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ABSTRACT: We characterized Streptococcus pneumoniae serotype 6D (Sp6D) from previously identified Sp6B among Jewish and Bedouin children in southern Israel, during a decade before vaccination. Sp6D constituted 6.7% of the presumed Sp6B. Sp6D strains belonged to 20 sequence types that were differentially distributed among the 2 ethnic groups.
Journal of clinical microbiology 02/2013; · 4.16 Impact Factor
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ABSTRACT: BACKGROUND:: We aimed to determine whether serotype 1 (SP1) invasive pneumococcal disease (IPD) can be distinguished by demographic, clinical and laboratory characteristics from IPD caused by the other most common serotypes (MCS) in our region: 5, 14, 6A, 6B, 19A, 19F, 23F. METHODS:: Data for all IPD episodes in children <18 years old treated at the Soroka University Medical Center during 2000-2009 were retrospectively retrieved. Episodes caused by SP1-IPD were compared with those caused by MCS-IPD (both grouped and individual serotypes). Analyses were adjusted for age and ethnicity. RESULTS:: 94 SP1-IPD and 250 MCS-IPD episodes were documented. SP1-IPD cases were older (68.3 ± 52.6 months vs.30.4 ± 39.2 months; P< 0.001) and more likely to be found in Bedouin children than MCS-IPD (87.5% vs. 58.6%; P< 0.001). SP1 was less frequently isolated from patients with underlying disease than MCS (14.9% vs. 31.6 %; P< 0.001; RR 0.15 [95% CI: 0.07-0.32]). SP1 was more often associated with bacteremic pneumonia and primary peritonitis than MCS (70.2% vs. 38.4% and 7.4% vs. 0.8%, respectively; P< 0.001); the proportion of bacteremia without focus was higher in MCS-IPD (32.3% vs. 12.5 %; P< 0.001). There were no differences in hospitalization and mortality rates (70.2% vs. 68.0% [P = 0.22] and 4.3% vs. 5.6% [P = 0.26], respectively). CONCLUSIONS:: SP1 was found less frequently than MCS in children with underlying diseases, but was more frequent in older and Bedouin children with IPD. SP1was more frequently associated with bacteremic pneumonia and primary peritonitis than MCS grouped.
The Pediatric Infectious Disease Journal 01/2013; · 3.58 Impact Factor
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ABSTRACT: This study aimed to compare the clonal distribution of common pneumococcal strains not included in the 7-valent pneumococcal conjugate vaccine (PCV7) that were isolated from cases of acute otitis media (AOM) and invasive pneumococcal disease (IPD) in two distinct ethnic populations in southern Israel during the decade (1999 to 2008) preceding PCV7 implementation. Isolates recovered from Jewish and Bedouin children <5 years old were characterized by antibiotic resistance and molecular epidemiology using pulsed-field gel electrophoresis and multilocus sequence typing. Of 5,236 AOM and 425 IPD isolates, 43% and 57% were from Jewish and Bedouin children, respectively. PCV7 accounted for 54% and 45% of the AOM and IPD episodes, respectively. Eleven major non-PCV7 serotypes (1, 3, 5, 6A, 7F, 12F, 15B/C, 19A, 21, 33F, and 35B) constituted 31% and 42% of the AOM and IPD episodes, respectively. The clonal distributions of the 11 non-PCV7 serotypes and their antibiotic susceptibilities were significantly different among the two ethnic populations in both the AOM and IPD groups. About half of the AOM and IPD cases resulted from non-PCV7 pneumococci, even before PCV7 implementation. The significant differences between the two ethnic populations suggest that lifestyle and microenvironment are major determinants in the clonal distribution of disease-causing pneumococci. Post-PCV7 surveillance is important in understanding non-PCV7 clonal expansion in the two distinct populations.
