Karen B Fowler

University of Alabama at Birmingham, Birmingham, Alabama, United States

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Publications (64)432.94 Total impact

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    ABSTRACT: Background: Congenital CMV infection (cCMV) is a common congenital infection and a significant contributor to non-genetic sensorineural hearing loss (SNHL). Real-time PCR of newborn saliva specimens has been shown to be highly sensitive and specific compared to culture based methods for CMV screening. Although both saliva and urine samples are known to be acceptable for identifying infants with cCMV, it is thought that urine samples may contain more virus and thus, are optimal for cCMV screening. The objective is to compare viral load (VL) levels between saliva and urine samples from a large cohort of infants with cCMV infection identified through a newborn screening program. Methods: As part of the NIDCD CHIMES study, newborns at 7 U.S. medical centers were screened for CMV by saliva and dried blood spot PCR. Infants who screened positive were enrolled in a follow-up study to confirm congenital infection by testing saliva and urine samples using a previously described real-time PCR assay. CMV viral load in saliva samples obtained at screening and enrollment was compared to urine collected at enrollment in follow-up. Results: Of the 100,332 newborns screened for CMV from 2007 to 2011, viral load levels in both saliva and urine samples were available in 73% (336/462) of infants with confirmed cCMV. Of these, 36% (121/336) were enrolled within the first 3 weeks of life. The median viral load level in saliva at screening and enrollment (2.x106 IU/ml and 1.1x107 IU/ml, respectively) was significantly higher than in urine (8.3x105 IU/ml; p < 0.0001). There was no significant difference between VL in saliva and urine in infants with and without symptomatic disease and with and without congenital SNHL. In the smaller cohort of infants enrolled within 3 weeks of birth, median saliva VL at screening and enrollment (1.1x106 IU/ml vs. 9.3x106 IU/ml, respectively) was higher than urine VL (7.9x105IU/ml; p < 0.0001) . Conclusion: Infants with congenital CMV infection shed large amounts of virus in both saliva and urine. However, saliva samples contained higher viral load than urine, are easier to collect and do not require DNA extraction. Therefore, we propose that saliva should be considered the ideal specimen and real-time PCR of saliva is appropriate for both newborn screening and diagnosis of cCMV.
    IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
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    ABSTRACT: Background: Congenital CMV (cCMV) is the leading non-genetic cause of sensorineural hearing loss (SNHL) in the U.S. Approximately 40-60% of infants with symptomatic cCMV infection develop long term sequelae such as hearing loss. Currently, there are no identified predictors of hearing loss. The objectiveis to determine clinical predictors of SNHL in infants with symptomatic cCMV infection. Methods: Findings from a longitudinal follow-up study of children with symptomatic cCMV at the University of Alabama (UAB) were analyzed. Infants were considered to have symptomatic cCMV infection if they were positive for CMV by saliva or urine rapid culture and had findings suggestive of congenital infection at birth. Infants with jaundice, petechiae, purpura, hepatosplenomegaly, elevated aspartate aminotransferase, thrombocytopenia and lacked CNS involvement were considered to have transient symptoms. Infants with microcephaly, seizures, abnormal neurological examination, and abnormal neuroimaging findings with/without any of the transient symptoms were categorized as the group with CNS involvement. Incidence of SNHL was compared between the groups with transient symptoms, CNS involvement and only petechial rash. Results: 176 infants with symptomatic cCMV infection were followed at UAB. CNS involvement and transient findings were found in 56% and 31% of infants, respectively while 13% of infants only had a petechial rash. Hearing outcome was available in 96% of study children. The overall incidence of hearing loss was found to be highest in the group with CNS involvement followed by those with transient findings and infants with only a petechial rash [59% (54/92) vs. 39% (21/54) vs. 22% (5/23) respectively; p = 0.0004). SNHL at birth was significantly more frequent in infants with CNS involvement compared to infants with transient findings or only petechial rash [42% (39/92) vs. 24% (13/54) vs. 13% (3/23) respectively; p = 0.0019]. The incidence of late onset hearing loss was not significantly different between these groups (p = 0.08). Conclusion: Among infants with symptomatic cCMV infection, those with evidence of CNS involvement in the newborn period are at the greatest risk for SNHL overall and congenital hearing loss. However, findings in the newborn period are not predictive of late onset hearing loss.
    IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
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    ABSTRACT: Background: In pediatric renal transplant recipients, persistent EBV viremia is associated with post-transplant lymphoproliferative disease (PTLD), but immune correlates of persistent viremia remain poorly defined. In this study the relationship between circulating lymphocyte subsets and persistent EBV viremia was examined in pediatric renal transplant patients. Methods: Serial prospectively collected peripheral blood mononuclear cell samples from pediatric renal transplant patients were analyzed for CD4+ T cell subsets including Th1, Th2, Th17, CD4+ and CD8+ effector memory cells, and NK cells by flow cytometry for surface markers and intracellular cytokine staining. Patient demographics and EBV PCR results were extracted from patient records. Results: 36 samples were obtained from 11 renal transplant patients over six months. Six patients had negative EBV PCR results at all time points. Five patients were EBV PCR positive, one of which was transient, while four remained positive with average PCR viral load of 10,507 copies/ml [range 515-34,710]. The two groups were similar with respect to EBV recipient status, age at transplant, and change in eGFR during the study. Patients with EBV viremia had significantly higher absolute CD4 T cell counts compared to patients without EBV viremia (mean +/- SD, 1629+/-162 vs 903+/-82, p = 0.0002). Within CD4 T cells subsets, patients with EBV viremia had a significantly lower percentage of CD4+CCR4+ Th2 cells compared to those without EBV viremia (mean +/- SD, 3.80+/-0.80 vs 7.14+/-0.82, p = 0.019) as well as a significantly lower percentage of IL-4 producing CD4+ cells (0.67+/-0.075 vs 2.26+/-0.55, p = 0.002). No difference was seen in CD4+ or CD8+ effector memory, Th1, Th17 or NK cells. Conclusion: In this cohort, persistent EBV viremia was associated with a statistically greater number of circulating CD4+ T cells, but statistically fewer circulating CD4+ Th2 cells and a blunted IL-4+ response compared to that found in patients without viremia. These results suggest that impairment of Th2 responses may contribute to persistent EBV viremia in pediatric renal transplant recipients.
    IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
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    ABSTRACT: Viral culture of urine or saliva has been the gold standard for the diagnosis of congenital CMV infection. Results of rapid culture and PCR of urine and saliva from 80 children were compared to determine the utility of a real-time PCR assay for congenital CMV diagnosis. Urine PCR was positive in 98.8% of specimens. Three PCR-positive urine samples were culture-negative. Saliva PCR and culture were concordant in 78 specimens (97.5%). Two PCR-positive saliva samples were culture-negative. PCR of urine or saliva is equivalent to rapid culture for congenital CMV diagnosis. Additionally, saliva samples are easier to collect than urine.
    The Journal of Infectious Diseases 05/2014; · 5.85 Impact Factor
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    ABSTRACT: To evaluate differences in presentation and outcomes in children with symptomatic congenital cytomegalovirus (cCMV) identified on newborn screening (screened group) and those identified based on clinical findings at birth (referred group). Data on 178 infants with symptomatic cCMV were analyzed. Demographic characteristics, clinical and laboratory findings documented in the nursery, and sequelae data were compared between the screened and the referred groups using χ(2) or Fisher exact test. Two or more clinical findings were detected at birth in 91% of referred infants, and only 58% of screened infants (P < .001). Significantly more children in the referred group had hearing loss compared with screened infants (P = .009). Fifty-one percent of screened children were free of sequelae compared with only 28% of the referred group (P < .003). Infants with symptomatic cCMV identified based on clinical suspicion have more severe disease at birth and more commonly have sequelae than those identified on newborn screening. Inclusion of referral infants in many previous reports may have overestimated the severity of disease because of selection bias. Defining the complete spectrum of symptomatic disease due to cCMV and providing precise estimates of disease burden can only be gathered from large newborn screening studies.
