Legacy Pediatrics

Rochester, NY, United States

Legacy Pediatrics

Rochester, NY, United States

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Pichichero M.E.,Rochester General Hospital | Casey J.R.,Legacy Pediatrics | Almudevar A.,University of Rochester
Pediatric Infectious Disease Journal | Year: 2013

OBJECTIVE: We recently found that children who experience recurrent otitis media despite individualized care (stringently-defined otitis prone [sOP]) do not develop an antibody response to several vaccine candidate protein antigens expressed by Streptococcus pneumonia (Spn) and Haemophilus influenzae. Here we sought to determine if these same children also failed to develop antibody to routine pediatric vaccinations. STUDY DESIGN: One hundred forty sera collected from children age 6-24 months were analyzed. sOP (n = 34) and age-matched non-sOP (n = 34) children were assessed for IgG concentrations to diphtheria toxoid, tetanus toxoid, pertussis toxoid, filamentous hemagglutinin, pertactin (DTaP), polio, hepatitis B, H. influenzae type b capsule polyribosyl-ribitol- phosphate (PRP) and Spn capsular polysaccharide conjugate vaccine. RESULTS: IgG protective titers to diphtheria toxoid (P = 0.006), tetanus toxoid (P < 0.0001), pertussis toxoid (P < 0.0001), filamentous hemagglutinin (P = 0.001), pertactin (P = 0.005), hepatitis B (P < 0.0001), polio 3 (P = 0.03) and Spn 23F (P = 0.01) but not polio 1,2, PRP or Spn 6B, and 14 were decreased in sOP versus non-sOP children using generalized estimating equations. A high percentage of sOP children had nonprotective antibody values that persisted until 24 months of age despite routine boosters. CONCLUSION: sOP children may fail to achieve protective antibody concentrations after several routine vaccinations. Copyright © 2013 by Lippincott Williams & Wilkins.


Xu Q.,Rochester General Hospital | Almudervar A.,University of Rochester | Casey J.R.,Legacy Pediatrics | Pichichero M.E.,Rochester General Hospital
Emerging Infectious Diseases | Year: 2012

Antimicrobial treatments and vaccines can alter bacterial interactions in the nasopharynx, thereby altering disease processes. To better understand these interactions, we examined colonization rates of 3 respiratory bacterial pathogens among 320 children when healthy and at onset of acute otitis media (AOM). Bacterial interactions were analyzed with a repeated measures logistic regression model. Among healthy children, Streptococcus pneumoniae and Moraxella catarrhalis were synergistically (positively) associated. Colonization with S. pneumoniae when healthy, but not at onset of AOM, was competitively (negatively) associated with Staphylococcus aureus. Among children with AOM, competitive associations were found between Haemophilus influenzae and S. pneumoniae and between H. influenzae and M. catarrhalis; rates of colonization with H. influenzae were higher. Bacterial interactions result in differing pathogen prevalence during periods of health and at onset of AOM. H. influenzae might become a more common cause of AOM among children who receive pneumococcal conjugate vaccine.


Kaur R.,Rochester General Hospital | Casey J.,Legacy Pediatrics | Pichichero M.,Rochester General Hospital
Laryngoscope | Year: 2015

Objectives/Hypothesis: Acute otitis media (AOM) is a common bacterial infection in childhood that causes an inflammatory response in the middle ear. Leukocytes produce different inflammatory molecules in vitro when stimulated with Gram-positive and Gram-negative bacteria. The major causes of AOM are Streptococcus pneumoniae, nontypeable Haemophilus influenza, and Moraxella catarrhalis. We sought to assess differences in cytokines, chemokines, and expression of Toll-like receptors (TLRs) at onset of AOM based on bacterial culture results.Study Design: Middle ear fluid (MEF) from 66 children with AOM was studied.Methods: Innate immune genes, cytokines (interleukin [IL]-6, IL-8, IL-10, IL1-ß; tumor necrosis factor-α), chemokines (CCL2, CCL3, CCL4, CCR5, CXCR3), and Toll-like receptors (TLR2, TLR4, TLR9) expression was measured using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) from MEF collected in vivo by tympanocentesis.Results: Culture-positive MEF had higher levels of all cytokines and chemokines (9-300-fold) as compared to MEF that was culture negative. Polymerase chain reaction (PCR)-positive/culture-negative MEF for otopathogens showed significant differences (P<.01) in TLR2, TLR4, and TLR9 expression (6-31-fold), but cytokine and chemokine levels were similar compared to PCR-negative/culture-negative MEF. No significant differences were found in the cytokine/chemokine/TLR levels among the bacterial otopathogen species. However, higher levels of TLRs, and all the cytokine and chemokines were detected when more than one bacterial species was present compared to single otopathogens.Conclusions: Expression levels of proinflammatory cytokines/chemokines and TLRs are elevated in AOM children with a bacterial otopathogen, and are dependent on the number of bacterial species identified. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.


