Molecular Characterization of Mycoplasma pneumoniae Isolates in the United States from 2012 to 2018.

Mycoplasma pneumoniae is a major cause of community-acquired pneumonia. There are limited data in the United States on the molecular epidemiological characteristics of M. pneumoniae We collected 446 M. pneumoniae-positive specimens from 9 states between August 2012 and October 2018. Culture, antimicrobial susceptibility testing, P1 subtyping, and multilocus VNTR (variable-number tandem repeats) analysis (MLVA) were performed to characterize the isolates. Macrolide-resistant M. pneumoniae (MRMp) was detected in 37 (8.3%) specimens. P1 subtype 2 (P1-2) was the predominant P1 subtype (59.8%). P1 subtype distribution did not change significantly chronologically or geographically. The macrolide resistance rate in P1 subtype 1 (P1-1) samples was significantly higher than that in P1-2 (12.9% versus 5.5%). Six P1-2 variants were identified, including two novel types, and variant 2c was predominant (64.6%). P1-2 variants were distributed significantly differently among geographic regions. Classical P1-2 was more frequent in lower respiratory tract specimens and had longer p1 trinucleotide repeats. Classical P1-2 was most common in MRMp (35.7%), while variant 2c was most common in macrolide-susceptible M. pneumoniae (67.5%). Fifteen MLVA types were identified; 3-5-6-2 (41.7%), 4-5-7-2 (35.3%), and 3-6-6-2 (16.6%) were the major types, and four MLVA clusters were delineated. The distribution of MLVA types varied significantly over time and geographic location. The predominant MLVA type switched from 4-5-7-2 to 3-5-6-2 in 2015. MLVA type was associated with P1 subtypes and P1-2 variant types but not with macrolide resistance. To investigate the M. pneumoniae genotype shift and its impact on clinical presentations, additional surveillance programs targeting more diverse populations and prolonged sampling times are required.

Macrolide-Resistant Mycoplasma pneumoniae in the United States as Determined from a National Surveillance Program.

There are sparse data to indicate the extent that macrolide-resistant Mycoplasma pneumoniae (MRMp) occurs in the United States or its clinical significance. Between 2015 and 2018, hospitals in 8 states collected and stored respiratory specimens that tested positive for M. pneumoniae and sent them to the University of Alabama at Birmingham, where real-time PCR was performed for detection of 23S rRNA mutations known to confer macrolide resistance. MRMp was detected in 27 of 360 specimens (7.5%). MRMp prevalence was significantly higher in the South and East (18.3%) than in the West (2.1%). A2063G was the predominant 23S rRNA mutation detected. MICs for macrolide-susceptible M. pneumoniae (MSMp) were ≤0.008 µg/ml, whereas MICs for MRMp were 16 to 32 µg/ml. Patients with MRMp infection were more likely to have a history of immunodeficiency or malignancy. Otherwise, there were no other significant differences in the clinical features between patients infected with MRMp and those infected with MSMp, nor were there any differences in radiographic findings, hospitalization rates, viral coinfections, the mean duration of antimicrobial treatment, or clinical outcomes. There was no significant change in MRMp incidence over time or according to age, sex, race/ethnicity, or status as an inpatient or an outpatient. Patients with MRMp were more likely to have received a macrolide prior to presentation, and their treatment was more likely to have been changed to a fluoroquinolone after presentation. This is the first national surveillance program for M. pneumoniae in the United States. Additional surveillance is needed to assess the clinical significance of MRMp and to monitor changes in MRMp prevalence.

Intrauterine transmission of cytomegalovirus to infants of women with preconceptional immunity.

