Cytomegalovirus Culture Research Articles

Co-existence of Guillain-Barré syndrome and Behcet syndrome: A case report

A 40-year-old male patient was referred to our department with complains of recurrent oral ulcer for more than 20 years and vulvar ulcer for more than 10 years. He presented with a 3-month history of right external ophthalmoplegia. More than 10 days ago, the patient received ganglioside infusion. And one week ago, he developed numbness and pain of his lambs, and progressive myasthenia, accompanied by right blepharoptosis and dysuria. On exam, motor strength was graded 0/5 in the lower and the upper extremities. Deep tendon reflexes were diminished in extremities. His admission medical examination: hemoglobin (HGB), white cell and platelet counts were normal. C-reactive protein (CRP) was negative. Erythrocyte sedimentation rate (ESR) 53 mm/h. Antinuclear antibody (ANA), anti-dsDNA antibody, anti-Smith antibody, anti-cardiolipin antibody and human leucocyte antigen B51 were all within normal range. The etiological tests of influenza A pathogen, influenza B pathogen, parainfluenza virus, enterovirus and parvovirus were all negative. He tested positive for serum anti-GM1 IgG. Cerebrospinal fluid had a normal white cell count, an elevated protein content. Gram staining, culture and PCR detection for varicella-zoster virus, cytomegalovirus and herpes simplex virus were all negative. Antibodies associated with autoimmune encephalitis and paraneoplastic syndrome were negative in cerebrospinal fluid. Electromyography and nerve conduction studies showed a severe axonal damage affecting motor nerves. No obvious abnormalities were observed in his magnetic resonance imaging of brain and cavernous sinus. The patient was diagnosed with Behcet syndrome complicated with acute Guillain-Barre syndrome. He received intravenous methylprednisolone, intravenous immunoglobulin (IVIg) therapy, plasma exchange and rituximab treatment. After treatment, the patient's muscle strength of limbs was restored to grade 1, blepharoptosis and pain disappeared. The nervous system involvement of Behcet syndrome is relatively rare, especially combined with Guillain-Barre syndrome, which is easy to cause misdiagnosis. The treatment of Behcet syndrome complicated with acute Guillain-Barre syndrome includes the treatment of primary disease, plasma exchange and IVIg therapy. In addition, supportive treatment is very important for such patients. The focus of treatment is to avoid respiratory insufficiency, prevent deep vein thrombosis, monitor cardiac function and hemodynamics. Pain-relieving, physical exercise and psychological support are often under-recognized. The rehabilitation treatment is very important to improve the prognosis and quality of life of patients. What we need to learn is that when the symptoms and signs of the nervous system are difficult to be explained by neuro-Behcet syndrome alone, we should be alert to the possibility of other nervous system diseases.

Effects of cytomegalovirus infection on extravillous trophoblast cells invasion and immune function of NK cells at the maternal-fetal interface.

Cytomegalovirus (CMV) is one of the most common intrauterine infection virus, which can cause intrauterine transmission through the placenta, resulting in abortion, stillbirth and congenital malformations. In this study, the co‐culture extravillous trophoblast (EVT) HTR8/SVneo cell model of CMV infection was established in vitro. The toxicity of CMV infected EVT was determined, and then, the cell invasion experiment was conducted to evaluate the effect on the invasion ability of EVT cell lines. Western blot and real‐time PCR were used to detect the related cytokines in the PI3K/AKT signalling pathway in cells. Flow cytometry was used to detect the immune function related factors of the supernatant of CMV culture on decidual NK cells. The TCID50 of CMV virus was 10−5.4. The results of immunofluorescence showed that a large number of fluorescent green of CMV pp65 antigen signals appeared in the cytoplasm of CMV infection group. CMV could infect and replicate EVT cells and inhibited cell proliferation. The expression of proteins PDK1, AKT‐S473 and AKT‐S308 was significantly increased in CMV infection group. The levels of IL‐17, IL‐4 and IFN‐γ were 8.7 ± 0.48%, 12.17 ± 0.61% and 6.66 ± 0.25%, respectively, in CMV infection group. The above results indicated that CMV infection inhibited EVT cells proliferation, weakened the invasion ability and inhibited the immune function of NK cells at the maternal‐fetal interface, resulting in the abnormal maternal‐fetal crosstalk.