Casey J.R.,Legacy Pediatrics | Pichichero M.E.,Rochester General Hospital
Clinical Pediatrics | Year: 2014

We determined the cost of care for 2 diagnosis and management approaches for acute otitis media (AOM) among children 6 to 30 months old. A case-control design was used. Cases included 208 children diagnosed with AOM based on a bulging tympanic membrane (TM) and treated with amoxicillin/clavulanate. Controls (5:1 ratio) included 1020 children with AOM diagnosed not requiring bulging of the TM and treated with amoxicillin. Fewer cases (49%) than controls (69%) were diagnosed with AOM (P <.001), fewer were diagnosed with recurrent AOM or AOM treatment failure (0.34 vs 1.6/child; P <.0001), and fewer had insertion of tympanostomy tubes (6.3% vs 14.8%) due to recurrent AOM (P <.0001). The combined direct payments and indirect costs for management of AOM were $539/case versus $1,023/control. Using Rochester NY payments generalized to the US birth cohort, this case diagnosis and treatment strategy could save $1.008 billion per year. © 2014 The Author(s).


Xu Q.,Rochester General Hospital | Casey J.R.,Legacy Pediatrics | Pichichero M.E.,Rochester General Hospital
Mucosal Immunology | Year: 2015

Mucosal immunity has a crucial role in controlling human respiratory tract infections. This study characterizes the naturally acquired mucosal antibody levels to three Streptococcus pneumoniae (Spn) protein antigens, pneumococcal histidine triad protein D (PhtD), pneumococcal choline binding protein A (PcpA), and pneumolysin (Ply), and assesses the association of the mucosal antibody levels with occurrence of acute otitis media (AOM) caused by Spn. Both nasopharyngeal (NP) immunoglobulin G (IgG) and IgA levels to all three proteins slightly decreased in children from 6 to 9 months of age and then gradually increased through 24 months of age. Spn NP colonization was associated with higher mucosal antibody levels to all three proteins. However, children with Spn AOM had 5-8-fold lower IgG and 3-6-fold lower IgA levels to the three proteins than children without AOM but asymptomatically colonized with Spn. Antigen-specific antibody levels in the middle ear fluid (MEF) were correlated with antibody levels in the NP. Children with AOM caused by Spn had lower antibody levels in both the MEF and NP than children with AOM caused by other pathogens. These results indicate that higher naturally acquired mucosal antibody levels to PhtD, PcpA and Ply are associated with reduced AOM caused by Spn. © 2015 Society for Mucosal Immunology.


Sharma S.K.,Rochester General Hospital | Casey J.R.,Legacy Pediatrics | Pichichero M.E.,Rochester General Hospital
Journal of Infectious Diseases | Year: 2012

A low level of serum antibody to antigens expressed by Streptococcus pneumoniae has been proposed to explain the susceptibility of children to recurrent episodes of acute otitis media (hereafter, "otitis-prone children"). By use of enzyme-linked immunospot assays, the percentages of memory B cells to pneumococcal protein antigens PhtD, LytB, PcpA, PhtE, and Ply were compared between otitis-prone and non-otitis-prone children at the time of acute otitis media or nasopharyngeal colonization with S. pneumoniae. We found significantly lower percentages of memory B cells to 3 pneumococcal protein antigens (PhtD, PhtE, and Ply) and reduced antigen-specific immunoglobulin G concentrations in otitis-prone children, compared with non-otitis-prone children. © The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.


Kaur R.,Rochester General Hospital | Casey J.R.,Legacy Pediatrics | Pichichero M.E.,Rochester General Hospital
Pediatric Infectious Disease Journal | Year: 2011

Background: Streptococcus pneumoniae (Spn) is one of the common bacteria responsible for episodic acute otitis media (AOM; non-otitis-prone), recurrent AOM (otitis-prone), and AOM treatment failure (AOMTF) in children. Objective: From a population of 268 children, we sought to compare the serum IgG antibody titers of 5 different Spn proteins (PhtD, LytB, PcpA, PhtE, and Ply) that are vaccine candidates in children with episodic AOM (n = 34), who were otitis prone (n = 35) and who had AOMTF (n = 25) caused by Spn. Methods: Antibody was quantitated by enzyme-linked immunosorbent assay. Results: At their AOM visit, anti-PhtD,-LytB,-PhtE, and-Ply IgG antibody titers in otitis-prone children were significantly lower compared with non-otitis-prone children (P < 0.05) and children with AOMTF (P < 0.05). On comparing acute to convalescent geometric mean IgG antibody titers after AOM against the 5 proteins we found that otitis-prone, AOMTF, and non-otitis-prone children had no significant change in titers (except for PhtE in children with AOMTF), but detailed analysis showed that about one-third of the children in each cohort had a 2-fold rise in antibody to the studied antigens. Although non-otitis-prone children had significant increases (P < 0.001) between 6 and 24 months of age in anti-PhtD, PcpA, PhtE, and Ply IgG antibody titers as a consequence of nasopharyngeal colonization and AOM, otitis-prone children either failed to show rises or the rises were significantly less than the non-otitis-prone children. Conclusion: Otitis-prone and AOMTF children mount less of an IgG serum antibody response as compared with non-otitis-prone children to Spn proteins after AOM and nasopharyngeal colonization. © 2011 Lippincott Williams & Wilkins.