Journal of clinical microbiology 08/2012; 50(11):3472-7. · 4.16 Impact Factor
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ABSTRACT: In immunogenicity trials of pneumococcal conjugate vaccines (PCVs), only IgG antibody concentrations to pneumococcal capsular polysaccharides (PPSs) are usually determined, along with the opsonophagocytic activity (OPA) of antipneumococcal antibodies. We aimed to determine the role of both IgG and IgM in OPA in toddlers receiving one dose of 9-valent PCV (PCV9). The IgG and IgM antibody concentrations to PPSs of serotypes 6A, 9V, 14, 19F, and 23F were measured by enzyme immunoassay in sera from toddlers (ages 18 to 35 months) 1 month after a single PCV9 dose. The OPA for the same serotypes was measured by multiplexed opsonophagocytosis assay (MOPA). Further, IgG and IgM concentrations and MOPA were measured to PPS of serotypes 6A, 14, and 19F in sera collected 12 months after vaccination. The detected MOPA titers were high in comparison to the IgG concentrations 1 month after immunization. The IgM concentrations were higher than IgG concentrations for serotypes 6A and 14 (P < 0.001) and as high as IgG for serotypes 9V, 19F, and 23F. Correlation of the IgM antibody concentrations with MOPA (r = 0.35 to 0.65) was stronger compared to that of the IgG antibodies (r = 0.07 to 0.41). The depletion of IgG antibodies in three sets of pooled sera only slightly decreased the OPA activity against serotype 14. At 12 months after immunization, 50 to 100% of serum samples still showed detectable MOPA activity against serotypes 6A, 14, and 19F. Our results suggest that IgM contributes to OPA 1 month after a single PCV9 vaccination in toddlers and that functionally active IgM and IgG antibodies persist for at least a year.
Clinical and vaccine immunology: CVI 08/2012; 19(10):1618-23. · 2.37 Impact Factor
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ABSTRACT: The 7-valent pneumococcal conjugate vaccine (PCV7) was initially licensed for use as 3 infant doses and a booster (3+1). However, 2 infant doses plus a booster schedules only (2+1) are widely used. We compared the effect of these two schedules on pneumococcal carriage in young children. We also assessed the effect of a 2-dose schedule in the second year ("catch-up" schedule; 0+2).
Subjects (n=733) were randomized to the 2+1 (4, 6, 12 m), 3+1 (2, 4, 6, 12 m) or 0+2 (12, 18 m) schedules. Blood samples for serotype-specific IgG (SSIgG) determination were obtained at 2, 7, 13, 19 months, and nasopharyngeal+oropharyngeal pneumococcal cultures were obtained at 2, 4, 6, 7, 12, 13, 18, 19, 24, 30 months.
After primary infant PCV7 series, SSIgG was significantly lower for four out of seven serotypes in children receiving 2 doses compared to 3 doses, particularly for serotypes 6B and 23F. This was associated with a higher acquisition and prevalence rates of vaccine serotype carriage in the 2-dose group, particularly serotypes 6A and 6B. After the booster dose at 12 months of age, most differences were not significant anymore. A single PCV7 dose at age 12 months in previously unvaccinated subjects ("catch up" schedule) resulted in poor SSIgG concentrations for three out of seven serotypes, resulting in higher acquisition and prevalence rates of vaccine serotypes (grouped) compared to infants receiving a booster dose at 12 months (2+1 and 3+1 groups). Similarly, serotypes 6B and 6A also showed significantly higher carriage rates after a single dose at 12 months. After the second catch-up dose at 18 months, the rates were similar to those in the 2+1 or 3+1 schedules, except for serotype 6A.
Three infant doses seem to better protect against PCV7-serotype acquisition and carriage than two. However, after booster, most of these differences disappear. A 2-dose second year catch-up campaign may enhance the reduction of PCV7-serotype spread in the community.
Vaccine 06/2012; 30(34):5132-40. · 3.77 Impact Factor
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ABSTRACT: Data are scarce with regard to risk factors for acute community-acquired alveolar pneumonia (CAAP) in children, but it is known that children with sleep-disordered breathing (SDB) experience more respiratory infections. We aimed to assess whether SDB is a risk factor for CAAP in early childhood.