Utility of Neonatal Ophthalmologic Examination for Detection of Infectious Etiologies for Symmetric Intrauterine Growth Restriction

To determine the utility of ophthalmologic examination as part of evaluation for infection in infants with intrauterine growth restriction (IUGR). This is a single-institution retrospective chart review of neonates diagnosed with symmetric IUGR or small for gestational age (SGA) who underwent complete ophthalmologic consultation to assess for intraocular findings suggestive of congenital infection. Data collected included other factors that may cause IUGR, findings of general and ophthalmologic examinations, and results of investigation for intrauterine infection. Cost minimization analysis was also performed. One hundred neonates met the study's inclusion criteria (IUGR, n=24; SGA, n=45; IUGR and SGA, n=31). The mean gestational age at birth was 34.6±3.0weeks, and the mean birth weight was 1691±530g; 74% had an identifiable risk factor for IUGR and 84 patients underwent investigation for intrauterine infection. Two of the 73 patients who had urine culture for cytomegalovirus (CMV) were positive (1 of whom had systemic signs of severe congenital infection without eye involvement, the other who had no clinical signs of congenital CMV); evaluations for infection were negative otherwise. No patients had any ophthalmologic signs of congenital infection. Current literature suggests that routine evaluation of neonates with isolated IUGR for congenital infection may be low-yield and not cost-effective. Our study found that routine ophthalmologic evaluation in newborns with symmetric IUGR who have no systemic signs of intrauterine infection is of little value.

Case 1: A Term Male Infant with Hypoglycemia and Hyperbilirubinemia as Initial Presentation

A white male infant is born at term via spontaneous vaginal delivery to a 28-year-old woman at an outside facility. The parents do not have a consanguineous relationship, and the mother has had no pregnancy or delivery complications. The neonate weighs 3,170 g (11th–25th percentile), with a head circumference of 33.5 cm (4th–10th percentile) and length of 54.5 cm (76th–90th percentile). His skin is pale and multiple cafe-au-lait spots are found on his torso and extremities. He has micrognathia with an elongated head shape, a prominent occiput, and a flat anterior fontanelle. He is admitted to the NICU for hypoglycemia and receives antibiotics for 48 hours while sepsis is ruled out. Herpes simplex virus, cytomegalovirus, and peripheral blood cultures are negative. He continues to have refractory hypoglycemia and further tests reveal significant elevated γ-glutamyl transpeptidase (GGT) relative to mildly elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT), elevated direct hyperbilirubinemia, and mildly prolonged coagulation studies. Abdominal ultrasonography findings are normal. At 6 days of age, he begins to feed poorly so a nasogastric tube is placed for enteral feeds. The following day he is transferred to our facility for specialty consultation because of persistent hyperbilirubinemia and significantly elevated GGT. Upon admission to our unit he is noted to be an alert, active infant with normal male genitalia, but has bronze-colored skin and a large anterior fontanelle. His laboratory findings on admission reveal the following: sodium, 136 mEq/L (136 mmol/L); potassium, 6.9 mEq/L (6 mmol/L); chloride, 19 mEq/L (19 mmol/L); AST, 138 U/L (2.3 μkat/L); ALT, 97 U/L (1.6 μkat/L); …

1751. The Impact of Prophylactic Systemic Antibiotics (PSA) on Cytomegalovirus (CMV) Infection: A Post-hoc Analysis of a Randomized Controlled Trial (RCT) in Hematopoietic Cell Transplantation (HCT) Recipients

BackgroundProphylactic systemic antibiotics (PSA) during conditioning regimen-induced neutropenia after hematopoietic cell transplantation (HCT) reduce bacteremia but may disrupt the gut microbiota, potentially affecting viral immunity and risk for viral infections. Prior studies suggest a critical role of gut microbiota in the reconstitution of CMV-specific CD8+ T cells and in protection from respiratory viral infections after HCT (J Immunol 2007; 178: 5209; Blood 2018; 131:2978). To identify whether PSA is associated with differences in CMV infection outcomes after HCT, we conducted a post-hoc analysis of CMV infection in the only RCT of PSA exclusively performed in HCT recipients (Infection 1986; 14:115). In that trial, HCT patients received either PSA (ticarcillin/tobramycin/vancomycin or mezlocillin/ceftizoxime) or no systemic antibiotics during neutropenia (absolute neutrophil count <500/mm3).MethodsA post-hoc analysis was performed of a previously conducted RCT in the pre-antiviral era (1984–1986) at the Fred Hutch. Patients received unscreened blood products and were tested weekly by CMV culture in throat, and disease was evaluated by tissue biopsy or bronchoalveolar lavage. CMV disease was confirmed by chart review. We compared the cumulative incidence of CMV at any site, CMV throat shedding, and CMV disease between randomization groups by day 100 post-transplant, treating death as a competing risk. Overall survival was also compared using Kaplan–Meier method.Results119 and 125 allograft recipients were randomized to PSA and no prophylaxis, respectively. Baseline characteristics in both groups were balanced. CMV infection at any site and CMV throat shedding were greater in the PSA group (Figures 1 and 2); CMV disease was numerically reduced in the no PSA group (Figure 3). Overall survival by day 100 was not different between the groups (Figure 4).ConclusionCMV infection risk appeared to be increased in recipients of PSA with a significant anaerobic spectrum. While current PSA regimens have narrower spectrum activity, these results provide the rationale to study if changes in gut microbiota play a role in CMV reactivation and adaptive immunity after HCT. Disclosures All authors: No reported disclosures.

