Xiaotian Zheng

Post-Infectious Functional Gastrointestinal Disorders in Children

OBJECTIVE To investigate the development of functional gastrointestinal disorders (FGIDs) after an episode of acute bacterial gastroenteritis (AGE) in children. STUDY DESIGN A cohort study of children 3 to 19 years old with a positive result on a bacterial stool culture. 44 patients in each arm (unidirectional alpha of 0.05, power of 0.80). Children presenting at two pediatric hospitals (United States and Italy) for AGE who tested positive for bacteria on stool culture (2001-2005) were contacted at least 6 months after the episode. Exposed children were matched with control subjects of similar age and sex consulting to the same hospitals for trauma or well-child visit within 4 weeks of the index case. Symptoms were evaluated with a validated questionnaire for FGIDs assessing pain, diarrhea, and disability. RESULTS 88 patients (46 boys; mean age, 8.1 years; age range, 3-19 years) were recruited. Bacteria included Salmonella (54%), Campylobacter (32%), and Shigella (14%). 36% of exposed patients and 11% of control subjects complained of abdominal pain (P < .01). 87% had irritable bowel syndrome and 24% had dyspepsia. 56% reported onset of pain following the AGE. CONCLUSION There is a significant increase in cases of FGIDs after bacterial infections in children.

High-risk adenovirus-infected pediatric allogeneic hematopoietic progenitor cell transplant recipients and preemptive cidofovir therapy.

Abstract:  ADV has emerged as an important pathogen in children undergoing allogeneic HPCT. A prospective study of the epidemiology of ADV infection and preemptive therapy of high risk ADV infections in children undergoing HPCT was undertaken. Cultures of throat, urine, and stool for viral pathogens and plasma for ADV PCR were obtained prior to transplantation, weekly for the first 100 days, and then monthly for one yr. Children developing high‐risk ADV infections were treated preemptively with cidofovir 1 mg/kg/day given three times weekly for three wk. A case‐controlled study was performed to identify risk factors for high‐risk ADV infections. Seven (18%) of the 38 subjects developed high‐risk ADV infections usually within 100 days of HPCT and were preemptively treated with i.v. cidofovir at a dose of 1 mg/kg/dose three times weekly for nine doses. High‐risk ADV infections resolved in all seven patients without renal toxicity. CMV viremia occurred in two of seven patients during or shortly after therapy with cidofovir. A case–control study did not identify any risk factors that achieved statistical significance. Treatment with a modified dosing regimen of cidofovir was well‐tolerated and high‐risk ADV infections resolved in all patients.

Prospective Evaluation of Rapid Antigen Tests for Diagnosis of Respiratory Syncytial Virus and Human Metapneumovirus Infections

ABSTRACT Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two important viral pathogens that cause respiratory tract infections in the pediatric population. The rapid detection of these agents allows the prompt isolation and treatment of infected patients. In the present prospective study, we evaluated the performances of four rapid antigen detection assays, including a rapid chromatographic immunoassay (CIA) for RSV (Directigen EZ RSV; Becton Dickinson, Sparks, MD), a direct fluorescent-antibody assay (DFA) for RSV (Bartels; Trinity Biotech, Carlsbad, CA), and two DFAs for hMPV manufactured by Diagnostic Hybrids Inc. (DHI; Athens, OH) and Imagen (Oxoid Ltd., Basingstoke, Hampshire, United Kingdom). The clinical specimens tested comprised 515 nasopharyngeal aspirates submitted to the Clinical Microbiology Laboratory at Hartford Hospital from 1 November 2006 to 21 April 2007. Compared to the results of real-time reverse transcription-PCR (RT-PCR), the CIA had a sensitivity of 79.8% and a specificity of 89.5%. The RSV DFA with Bartels reagents showed a sensitivity of 94.1% and a specificity of 96.8%. For hMPV, the sensitivity and specificity were 62.5% and 99.8%, respectively, for the DHI DFA and 63.2% and 100%, respectively, for the Imagen DFA. The hands-on and test turnaround times for CIA were 10 and 30 to 60 min, respectively, and the hands-on and test turnaround times for the RSV and hMPV DFAs were 30 and 105 min, respectively. We conclude that while the RSV CIA is user-friendly, it lacks sensitivity and specificity, especially during off-peak months. In contrast, the RSV DFA is more sensitive and specific, but interpretation of its results is subjective and it demands technical time and expertise. Similarly, both hMPV DFAs are highly specific in comparison to the results of RT-PCR, but their sensitivities await further improvements.

