Helen Y. Chu

Respiratory Syncytial Virus Transplacental Antibody Transfer and Kinetics in Mother-Infant Pairs in Bangladesh

BACKGROUND Pneumonia is the leading cause of childhood mortality globally. Respiratory syncytial virus (RSV) is the most important viral cause of pneumonia. Maternal serum antibody protects infants from RSV disease. The objective of our study was to characterize RSV antibody levels in mother-infant pairs. METHODS Serial serum samples were collected from mother-infant pairs in Bangladesh from the third trimester of pregnancy to 72 weeks postpartum and tested using an RSV antibody microneutralization assay. Serologic infection was defined as a 4-fold increase in antibody titer. Maternal antibody half-life was calculated using infant antibody titers from birth to 20 weeks. RESULTS The ratio of infant cord blood to maternal serum RSV antibody titers in 149 mother-infant pairs was 1.01 (95% confidence interval [CI], .99-1.03). Maternal RSV antibody titers in the third trimester and at birth were strongly correlated (R = 0.68). Antibody half-life was 38 days (95% CI, 36-42 days). Higher cord blood RSV antibody titers were associated with a lower risk of serologic infection (P = .01) and maintenance of antibody titer above a potentially protective threshold (P < .001). CONCLUSIONS Efficient transplacental transfer of RSV-specific antibody from mother to the fetus was documented in mother-infant pairs in Asia. Higher cord blood antibody titers were associated with protection from serologic infection.

Molecular epidemiology of human rhinovirus infections in the pediatric emergency department.

Abstract Background Human rhinovirus (HRV) infections are highly prevalent, genetically diverse, and associated with both mild upper respiratory tract and more severe lower tract illnesses (LRTI). Objective To characterize the molecular epidemiology of HRV infections in young children seeking acute medical care. Study design Nasal swabs collected from symptomatic children <3 years of age receiving care in the Emergency and Urgent Care Departments at Seattle Childrens Hospital were analyzed by a rapid polymerase chain reaction (PCR) system (FilmArray®) for multiple viruses including HRV/enterovirus. HRV-positive results were confirmed by laboratory-developed real-time reverse transcription PCR (LD-PCR). Clinical data were collected by chart review. A subset of samples was selected for sequencing using the 5′ noncoding region. Associations between LRTI and HRV species and genotypes were estimated using logistic regression analysis. Results Of 595 samples with HRV/enterovirus detected by FilmArray, 474 (80%) were confirmed as HRV by LD-PCR. 211 (96%) of 218 selected samples were sequenced; HRV species A, B, and C were identified in 133 (63%), 6 (3%), and 72 (34%), respectively. LRTI was more common in HRV-C than HRV-A illness episodes (adjusted OR [95% CI] 2.35[1.03–5.35). Specific HRV-A and HRV-C genotypes detected in multiple patients were associated with a greater proportion of LRTI episodes. In 18 patients with >1 HRV-positive illness episodes, a distinct genotype was detected in each. Conclusion Diverse HRV genotypes circulated among symptomatic children during the study period. We found an association between HRV-C infections and LRTI in this patient population and evidence of association between specific HRV genotypes and LRTI.

Respiratory syncytial virus disease: prevention and treatment.

Respiratory syncytial virus (RSV) is one of the most clinically important viruses infecting young children, the elderly, and the immunocompromised. Over the past decade, the most significant advance in the prevention of RSV disease has been the development of high-titered antibody products. Infection control is the only other strategy to prevent RSV disease. A humanized monoclonal antibody directed against the fusion (F) protein palivizumab, (Synagis®, MedImmune, Inc., Gaithersburg, MD), is given routinely on a monthly basis to premature infants and young children less than 24 months of age with underlying medical problems including prematurity, chronic lung disease, or cardiac disease to prevent RSV disease and hospitalization. Other products utilizing polyclonal or monoclonal antibodies or antibody fragments against the F protein have been developed and some already tested in patient populations. The only licensed antiviral treatment available today is ribavirin, a guanosine analogue generally administered as a small particle aerosol to immunocompromised patients with lower respiratory tract disease due to RSV. This drug has also been utilized in oral and intravenous forms, again mainly in immunocompromised patients. Promising new antiviral agents under development by multiple pharmaceutical and biotechnology companies include small molecule fusion inhibitors, attachment inhibitors, inhibitors of RNA synthesis, and small interfering RNA particles (siRNA).

