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Biomedical subjects

Ron Dagan

Publications and source records attributed to Ron Dagan.

At least 55 records · Page 3Linked to original sources
PubMed2004

Epidemiology of invasive Streptococcus pneumoniae among Navajo children in the era before use of conjugate pneumococcal vaccines, 1989-1996.

Streptococcus pneumoniae is the most common cause of invasive bacterial disease among children worldwide. The authors aimed to determine the incidence, clinical characteristics, and serotype distribution of invasive pneumococcal disease (IPD) among Navajo children in the southwestern United States. Active population-based laboratory surveillance for IPD among resident members of the Navajo Nation under 18 years of age was conducted between 1989 and 1996. During this 8-year period, 706 cases of IPD were identified. The rate of disease varied by age, with the highest rate being observed among children aged 6-11 months (727 cases/100,000 person-years), followed by children aged 0-11 months, 0-23 months, and 0-59 months (568, 537, and 272 cases/100,000 person-years, respectively). Among children aged 0-23 months, 60.3% of cases were caused by serotypes in the seven-valent conjugate pneumococcal vaccine (71.5% from 1989-1993 and 58.3% from 1994-1996). Navajo children are at increased risk of IPD in comparison with the general US population. The distribution of disease-causing serotypes is similar to that of many countries in the developing world. Prevention strategies should include the use of licensed pneumococcal protein conjugate vaccine; however, a substantial proportion of disease is caused by nonvaccine serotypes. These data are critical for assessing the impact of these vaccines in this high-risk population.

Age Distribution↗
PubMed2004

Fever after immunization: current concepts and improved future scientific understanding.

Fever is a common clinical complaint in adults and children with a variety of infectious illnesses, as well as a frequently reported adverse event following immunization. Although the level of measured temperature indicative of a "fever" was first defined in 1868, it remains unclear what role fever has as a physiologic reaction to invading substances, how best to measure body temperature and compare measurements from different body sites, and, consequently, how to interpret fever data derived from vaccine safety trials or immunization safety surveillance. However, even with many aspects of the societal, medical, economic, and epidemiologic meanings of fever as an adverse event following immunization (AEFI) still elusive, it is a generally benign--albeit common--clinical sign. By standardizing the definition and means of assessment of fever in vaccine safety studies, thereby permitting comparability of data, we hope to arrive at an improved understanding of its importance as an AEFI.

Adult↗
PubMed2004

Nasopharyngeal carriage of Streptococcus pneumoniae by adults and children in community and family settings.

The rate of Streptococcus pneumoniae carriage among adults was compared with that among children (age, < or =6 years) in the same population. Nasopharyngeal culture results for 1300 adults and 404 children were analyzed. S. pneumoniae was carried by only 4% of the adults, compared with 53% of children in the same community. Young age, day care center attendance, having young siblings, and no antibiotic use during the month before screening were associated with the high carriage rate among children, whereas the only risk factor associated with carriage among adults was the presence of a respiratory infection on the screening day. S. pneumoniae serotype distribution and antibiotic resistance patterns differed between adults and children. Isolates of the same serotype--even of the same clone--differed in their antibiotic susceptibility patterns between children and adults. In a subanalysis of 151 pairs of children and their parents and of 32 pairs of siblings, intrafamilial transmission of S. pneumoniae could not be demonstrated.

Adolescent↗
PubMed2004

Four antibiotic-resistant Streptococcus pneumoniae clones unrelated to the pneumococcal conjugate vaccine serotypes, including 2 new serotypes, causing acute otitis media in southern Israel.

