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Biomedical subjects

Melinda M Pettigrew

Publications and source records attributed to Melinda M Pettigrew.

10 recordsLinked to original sources

Association of surfactant protein A polymorphisms with otitis media in infants at risk for asthma.

BACKGROUND: Otitis media is one of the most common infections of early childhood. Surfactant protein A functions as part of the innate immune response, which plays an important role in preventing infections early in life. This prospective study utilized a candidate gene approach to evaluate the association between polymorphisms in loci encoding SP-A and risk of otitis media during the first year of life among a cohort of infants at risk for developing asthma. METHODS: Between September 1996 and December 1998, women were invited to participate if they had at least one other child with physician-diagnosed asthma. Each mother was given a standardized questionnaire within 4 months of her infant's birth. Infant respiratory symptoms were collected during quarterly telephone interviews at 6, 9 and 12 months of age. Genotyping was done on 355 infants for whom whole blood and complete otitis media data were available. RESULTS: Polymorphisms at codons 19, 62, and 133 in SP-A1, and 223 in SP-A2 were associated with race/ethnicity. In logistic regression models incorporating estimates of uncertainty in haplotype assignment, the 6A4/1A5haplotype was protective for otitis media among white infants in our study population (OR 0.23; 95% CI 0.07,0.73). CONCLUSION: These results indicate that polymorphisms within SP-A loci may be associated with otitis media in white infants. Larger confirmatory studies in all ethnic groups are warranted.

Alleles↗

Predictors for Haemophilus influenzae colonization, antibiotic resistance and for sharing an identical isolate among children attending 16 licensed day-care centers in Michigan.

BACKGROUND: Nontypable Haemophilus influenzae is an important cause of otitis media in children. Children attending day-care centers are at an increased risk for nontypable H. influenzae colonization and otitis media. We describe the prevalence of nontypable H. influenzae colonization, antibiotic resistance and predictors for colonization and sharing an identical isolate with at least 1 other child in the same day-care centers among children attending 16 day-care centers. METHODS: Throat swabs of 198 children < 3 years old attending 16 day-care centers were cultured for H. influenzae. Day-care center directors and parents completed risk factors questionnaires. Nontypable H. influenzae isolates were screened for antibiotic resistance and genotyped. Statistics were performed using SAS software (SAS Institute, Inc., Cary, NC). RESULTS: We isolated 179 unique nontypable H. influenzae strains from 127 participants. Colonization ranged from 0% to 95% among day-care centers. As individual factors, exposure to tobacco smoke was associated with colonization (P = 0.05), and racial self-identifications as "other" (nonwhite, nonblack) was protective (P = 0.035), whereas as "black" was protective for sharing (P = 0.03). Pacifier use was associated with sharing (P = 0.04), but not with colonization. As day-care centers factors, rates of colonization and sharing were higher in day-care centers with > or = 5 classrooms (P < 0.01 and P = 0.03), with such suboptimal hygiene habits as minimal hand washing by staff after eating (P < 0.002 and P < 0.01) or by children after wiping their own nose (P = 0.01 and P = 0.003). Of colonized children, 41% presented a beta-lactamase-producing strain. Colonized children were more likely to carry resistant strains if they were taking an antibiotic (P = 0.02). CONCLUSION: Although day-care center colonization varied, the overall colonization rate was high. Colonization with nontypable H. influenzae, with beta-lactamase-producing strain and sharing were, mostly, associated with modifiable risk factors.

Carrier State↗

Variation in the presence of neuraminidase genes among Streptococcus pneumoniae isolates with identical sequence types.

Streptococcus pneumoniae frequently colonizes the upper respiratory tract of young children and is an important cause of otitis media and invasive disease. Carriage is more common than disease, yet the genetic factors that predispose a given clone for disease are not known. The relationship between capsule type, genetic background, and virulence is complex, and important questions remain regarding how pneumococcal clones differ in their ability to cause disease. Pneumococcal neuraminidase cleaves sialic acid-containing substrates and is thought to be important for pneumococcal virulence. We describe the distribution of multilocus sequence types (ST), capsule type, and neuraminidase genes among 342 carriage, middle ear, blood, and cerebrospinal fluid (CSF) pneumococcal strains from young children. We found 149 STs among our S. pneumoniae isolates. nanA was present in all strains, while nanB and nanC were present in 96% and 51% of isolates, respectively. The distribution of nanC varied among the strain collections from different tissue sources (P = 0.03). The prevalence of nanC was 1.41 (95% confidence interval, 1.11, 1.79) times higher among CSF isolates than among carriage isolates. We identified isolates of the same ST that differed in the presence of nanB and nanC. These studies demonstrate that virulence determinants, other than capsule loci, vary among strains of identical ST. Our studies suggest that the presence of nanC may be important for tissue-specific virulence. Studies that both incorporate MLST and take into account additional virulence determinants will provide a greater understanding of the pneumococcal virulence potential.