Respiratory Tract Infections Due to Human Metapneumovirus in Immunocompromised Children

Abstract Background The clinical presentation and management of human metapneumovirus (hMPV) infections in immunocompromised children is not well understood. Methods We performed a retrospective evaluation of pediatric patients with laboratory-confirmed hMPV infections and underlying hematologic malignancy, solid tumors, solid organ transplant, rheumatologic disease, and/or receipt of chronic immunosuppressants. Data were analyzed using t tests and Fisher’s exact tests. Results Overall, 55 patients (median age: 5 years; range: 5 months–19 years) with hMPV infection documented between 2006 and 2010 were identified, including 24 (44%) with hematologic malignancy, 9 (16%) undergoing hematopoietic stem cell transplant, 9 (16%) with solid tumors, and 8 (15%) with solid organ transplants. Three (5%) presented with fever alone, 35 (64%) presented with upper respiratory tract infections, and 16 (29%) presented with lower respiratory tract infections (LRTI). Twelve (23%) patients required intensive care unit admission and/or supplemental oxygen ≥28% FiO2. Those with severe disease were more likely to be neutropenic (P = .02), but otherwise did not differ by age (P = .27), hematopoietic stem cell transplant recipient status (P = .19), or presence of lymphopenia (P = .09). Nine (16%) patients received treatment with ribavirin, intravenous immunoglobulin, or both. Three children (5%) died of hMPV pneumonia. Conclusions Immunocompromised pediatric patients with hMPV infection have high rates of LRTI and mortality. The benefits of treatment with ribavirin and intravenous immunoglobulin in this patient population require further evaluation.

Clinical Presentation and Birth Outcomes Associated with Respiratory Syncytial Virus Infection in Pregnancy

Background Respiratory syncytial virus (RSV) is the most important cause of viral pneumonia in children worldwide. A maternal vaccine may protect both the mother and infant from RSV illness. The epidemiology and clinical presentation of RSV in pregnant and postpartum women is not well-described. Methods Data were collected from a prospective, randomized trial of influenza immunization in pregnant women in rural southern Nepal. Women were enrolled in their second trimester of pregnancy and followed until six months postpartum. Active weekly home-based surveillance for febrile respiratory illness was performed. Mid-nasal swabs collected with episodes of respiratory illness were tested for RSV by real-time polymerase chain reaction. Results RSV was detected in 14 (0.4%) illness episodes in 3693 women over 3554 person-years of surveillance from 2011–2014. RSV incidence was 3.9/1000 person-years overall, and 11.8/1000 person-years between September and December. Seven (50%) women sought care for RSV illness; none died. Of the 7 (50%) illness episodes during pregnancy, all had live births with 2 (29%) preterm births and a median birthweight of 3060 grams. This compares to 469 (13%) preterm births and a median birthweight of 2790 grams in women without RSV during pregnancy. Of the 7 mothers with postpartum RSV infection, RSV was detected in 4 (57%) of their infants. Conclusions RSV was an uncommon cause of febrile respiratory illness in mothers during pregnancy in Nepal. These data will inform prevention and therapeutic strategies against RSV in resource-limited settings.

Impact of rapid influenza PCR testing on hospitalization and antiviral use: A retrospective cohort study

Rapid PCR‐based influenza tests are increasingly used as point‐of‐care diagnostics in hospitals and clinics. To our knowledge, no prior studies have described clinical outcomes with implementation of rapid PCR‐based influenza tests in hospitalized adult inpatients. Electronic medical records were used to assess differences in laboratory testing time and antiviral use among a subset of 175 consecutive adult inpatients tested for influenza in two respiratory seasons before and after implementation of rapid PCR‐based influenza testing at an academic medical center. Of the 350 hospitalized inpatients included in this analysis, 96 (27%) were over 65 years of age and 308 (88%) had a comorbid condition. The overall time to result decreased significantly from 25.2 to 1.7 hr (P < 0.001) after implementation of rapid PCR‐based influenza testing. Among influenza‐negative patients, the frequency of oseltamivir initiation remained unchanged (before: 43% vs. after: 45%; P = 0.60), though the median duration of oseltamivir was significantly decreased from 1.1 to 0.0 days (P < 0.001). By providing an earlier result to clinicians, rapid PCR‐based influenza tests may decrease unnecessary antiviral use among adult inpatients who test negative for influenza. J. Med. Virol. 87:2021–2026, 2015.