We conducted a prospective, nested, case-control study assessing children < 5 years old who had been given a diagnosis of CAAP based on World Health Organization radiographic criteria. Demographic and clinical data were collected. SDB symptoms were documented using a structured questionnaire. CAAP study and retrospective sleep laboratory databases were compared. SDB presence and severity were determined by questionnaire and polysomnography (PSG).
A total of 14,913 children underwent chest radiography during the study period; 1,546 children with radiographically proven CAAP (58% boys) and 441 control subjects (54% boys) were prospectively enrolled. Frequent snoring was reported in 18.6% vs 2.9% subjects with CAAP and control subjects, respectively (P < .001). The respective figures for subjects with CAAP and control subjects for restless sleep, nocturnal breathing problems, abnormal behavior, and chronic rhinorrhea were 21.6% vs 5.3%, 5% vs 1.4%, 6.4% vs 0.2%, and 12.9% vs 1.8%, (P < .001 for each). Fifty children (3.3%) with CAAP vs three control subjects (0.7%) underwent adenoidectomy (P < .001). PSG diagnosis of obstructive sleep apnea had been established previously in 79 patients (5%) with CAAP vs six (1.3%) of the control subjects (OR, 3.7 [95% CI, 1.6-10.0]; P < .001), with higher severity in patients with CAAP than in control subjects.
SDB is common in children with CAAP and is possibly a predisposing risk factor for CAAP in children < 5 years old. We recommend considering SDB in young children who are given a diagnosis of CAAP.
Chest 11/2011; 141(5):1210-5. · 5.25 Impact Factor
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ABSTRACT: Association of pneumococcal nasopharyngeal carriage with the concentration and opsonophagocytic activity (OPA) of serum serotype-specific antibodies was determined for toddlers 1 month after immunization with a 9-valent pneumococcal conjugate vaccine. Higher anti-serotype 14 and anti-serotype 19F IgG and anti-serotype 14 IgM correlated with a lowered probability of pneumococcal acquisition. Postvaccination OPA did not correlate with pneumococcal carriage.
Clinical and vaccine immunology: CVI 11/2011; 19(1):96-9. · 2.37 Impact Factor
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ABSTRACT: Our objective was to compare the inter-observer level of agreement in diagnosing pneumonia using the World Health Organization (WHO) guidelines for the interpretation of radiographs. We conducted a prospective study in a pediatric emergency room. Fifteen observers (13 pediatricians, 2 radiologists) interpreted 200 pediatric (<5 years old) chest radiographs using the WHO guidelines. Observers were blinded to the clinical presentation. Results were analyzed for kappa values. Individual readings were compared to two "gold standard" teams: (1) radiologist and pediatrician and (2) two radiologists. Results: Alveolar pneumonia, non-alveolar pneumonia, and no pneumonia were found (by radiologists) in 12.8%, 2.7%, and 78.6% of readings, respectively. The mean kappa values for alveolar pneumonia, non-alveolar pneumonia, and no pneumonia of observers versus the team consisting of a radiologist and a pediatrician were 0.73, 0.23, and 0.61, respectively. For non-alveolar pneumonia, the mean kappa value was higher for the gold standard consisting of a radiologist and a pediatrician when compared to the two-radiologist team. Pediatricians overdiagnosed "non-alveolar pneumonia" compared with radiologists. In contrast, for the alveolar pneumonia and no-pneumonia diagnoses, no significant differences were found. CONCLUSIONS: The WHO guidelines for interpretation of chest radiographs result in high level of agreement between readers for the definition of "alveolar pneumonia" and "no pneumonia" but poor agreement for non-alveolar pneumonia. The disagreement with regard to the latter was associated with overdiagnosis by pediatricians, which may lead to overtreatment. We believe that radiographic non-alveolar pneumonia should not be an endpoint for clinical trials and research, nor should it be implemented in clinical setting.