This study examined the prevalence of antibiotic-resistant clones that belong to serotypes not included in the pneumococcal conjugate vaccines and that cause a significant percentage of acute otitis media (AOM) in children in southern Israel. During 1998-2001, 2467 pneumococcal isolates, obtained from middle-ear fluid of children <3 years old with AOM, were characterized by antimicrobial susceptibility testing, serotype testing, and pulsed-field gel electrophoresis. Non-vaccine type (NVT) strains constituted 477 (19%) of the 2467 isolates, of which 173 (36%) belonged to only 4 serotypes: 35B, 33F, 21, and 15B/C. For serotype 35B, 47 (96%) of 49 strains were penicillin nonsusceptible, and 93% constituted a single clone; for serotype 33F, 31 (82%) of 38 strains were penicillin nonsusceptible, and 95% constituted a single clone; for serotype 21, 38 (93%) of 41 strains were penicillin nonsusceptible, and 93% constituted a single clone; for serotype 15B/C, 22 (49%) of 45 strains were penicillin nonsusceptible, and 42% constituted a single clone. Two of these clones have not been described elsewhere. The high prevalence of NVT clones should increase the awareness of the potential for replacement of the vaccine strains with these NVT antibiotic-resistant strains.

Acute Disease↗
PubMed2004

Does co-infection with Giardia lamblia modulate the clinical characteristics of enteric infections in young children?

BACKGROUND: Giardia lamblia (G. lamblia) is a prevalent enteric pathogen causing both asymptomatic carriage and diarrheal illness among children worldwide. In this study we examined the hypothesis that G. lamblia may modulate the effect of other enteric pathogens during concurrent infection. METHODS: Bedouin (n = 238) infants were followed from birth to ages 18-23 months. Morbidity was ascertained by weekly home interviews and infant's stools were collected fortnightly. The risk for and severity of diarrheal disease were compared between episodes caused by enteric pathogens other than G. lamblia alone and G. lamblia-mixed episodes. RESULTS: In 59 of 293(20.1%) diarrhea episodes two or more pathogens were detected. In two thirds of the mixed episodes G. lamblia was involved. Neither the incidence of diarrhea nor the mean diarrheal episode duration differed between follow up months in which G. lamblia was or was not detected, when age specific or age adjusted values were compared. There were no differences in severity of episodes for single or G. lamblia-mixed infections except for rotavirus. Episodes with rotavirus alone were more severe as compared to episodes where co-infection with G. lamblia was found. CONCLUSIONS: The results of this study do not confirm the hypothesis that G. lamblia modulates the clinical effect of infection with other enteric agents. However, the findings of the change in severity of infection with rotavirus suggest that this question warrants further investigation.

Academic Medical Centers↗
PubMed2004

Antimicrobial resistance among pediatric respiratory tract infections: clinical challenges.

Considerable development of antimicrobial resistance has occurred in the major pediatric bacterial pathogens, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. However, most of the respiratory infections that children suffer are viral and self-limiting, and only a small percentage of them will develop secondary bacterial infections with the pathogens listed. The challenge for rational antibiotic use is to determine which patients can be treated conservatively and which require antimicrobial intervention to avoid prolonged discomfort or development of permanent sequelae. The basis for rational use of antibiotic in the era of resistance in these major pathogens is to avoid overuse of antimicrobial agents, tailor treatment to identified pathogens as much as possible, and base empiric treatment on the disease being treated and the susceptibility of the probable pathogens at breakpoints based on pharmacokinetic and pharmacodynamic parameters. With appropriate dosing regimens based on these parameters and despite development of resistance, amoxicillin is still one of the most active oral agents against S. pneumoniae and non-beta-lactamase producing strains of H. influenzae, whereas amoxicillin-clavulanate is active against beta-lactamase-producing strains of H. influenzae and M. catarrhalis. Parenteral ceftriaxone and oral and parenteral fluoroquinolones are active against all 3 species, but fluoroquinolones should be used with utmost caution when all other options have been considered because of concerns about toxicity and development of resistance. Introduction of a 7-valent conjugate pneumococcal vaccine in the United States in 2000 reduced the prevalence of invasive pneumococcal disease in children younger than 2 years old, but, as of 2001, had not had a major impact on decreasing antimicrobial resistance.

Adolescent↗
PubMed2004

Impact of prolonged treatment with trimethoprim-sulfamethoxazole on the human gut flora.