Bacterial Typing Techniques↗

Genomic subtraction followed by dot blot screening of Streptococcus pneumoniae clinical and carriage isolates identifies genetic differences associated with strains that cause otitis media.

Streptococcus pneumoniae strains are the leading cause of bacterial otitis media, yet little is known about specific bacterial factors important for this disease. We utilized a molecular epidemiological approach involving genomic subtraction of the S. pneumoniae serogroup 19 middle ear strain 5093 against the laboratory strain R6. Resulting subtraction PCR (sPCR) products were used to screen a panel of 93 middle ear, 90 blood, 35 carriage, and 58 cerebrospinal fluid isolates from young children to identify genes found more frequently among middle ear isolates. Probe P41, similar to a hypothetical protein of Brucella melitensis, occurred among 41% of middle ear isolates and was found 2.8 (95% confidence interval [CI], 1.32 to 6.5), 3.3 (95% CI, 1.9 to 5.7), and 1.8 (95% CI, 1.1 to 3.0) times more frequently among middle ear strains than carriage, blood, or meningitis strains, respectively. sPCR fragment H10, similar to an unknown Streptococcus agalactiae protein, was present in 31% of middle ear isolates and occurred 3.6 (95% CI, 1.2 to 11.2), 2.8 (95% CI, 1.5 to 5.4), and 2.6 (95% CI, 1.2 to 5.5) times more often among middle ear isolates than carriage, blood, or meningitis strains, respectively. These studies have identified two genes of potential importance in otitis media virulence. Further studies are warranted to outline the precise role of these genes in otitis media pathogenesis.

Blood↗

An array of diverse microbial genomes.

Methods for comparing gene frequencies across large, epidemiologically defined bacterial collections are limited. A novel microarray technology has been developed called 'library on a slide'. In this technology, hundreds of entire microbial genomes are arrayed, rather than sequences of a single genome or sets of genes. These slides can then be probed for the presence of specific genes allowing researchers to draw inferences regarding important differences between related strains that differ in their pathogenic potential.

Bacteria↗

Infant otitis media and the use of secondary heating sources.

BACKGROUND: This prospective study investigated the association of exposure to indoor secondary heating sources with otitis media and recurrent otitis media risk in infants. STUDY DESIGN: We enrolled mothers living in nonsmoking households and delivering babies between 1993 and 1996 in 12 Connecticut and Virginia hospitals. Biweekly telephone interviews during the first year of life assessed diagnoses from doctors' office visits and use of secondary home heating sources, air conditioner use, and day care. Otitis media episodes separated by more than 21 days were considered to be unique episodes. Recurrent otitis media was defined as 4 or more episodes of otitis media. Repeated-measures logistic regression modeling evaluated the association of kerosene heater, fireplace, or wood stove use with otitis media episodes while controlling for potential confounders. Logistic regression evaluated the relation of these secondary heating sources with recurrent otitis media. RESULTS: None of the secondary heating sources were associated with otitis media or with recurrent otitis media. Otitis media was associated with day care, the winter heating season, birth in the fall, white race, additional children in the home, and a maternal history of allergies in multivariate models. Recurrent otitis media was associated with day care, birth in the fall, white race, and a maternal history of allergies or asthma. CONCLUSION: We found no evidence that the intermittent use of secondary home heating sources increases the risk of otitis media or recurrent otitis media. This study confirms earlier findings regarding the importance of day care with respect to otitis media risk.

Environmental Exposure↗

Diversity and sharing of Haemophilus influenzae strains colonizing healthy children attending day-care centers.

BACKGROUND: Children attending day-care centers (DCCs) are at risk for Haemophilus influenzae nasopharyngeal colonization and acute otitis media. The degree to which a given strain circulates within a day-care center and the heterogeneity of strains among DCCs in a geographic area are not well-characterized. This study describes the prevalence rates of H. influenzae colonization in a large number of children attending day-care centers and examines the genetic diversity of colonizing strains and the degree of sharing among children. METHODS: Throat cultures were collected from 198 healthy children <3 years old attending 16 day-care centers in Michigan. All H. influenzae isolates were genetically typed by enterobacterial repetitive intergenic consensus PCR as the initial screening technique to identify unique strains within each child. Pulsed field gel electrophoresis was used subsequently to examine the genetic diversity of strains between children. RESULTS: There were 127 (64%) children colonized with H. influenzae. Wide variation in rates of colonization was identified among day-care centers (0 to 95%). A total of 179 genetically unique H. influenzae strains were isolated, and 47 children (37%) were colonized with 2 or more genetically distinct H. influenzae organisms. Evidence of sharing of the same strain in different children was found in 13 of 15 colonized DCCs and 23% of genotypically unique strains were shared. CONCLUSION: The degree of sharing of H. influenzae among children in this study suggests transmission of these potentially pathogenic microorganisms in day-care centers.