European Journal of Pediatrics 08/2011; 171(2):369-74. · 1.88 Impact Factor
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ABSTRACT: To determine the dynamics of serotype prevalence, potential coverage by pneumococcal conjugate vaccines (PCV) and antibiotic resistance patterns of Streptococcus pneumoniae causing acute otitis media (AOM) in children in southern Israel before PCV7 introduction in the routine immunization program in Israel.
All S. pneumoniae isolates from middle ear fluid from children with AOM during 1999-2008 were included. Prospectively collected demographic data on S. pneumoniae serotypes and antibiotic resistance patterns were analyzed.
A total of 14,911 tympanocenteses yielded 5281 (35%) S. pneumoniae. Proportion of S. pneumoniae-AOM did not vary significantly (overall 35%; 33% in 2007; 38% in 2002 and 2003). The most frequent serotypes were 19F, 14, 23F and 19A; in both Jewish and Bedouin children; serotypes 6A and 19A contributed 6% and 10%, respectively, of all S. pneumoniae isolates. Serotypes included in PCV7, PCV10 and PCV13 represented 60%, 64%, 85% in Jewish children vs. 49%, 55% and 74%, respectively, in Bedouin children (P < 0.001). Nonsusceptibility to TMP/SMX decreased significantly, in parallel with a significant increase in the nonsusceptibility to erythromycin, clindamycin and in multidrug resistant (MDR) isolates. No changes were recorded in the proportion of S. pneumoniae isolates with penicillin MIC ≥ 1.0 μg/ml. The proportion of penicillin- and erythromycin-nonsusceptible and of MDR serotype 6A and 19A isolates increased significantly in Bedouin children.
(1) No significant changes were recorded in the yearly proportions of serotypes 23F, 19F, 19A, 14 and 6A in both ethnic populations; (2) Potential coverage of the 3 PCVs was higher in Jewish children than in Bedouin children; (3) The relatively high coverage of macrolides- and multidrug-resistant S. pneumoniae by PCV13 and lack of increase in penicillin, erythromycin and multidrug nonsusceptibility among non-PCV13 isolates is encouraging.
Vaccine 06/2011; 29(25):4202-9. · 3.77 Impact Factor
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ABSTRACT: We aimed at estimating pneumococcal serotype-specific disease potential in pediatric community-acquired alveolar pneumonia (CAAP), by comparing nasopharyngeal pneumococcal carriage during disease to carriage in healthy children.
Pneumococcal nasopharyngeal cultures were obtained from children < 5 years old admitted to the emergency room or hospitalized with radiologically diagnosed CAAP and from healthy controls. Disease potential was estimated by calculating serotype-specific odds ratios (OR) of a given serotype to be carried during disease compared with healthy children (after adjustment for age, ethnicity, previous antibiotic therapy, and season).
A total of 603 and 1504 isolates were obtained from CAAP and healthy children, respectively. A significant OR > 1.0 of a specific serotype being carried during disease (suggesting a higher disease potential) was observed with serotypes (by decreasing rank) 1, 5, 22F, 7F, 14, 9V, and 19A. A significant OR < 1.0 of being carried during disease (suggesting a lower disease potential) was observed with serotypes 6A, 6B, 23A, and 35B. Carriage of PCV7 serotypes (grouped) during CAAP was highest in age group 6 to 17 months. PCV10 and PCV13 provided significantly higher coverage for both 6 to 17 and 18 to 35 month age groups.
It is suggested that serotypes 1, 5, 7F, 9V, 14, 19A, and 22F have a higher disease potential for childhood pneumonia than do serotypes 6A, 6B, 23A, and 35B.
The Pediatric Infectious Disease Journal 03/2011; 30(3):227-33. · 3.58 Impact Factor
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ABSTRACT: The 7-valent CRM197 pneumococcal conjugated vaccine (PCV7) was originally licensed using 3 primary doses during infancy and a booster in the second year of life. We compared the originally licensed regimen to 2 widely used alternative regimens.
Five hundred forty-three infants were randomized to receive PCV7 at 2, 4, 6, and 12 months (3 + 1), at 4, 6, and 12 months (2 + 1), or at 2, 4, and 6 months (3 + 0). Blood was drawn at 2, 7, 13, and 19 months. Serotype-specific IgG concentrations were determined by ELISA.