The case of a mentally ill man inadvertently treated with trimethoprim-sulfamethoxazole (TMP-SMX) for 2 y is presented. Quantitative stool cultures revealed a substantially suppressed Gram-negative aerobic flora, while Enterococcus spp. and anaerobes were not affected. Yeasts were moderately increased. TMP-SMX represents an attractive antimicrobial for immunocompromized patients who need the integrity of their intestinal anaerobic flora for colonization resistance.

Adult↗
PubMed2004

Tolerability and immunogenicity of an eleven valent mixed carrier Streptococcus pneumoniae capsular polysaccharide-diphtheria toxoid or tetanus protein conjugate vaccine in Finnish and Israeli infants.

BACKGROUND: To have wide global coverage of pneumococcal serotypes, the number of serotypes covered by the current 7-valent pneumococcal conjugate vaccine must be increased. We have studied the safety and immunogenicity of an 11-valent mixed carrier vaccine (PncDT11) in infants. METHODS: The study vaccine contained polysaccharide antigens of serotypes 1, 4, 5, 7F, 9V, 19F and 23F conjugated to tetanus protein and serotypes 3, 6B, 14 and 18C conjugated to diphtheria toxoid. The vaccine was administered to Finnish (n = 117) and Israeli (n = 135) infants at ages 2, 4, 6 and 12 months concomitantly with other vaccines used in national vaccination programs. IgG antibodies to polysaccharides were determined by enzyme immunoassay from serum samples taken at ages 2, 7, 12 and 13 months. After each injection the infants were followed for 30 min to detect any immediate adverse reactions, and parents were given a diary card to report any adverse events during the next 5 days. RESULTS: No severe adverse reactions occurred, and immediate adverse reactions were rare. After each dose approximately 30% of the vaccinees experienced local reactions of which pain was the most common. Fever of >38 degrees C was reported in 33 to 53% of the vaccinees and high fever (>40 degrees C) was reported 6 times. The PncDT11 vaccine was immunogenic. The antibody concentrations after primary immunization series were higher in Israeli than in Finnish infants, but the differences were not significant for most serotypes. The difference was most marked at 13 months, a time point at which the difference was significant in 10 of 11 serotypes. CONCLUSION: PncDT11 is safe and immunogenic in infants. The use of 11-valent pneumococcal vaccine would increase the serotype coverage beyond the currently available 7-valent vaccine.

Antibodies, Bacterial↗
PubMed2004

Relationship among peripheral leukocyte counts, etiologic agents and clinical manifestations in acute otitis media.

OBJECTIVES: To analyze the peripheral leukocyte counts of children with acute otitis media (AOM) in relation to etiology, age, clinical symptoms and signs, prior antibiotic treatment, previous AOM history and pathogen eradication during antibiotic therapy. PATIENTS AND METHODS: Leukocyte counts were determined at diagnosis and on days 4 to 6 of therapy in patients age 3 to 36 months with AOM enrolled in double tympanocentesis studies. Clinical status was determined by a clinical score evaluating severity of fever, irritability and tympanic membrane redness and bulging. RESULTS: Of 771 enrolled patients, culture-positive middle ear fluid was reported in 590 (77%): 294 (50%) Haemophilus influenzae; 150 (25%) Streptococcus pneumoniae; 127 (21%) H. influenzae and S. pneumoniae together; 9 (2%) Moraxella catarrhalis; and 10 (2%) others. Mean leukocyte count +/- sd in patients with AOM caused by S. pneumoniae (15.7 +/- 6.7 cells x 10/mm) was significantly higher than those of patients with AOM caused by H. influenzae (13.7 +/- 5.8 cells x 10/mm) and patients with culture-negative AOM (13.8 +/- 5.6 cells x 10/mm), P < 0.01 for each comparison. Mean absolute neutrophil count (ANC) +/- sd was higher in patients with AOM caused by S. pneumoniae (8.6 +/- 5.1 cells x 10/mm) than in patients with AOM caused by H. influenzae (6.5 +/- 4.0 cells x 10/mm) or culture-negative patients (6.5 +/- 4.4 cells x 10/mm), P < 0.05 for each comparison. When multivariant regression analysis was used, S. pneumoniae etiology and fever (body temperature > or = 38 degrees Celsius) were independent factors, each significantly associated with leukocyte and ANCs. A significant correlation was found between leukocyte and ANCs and higher clinical scores in patients with pneumococcal AOM (P = 0.01, r = 0.21 and P < 0.01, r = 0.27, respectively). The mean leukocyte count on Days 4 to 6 was lower than on Day 1 (11.5 +/- 4.1 compared with 14.2 +/- 6.0 cells x 10/mm, P < 0.01). When paired (Day 1 and Days 4 to 6) examinations were analyzed, the leukocyte counts were lower on Days 4 to 6 irrespective of bacterial eradication or persistence. CONCLUSIONS: Significantly higher leukocyte counts and ANCs were found in pneumococcal AOM than in AOM caused by H. influenzae or in culture-negative AOM. A significant decrease in leukocyte counts was found during antibiotic therapy for AOM, regardless of etiology and bacteriologic outcome. Isolation of S. pneumoniae and fever were each significantly associated with increased peripheral leukocyte and ANCs.