BACKGROUND: Preconceptional immunity against cytomegalovirus (CMV) provides only partial protection against intrauterine transmission of the virus. Whether congenital CMV infection in the offspring of women who are seropositive for CMV can occur after maternal reinfection with a different strain of CMV is unknown. METHODS: Serum specimens from 46 women with preconceptional immunity against CMV that were obtained during the previous pregnancy and the current pregnancy were analyzed for antibodies against the strain-specific epitopes of CMV glycoprotein H. Virus-neutralizing activity in maternal serum samples was measured against the AD169 laboratory strain of CMV and the CMV isolates available from seven infected infants. In addition, the nucleotide sequences of the glycoprotein H gene from the seven CMV isolates were determined. RESULTS: Eleven of the 16 mothers with infected infants (69 percent) had antibodies against the glycoprotein H epitopes present on two laboratory strains of CMV, AD169 and Towne. Ten of the 16 mothers with infected children (62 percent) acquired new antibody specificities against glycoprotein H, as compared with only 4 of the 30 mothers of uninfected infants (13 percent, P<0.001). The samples obtained at the time of the current delivery from four of the seven mothers contained at least twice as many neutralizing antibodies against the CMV isolated from their infants as were present in the samples obtained at the previous delivery. The specificity of the newly acquired maternal antibodies reflected the amino acid sequence of the glycoprotein H epitope of CMV from these four infants. CONCLUSIONS: In women who are seropositive for CMV, reinfection with a different strain of CMV can lead to intrauterine transmission and symptomatic congenital infection.

Longitudinal investigation of hearing disorders in children with congenital cytomegalovirus.

This investigation consisted of a longitudinal study of the effects of congenital cytomegalovirus (CMV) infection on hearing sensitivity in 860 children with documented asymptomatic or symptomatic congenital CMV infection. Of the 651 children with asymptomatic CMV infection, 48 (7.4%) developed sensorineural hearing loss (SNHL), compared to 85 (40.7%) of the children with symptomatic CMV infection. Children in both groups experienced latent effects consisting of delayed onset of loss, threshold fluctuations, and/or progressive loss of hearing. It can be concluded that congenital CMV infection is a leading cause of SNHL in children. The late onset and progression of loss necessitates continued monitoring of hearing sensitivity in this population.

Symptomatic congenital cytomegalovirus infection in infants born to mothers with preexisting immunity to cytomegalovirus.

OBJECTIVES: To determine the frequency of symptomatic congenital cytomegalovirus (CMV) infection in the offspring of women with a recurrent maternal CMV infection and to characterize the demographic and newborn findings. METHODS: Study subjects consisted of infants with symptomatic congenital CMV infection identified by a newborn virologic screening program at the University of Alabama Hospital between 1991 and 1997 and were enrolled in a long-term follow-up study. Maternal infections were categorized by an analysis of archival serum specimens collected before pregnancy and at the time of delivery. Demographic data and clinical findings at birth were collected from maternal and newborn hospital records and from parents at the time of initial evaluation. RESULTS: Of the 47 infants with symptomatic congenital CMV infection identified during the study period, 8 were born to mothers with a confirmed nonprimary or recurrent CMV infection. The type of maternal infection could be ascertained in only approximately 43% (20/47) of the children with symptomatic congenital CMV infection born at the University of Alabama Hospital during the study period. There were no significant differences in demographic characteristics of the recurrent infection group and the infants who were born to mothers with either primary CMV infection during pregnancy or unclassified maternal infection. Similarly, the range of severity of clinical abnormalities during the newborn period did not differ in the two groups of children. Furthermore, there were no significant differences in the incidence of sequelae at long-term follow-up in the two groups of children. CONCLUSIONS: Symptomatic congenital CMV infection can occur after a nonprimary or recurrent maternal infection. However, the exact incidence of symptomatic congenital CMV infection among children born to women with preexisting immunity remains to be defined.

Newborn hearing screening: will children with hearing loss caused by congenital cytomegalovirus infection be missed?

OBJECTIVE: To predict whether universal newborn auditory screening will identify most infants with sensorineural hearing loss (SNHL) caused by congenital cytomegalovirus (CMV) infection. STUDY DESIGN: A cohort of 388 children born between 1980 and 1996 at one hospital and identified during the newborn period as having congenital CMV infection received repeated hearing evaluations to assess whether hearing loss had occurred. RESULTS: SNHL was detected in 5.2% of all infants at birth. Late-onset SNHL occurred among the children throughout the first 6 years of life. By the age of 72 months, the cumulative incidence of SNHL was 15.4% in the cohort. Children with clinically apparent disease at birth had significantly more SNHL than children without any apparent disease (22.8% vs 4.0% at 3 months and 36.4% vs 11.3% at 72 months of age). CONCLUSIONS: Universal screening of hearing in neonates will detect less than half of all SNHL caused by congenital CMV infection. Because most infants with congenital CMV infection are without symptoms at birth, these children are unlikely to be recognized as being at risk for SNHL and will not receive further hearing evaluations to detect late-onset hearing loss. A combined approach of universal screening of neonates for hearing, as well as for detection of congenital CMV infection, needs to be considered.