In the 2 + 1 group, postprimary IgG concentrations against serotypes 6B, 14, 18C, and 23F were reduced compared with the 3 + 1 or 3 + 0 groups. Both 3 + 1 and 2 + 1 groups showed marked booster response, but the 2 + 1 group had reduced concentrations against serotypes 6B, 18C, 23F. At 19 months, IgG antibodies decreased in both 3 + 1 and 2 + 1 groups but the 2 + 1 group had significantly lower concentrations against serotypes 6B, 18C, and 23F. IgG concentrations decreased in the 3 + 0 group during the second year and were significantly lower than those of 3 + 1 and 2 + 1 for all serotypes at 13 and 19 months.
Significant differences in immunogenicity were documented between the reduced and the licensed regimens. The clinical implications of these differences require further studies.
The Pediatric Infectious Disease Journal 08/2010; 29(8):756-62. · 3.58 Impact Factor
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ABSTRACT: The antibody response to pneumococcal conjugate vaccines (PCVs) in infants is variable. Factors responsible for this variability have not been fully elucidated. The objective of this study was to investigate whether pneumococcal carriage around the time of the first dose of 7-valent PCV (PCV7) affects serotype-specific immunologic response.
Healthy 2-month old infants were randomized to receive 2 (at the ages of 4 and 6 months) or 3 (at the ages of 2, 4, and 6 months) PCV7 doses and a booster dose (at the age of 12 months). Nasopharyngeal or oropharyngeal specimens were obtained for culture shortly before the first PCV7 dose. Serotype-specific immunoglobulin (Ig) G levels were measured at ages 2, 7, and 13 months.
Of 545 children studied, 332 received a booster dose. The most common serotypes carried around the time of the first PCV7 dose were 6B (n = 37), 19F (n = 22), and 23F (n = 14). In carriers before the first dose, the IgG response to the carried serotype after 2 or 3 doses was significantly lower than in noncarriers. In contrast, response to the noncarried serotypes was not affected. Although all children responded to the booster dose, the response to the originally carried serotype was generally lower.
Serotype-specific hyporesponsiveness to PCV7 after pneumococcal carriage in infants is demonstrated for the first time. This phenomenon was common, lasted for at least several months, and was only partially overcome by the 12-month booster.
isrctn.org identifier: ISRCTN28445844.
The Journal of Infectious Diseases 04/2010; 201(10):1570-9. · 6.41 Impact Factor
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ABSTRACT: Respiratory tract infections are a major cause of morbidity and mortality in children under the age of 5 years. The child population in southern Israel is divided into two main groups, Jewish and Bedouin, who differ in their socioeconomic status, with the Bedouin population living in lower socioeconomic conditions and overcrowding. Almost all children in southern Israel are treated at the Soroka University Medical Center.
To compare the epidemiological and clinical data of Bedouin and Jewish children with community acquired pneumonia (CAP), who were treated at the Soroka University Medical Center.
All chest X-rays of children under the age of 5 years, taken at the Pediatric Emergency room (PER) between the dates 4.11.2001 and 31.12.2007, were evaluated for pneumonia. Demographic and clinical data were collected to determine morbidity, hospitalization and mortality rates. Blood cultures and nasopharyngeal washes were taken to determine the pathogens of CAP.
A total of 38,045 chest radiographs were evaluated; CAP was diagnosed in 5,965 of them (15.6%). The risk of presenting to the PER with CAP in children under the age of 5 years was 8.3% in Bedouin children and 5.4% in Jewish children (p < 0.01). The cumulative risk for hospitalization due to CAP in children under the age of 5 years was 5.8% for the Bedouin children and 2.2% for the Jewish children (p < 0.01). The Bedouin children were younger than the Jewish children (43.5% under 1 year of age vs. 23.7% respectively, p < 0.01). Tachypnea, hypoxemia and mortality rates (71.9% vs. 61%, 31.7% vs. 18.6% and 3% vs. 0.3%, p < 0.01 respectively) were higher in Bedouin children than in Jewish children.