2591. The Role of Neutralizing Antibodies (nAb) Against Cytomegalovirus (CMV) Epithelial Cell-entry in Patients with Self-limited (SL) CMV infection after Hematopoietic Cell Transplantation (HCT)

BackgroundCMV transmission after HCT occurs in 20–30% of CMV-seronegative recipients with CMV-seropositive donors (i.e., CMV D+/R−) and a distinct subset develop transient CMV DNAemia without progression to culture positivity in the absence of antivirals (BMT 1992; 9:221; J Med Virol 2019; 91:1128). The mechanism of SL CMV infection is unknown but may involve nAb, which have been implicated in primary viral clearance, including nAb that inhibit viral epithelial and endothelial cell-entry via CMV pentameric complex (PC). We aimed to describe viral kinetics and the influence of nAb on CMV infection progression in SL CMV-infected patients and controls within a unique cohort from the pre-antiviral era.MethodsWeekly serum samples from 456 CMV D+/R− allogeneic HCT patients collected between 1978–95 were screened using quantitative CMV DNA PCR. Patients with CMV DNAemia in the first 100 days after HCT followed by a sustained return to undetectable levels without positive surveillance CMV cultures were defined as having SL CMV infection. SL CMV-infected patients were matched 1:1:1 to CMV-infected controls (patients with CMV infection by culture in the same period after HCT ± 14 days) and non-infected controls (patients without CMV DNA or culture positivity) to compare viral kinetics and nAb. A modified nAb assay was used to evaluate serum nAb activity against CMV PC-mediated cell entry (Vaccine 2008; 26:5760; JID 2019; in press).ResultsWe identified 9 patients with SL CMV infection and baseline demographics are shown (Table 1). SL CMV-infected patients had a median of 21 days (range 7–54 days) until first positive CMV DNAemia. The median peak CMV DNAemia was 94.2 IU/mL (range 40.2–225.9 IU/mL) and 46,118 IU/mL (range 1,132–284,362 IU/mL) in SL CMV-infected and CMV-infected controls respectively. There was no difference in nAb titers between groups at infection day 0 or in the preceding 4 weeks (Figure 1, Figure 2).ConclusionnAb against CMV PC-mediated cell entry did not appear to play a critical role in viral clearance in SL CMV infection after CMV D+/R- allogeneic HCT. Our study illustrates the potential for clearance of relatively low CMV DNAemia after HCT without the addition of antivirals. CMV-specific T-cell immunity or innate immune mechanisms may be more important in early viral control. Disclosures All authors: No reported disclosures.

Breast Milk-Transmitted Cytomegalovirus Infection in Preterm Infants

Purpose The purpose of this study is to describe the rate of cytomegalovirus (CMV) virolactia, and the prevalence of breast milk (BM)-transmitted postnatal CMV infection among premature infants after freeze-thawing (FT) and Holder pasteurization (HP) of breast milk. Methods This is a single-center, retrospective study of 312 infants born at less than 32 weeks of gestation, or with a birth weight less than 1,500 g from January 2013 to June 2017. All infants were screened for CMV-specific immunoglobulin (Ig) G and IgM at birth. Initial CMV specific polymerase chain reaction (PCR) and CMV culture were performed on mothers’ BM and babies’ urine within the first 21 days of life. FT and HP of BM was used to prevent the transmission of CMV. For the surveillance of postnatal CMV infection, CMV culture and CMV specific PCR of urine from babies were repeated one to two months after the initial screening. Screening for viremia and viruria was performed if postnatal CMV infection was suspected. Results Among 178 BM samples obtained from mothers of CMV-IgG-seropositive infants, 80 (44.9%) were CMV PCR positive. CMV deoxyribonucleic acid (DNA) was detected in five of the 22 BM samples (22.7%) obtained from the mothers of CMV-IgG seronegative infants. When CMV DNA load in BM was measured before and after HP, various results were shown. Sixty-three infants out of 232 (27.2%) were evaluated for postnatal CMV infection and four infants out of 63 (6.3%) were infected. Conclusion Interventions to prevent BM-transmitted CMV infection can reduce the chance of postnatal CMV infection, but not completely eliminate it. Keywords: Cytomegalovirus; Infection; Human milk; Freeze-thawing; Holder pasteurization; Premature infant

