double-blind, placebo-controlled phase 1 studies involving a total of 103 healthy adults who received two intramuscular injections of Vaxfectin-adjuvanted plasmid DNA vaccine or placebo 21 days apart. Vaccine cohorts received either a monovalent vaccine containing an A/Vietnam/1203/04 H5 hemagglutinin-encoding plasmid or a trivalent vaccine with plasmids encoding H5, NP, and M2 proteins in doses from 0.1 to 1mg of DNA/injection. All doses were well tolerated without vaccine-related serious adverse events or discontinuations. In the monovalent cohorts, hemagglutination inhibition (HI) titers of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =40 and 4-fold rises from baseline were achieved in 47-67% of subjects and H5-specific T-cell responses in 75-100%. Trivalent cohorts had lower HI response rates (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or = 20%), but 72% of subjects achieved T-cell and/or antibody responses to one or more antigens. Vaxfectin-adjuvanted monovalent H5 DNA vaccines were well tolerated and induced HI response rates and titers in the reported range of inactivated protein-based H5 vaccines, suggesting that adjuvanted DNA vaccines with rapid vaccine production could be useful for pandemic control.