PER visits due to CAP are common, especially in Bedouin children. Bedouin patients were younger, with a more severe clinical course and with higher rates of morbidity, hospitalization and mortality than Jewish children. Improving living conditions, parental perception of disease severity and immunization programs (e.g. pneumococcal and influenza vaccine) could lead to a reduction in the gap between the two populations.
Harefuah 03/2010; 149(3):137-42, 196.
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ABSTRACT: Culture-negative AOM is often milder and associated with lower local/systemic inflammatory responses than culture-positive AOM.
To compare the clinical outcome of culture-negative AOM with that of culture-positive AOM children.
Children aged 3 to 35 months with AOM were enrolled in 11 double-tympanocentesis antibiotic efficacy studies documenting both bacteriologic (days 4-6 of treatment) and clinical outcome (days 11-14, end of treatment). Univariate analysis (age, gender, ethnicity, previous AOM history, and antibiotic treatment) between culture-negative and culture-positive AOM patients was performed by Student t test, ANOVA, or chi2 test. Those found to be significant were further submitted to multivariable regression analysis.
A total of 1088 patients (mean age, 11.95 +/- 5.96 months, 209 culture-negative and 879 culture-positive AOM) were enrolled. No differences were recorded between culture-negative AOM and culture-positive AOM patients in age, gender, ethnicity and number of previous episodes. Seventy-four percent (650/879) culture-positive AOM patients achieved bacteriologic eradication within 3 to 5 days. Successful outcome (cured + improved) was recorded in 90% (189/209) culture-negative AOM patients versus 86% (758/879) in culture-positive AOM (P = 0.086). Successful clinical outcome was more frequent in culture-negative than in culture-positive AOM without bacteriologic eradication (90% vs. 67% [154/229], P < 0.001). No difference in successful clinical outcome was found between culture-negative versus culture-positive AOM patients with bacterial eradication (90% vs. 93% [604/650], P = 0.24). Overall, the inclusion of culture-negative AOM patients in the evaluation of clinical failures rates in study patients decreased the total clinical failure rate by 9%. We present a hypothetical antibiotic efficacy study enrolling 300 patients in whom 2 drugs with different bacteriologic efficacy rates (A-90% and B-60%) were used. When the culture-negative cases (5% clinical failure) enrolled increased from 50/300 (16.7%) to 150/300 (50%), the overall clinical failure rate decreased by 36% (from 17.4% to 11.2%, P = 0.08) for the less efficacious drug, while remaining unmodified for the more efficacious drug (9.6% and 8.8%, respectively).
(1) Clinical outcome in culture-negative AOM was similar to that of culture-positive AOM with bacteriologic eradication and both were superior to that of culture-positive AOM without eradication; (2) Inclusion of culture-negative AOM patients in series aiming at antibiotic efficacy may falsely improve the clinical outcome for antibiotics with reduced ability to eradicate AOM pathogens.
The Pediatric Infectious Disease Journal 12/2009; 28(12):1105-10. · 3.58 Impact Factor
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ABSTRACT: There are few data about the epidemiology of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) among children in Israel. This study was intended to identify risk factors for CA-MRSA colonization in healthy infants, to characterize the molecular features of colonizing organisms, and to determine whether they are responsible for health care-associated (HA) infections. Nasal cultures and demographic details were collected from a cohort of healthy infants at 5 visits between the ages of 2 and 12 months. Clinical characteristics of pediatric MRSA bloodstream infections (2001 to 2006) and wound cultures collected over 6 months were also studied. Clonal structure was evaluated by multilocus sequence typing. Isolates were studied for the staphylococcal cassette chromosome mec (SCCmec) type and for the presence of Panton-Valentine leukocidin (PVL) genes. MRSA was cultured at least once from 45 of 659 infants (346 Jewish and 313 Bedouin infants). Forty of 45 (89%) isolates were from Bedouin infants. Twenty-nine of 45 (64.4%) belonged to a new clonal complex, designated CC913, that carries SCCmec IV but not the PVL genes. CC913 was also isolated from 9/14 blood cultures and 7/8 wounds. All CC913 infections occurred in Bedouin children, and all but two were HA. In conclusion, Bedouin origin was the main risk factor for carriage of CA-MRSA. CC913 was dominant both in healthy carriers and as a cause of pediatric HA-MRSA bloodstream infections.