Kaur R.,Rochester General Hospital | Casey J.R.,Legacy Pediatrics | Pichichero M.E.,Rochester General Hospital
Pediatric Infectious Disease Journal | Year: 2013

OBJECTIVE: We sought to determine whether recurrent acute otitis media (rAOM) occurring within 30 days of amoxicillin/clavulanate treatment was caused by bacterial relapse or new pathogens. METHODS: Pneumococcal conjugate vaccinated children, age 6-36 months, enrolled in a prospective, longitudinal study experiencing rAOM <1 month after completing amoxicillin/clavulanate therapy were studied. AOM episodes occurred between June 2006 and November 2012. Multilocus sequence typing was used to genotype isolates. RESULTS: Sixty-six children were in the study cohort; 63 otopathogens were recovered from middle ear fluid after tympanocentesis. Nontypeable Haemophilus influenzae (NTHi) accounted for 47% of initial AOMs versus 15% by Streptococcus pneumoniae (Spn), P < 0.0001. NTHi accounted for 42% of rAOM versus 24% by Spn (P value = 0.04). NTHi was the main otopathogen that caused true bacteriologic relapses (77%). β-lactamase-producing NTHi and penicillin nonsusceptible Spn were not more common in rAOM than initial AOM infections. Among 21 paired (initial and rAOM events) NTHi isolates genotyped, 13 (61.9%) were the same organism; 1 of 9 (11.1%) of paired Spn isolates was the same (P value = 0.017). rAOM occurring within a week of stopping amoxicillin/clavulanate was a different pathogen in 21% of cases, 8-14 days later in 33%, 15-21 days in 41% and 22-30 days in 57% (P = 0.04). CONCLUSIONS: In amoxicillin/clavulanate-treated children, NTHi was the main otopathogen that caused true bacteriologic relapses. New pathogens causing rAOM versus persistence of the initial pathogen significantly increased week to week. Neither relapses nor new infections were caused more frequently by β-lactamase producing NTHi or penicillin nonsusceptible Spn. Copyright © 2013 by Lippincott Williams & Wilkins.


Kaur R.,Rochester General Hospital | Casey J.R.,Legacy Pediatrics | Pichichero M.E.,Rochester General Hospital
Vaccine | Year: 2011

Non-typeable Haemophilus influenzae (NTHi) is the most common bacteria responsible for episodic acute otitis media (AOM; non-otitis prone), recurrent AOM (rAOM; otitis prone) and AOM treatment failure (AOMTF) in children. In this 3.5 years of prospective study, we measured the serum antibody response to outer membrane proteins D, P6 and OMP26 of NTHi in children with AOM (n = 26), rAOM (n = 32), AOMTF (n = 27). The geometric mean titers (GMTs) of IgG at their acute AOM visit against Protein D in otitis prone children were significantly lower compared to AOMTF (p value < 0.01) and non-otitis prone (p value < 0.03) children; otitis prone children had significantly lower IgG levels to P6 compared to AOMTF children (p value <0.02); otitis prone children had significantly lower IgG levels to OMP26 compared to AOMTF children (p value < 0.04). Comparing acute to convalescent titers after AOM, otitis prone and AOMTF children had no significant change in total IgG against all the three proteins, while non-otitis prone children had significant increases to Protein D. Anti-protein D, P6 and OMP26 antibody levels measured longitudinally during NP colonization between age 6 and 24 months in 10 otitis prone children and 150 non-otitis prone children showed <2-fold increases over time in otitis prone children compared to >4 fold increases in the non-otitis prone children (p value < 0.001). We conclude that otitis prone children mount less of an IgG serum antibody response toward Protein D, P6 and OMP26 after AOM which may account for recurrent infections. The data on acute sera of otitis prone vs non-otitis prone children and the acute-to-convalescence response in non-otitis prone children point to a possible link of anti-PD to protection. Moreover, the data suggest that otitis prone children should be evaluated for their responses to Protein D, P6 and OMP26 vaccine antigens of NTHi. © 2010 Elsevier Ltd.


Xu Q.,Rochester General Hospital | Casey J.R.,Legacy Pediatrics | Chang A.,Rochester General Hospital | Pichichero M.E.,Rochester General Hospital
Pediatric Infectious Disease Journal | Year: 2012

Of 368 acute otitis media (AOM) cases among 7-valent pneumococcal conjugate-vaccinated children, 43.5% were colonized by multiple otopathogens in the nasopharynx but only 7.1% experienced polymicrobial AOM. When co-colonization occurred, Haemophilus influenzae predominated over all Streptococcus pneumoniae strains except 19A strains to cause AOM. Haemophilus influenzae and Streptococcus pneumoniae both predominated over Moraxella catarrhalis to cause AOM. © 2012 Lippincott Williams & Wilkins.

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