Increased Activity of Coxsackievirus B1 Strains Associated with Severe Disease among Young Infants in the United States, 2007—2008

BACKGROUND Enterovirus infections are very common and typically cause mild illness, although neonates are at higher risk for severe illness. In 2007, the Centers for Disease Control and Prevention (CDC) received multiple reports of severe neonatal illness and death associated with coxsackievirus B1 (CVB1), a less common enterovirus serotype not previously associated with death in surveillance reports to the CDC. METHODS This report includes clinical, epidemiologic, and virologic data from cases of severe neonatal illness associated with CVB1 reported during the period from 2007 through 2008 to the National Enterovirus Surveillance System (NESS), a voluntary, passive surveillance system. Also included are data on additional cases reported to the CDC outside of the NESS. Virus isolates or original specimens obtained from patients from 25 states were referred to the CDC picornavirus laboratory for molecular typing or characterization. RESULTS During 2007-2008, the NESS received 1079 reports of enterovirus infection. CVB1 accounted for 176 (23%) of 775 reported cases with known serotype, making it the most commonly reported serotype for the first time ever in the NESS. Six neonatal deaths due to CVB1 infection were also reported to the CDC during that time. Phylogenetic analysis of the 2007 and 2008 CVB1 strains indicated that the increase in cases resulted from widespread circulation of a single genetic lineage that had been present in the United States since at least 2001. CONCLUSIONS Healthcare providers and public health departments should be vigilant to the possibility of continuing CVB1-associated neonatal illness, and testing and continued reporting of enterovirus infections should be encouraged.

Detection of human parechovirus (HPeV)-3 in spinal fluid specimens from pediatric patients in the Chicago area

BACKGROUND The human parechoviruses (HPeV) have recently been recognized as important viral pathogens causing various illnesses including sepsis and meningitis in children. However, data from the United States is limited. OBJECTIVES To better understand the epidemiology of HPeV in the United States and its role in pediatric disease through detection and typing of the virus in cerebrospinal fluid specimens. STUDY DESIGN Four hundred and twenty-one spinal fluid samples collected from 373 patients ranging in age from 1 day to 18 years were tested using a real-time reverse transcription-PCR assay. The specimens were originally collected for routine viral and bacterial testing to assist in the diagnosis of meningitis or sepsis. Amplification products of the VP1 region in the virus genome were sequenced to identify the parechovirus type. RESULTS Ten positive specimens were identified from 10 different patients. All ten samples were typed as HPeV3 and were negative for bacteria by culture, and for enterovirus and herpes simplex virus by PCR. All of the HPeV3-infected patients were young infants ranging in age from 6 to 59 days. Infants in whom HPeV3 was detected had significantly decreased peripheral white blood cell counts. Positive specimens were all from the summer and early fall. CONCLUSIONS HPeV3 infection of the central nervous system is found in very young infants in certain years during the summer and early fall, and is associated with leukopenia. Real-time RT-PCR is an effective tool for rapid detection of these infections, and could help prevent unnecessary hospitalization and antibiotic use in HPeV infected infants. More widespread use of this tool in diagnosing HPeV infection would aid in further clarifying the prevalence of this disease in the United States.

Macrolide-Resistant Mycoplasma pneumoniae, United States.