Molecular epidemiology of respiratory syncytial virus transmission in childcare

Abstract Background Respiratory syncytial virus (RSV) is the most important cause of serious respiratory infections in young children. No prior studies using molecular techniques to examine RSV transmission in the community childcare setting have been performed. Objectives We seek to characterize the molecular epidemiology of RSV transmission in childcare to evaluate the impact of RSV disease in a community-based population. Methods We sequenced RSV-positive nasopharyngeal samples from a prospective longitudinal study of respiratory illnesses among children enrolled in childcare during three winter seasons. Phylogenetic analysis was performed to identify unique viral strains. Results RSV was detected in 59 (11%) illnesses. Compared to RSV-negative illnesses, RSV-positive illnesses were associated with longer symptom duration and increased frequency of health care visits. Another respiratory virus was detected in 42 (71%) RSV-positive illnesses. RSV viral load did not differ between RSV-positive illnesses with and without another respiratory virus identified (P =0.38). In two childcare rooms, 50% of the children had RSV detected within six days of the first case. Five (38%) of 13 illness episodes from one childcare room were sequenced and shown to be the same viral strain, suggesting rapid child-to-child transmission within the room over a 16 day period. Conclusions RSV is rapidly transmitted within childcare. Childcare facilities may serve as ideal sites for evaluation of new prevention strategies given the high burden of RSV disease in this population and the rapidity of RSV spread between children.

Clinical outcomes in outpatient respiratory syncytial virus infection in immunocompromised children

Immunocompromised patients are at high risk for morbidity and mortality due to respiratory syncytial virus (RSV) infection. Increasingly, pediatric patients with malignancy or undergoing transplantation are managed primarily as outpatients. Data regarding the clinical presentation and outcomes of RSV in the outpatient pediatric immunocompromised population are limited.

Rhinovirus Disease in Children Seeking Care in a Tertiary Pediatric Emergency Department

BACKGROUND Rhinovirus is the most common cause of viral respiratory tract infections in children. Virologic predictors of lower respiratory tract infection (LRTI), such as viral load and the presence of another respiratory virus (coinfection), are not well characterized in pediatric outpatients. METHODS Mid-nasal turbinate samples were collected from children presenting for care to the Seattle Childrens Hospital emergency department (ED) or urgent care with a symptomatic respiratory infection between December 2011 and May 2013. A subset of samples was tested for rhinovirus viral load by real-time polymerase chain reaction. Clinical data were collected by chart reviews. Multivariate logistic regression was used to evaluate the relationship between viral load and coinfection and the risk for LRTI. RESULTS Rhinovirus was the most frequent respiratory virus detected in children younger than 3 years. Of 445 patients with rhinovirus infection, 262 (58.9%) had LRTIs, 231 (51.9%) required hospital admission and 52 (22.5%) were hospitalized for 3 days or longer. Children with no comorbidities accounted for 142 (54%) of 262 rhinovirus LRTIs. Higher viral load was significantly associated with LRTI among illness episodes with rhinovirus alone (OR, 2.11; 95% confidence interval [CI], 1.24-3.58). Coinfection increased the risk of LRTI (OR, 1.83; 95% CI, 1.01-3.32). CONCLUSIONS Rhinovirus was the most common pathogen detected among symptomatic young children in a pediatric ED who had respiratory viral testing performed, with the majority requiring hospitalization. Higher rhinovirus viral load and coinfection increased disease severity. Virologic data may assist clinical decision making for children with rhinovirus infections in the pediatric ED.

Hemophagocytic Lymphohistiocytosis Secondary to Human Immunodeficiency Virus-Associated Histoplasmosis.

Hemophagocytic lymphohistiocytosis (HLH) in immunocompromised hosts is a fulminant syndrome of immune activation with high rates of mortality that may be triggered by infections or immunodeficiency. Rapid diagnosis and treatment of the underlying disorder is necessary to prevent progression to multiorgan failure and death. We report a case of HLH in a patient with human immunodeficiency virus, disseminated histoplasmosis, Mycobacterium avium complex, and Escherichia coli bacteremia. We discuss management of acutely ill patients with HLH and treatment of the underlying infection versus initiation of HLH-specific chemotherapy.