Acute Disease↗
PubMed2004

Potential role of fluoroquinolone therapy in childhood otitis media.

Increased resistance of pneumococci and other pathogens to available antibiotics raises concerns about bacteriologic and clinical failure in children with acute otitis media. Few therapeutic options exist for patients with recurrent infections or recent treatment failure. The limited experience from the compassionate use of fluoroquinolones in pediatrics and pediatric studies has not been linked unequivocally with arthrotoxicity, the primary safety concern in children. Newer 8-methoxyfluoroquinolones may have a role in selected cases associated with multidrug-resistant pathogens.

Anti-Infective Agents↗
PubMed2004

The potential effect of widespread use of pneumococcal conjugate vaccines on the practice of pediatric otolaryngology: the case of acute otitis media.

PURPOSE OF REVIEW: This review provides the otolaryngologist with the evolving understanding of various aspects of pneumococcal conjugate vaccines (PCVs) that are related to their effect on the respiratory tract RECENT FINDINGS: The efficacy of PCVs against invasive pneumococcal disease and pneumonia is well established and is documented in several well-conducted studies. However, the effect of PCVs on otitis media is less obvious and more complex. PCVs clearly reduce diseases caused by vaccine-type (VT) pneumococci, but replacement of VT serotypes by non-VT serotypes in nasopharyngeal carriage of Streptococcus pneumoniae is responsible for the increase in acute otitis media (AOM) caused by non-VT serotypes. Furthermore, an increased rate of AOM caused by Haemophilus influenzae and Moraxella catarrhalis was found. Since most antibiotic-resistance in S. pneumoniae is confined to VT serotypes, vaccine use also reduces antibiotic resistance. The reduction of carriage by PCVs is responsible for the reduction of spread of VT pneumococci (herd immunity). Thus a modification of AOM rather than just a simple reduction is seen with the widespread use of PCV. SUMMARY: Acute otitis media in the era of widespread use of PCV is modified. A disease with reduced VT serotypes, reduced antibiotic resistance, and a lower rate of sequelae is to be expected. However, replacement with potential virulent organisms and development of antibiotic resistance in non-VT pneumococci is a possibility that needs careful monitoring.

Acute Disease↗
PubMed2004

Reduction of antibody response to an 11-valent pneumococcal vaccine coadministered with a vaccine containing acellular pertussis components.