    The Journal of pediatrics 01/2014; · 4.02 Impact Factor
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    ABSTRACT: Background & objectives: Most studies on the clinical presentation with influenza viruses have been conducted in outpatient or inpatient medical facilities with only a few studies in community settings. Clinical differences between influenza A (H1N1) pdm 09 and influenza B virus infections have importance for community-based public health surveillance. An active community surveillance at the time of emergence of pandemic influenza provided us with an opportunity to compare the clinical features among patients infected with influenza A (H1N1) pdm09 virus and those with influenza B virus co-circulating in an active community-based weekly surveillance in three villages in Faridabad, Haryana, north India. Methods: Active surveillance for febrile acute respiratory infection (FARI) was carried out in a rural community (n=16,182) in the context of an inactivated trivalent influenza vaccine trial (among children <11 yr). Individuals with FARI were assessed clinically by nurses and respiratory samples collected and tested for influenza viruses by real time RT-PCR from November 2009 to August 2010. Clinical symptoms of patients with influenza A (H1N1) pdm 09 and influenza B infection were compared. Results: Of the 4796 samples tested, 822 (17%) were positive for influenza virus. Of these, 443 (54%) were influenza A (H1N1) pdm09, 373 (45%) were influenza B and six were other subtypes/mixed infections. The mean age was lower for patients with influenza B (16.4 yr) than influenza A (H1N1) pdm09 infection (18.7 yr; P=0.04). Among children aged 5-18 yr, chills/rigours (OR 4.0; CI 2.2, 7.4), sore throat (OR 6.8; CI 2.3, 27.3) and headache (OR2.0; CI 1.3, 3.3) were more common in influenza A (H1N1) pdm09 infection than in influenza B cases. Chills/rigours (OR 2.4; CI 1.4, 4.0) and headache (OR 1.7; CI 1.0, 2.7) were associated with influenza A (H1N1) pdm09 infection in those >18 yr. No significant differences were seen in children <5 yr. Conclusion: Our findings show that the differences in the clinical presentation of influenza A(H1N1)pdm09 and influenza B infections are not likely to be of clinical or public health significance.
    The Indian Journal of Medical Research 12/2013; 138(6):962-8. · 2.06 Impact Factor
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    ABSTRACT: Background: Cytomegalovirus (CMV) is the leading non-genetic cause of sensorineural hearing loss (SNHL). Children with congenital CMV infection excrete CMV for a variable time period during childhood. It has been suggested that shorter duration of shedding in urine was associated with SNHL but this association remains to be confirmed. Most studies to date have examined CMV excretion patterns in urine. The objective of this study was to examine duration and the amount of salivary CMV shedding by PCR in a large cohort of children with congenital CMV infection. Methods: As part of an ongoing multicenter study (CHIMES study), infants born at seven hospitals in the U.S. were screened for congenital CMV infection. Saliva specimens collected at newborn screening, at enrollment into the follow-up study (3-6 wks), and at every 6 months up to 48 months of age were tested for CMV using real-time PCR. All CMV-infected infants underwent audiologic evaluation in early infancy. Results: Of the CMV-infected children, 102 children had virus shedding data at all follow-up visits up to 24 months of age and were included. Twenty three infants treated with gancyclovir/valgancyclovir were excluded. The cohort included 12 infants with SNHL at birth. The median duration of CMV shedding in saliva in the study subjects was 24±9.8 months. There was no significant difference in the duration of shedding for infants with and without hearing loss at birth (p = 1). There was no significant difference between viral load at birth (1.23x107 vs. 2.2x106 copies/ml) and at 24 months (4.78x102 vs. 4x102 copies/ml) between infants with and without hearing loss. Among infants with saliva PCR data available at 36 and 48 months, 54/109 (49.5%) tested positive by PCR at 36 months and 22/74 (29.7%) infants were positive at 48 months. Conclusion: Most infants with congenital CMV infection shed CMV in saliva for a median of two years after birth. There is no significant difference between duration of shedding of CMV between infants with and without SNHL at birth. There was also no significant difference in saliva viral load at birth and at 24 months of age between children with and without SNHL.