Cytomegalovirus Pneumonia In Critically Ill Patients

Cytomegalovirus (CMV) belongs to the human s-herpes virus group with a high seroprevalence in adults, and it is one of the important causes of morbidity and mortality in immunosuppressed patients, i.e, patients with organ transplantation, hematology malignancy and Acquired Immune Deficiency Syndrome (AIDS). The infection is usually latent. Reactivation also occurs in critically ill immunocompetent patients and is associated with prolonged ICU stay and increased mortality. Reactivation occurs when cell mediated immunity is disturbed. Cytomegalovirus infection is rarely monitored and remains unrecognized in critical ill patients1, 2 and CMV incidence is between 0 to 36% in the critically ill population. Infection usually occurs between four to 12 days after hospitalization in ICU with sepsis, mechanical ventilation more than 21 days, and multiple blood transfusions as potential risk factors for CMV reactivation.3 Rapid and accurate diagnosis of the etiology of pneumonia is needed in critically ill patients for a better outcome.4 Cytomegalovirus infection can be detected in tissue biopsy and rapid Polymerase Chain Reaction (PCR) CMV cultures of urine and bronchoalveolar lavage (BAL) fluid with shell vial method.5

Detection of Cytomegalovirus (CMV) in Saliva of Congenitally Infected Neonates

BackgroundCongenital cytomegalovirus (cCMV) infection is a significant, but potentially under-recognized health threat. Approximately 1 of 150 neonates in the US is born with cCMV infection, with 20% exhibiting long-term health problems due to infection. Both targeted CMV testing of newborns with failed hearing screens and universal CMV screening of all newborns have been proposed as approaches to identify infected newborns early in life. Congenital CMV infection can be diagnosed by testing a newborn’s saliva, urine, or blood by CMV qPCR or culture. Dried blood spots for use in qPCR assays have been shown to be a minimally sensitive specimen. Of the three specimens that are recommended, only saliva is simple, noninvasive and easy to collect.MethodsIn this study, we have validated a real-time (TaqMan) PCR assay for use in testing saliva samples from neonates for the presence of CMV. In conjunction with compatible clinical findings, a CMV positive PCR result forms the basis for a clinical diagnosis. The assay was shown to be specific for CMV, with no cross-reactivity detected for other human herpesviruses or for other human viral pathogens. Since CMV shedding levels from cCMV cases are known to be above the analytical limit of detection for the assay, and samples are collected in a nonsterile environment in which incidental CMV shedding may be present from other neonatal or pediatric patients, the reporting cutoff for this assay was set at 1000 IU/mL. Following analytical validation of the assay, stored (-80°C) residual de-identified clinical saliva samples were tested. The comparator assay was CMV cell culture, and the clinical diagnosis was used to resolve discrepant results.ResultsA total of 9 saliva samples, collected at approx. 1 month of age (or earlier) were tested by both assays. Two samples were negative by both assays and 6 samples were positive by both assays. A single sample was positive by qPCR but negative by cell culture; the qPCR value for this sample was 15,100 IU/mL. This infant had two positive urine cultures, a positive saliva shell vial culture and was clinically confirmed to have cCMV infection.ConclusionThis study suggests improved sensitivity of qPCR over CMV cell culture for identification of neonates congenitally infected with CMV.Disclosures M. Wissel, Viracor Eurofins Laboratories: Employee, Salary S. Cravens, Viracor Eurofins Laboratories: Employee, Salary A. Berg, Viracor Eurofins Laboratories: Employee, Salary A. Widen, Viracor Eurofins Laboratories: Employee, Salary M. Altrich, Viracor Eurofins Laboratories: Employee, Salary S. Kleiboeker, Viracor Eurofins Laboratories: Employee, Salary

“Targeted” Screening for Cytomegalovirus (CMV)-Related Hearing Loss: It’s Time for Universal CMV Screening in the NICU!