Macrolide-resistant Mycoplasma pneumoniae (MRMP) is highly prevalent in Asia and is now being reported from Europe. Few data on MRMP are available in the United States. Using genotypic and phenotypic methods, we detected high-level MRMP in 13.2% of 91 M. pneumoniae–positive specimens from 6 US locations.

Antimicrobial Susceptibilities of Invasive Pediatric Abiotrophia and Granulicatella Isolates

ABSTRACT Abiotrophia and Granulicatella species have been associated with various infections. Antimicrobial susceptibility data for these nutritionally variant streptococcus-like organisms, especially for pediatric isolates, are very limited. Little is known about the genetic bases of their resistance mechanisms. We report the results of identification to bacterial species level, antimicrobial susceptibility testing, macrolide resistance testing, and detection of genes encoding that resistance for a collection of 15 pediatric clinical isolates from normally sterile sites. Our results indicate that the prevalence of beta-lactam and macrolide resistance is high and that both erm and mef are found in these isolates.

Impact of Rotavirus Vaccination on Hospital-Acquired Rotavirus Gastroenteritis in Children

OBJECTIVE: Data show that after the implementation of routine rotavirus vaccination for infants in the United States, community-acquired (CA) rotavirus cases declined substantially in the 2007–2008 season. The impact of community-based rotavirus vaccination on the substantial burden of hospital-acquired (HA) rotavirus has not been documented. PATIENTS AND METHODS: We assessed CA and HA rotavirus, respiratory syncytial virus, and influenza infections at Childrens Memorial Hospital for 5 winter seasons (defined as occurring from September through May) from 2003 to 2008. We also report rotavirus data from the 2008–2009 season. RESULTS: A similar dramatic decline (>60% compared with the median of previous seasons) occurred in the rates of cases of both CA (P < .0001) rotavirus hospitalizations and HA (P < .01) rotavirus infections in the 2007–2008 season compared with previous seasons, whereas the rates of CA and HA influenza and respiratory syncytial virus, respectively, remained stable. Improvements in hand-hygiene compliance did not correlate with a reduction in the transmission rate of rotavirus in the hospital. Both CA and HA rotavirus rates remained much lower in the 2008–2009 than in the 2003–2007 seasons. CONCLUSIONS: Community-based rotavirus vaccination is associated with a substantial reduction in the number of children who are admitted with rotavirus. These data also indicate that routine community-based rotavirus infant vaccination protects hospitalized children from acquiring rotavirus. Vaccination efforts should be encouraged as a strategy to affect the substantial burden of HA rotavirus.

Standardized Methods and Quality Control Limits for Agar and Broth Microdilution Susceptibility Testing of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum

ABSTRACT An international multilaboratory collaborative study was conducted to develop standard media and consensus methods for the performance and quality control of antimicrobial susceptibility testing of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum using broth microdilution and agar dilution techniques. A reference strain from the American Type Culture Collection was designated for each species, which was to be used for quality control purposes. Repeat testing of replicate samples of each reference strain by participating laboratories utilizing both methods and different lots of media enabled a 3- to 4-dilution MIC range to be established for drugs in several different classes, including tetracyclines, macrolides, ketolides, lincosamides, and fluoroquinolones. This represents the first multilaboratory collaboration to standardize susceptibility testing methods and to designate quality control parameters to ensure accurate and reliable assay results for mycoplasmas and ureaplasmas that infect humans.

Outbreak of Life-Threatening Coxsackievirus B1 Myocarditis in Neonates

In the summer and fall of 2007, we observed a unique cluster of cases of severe coxsackievirus B1 (CVB1) infection among Chicago area neonates. Eight neonates had closely related strains of CVB1 that were typed at the Centers of Disease Control and Prevention; 2 other neonates had CVB infections, 1 of which was further identified as serotype CVB1. All had severe myocarditis; 1 neonate underwent heart transplantation, and 1 died of severe left ventricular dysfunction.