    IDWeek 2013 Meeting of the Infectious Diseases Society of America; 10/2013
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    ABSTRACT: Data on influenza illness rates with population denominators are needed to quantify overall morbidity and to prioritize public health intervention strategies. The rates of influenza A(H1N1)pdm09 infection during pandemic phases were determined in a longitudinal community cohort study as part of an influenza vaccine study in a rural community of North India. During the 711 731 person-weeks of surveillance, a total of 1410/7571 (19%) febrile acute respiratory illness cases were positive for influenza. Of these, 749 (53%) were influenza A(H1N1)pdm09, 643 (46%) influenza B, and 18 (1%) influenza A (H3N2). The overall incidence rate of influenza-associated febrile acute respiratory illness was 128/1000 person-years. The incidence rates of influenza A(H1N1)pdm09 were high during both the pandemic phase (179/1000 person-years; November 2009 to January 2010) and post-pandemic phase (156/1000 person-years; August to October 2010), with children <18 years of age being at the greatest risk of influenza infection in the community. These findings provide important information for planning clinical and public health intervention strategies to mitigate the impact of influenza epidemics.
    International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 09/2013; · 2.17 Impact Factor
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    ABSTRACT: Population-based active surveillance in India showed higher incidence rates for influenza A(H1N1)pdm09 among children during pandemic versus postpandemic periods (345 vs. 199/1,000 person-years), whereas adults had higher rates during postpandemic versus pandemic periods (131 vs. 69/1,000 person-years). Demographic shifts as pandemics evolve should be considered in public health response planning.
    Emerging Infectious Diseases 09/2012; 18(9):1472-5. · 6.79 Impact Factor
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    ABSTRACT: 18,500 laboratory-confirmed deaths caused by the 2009 pandemic influenza A H1N1 were reported worldwide for the period April, 2009, to August, 2010. This number is likely to be only a fraction of the true number of the deaths associated with 2009 pandemic influenza A H1N1. We aimed to estimate the global number of deaths during the first 12 months of virus circulation in each country. We calculated crude respiratory mortality rates associated with the 2009 pandemic influenza A H1N1 strain by age (0-17 years, 18-64 years, and >64 years) using the cumulative (12 months) virus-associated symptomatic attack rates from 12 countries and symptomatic case fatality ratios (sCFR) from five high-income countries. To adjust crude mortality rates for differences between countries in risk of death from influenza, we developed a respiratory mortality multiplier equal to the ratio of the median lower respiratory tract infection mortality rate in each WHO region mortality stratum to the median in countries with very low mortality. We calculated cardiovascular disease mortality rates associated with 2009 pandemic influenza A H1N1 infection with the ratio of excess deaths from cardiovascular and respiratory diseases during the pandemic in five countries and multiplied these values by the crude respiratory disease mortality rate associated with the virus. Respiratory and cardiovascular mortality rates associated with 2009 pandemic influenza A H1N1 were multiplied by age to calculate the number of associated deaths. We estimate that globally there were 201,200 respiratory deaths (range 105,700-395,600) with an additional 83,300 cardiovascular deaths (46,000-179,900) associated with 2009 pandemic influenza A H1N1. 80% of the respiratory and cardiovascular deaths were in people younger than 65 years and 51% occurred in southeast Asia and Africa. Our estimate of respiratory and cardiovascular mortality associated with the 2009 pandemic influenza A H1N1 was 15 times higher than reported laboratory-confirmed deaths. Although no estimates of sCFRs were available from Africa and southeast Asia, a disproportionate number of estimated pandemic deaths might have occurred in these regions. Therefore, efforts to prevent influenza need to effectively target these regions in future pandemics. None.
    The Lancet Infectious Diseases 06/2012; 12(9):687-95. · 19.97 Impact Factor
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    ABSTRACT: The burden of disease due to influenza is not well characterized for children in developing countries and the effectiveness of available influenza vaccines in lower resource settings has not been established. We initiated a prospective, longitudinal, phase IV, household-randomized, controlled, observer-blinded three year study (2009-2011) in a rural community of India to measure the total and indirect household protective effects of immunizing children ages 6 months through 10 years with seasonal inactivated trivalent influenza vaccine (TIV) or a control vaccine (n=3697). Active weekly surveillance was conducted year round with home visits for identification of febrile acute respiratory illness (FARI) conducted for all vaccine recipients and household members (n=18,220). Nasal and throat swabs were collected from each FARI episode for influenza detection by real-time reverse transcription polymerase chain reaction. The primary outcome was reduction in laboratory confirmed influenza infections in the influenza vaccine versus control vaccine group, with secondary outcome assessing indirect effects among the entire study population. This report describes the study site, cluster study design, choice of study and control vaccines, and the initial enrollment in the study.