BackgroundCongenital CMV infection is the leading cause of non-genetic sensorineural hearing loss in infancy. Antiviral therapy has been shown to improve hearing outcomes, and thus “targeted” CMV screening for newborns who do not pass the hearing screen has been recommended. Diagnosis of congenital CMV infection requires that the infant be tested for CMV in the first 3 weeks of age. Our objective was to determine when infants in the neonatal intensive care unit (NICU) have their first hearing screen performed and thus inform the practice of targeted screening for determination of CMV-related hearing loss.MethodsRetrospective review of the electronic health records of all infants admitted to the Level 4 outborn NICU at Nationwide Children’s Hospital, Columbus, OH from August 2016 to May 2017. Demographic and clinical data were obtained, and the age that the first hearing screen was performed was assessed.ResultsDuring the 10 month study period, 362 infants were admitted to the NICU and had a first hearing screen performed. The majority of neonates (204, 56%) had a first hearing screen performed in the first 3 weeks of age. However, 158 (44%; median birth weight [IQR], 1072 g [747–1766]; median gestational age [IQR], 28 weeks [25–32]) infants received the first hearing screen at >3 weeks of age when a positive CMV PCR or culture cannot distinguish congenital infection from intrapartum/postnatal acquisition of CMV. Of the 158 infants, 20 (13%) did not pass the first hearing screen (13, unilateral; 7, bilateral), and subsequently, 9 of them did pass a second hearing screen. However, 11 of the 20 infants did not pass a second hearing screen and had urine CMV PCR testing, and 1 (9%) was positive. This latter infant’s newborn dried blood spot CMV DNA PCR was negative so a diagnosis of congenital CMV infection was not possible.ConclusionTargeted screening in the NICU for CMV-related hearing loss is problematic as a substantial number of infants do not have a hearing screen performed until after 21 days of age, thus representing a missed opportunity for diagnosis of congenital CMV infection and institution of antiviral therapy if indicated. Our findings support universal CMV screening of neonates on admission to the NICU.Disclosures O. Adunka, MED-EL Corporation: Consultant, Consulting fee, Educational grant and Research support; Advanced Bionics: Consultant, Consulting fee and Licensing agreement or royalty; Advanced Cochlear Diagnostics: President, Ownership interest; AGTC Corporation: Consultant, Consulting fee

Characteristics and prognosis of hepatic cytomegalovirus infection in children: 10 years of experience at a university hospital in Korea.

PurposeStudies on cytomegalovirus (CMV) infections in immunocompetent children are lacking, and minimal information is available in the medical literature on hepatic manifestations and complications of CMV. The aims of this study were to evaluate the clinical characteristics, laboratory data, and prognosis of children with CMV hepatitis, and to investigate its prevalence at a single medical center in Korea over a 10-year period.MethodsOne hundred thirty-two children diagnosed with CMV infection based on specific markers (anti-CMV IgM, CMV polymerase chain reaction in blood and urine, or CMV culture of urine) were included in the study. Clinical and biochemical characteristics, immunological markers, and outcomes of hepatic CMV infection were determined.ResultsThe median age of patients (n=132) was 8.5 months (range, 14 days–11.3 years). Peak total bilirubin and alanine aminotransferase levels in serum ranged from 0.11–21.97 mg/dL, and 5–1,517 IU/L, respectively. Alanine aminotransferase remained elevated from 2–48 weeks. Jaundice was the most common clinical feature of hepatic CMV infection during infancy. The hematologic findings revealed anemia, leukocytosis, and monocytosis in CMV-infected patients. All participants recovered without administration of ganciclovir.ConclusionIn children with CMV hepatitis, fever was the most common symptom at presentation, and jaundice was the most common clinical feature of hepatic CMV infection in infants younger than 3 months of age. Hepatic CMV infection in immunocompetent children is often a self-limited illness that does not require antiviral therapy, as most patients in this study had favorable outcomes.

Cytomegalovirus infection and neonatal outcome in extremely preterm infants after freezing of maternal milk.