Journal of clinical microbiology 12/2009; 48(2):531-8. · 4.16 Impact Factor
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ABSTRACT: The rise of antimicrobial resistance in many pathogens presents a major challenge to the treatment and control of infectious diseases. Furthermore, the observation that drug-resistant strains have risen to substantial prevalence but have not replaced drug-susceptible strains despite continuing (and even growing) selective pressure by antimicrobial use presents an important problem for those who study the dynamics of infectious diseases. While simple competition models predict the exclusion of one strain in favour of whichever is 'fitter', or has a higher reproduction number, we argue that in the case of Streptococcus pneumoniae there has been persistent coexistence of drug-sensitive and drug-resistant strains, with neither approaching 100 per cent prevalence. We have previously proposed that models seeking to understand the origins of coexistence should not incorporate implicit mechanisms that build in stable coexistence 'for free'. Here, we construct a series of such 'structurally neutral' models that incorporate various features of bacterial spread and host heterogeneity that have been proposed as mechanisms that may promote coexistence. We ask to what extent coexistence is a typical outcome in each. We find that while coexistence is possible in each of the models we consider, it is relatively rare, with two exceptions: (i) allowing simultaneous dual transmission of sensitive and resistant strains lets coexistence become a typical outcome, as does (ii) modelling each strain as competing more strongly with itself than with the other strain, i.e. self-immunity greater than cross-immunity. We conclude that while treatment and contact heterogeneity can promote coexistence to some extent, the in-host interactions between strains, particularly the interplay between coinfection, multiple infection and immunity, play a crucial role in the long-term population dynamics of pathogens with drug resistance.
Journal of The Royal Society Interface 11/2009; 7(47):905-19. · 4.40 Impact Factor
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ABSTRACT: This study describes the epidemiologic, microbiologic, and otologic features and selected signs and symptoms of acute otitis media (AOM) caused by Moraxella catarrhalis and compares them with AOM caused by other bacterial pathogens.
Patients aged <5 years with culture-positive AOM from whom a middle ear fluid specimen was obtained and cultured during 1999-2006 were enrolled in the study.
Of a total of 12,799 AOM episodes, 8198 (64%) were culture positive, with isolation of 10,382 pathogens: Haemophilus influenzae, 4982 (48.0%); Streptococcus pneumoniae, 4450 (42.9%); M. catarrhalis, 501 (4.8%); and group A streptococci, 449 (4.3%). The distribution of single versus mixed M. catarrhalis infection was significantly different compared with the 3 other pathogens (165 cases [32.9%] as a single pathogen of all M. catarrhalis AOM episodes vs 3108 [62.4%] in AOM caused by H. influenzae, 2592 [58.2%] in AOM caused by S. pneumoniae, and 304 [67.7%] in AOM caused by group A streptococci; P < .001 for all comparisons). In multivariate analysis, M. catarrhalis AOM was more frequent in patients experiencing their first AOM episode versus recurrent AOM and mixed infections. M. catarrhalis AOM was associated with lower proportions of spontaneous perforation of tympanic membrane compared with all other pathogens. None of the AOM episodes caused by M. catarrhalis was associated with mastoiditis.
Compared with AOM caused by other pathogens, AOM caused by M. catarrhalis is characterized by a higher proportion of mixed infections, younger age at diagnosis, a lower proportion of spontaneous perforation of the tympanic membrane, and no mastoiditis.