In pneumococcal conjugate vaccines (PCVs), polysaccharide antigens are often conjugated to protein carriers related to other common vaccines. It is therefore important to test PCV interaction with other pediatric vaccines when administered simultaneously. We assessed the immune response to an 11-valent PCV conjugated to diphtheria and tetanus carriers (PncD/T11), administered concomitantly, but in separate sites, with a combined vaccine containing epitopes related antigenically to the carriers: polyribosylribitol phosphate-tetanus tox oid (PRP-T), diphtheria toxoid (DT), and tetanus toxoid (TT). In addition, these combinations contained inactivated poliovirus vaccine (IPV) and either whole-cell pertussis (wP) or acellular pertussis (aP) components. After coadministration of PncD/T11 with the combined vaccine containing wP (DTwP/IPV/PRP-T), the responses to all polysaccharides in the PncD/T11 were satisfactory. In contrast, when coadministered with an aP-containing combination (DTaP/IPV/PRP-T), the response to all seven pneumococcal conjugates to TT was significantly reduced after primary and booster immunization. The pneumococcal conjugates to DT were not significantly reduced after the primary series, but were somewhat reduced after booster. It is likely that some suppression of the tetanus-mediated response occurred even when the PncD/T11 was coadministered with wP, but this suppression was masked by the adjuvant effect of wP. By replacing wP with aP, this adjuvant effect was removed, unmasking the suppression of the tetanus-mediated response. With the increasing use of multiple aP-containing vaccines in infancy, novel approaches to adjuvants and carrier protein technology are likely to be required.

Antibodies, Bacterial↗
PubMed2004

Differences in membrane fluidity and fatty acid composition between phenotypic variants of Streptococcus pneumoniae.

Phase variation in the colonial opacity of Streptococcus pneumoniae has been implicated as a factor in the pathogenesis of pneumococcal disease. This study examined the relationship between membrane characteristics and colony morphology in a few selected opaque-transparent couples of S. pneumoniae strains carrying different capsular types. Membrane fluidity was determined on the basis of intermolecular excimerization of pyrene and fluorescence polarization of 1,6-diphenyl 1,3,5-hexatriene (DPH). A significant decrease, 16 to 26% (P < or = 0.05), in the excimerization rate constant of the opaque variants compared with that of the transparent variants was observed, indicating higher microviscosity of the membrane of bacterial cells in the opaque variants. Liposomes prepared from phospholipids of the opaque phenotype showed an even greater decrease, 27 to 38% (P < or = 0.05), in the pyrene excimerization rate constant compared with that of liposomes prepared from phospholipids of bacteria with the transparent phenotype. These findings agree with the results obtained with DPH fluorescence anisotropy, which showed a 9 to 21% increase (P < or = 0.001) in the opaque variants compared with the transparent variants. Membrane fatty acid composition, determined by gas chromatography, revealed that the two variants carry the same types of fatty acids but in different proportions. The trend of modification points to the presence of a lower degree of unsaturated fatty acids in the opaque variants compared with their transparent counterparts. The data presented here show a distinct correlation between phase variation and membrane fluidity in S. pneumoniae. The changes in membrane fluidity most probably stem from the observed differences in fatty acid composition.

Cell Membrane↗
PubMed2004

Relative importance of nasopharyngeal versus oropharyngeal sampling for isolation of Streptococcus pneumoniae and Haemophilus influenzae from healthy and sick individuals varies with age.

Streptococcus pneumoniae and Haemophilus influenzae carriage is a useful index for measuring the emergence of resistance and outcome in vaccination trials. We performed a study to determine which sampling site, nasopharynx (NP) or oropharynx (OP), yields the highest rate of S. pneumoniae and H. influenzae isolation at different ages. Both NP and OP cultures were obtained from 216 children aged <60 months and their mothers. The total S. pneumoniae carriage rate was 68% among children and 15% among mothers (P < 0.001). Using NP alone for the isolation of S. pneumoniae would have missed 2, 2, and 42% and using OP alone would have missed 77, 66, and 45% of S. pneumoniae in children aged 0 to 23 months, 24 to 59 months, and mothers, respectively. Using NP cultures alone for H. influenzae would have missed 23, 24, and 81% of the isolates, respectively. The respective figures for H. influenzae isolation from OP alone are 38, 29, and 9%. In children, S. pneumoniae was carried mainly in the NP while H. influenzae was equally carried in the NP and OP. In mothers, S. pneumoniae was carried equally in the NP and OP while H. influenzae was carried significantly more often in the OP. In children, H. influenzae colonization increased during illness, mainly in the NP. Culturing only one site significantly reduced the recovery of H. influenzae at all ages. NP cultures for S. pneumoniae detected close to 100% of isolates in children but only 58% of isolates in mothers.

Adult↗