Cytomegalovirus (CMV) infection acquired from breast milk can cause serious illness in extremely preterm (EPT) infants (<28 weeks). Some neonatal centers freeze maternal milk (MM) to prevent CMV transmission; however, this practice is controversial. In this study, we assessed the CMV transmission rate and neonatal outcome in EPT infants after routine freezing of all MM. EPT infants (n = 140) and their mothers were randomized to the intervention group (only freeze-thawed MM) or the control group (combined fresh and freeze-thawed MM). Freeze-thawed MM was frozen at -20°C for ≥3 days before thawing. Mothers had serological tests for CMV, and MM was analyzed for CMV by polymerase chain reaction and CMV culture. Infants underwent CMV screening with urine analysis by CMV-polymerase chain reaction and CMV culture until 12 weeks of age. Congenital CMV infection was detected in 2% of screened infants. The CMV transmission rate in infants fed with CMV-DNA positive milk was 8% (3 of 37) in the intervention group and 6% (2 of 33) in controls. All infants infected by CMV were asymptomatic. The final per-protocol analysis included 56 infants in the intervention group and 65 controls. Neonatal mortality was comparable between the groups (7% vs. 6%). Neonatal morbidity was similar, except for late onset Candida sepsis, which was more frequent in the controls (12% vs. 0%). Routine freezing of all MM did not affect the rate of CMV transmission but may help to prevent fungal sepsis in EPT infants. This observation merits further investigation.

Evaluation of Serial Urine Viral Cultures for the Diagnosis of Cytomegalovirus Infection in Neonates and Infants

Cytomegalovirus (CMV) is the most common cause of congenital infection worldwide. Urine viral culture is the standard for CMV diagnosis in neonates and infants. The objectives of this study were to compare the performance of serial paired rapid shell vial cultures (SVC) and routine viral cultures (RVC), and to determine the optimal number of cultures needed to detect positive cases. From 2001 to 2011, all paired CMV SVC and RVC performed on neonates and infants less than 100 days of age were recorded. Testing episodes were defined as sets of cultures performed within 7 days of one another. A total of 1264 neonates and infants underwent 1478 testing episodes; 68 (5.4%) had at least one episode with a positive CMV culture. In episodes where CMV was detected before day 21 of life, the first specimen was positive in 100% (16/16) of cases. When testing occurred after 21 days of life, the first specimen was positive in 82.7% (43/52) of cases, requiring three cultures to reach 100% detection. The SVC was more prone to assay failure than RVC. Overall, when RVC was compared to SVC, there was 86.0% positive agreement and 99.9% negative agreement. In conclusion, three serial urine samples are necessary for detection of CMV in specimens collected between day of life 22 and 99, while one sample may be sufficient on or before day of life 21. Though SVC was more sensitive than RVC, the risk of SVC failure supports the use of multimodality testing to optimize detection.

The C in TORCH: A Cost-Effective Alternative to Screening Small-for-Gestational-Age Infants

Background: Infants born with birth weights under the 10th percentile for their gestational age are classified as small for gestational age (SGA). TORCH infections are reported to be associated with SGA infants. With the low incidence of infections, screening is likely to be expensive and of low utility. Objective: The objective of this study was to determine the utility and cost-effectiveness of screening SGA infants with TORCH serology titers, urine cytomegalovirus (CMV) cultures and cranial ultrasounds. Methods: A retrospective review was conducted on all infants admitted to the neonatal intensive care unit (NICU) at Los Angeles County and University of Southern California (LAC+USC) Medical Center from January 2003 to December 2011 with a diagnosis of SGA or intrauterine growth restriction. Birth characteristics such as birth weight, length, head circumference and gestational age were recorded. TORCH titer results, urine CMV results and cranial ultrasound findings were collected. Results: Between 2003 and 2011, 232 SGA infants were admitted to the NICU at LAC+USC Medical Center. Of these, 117 infants (50%) had TORCH titer testing performed; there was only 1 positive CMV IgM and 1 positive HSV IgM result. Repeat urine CMV testing was performed on 109 infants (47%), with a total of 296 urine CMV samples collected from these infants; 6 infants had positive results, of whom 3 had repeat positive urine CMV samples. Overall, 149 of the infants had a cranial ultrasound done, none of which were positive for calcifications. Conclusions: TORCH titer testing, urine CMV screening and cranial ultrasound screening are of low yield in screening clinically asymptomatic SGA infants for TORCH infections. Given the low number of positive results, a cost-effective alternative of selective TORCH testing may be limited to infants with additional clinical findings. This study serves as a reminder to periodically examine testing practices and patient population to maximize cost-effectiveness.