Clinical Infectious Diseases 11/2009; 49(11):1641-7. · 9.15 Impact Factor
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ABSTRACT: The major aim of this study was to establish the molecular epidemiology dynamics of Streptococcus pneumoniae serotype 6A in acute otitis media, before the introduction of the 7-valent pneumococcal conjugate vaccine.
Acute otitis media in Jewish and Bedouin children <5 years old undergoing tympanocentesis during 1999 to 2006, were studied. Serotype 6A was identified by the Quellung reaction and by polymerase chain reaction (PCR) of the wciN gene, to differentiate between 6A and 6C. Antibiogram and molecular typing by pulsed field gel electrophoresis were performed on all 6A isolates. Multilocus sequence typing was performed on representative isolates of each clone. The 7-valent conjugate vaccine had not yet been licensed in Israel during the study period.
Serotype 6A constituted 5.8% (254/4408) of all pneumococcal acute otitis media episodes. The yearly proportion of serotype 6A among the Jewish children showed no distinct trend, whereas among the Bedouin children serotype 6A exhibited a significant increase, from 3.0% in 1999 to 7.6% in 2006. Among the Jewish children a single penicillin-nonsusceptible and erythromycin-resistant clone, ST-473, constituted 73.6% of the strains and dominated throughout the study period. Among the Bedouin children, the proportions of the most common, penicillin-nonsusceptible clone, ST-1988, gradually decreased, from 44.1% in 1999 to 2000 to 21.4% in 2005 to 2006, concurrently with the expansion of a multidrug-resistant clone, ST-457, from 5.9% in 1999 to 2000 to 28.6% in 2005 to 2006.
The expansion of multidrug-resistant serotype 6A clone occurred before the introduction of the vaccine. Continued surveillance following vaccine introduction is warranted to further investigate its efficacy on vaccine-related serotypes.
The Pediatric Infectious Disease Journal 11/2009; 29(2):126-30. · 3.58 Impact Factor
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ABSTRACT: To determine the involvement of human metapneumovirus (HMPV) in childhood community-acquired alveolar pneumonia (CAAP) and compare the demographic, clinical, and laboratory features of HMPV-associated CAAP and CAAP associated with other respiratory viruses.
Nasopharyngeal wash specimens obtained prospectively over a 4-year period from children age < 5 years evaluated in the emergency department with radiologically diagnosed CAAP and from healthy controls were tested for HMPV by reverse-transcriptase polymerase chain reaction and for respiratory syncytial virus (RSV), adenovirus, influenza and parainfluenza viruses by direct immunofluorescence and culture.
HMPV was detected in 108 of 1296 patients (8.3%) versus RSV in 23.1%, adenovirus in 3.4%, influenza A virus in 2.9%, and parainfluenza viruse in 2.9%. During the period of peak activity (November to May), HMPV was detected in 95 of 1017 patients (9.3%) and in 3 of 136 controls (2.2%) (P = .005). The patients with HMPV were older than those with RSV (P < .001) with a more common history of acute otitis media requiring tympanocentesis (P = .032), wheezing (P = .001) and gastrointestinal symptoms (P < .001) and a lower hospitalization rate (P = .005).
The high detection rate suggests an important role for HMPV in childhood CAAP. Our findings identify demographic and clinical features of HMPV-positive CAAP and its age-related impact on hospital admissions.
The Journal of pediatrics 09/2009; 156(1):115-20. · 4.02 Impact Factor
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ABSTRACT: Evaluation of the effect of new conjugate vaccines on nasopharyngeal carriage of Streptococcus pneumoniae (pneumococcus) has been based on simple comparisons of the prevalence of carriage in vaccinees and controls. However, the definition and measurement of vaccine efficacy should be based on knowledge of the actual mechanism of the vaccine's effect. According to current knowledge, conjugate vaccines affect acquisition. We propose a simple-to-use method to measure vaccine efficacy against serotype-specific acquisition that needs only cross-sectional measurements of carriage. We demonstrate the use of the method by application to a data set where it is also possible to estimate efficacy against acquisition from longitudinal measurements.
Vaccine 07/2009; 27(29):3831-7. · 3.77 Impact Factor