Progressive and fluctuating sensorineural hearing loss in children with asymptomatic congenital cytomegalovirus infection.

OBJECTIVE: To determine the prevalence and temporal changes of sensorineural hearing loss (SNHL) among children with clinically inapparent (asymptomatic) congenital cytomegalovirus (CMV) infection identified from a cohort of newborn infants screened for congenital CMV infection. METHODS: The study population consisted of 307 children with documented asymptomatic congenital CMV infection, 76 uninfected siblings of children with asymptomatic congenital CMV infection, and 201 children whose neonatal screen for congenital CMV infection showed negative results. Audiologic evaluations were completed for all children to determine their hearing status. RESULTS: SNHL occurred only in children with congenital CMV infection. Of the children with asymptomatic congenital CMV infection, 22 (7.2%; 95% confidence interval, 4.5% to 10.6%) had SNHL. Among the children with hearing loss, further deterioration of hearing occurred in 50.0%, with the median age at first progression at 18 months (range, 2 to 70 months). Delayed-onset SNHL was observed in 18.2% of the children, with the median age of detection at 27 months (range, 25 to 62 months). Fluctuating SNHL was documented in 22.7% of the children with hearing loss. CONCLUSIONS: Asymptomatic congenital CMV infection is likely a leading cause of SNHL in young children. The continued deterioration of hearing and delayed onset of SNHL in these children emphasizes the need for continued monitoring of their hearing status.

Neuroradiographic findings in the newborn period and long-term outcome in children with symptomatic congenital cytomegalovirus infection.

OBJECTIVE: To determine whether newborn cranial computed tomographic (CT) scan abnormalities predict an adverse neurodevelopmental outcome in children with symptomatic congenital cytomegalovirus (CMV) infection and to examine the association between clinical findings at birth and imaging abnormalities. METHODS: The data from 56 children with symptomatic congenital CMV infection who underwent cranial CT scans as newborns and were enrolled in a long-term follow-up study were analyzed. The incidence of sequelae was compared between the groups of children with normal and abnormal imaging studies. The relationship between CT scan results and other newborn findings was also examined. RESULTS: Abnormal CT scans were noted in 70% of subjects; intracerebral calcification was the most frequent finding. Most of the children with an abnormal newborn CT scan (90%) developed at least one sequela, compared with 29% of those with a normal study. Only 1 child with a normal CT scan had an IQ < 70, in contrast to 59% of those with imaging abnormalities. In addition, almost half of the children with CT abnormalities had an IQ < 50 compared with none of those with a normal CT scan. Newborn CT abnormalities were also associated with an abnormal hearing screen at birth and hearing loss on follow-up. None of the neonatal neurologic findings were predictive of an abnormal CT scan. CONCLUSION: In neonates with symptomatic congenital CMV infection, a cranial CT scan is a good predictor of an adverse neurodevelopmental outcome. In addition, newborn clinical and laboratory findings did not predict neuroradiographic abnormalities in neonates with symptomatic congenital CMV infection.

Hearing loss and congenital symptomatic cytomegalovirus infection: a case report of multidisciplinary longitudinal assessment and intervention.

More than 6000 children born annually in this country have hearing loss resulting from congenital cytomegalovirus (CMV) infection, the leading nonhereditary congenital cause of hearing loss in children. This exemplary congenital symptomatic CMV case focuses on the results of longitudinal audiologic, educational, medical, psychological, and visual evaluations and intervention. Decreased ocular motor control and visual acuity were observed as was bilateral deterioration of hearing from 3 days though 9 years of age. Treatment with dexamethasone and histamine resulted in almost complete reversal of the most recent progression of hearing loss in the left ear.

Maternal age and congenital cytomegalovirus infection: screening of two diverse newborn populations, 1980-1990.