    Vaccine 06/2012; 30(35):5235-9. · 3.77 Impact Factor
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    ABSTRACT: Background: Congenital cytomegalovirus (CMV) infection is the most common intrauterine infection affecting 0.5-1% of all neonates. Congenitally infected children excrete virus for prolonged periods and persistent viral shedding might be associated with an increased risk of late sequelae. Most previous studies have examined urinary viral excretion. The objective of this study is to examine the duration of salivary shedding of CMV over the first two years of age in a longitudinal cohort of children with congenital CMV infection. Methods: Infants born at seven medical centers in the U.S. between March 2007 and December 2008 were screened for congenital CMV infection as part of the NIDCD CHIMES study. Available saliva specimens collected at newborn screening, at enrollment (median 37days), and at 7, 12, 18 and 24 months of age were tested for CMV using rapid culture and real-time PCR. Results: Ninety infants were found to be CMV positive at birth (and confirmed at enrollment) and had at least one follow-up visit. All 90 had positive saliva specimens by rapid culture at screening and the rate declined to 26% (16/61) by 24 months of age. Saliva was positive by PCR in 100% of infants at screening and declined to 41% (25/61) positive by 24 months of age. Mean duration of shedding was 9.1 ± 6.6 months by rapid culture compared with 14.6±6.6 months by PCR (p<0.001). There was no difference in the duration of shedding, assessed by PCR, between 81 infants with asymptomatic infection (14.3±6.6 mo) and 9 infants with symptomatic infection (17.0±6.0 mo). Although saliva viral load was higher in screening samples from infants with symptomatic infection (Median 3.6 x 107 ge/mL) compared to those with asymptomatic infection at birth (Median 5.0 x 106 ge/mL, p=0.047), this difference did not persist at 24 months of age. Conclusion: A substantial number of infants with congenital CMV infection shed virus in saliva during the first two years of age, and the duration of shedding does not differ between infants with symptomatic and asymptomatic infection. Real-time PCR appears to be more sensitive than rapid viral culture at detecting CMV over time in the saliva.
    Infectious Diseases Society of America 2011 Annual Meeting; 10/2011
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    ABSTRACT: Cytomegalovirus (CMV), the most common cause of congenital infection, exhibits extensive genetic variability. We sought to determine whether multiple CMV strains can be transmitted to the fetus and to describe the distribution of genotypes in the saliva, urine, and blood. Study subjects consisted of a convenience sampling of 28 infants found to be CMV-positive on newborn screening as part of an ongoing study. Genotyping was performed on saliva specimens obtained during newborn screening and urine, saliva, and blood obtained at a later time point within the first 3 weeks of life. Six (21.4%) of the 28 saliva samples obtained within the first 2 days of life contained >1 CMV genotype. Multiple CMV genotypes were found in 39% (5/13) of urine, saliva, and blood samples obtained within the first 3 weeks of life from 13 of the 28 newborns. There was no predominance of a CMV genotype at a specific site; however, 4 infants demonstrated distinct CMV strains in different compartments. Infection with multiple CMV strains occurs in infants with congenital CMV infection. The impact of intrauterine infection with multiple virus strains on the pathogenesis and long-term outcome remains to be elucidated.
    The Journal of Infectious Diseases 10/2011; 204(7):1003-7. · 5.85 Impact Factor
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    ABSTRACT: Human metapneumovirus (hMPV) causes acute respiratory infections in children and adults. It is classified into two major genetic lineages and each lineage into two sublineages. The purpose of the study was to identify and characterize hMPV in children who presented to the All India Institute of Medical Sciences, New Delhi, India with acute respiratory infection from April 2005 to March 2007. By reverse-transcription polymerase chain reaction, hMPV was detected in 21 (3%) of the 662 nasopharyngeal samples from children with acute respiratory infection and in none of the 120 control children. Seven of the 21 (33%) children infected with hMPV required hospital admission for pneumonia or bronchiolitis. Most hMPV detections were during the winter and spring seasons. The majority (67%, 11/21) of children positive for hMPV were within 24 months of age. Phylogenetic analysis of partial F and N gene and the full G gene sequences showed three sub-lineages of hMPV circulated during the study period, B1, B2, and the novel sub-lineage A2b. The circulation pattern of hMPV genotypes varied by season. Comparison of the F and G genes of eight strains revealed incongruencies in lineage assignments, raising the possibility that recombination had occurred. Sequence analysis also revealed the F gene was relatively conserved whereas the G gene was more variable between the A and B lineages. This study demonstrates that hMPV is an important contributor to acute respiratory infection in children in India, resulting in both outpatient visits and hospitalizations.