Carrier State↗

Association of early-onset otitis media in infants and exposure to household mould.

Otitis media is one of the most common infections of early childhood. Children who first experience acute otitis media at an early age (before 6 months) are at increased risk for recurrent otitis media. This prospective study investigated exposure to measured levels of airborne household mould and the risk of early otitis media in the first 6 months of life among a cohort of infants at high risk for asthma. Between September 1996 and December 1998, women were invited to participate if they had at least one other child with physician-diagnosed asthma. Mothers were given a standardised questionnaire within 4 months of their infant's birth. Airborne mould samples were also taken at this time, and culturable fungi were categorised into four levels according to the report of the Commission of European Communities: 0 (undetectable), 1-499 colony forming units (CFU)/m(3) (low), 500-999 CFU/m(3) (medium), > or =1000 CFU/m(3) (high). Infant respiratory symptoms were collected during quarterly telephone interviews at 6, 9 and 12 months of age. Of the 806 children in the study, 27.8% experienced otitis media before six months of age. Household levels of Penicillium and Cladosporium were modestly associated with the number of otitis media episodes (P = 0.056 and 0.081 respectively). After controlling for potential confounders, Penicillium and Cladosporium were not associated with early otitis media. High levels of 'other' mould (defined as total spore count minus counts for Penicillium, Cladosporium, and yeast) were associated with early otitis media (OR 3.49; 95% CI [1.38, 8.79]). We also found associations between day-care outside of the home and birth during the summer or fall season with early otitis media. This study is suggestive of a relationship between otitis media and mould that warrants further study.

Age of Onset↗

Prevalence of the hifBC, hmw1A, hmw2A, hmwC, and hia Genes in Haemophilus influenzae Isolates.

Adherence of Haemophilus influenzae to respiratory epithelial cells is the first step in the pathogenesis of H. influenzae infection and is facilitated by the action of several adhesins located on the surface of the bacteria. In this study, prevalences of hifBC, which represent the pilus gene cluster; hmw1A, hmw2A, and hmwC, which represent high-molecular-weight (HMW) adhesin genes; and hia, which represents H. influenzae adhesin (Hia) genes were determined among clinical isolates of encapsulated type b (Hib) and nonencapsulated (NTHi) H. influenzae. hifBC genes were detected in 109 of 170 (64%) Hib strains and in 46 of 162 (28%) NTHi isolates (P = 0.0001) and were more prevalent among the invasive type b strains than invasive NTHi strains (P = 0.00003). Furthermore, hifBC genes were significantly more prevalent (P = 0.0398) among NTHi throat isolates than NTHi middle ear isolates. hmw1A, hmw2A, hmwC, and hia genes were not detected in Hib strains. Among NTHi isolates, the prevalence of hmw1A was 51%, the prevalence of hmw2A was 23%, the prevalence of hmwC was 48%, and the prevalence of hia was 33%. The hmw genes were significantly more prevalent among middle ear than throat isolates, while hia did not segregate with a respiratory tract site. These results show the variability of the presence of adhesin genes among clinical H. influenzae isolates and suggest that hemagglutinating pili may play a larger role in H. influenzae nasopharyngeal colonization than in acute otitis media whereas the HMW adhesins may be virulence factors for acute otitis media.

Adhesins, Bacterial↗

Duration of breastfeeding, daycare, and physician visits among infants 6 months and younger.

PURPOSE: To describe the association between duration of breastfeeding and an illness requiring a visit to a health care provider within the past 30 days (IRHP) among infants </= 6 months. METHODS: Participants were breastfeeding women who delivered at a birthing center in suburban Detroit, Michigan and women employed by a company in Omaha, Nebraska. Subjects were interviewed by telephone at 3,6,9, and 12 weeks postpartum and by mailed questionnaire at 6 months postpartum. RESULTS: Of the 674 breastfeeding women, 233 (34.5%) reported an IRHP. An IRHP was more likely among infants attending daycare (RR = 1.60; 95% CI 1.30, 1.96). There was an interaction between duration of breastfeeding, the number of children in the household, and IRHP (p < 0.0001). For firstborn children, each additional week of breastfeeding decreased the likelihood of an IRHP by 4%. An increased duration of breastfeeding was not significantly protective against an IRHP for infants living with additional children in the household. CONCLUSIONS: Breastfeeding offers protection against an IRHP among firstborn children. Having additional children in the household or attending daycare outside of the home may diminish these benefits.

Adolescent↗