Posterior Fossa Cyst on Prenatal Ultrasonography

Posterior fossa cyst on prenatal ultrasonography. (Figure 1) Figure 1. Postnatal sagittal T1-weighted and contrast enhanced axial T1-weighted images demonstrate intact cerebellar vermis and retrocerebellar cerebrospinal fluid containing cystic structure with dura folds (arrows). ### Prenatal and Birth Histories The caesarian section delivery at 35 weeks of gestation had no complications. ### Physical Examination Routine laboratory results were within normal limits. Urine cytomegalovirus culture result was negative. Feeding, voiding, and stooling were progressing uneventfully. A postnatal head ultrasonogram confirmed the earlier finding of a posterior fossa cyst. The infant and her mother were transferred to the level 3 neonatology unit of the hospital for further evaluation and precise diagnosis. Brain magnetic resonance imaging (MRI) revealed an intact cerebellar vermis and a retrocerebellar cerebrospinal fluid–containing cystic structure that demonstrated dura folds. There …

Pathogenic analysis of solid organ transplant recipients with pulmonary opportunistic infections via bronchoscopy

To evaluate the diagnostic utility of bronchoscopy in solid organ transplant recipients with pulmonary opportunistic infections. From December 2006 to September 2011, 117 cases of bronchoscopy with protected specimen brush and bronchoalveolar lavage were performed in 114 solid organ transplant recipients at Tianjin First Central Hospital. The indication for bronchoscopy was suspected pulmonary infections. The bronchoscopic manifestations were described and the specimens analyzed with regards to bacteriology, cytomegalovirus, P carinii, mycobacterium tuberculosis and other fungal cultures. A definite infectious etiology was confirmed in 63 patients (53.8%). And opportunistic infections were the most frequent etiology (56/63, 88.9% including 7 cases with two mixed opportunistic infections). Among 63 pathogens, P carinii was demonstrated in 36 episodes, cytomegalovirus in 24 episodes and mycobacterium tuberculosis in 3 episodes. Bacterial infections (mainly Gram-negative) accounted for 16 of 63 episodes (25.9% including 9 cases with mixed opportunistic/bacterial infection). In accordance with the diagnostic results, antibiotic treatment was changed in 45 cases. As an extremely useful tool, bronchoscopy is of great value for pathogenic detection in transplant recipients with suspected pulmonary infections, especially for opportunistic infections. And the bronchoscopic findings may guide targeted antimicrobial therapy.

Ischemic colitis during interferon-ribavirin therapy for chronic hepatitis C: A case report

Ischemic colitis is a rare complication of interferon administration. Only 9 cases in 6 reports have been described to-date. This report describes a case of ischemic colitis during pegylated interferon and ribavirin treatment for chronic hepatitis C, and includes a review of the relevant literature. A 48-year-old woman was treated with pegylated interferon α-2a and ribavirin for chronic hepatitis C, genotype Ib. After 19 wk of treatment, the patient complained of severe afebrile abdominal pain with hematochezia. Vital signs were stable and serum white blood cell count was within the normal range. Abdominal computed tomography showed diffuse colonic wall thickening from the splenic flexure to the proximal sigmoid colon, which is the most vulnerable area for the development of ischemic colitis. Colonoscopy revealed an acute mucosal hyperemic change, with edema and ulcerations extending from the proximal descending colon to the sigmoid colon. Colonic mucosal biopsy revealed acute exudative colitis. Polymerase chain reaction and culture for Mycobacterium tuberculosis were negative and the cultures for cytomegalovirus, Salmonella and Shigella species were negative. After discontinuation of interferon and ribavirin therapy, abdominal pain and hematochezia subsided and, following colonoscopy showed improvement of the mucosal ulcerations. Ischemic colitis cases during interferon therapy in patients with chronic hepatitis C reported so far have all involved the descending colon. Ischemic colitis is a rarely encountered complication of interferon administration in patients with chronic hepatitis C and should be considered when a patient complains of abdominal pain and hematochezia.

Real-time PCR versus viral culture on urine as a gold standard in the diagnosis of congenital cytomegalovirus infection

Background Cytomegalovirus (CMV) infection is the most common cause of congenital infection. Whereas CMV PCR has replaced viral culture and antigen detection in immunocompromised patients because of higher sensitivity, viral culture of neonatal urine is still referred to as the gold standard in the diagnosis of congenital CMV infection. Objective To compare real-time CMV PCR with shell vial culture on urine in the diagnosis of congenital CMV, in a multicenter design. Study design A series of neonatal urines ( n = 340), received for congenital CMV diagnostics and routinely assessed with shell vial CMV culture, was retrospectively tested by real-time CMV PCR. Results The proportion of newborns found to be congenitally infected by real-time CMV PCR was 8.2% (28/340, 95%CI 5.6–11.8%), and 7.4% (25/340, 95%CI 4.9–10.8%) by rapid culture. When considering rapid culture as reference, real-time PCR was highly sensitive (100%), whereas sensitivity of rapid culture was 89.3% when considering real-time PCR as reference. Conclusions Our results, supported by analytical and clinical data on CMV DNA detection in neonatal urine, suggest enhanced sensitivity of recent PCR techniques when compared to viral culture. There is considerable rationale to favor real-time CMV PCR as a gold standard in the diagnosis of congenital CMV infection. A large-scale study combining both laboratory and clinical data is required to determine the exact time frame for sampling of neonatal urine when using real-time PCR.