    Journal of Medical Virology 10/2011; 83(10):1799-810. · 2.37 Impact Factor
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    ABSTRACT: Failure of a cytomegalovirus (CMV) real-time PCR assay targeting glycoprotein B (gB) was investigated. A multiplex assay targeting gB and immediate-early 2 (IE2) genes showed discordant results (gB negative and IE positive or a >10-fold-higher viral load with IE primers) in saliva from 14.6% of CMV-infected newborns. Sequencing revealed 3 patterns of gB variations.
    Journal of clinical microbiology 06/2011; 49(8):3033-5. · 4.16 Impact Factor
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    ABSTRACT: Congenital cytomegalovirus (CMV) infection is an important cause of hearing loss, and most infants at risk for CMV-associated hearing loss are not identified early in life because of failure to test for the infection. The standard assay for newborn CMV screening is rapid culture performed on saliva specimens obtained at birth, but this assay cannot be automated. Two alternatives--real-time polymerase-chain-reaction (PCR)-based testing of a liquid-saliva or dried-saliva specimen obtained at birth--have been developed. In our prospective, multicenter screening study of newborns, we compared real-time PCR assays of liquid-saliva and dried-saliva specimens with rapid culture of saliva specimens obtained at birth. A total of 177 of 34,989 infants (0.5%; 95% confidence interval [CI], 0.4 to 0.6) were positive for CMV, according to at least one of the three methods. Of 17,662 newborns screened with the use of the liquid-saliva PCR assay, 17,569 were negative for CMV, and the remaining 85 infants (0.5%; 95% CI, 0.4 to 0.6) had positive results on both culture and PCR assay. The sensitivity and specificity of the liquid-saliva PCR assay were 100% (95% CI, 95.8 to 100) and 99.9% (95% CI, 99.9 to 100), respectively, and the positive and negative predictive values were 91.4% (95% CI, 83.8 to 96.2) and 100% (95% CI, 99.9 to 100), respectively. Of 17,327 newborns screened by means of the dried-saliva PCR assay, 74 were positive for CMV, whereas 76 (0.4%; 95% CI, 0.3 to 0.5) were found to be CMV-positive on rapid culture. Sensitivity and specificity of the dried-saliva PCR assay were 97.4% (95% CI, 90.8 to 99.7) and 99.9% (95% CI, 99.9 to 100), respectively. The positive and negative predictive values were 90.2% (95% CI, 81.7 to 95.7) and 99.9% (95% CI, 99.9 to 100), respectively. Real-time PCR assays of both liquid- and dried-saliva specimens showed high sensitivity and specificity for detecting CMV infection and should be considered potential screening tools for CMV in newborns. (Funded by the National Institute on Deafness and Other Communication Disorders.).
    New England Journal of Medicine 06/2011; 364(22):2111-8. · 54.42 Impact Factor
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    ABSTRACT: Viruria and DNAemia patterns were investigated in 205 seroimmune women enrolled in a prospective cytomegalovirus (CMV) reinfection study. CMV DNA was detected at least once in urine and blood specimens from 83% and 52% of patients, respectively. At baseline, 39% of patients had viruria, and 24% had DNAemia. Intermittent viruria and viremia was observed throughout the study. There were no differences in baseline CMV positivity by polymerase chain reaction or in longitudinal DNAemia and viruria between the women with and without serological evidence of reinfection. In young seropositive women, CMV DNAemia and viruria are common, which suggests that naturally acquired immunity to CMV does not alter shedding patterns.