Cytomegalovirus (CMV) is the leading cause of congenital viral infection in the United States. To prevent damaging congenital CMV infections, it is necessary to have accurate population estimates of prevalence and to identify maternal factors associated with an elevated risk of congenital infection in the newborn. From 1980 through 1990, 17,163 offspring of predominantly low-income nonwhite women who delivered at a public hospital and 9892 newborns of predominantly mid- to upper-income white women who delivered at a private hospital were screened for congenital CMV infection. Women < 20 years old (adjusted prevalence odds ratio [POR], 4.8; 95% confidence interval [CI], 2.6-8.9) at the public hospital and all nonwhite women (adjusted POR, 1.6; 95% CI, 1.1-2.2) had an increased risk of delivering an infected newborn. Newborns of adolescent women in both populations had the highest prevalence of clinically apparent infection. Offspring of nonwhite low-income adolescents are at greatest risk for congenital CMV infection and more damaging sequelae.

The outcome of congenital cytomegalovirus infection in relation to maternal antibody status.

BACKGROUND: Intrauterine transmission of cytomegalovirus (CMV) can occur whether a mother has prior immunity or acquires CMV for the first time during pregnancy. The degree of protection afforded an infected infant by the presence of antibody in the mother before conception is uncertain. METHODS: We compared the outcomes of CMV-infected infants born to mothers who acquired primary CMV infection during pregnancy (primary-infection group) with those of CMV-infected infants born to mothers with immunity (recurrent-infection group). Screening for viruria identified 197 newborns with congenital CMV infection. Stored serum samples were used to categorize maternal infection as either primary or recurrent. We followed 125 infants from the primary-infection group and 64 from the recurrent-infection group. Serial medical, audiologic, psychometric, and eye examinations were used to identify sequelae of CMV infection. RESULTS: Only infants in the primary-infection group had symptomatic CMV infection at birth (18 percent). After a mean follow-up of 4.7 years, one or more sequelae were seen in 25 percent of the primary-infection group and in 8 percent of the recurrent-infection group. Thirteen percent of infants whose mothers had primary infection during pregnancy had mental impairment (IQ less than or equal to 70), as compared with none of those whose mothers had recurrent CMV infections. Sensorineural hearing loss was found in 15 percent of those in the primary-infection group and in only 5 percent of those in the recurrent-infection group. Bilateral hearing loss was identified only among children in the primary-infection group (8 percent). CONCLUSIONS: The presence of maternal antibody to CMV before conception provides substantial protection against damaging congenital CMV infection in the newborn. Primary maternal infection during pregnancy is associated with more severe sequelae of congenital CMV infection.

Sexually transmitted diseases in mothers of neonates with congenital cytomegalovirus infection.

To identify maternal risk factors for intrauterine transmission of cytomegalovirus (CMV), a case-control study of 175 mothers of neonates with congenital CMV infection was undertaken. Cases and 358 randomly selected controls delivered neonates between 1980 and 1988; in this interval neonates were routinely tested for viruria. Eighty-four percent of the study population was black and greater than 87% received prenatal care. Women with gonorrhea, trichomoniasis, or bacterial vaginosis had an increased risk of intrauterine transmission of CMV, as did those who were primigravid (odds ratios, 1.8-2.5). Women who were young, unmarried, and of lower income were almost four times more likely to deliver a CMV-infected newborn than were those who did not have all three of these factors. These results in a predominantly black, low-income population indicate a greater risk for congenital CMV infection in offspring of young, single, primigravid mothers. The association with gonorrhea and other sexually transmitted infections suggests that sexual activity is an important source of maternal CMV infections that result in congenital infection in this population.

Reissner's membrane in aging, Menière's disease, and profound sensorineural deafness.

The characteristics of Reissner's membrane from 47 human cochleae with mild endolymphatic hydrops, profound sensorineural deafness and normal ears were studied by light microscopy. The highest cell densities were observed in the zones adjacent to the limbus spiralis and the stria vascularis. The cell density of Reissner's in normal ears decreased with age concomitant with an increased formation of epithelial cell clusters. In hydrops, the density increased with the exception of the apical turn. However, sporadic loss of the cells in isolated areas of the membrane was observed. The ears with profound deafness showed no significant changes compared with age-related controls. No definite relationship between Reissner's cell density and hair cell loss or strial atrophy was observed.