Real-time PCR-based testing of saliva for cytomegalovirus at birth

Evaluation of: Boppana SB, Ross SA, Shimamura M et al. Saliva polymerase-chain-reaction assay for cytomegalovirus screening in newborns. N. Engl. J. Med. 364, 2111–2118 (2011).Cytomegalovirus (CMV) commonly causes congenital infection. As such, CMV is a prominent etiology for nongenetic sensori-neural hearing loss. However, screening examination in the perinatal and early infant period fails to identify most children at risk for CMV-produced hearing loss because of the absence of symptoms early in life. Furthermore, generalized screening for congenital CMV infection has yet to be implemented. Currently, newborns are tested via means of a rapid saliva culture but large-scale automation of this test would be difficult. Fortunately, newer potential replacement tests have been created. An important advance includes testing newborns via means of PCR using liquid or dried saliva samples. In a large-scale, prospective, multi-institutional study both types of salivary samples were compared with the gold standard of saliva culture. Of the 34,989 neonates tested, 0.5% or 177 samples tested positive for CMV. Testing of both liquid and dried saliva were sensitive (>97%) as well as specific (>98%) when measured against CMV culture. PCR testing of dried saliva has the potential benefit of adapting to generalized screening of neonates for congenital CMV infection. The advantages of early detection, intervention for and treatment of cases that are not clinically apparent needs to be carefully evaluated before proposing universal newborn screening for CMV infection as a valuable public health strategy.

Recurrent Gianotti-Crosti syndrome

To the Editor: Gianotti-Crosti syndrome (GCS) classically presents in children as a self-limited, symmetric erythematous papular eruption affecting the cheeks, extremities, and buttocks. While initial reports implicated hepatitis B virus as the etiologic agent, many other bacterial, viral, and vaccine triggers have since been described. A previously healthy 2-year-old boy presented with a 3-week history of a cutaneous eruption that initially appeared on his legs and subsequently progressed to affect his arms and face. Two weeks after onset of the eruption, he was immunized with intramuscular Vaxigrip influenza vaccination (Sanofi Pasteur), and new lesions appeared at the immunization site on his right upper arm. Physical examination demonstrated an afebrile child with erythematous papules on the cheeks, arms, and legs (Fig 1). He had a localized papular eruption on his right upper arm (Fig 2). There was no lymphadenopathy or hepatosplenomegaly. Laboratory investigations revealed leukocytosis (white cell count, 14,600/mm) with a normal differential, reactive thrombocytosis ( platelet count, 1,032,000/mm), a positive urine culture for cytomegalovirus, and positive IgM serology for Epstein-Barr virus (EBV). Histopathologic examination of a skin biopsy specimen from the right buttock revealed a perivascular and somewhat interstitial lymphocytic infiltrate in the superficial and mid-dermis with intraepidermal exocytosis of lymphocytes, mild spongiosis and papillary dermal edema. He was treated with 2.5% hydrocortisone cream, and the eruption resolved. Twelve months later, he presented with a similar papular eruption localized to the left upper arm at the site of a recent intramuscular influenza vaccination (Vaxigrip). Although an infection represents the most important etiologic agent, a second event involving immunomodulation might lead to further disease accentuation, thus explaining the association of GCS with vaccinations. In our case, there was evidence of both cytomegalovirus (CMV) and EBV infection as well as a recent history of immunization. Localized accentuation of papules at the immunization site was unusual, as previous cases of GCS following immunizations have had a widespread and typically symmetric eruption. It is possible that trauma from the injection or a component of the vaccine elicited a Koebner response, causing local accentuation. There are no previous reports of recurrence of vaccine-associated GCS. One report documented recurrence with two different infectious triggers. As GCS is a mild and selflimiting disease, further vaccinations are not contraindicated. Andrei I. Metelitsa, MD, FRCPC, and Loretta Fiorillo, MD, FRCPC