    The Journal of Infectious Diseases 11/2010; 202(12):1800-3. · 5.85 Impact Factor
  • Suresh B Boppana, Karen B Fowler, Shannon A Ross
    JAMA The Journal of the American Medical Association 07/2010; 304(4):407-408. · 29.98 Impact Factor
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    ABSTRACT: Reliable methods to screen newborns for congenital cytomegalovirus (CMV) infection are needed for identification of infants at increased risk of hearing loss. Since dried blood spots (DBS) are routinely collected for metabolic screening from all newborns in the United States, there has been interest in using DBS polymerase chain reaction (PCR)-based methods for newborn CMV screening. To determine the diagnostic accuracy of DBS real-time PCR assays for newborn CMV screening. Between March 2007 and May 2008, infants born at 7 US medical centers had saliva specimens tested by rapid culture for early antigen fluorescent foci. Results of saliva rapid culture were compared with a single-primer (March 2007-December 2007) and a 2-primer DBS real-time PCR (January 2008-May 2008). Infants whose specimens screened positive on rapid culture or PCR had congenital infection confirmed by the reference standard method with rapid culture testing on saliva or urine. Sensitivity, specificity, and positive and negative likelihood ratios (LRs) of single-primer and 2-primer DBS real-time PCR assays for identifying infants with confirmed congenital CMV infection. Congenital CMV infection was confirmed in 92 of 20,448 (0.45%; 95% confidence interval [CI], 0.36%-0.55%) infants. Ninety-one of 92 infants had positive results on saliva rapid culture. Of the 11,422 infants screened using the single-primer DBS PCR, 17 of 60 (28%) infants had positive results with this assay, whereas, among the 9026 infants screened using the 2-primer DBS PCR, 11 of 32 (34%) screened positive. The single-primer DBS PCR identified congenital CMV infection with a sensitivity of 28.3% (95% CI, 17.4%-41.4%), specificity of 99.9% (95% CI, 99.9%-100%), positive LR of 803.7 (95% CI, 278.7-2317.9), and negative LR of 0.7 (95% CI, 0.6-0.8). The positive and negative predictive values of the single-primer DBS PCR were 80.9% (95% CI, 58.1%-94.5%) and 99.6% (95% CI, 99.5%-99.7%), respectively. The 2-primer DBS PCR assay identified infants with congenital CMV infection with a sensitivity of 34.4% (95% CI, 18.6%-53.2%), specificity of 99.9% (95% CI, 99.9%-100.0%), positive LR of 3088.9 (95% CI, 410.8-23 226.7), and negative LR of 0.7 (95% CI, 0.5-0.8). The positive and negative predictive values of the 2-primer DBS PCR were 91.7% (95% CI, 61.5%-99.8%) and 99.8% (95% CI, 99.6%-99.9%), respectively. Among newborns, CMV testing with DBS real-time PCR compared with saliva rapid culture had low sensitivity, limiting its value as a screening test.
    JAMA The Journal of the American Medical Association 04/2010; 303(14):1375-82. · 29.98 Impact Factor
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    ABSTRACT: Cytomegalovirus (CMV) reinfections have been associated with damaging congenital infection and adverse outcomes in transplant recipients. To determine the frequency of and risk factors for CMV reinfections, 205 seropositive women were followed up prospectively. The appearance of new antibody specificity against 1 of 4 polymorphic epitopes was considered as evidence of CMV reinfection. Approximately one-third of the study participants (59 [29%] of 205) were noted to have CMV reinfection during follow-up. None of the exposure factors were associated with CMV reinfection. Women with antibodies against at least 1 of the 4 antigens at baseline had a 63% decreased risk of reinfection, suggesting a protective role for strain-specific immunity.
    The Journal of Infectious Diseases 02/2010; 201(3):386-9. · 5.85 Impact Factor

Publication Stats

3k Citations
432.94 Total Impact Points

Institutions

  • 1991–2014
    • University of Alabama at Birmingham
      • • Department of Pediatrics
      • • Department of Medicine
      Birmingham, Alabama, United States
  • 2006–2011
    • All India Institute of Medical Sciences
      • Department of Microbiology
      New Delhi, NCT, India
  • 2007
    • Cambridge Eco
      Cambridge, England, United Kingdom