Shannon A Ross

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

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Publications (16)168.83 Total impact

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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: 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: 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
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    ABSTRACT: This study was designed to determine whether elevated viral load in infants and young children is associated with congenital cytomegalovirus (CMV)-related hearing loss. Blood samples were obtained from 135 children with congenital CMV infection. CMV DNA in the peripheral blood was quantitated with a real-time polymerase chain reaction assay. Viral load measurements were analyzed in 3 different age groups (<2 months, 2-12 months, 12-36 months). In children with symptomatic and asymptomatic infection, CMV DNA levels were not different between children with hearing deficit and those with normal hearing in all 3 age groups. In children with asymptomatic infection, the positive predictive value of a peripheral blood viral load >3500 genomic equivalents per milliliter (ge/mL) at <2 months and 2 to 12 months of age is 8%, and at 12 to 36 months of age is 11.8%. However, the negative predictive value of a viral load <3500 ge/mL is 94.4% at <2 months of age, and 100% at 2 to 36 months of age. Peripheral blood viral load is not associated with hearing loss in children with congenital CMV infection. However, a viral load of <3500 ge/mL is associated with a lower risk of hearing loss in children born with asymptomatic congenital infection.
    The Pediatric Infectious Disease Journal 05/2009; 28(7):588-92. · 3.57 Impact Factor
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    ABSTRACT: Reliable methods for the detection of cytomegalovirus (CMV) strain-specific serological responses are lacking. We describe a simple and reliable enzyme-linked immunosorbent assay method developed to detect antibodies against the polymorphic epitopes within the two envelope glycoproteins of CMV, glycoproteins H and B. This assay is useful for the detection of serologic responses to CMV strains and the identification of CMV reinfections.
    Clinical and vaccine Immunology: CVI 12/2008; 16(2):288-90. · 2.60 Impact Factor
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    ABSTRACT: Infection and reinfection with multiple cytomegalovirus (CMV) strains have been shown to occur in immunocompromised individuals, sexually transmitted disease clinic attendees, and children attending day care centers. To characterize the CMV diversity in healthy seropositive individuals, 16 CMV PCR-positive specimens from 113 seropositive women were analyzed for glycoprotein gN and gB genotypes by cloning, followed by nucleotide sequencing of the plasmid DNA and/or restriction fragment length polymorphism (RFLP). The results showed that most (93.7%) of the PCR-positive specimens contained multiple gN and/or gB genomic variants, suggesting that the majority of women were infected with more than one virus strain. The results also showed that the RFLP technique might not be sufficiently sensitive to detect all of the genomic variants present in a sample.
    Journal of clinical microbiology 04/2008; 46(3):882-6. · 4.16 Impact Factor
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    ABSTRACT: Congenital cytomegalovirus (CMV) infection is a leading cause of sensorineural hearing loss (SNHL) in children. Whether connexin mutations are factors in the development of CMV-related hearing loss has not been explored. We examined gap junction protein beta-2 (GJB2) and gap junction protein beta-6 (GJB6) mutations in 149 children with congenital CMV infection and 380 uninfected neonates. Mutations in GJB2 and GJB6 were assessed by nucleotide sequencing and polymerase chain reaction (PCR) methods, respectively. The study population was predominantly African American, and 4.3% of the subjects were carriers of a connexin 26 mutation. The overall frequency of GJB2 mutations was significantly higher in the group of children with CMV infection and hearing loss (21%) compared with those with CMV infection and normal hearing (3%, p = 0.017) and the group of uninfected newborns (3.9%, p = 0.016). Eight previously reported mutations (M34T, V27I, R127H, F83L, R143W, V37I, V84L, G160S), and four novel mutations (V167M, G4D, A40T, and R160Q) were detected. None of the study children had the 342-kb deletion (delGJB6-D13S1830) in GJB6, which suggests that this mutation does not play a role in hereditary deafness in the African American population. Although GJB2 mutations were detected in children with and without CMV-related hearing loss, those with hearing loss had a higher frequency of GJB2 mutations.
    Pediatric Research 06/2007; 61(6):687-91. · 2.67 Impact Factor
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    ABSTRACT: To define hearing outcomes in children with congenital cytomegalovirus (CMV) infection born to mothers with non-primary CMV infection. A cohort of 300 children with congenital CMV infection identified by newborn virologic screening at the University of Alabama Hospital and a private community hospital in which the type of maternal infection could be classified constituted the study population. Maternal infections were categorized by analyzing serum samples. Children were followed prospectively and underwent serial audiologic evaluations. The frequency of hearing loss was not different between children born to mothers with non-primary infection (10%) and those with primary infection (11%). Significantly more children in the primary infection group had progressive and severe/profound hearing loss compared with children in the non-primary group. The frequency of bilateral, delayed onset, high-frequency, and fluctuating hearing loss was not different between the 2 groups. The mean age of diagnosis of hearing loss was 39 +/- 53 months for children born to mothers with non-primary infection and 13 +/- 21 months for the primary infection group (P = .16). Maternal preexisting seroimmunity to CMV does not provide complete protection against hearing loss in infants with congenital CMV infection.
    Journal of Pediatrics 04/2006; 148(3):332-6. · 4.04 Impact Factor
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    ABSTRACT: Women with sexually transmitted diseases (STDs) and bacterial vaginosis (BV) have increased rates of cytomegalovirus (CMV) seroprevalence and CMV seroconversion. To characterize the association between genital tract CMV infection and BV, vaginal wash specimens from 52 women attending an STD clinic were analyzed. Significantly more women with BV shed CMV in the lower genital tract than did women without BV. In addition, most of the women who were shedding CMV were infected with >1 virus strain. These results suggest that local CMV replication and infection with multiple CMV strains is facilitated by the presence of BV.
    The Journal of Infectious Diseases 12/2005; 192(10):1727-30. · 5.85 Impact Factor
  • Shannon A Ross, Suresh B Boppana
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    ABSTRACT: Cytomegalovirus (CMV) is the most common congenital infection in humans and an important cause of morbidity and mortality in immunocompromised hosts. Congenital CMV infection occurs in approximately 0.5 to 1 percent of all newborns in the United States and can result in significant neurological sequelae. The gold standard for diagnosing congenital CMV infection is isolation of the virus from infants within the first 2 weeks of life through conventional or rapid cell culture techniques. Newer molecular diagnostic methods to diagnose congenital CMV infection, including the nucleic acid amplification of viral DNA from the peripheral blood of infants, are being investigated, and the preliminary results show promise. However, more work must be done to standardize and validate these methods before they can be used routinely in establishing the diagnosis of congenital CMV infection.
    Seminars in Pediatric Infections Diseases 02/2005; 16(1):44-9.