Brian Rha

Persistence of Antibodies against Middle East Respiratory Syndrome Coronavirus.

To determine how long antibodies against Middle East respiratory syndrome coronavirus persist, we measured long-term antibody responses among persons serologically positive or indeterminate after a 2012 outbreak in Jordan. Antibodies, including neutralizing antibodies, were detectable in 6 (86%) of 7 persons for at least 34 months after the outbreak.

Emergency Department Visit Data for Rapid Detection and Monitoring of Norovirus Activity, United States

Noroviruses are the leading cause of gastroenteritis in the United States, but timely measures of disease are lacking. BioSense, a national-level electronic surveillance system, assigns data on chief complaints (patient symptoms) collected during emergency department (ED) visits to 78 subsyndromes in near real-time. In a series of linear regression models, BioSense visits mapped by chief complaints of diarrhea and nausea/vomiting subsyndromes as a monthly proportion of all visits correlated strongly with reported norovirus outbreaks from 6 states during 2007–2010. Higher correlations were seen for diarrhea (R = 0.828–0.926) than for nausea/vomiting (R = 0.729–0.866) across multiple age groups. Diarrhea ED visit proportions exhibited winter seasonality attributable to norovirus; rotavirus contributed substantially for children <5 years of age. Diarrhea ED visit data estimated the onset, peak, and end of norovirus season within 4 weeks of observed dates and could be reliable, timely indicators of norovirus activity.

Incidence of Norovirus-Associated Medical Encounters among Active Duty United States Military Personnel and Their Dependents

Background Norovirus is a leading cause of gastroenteritis episodes and outbreaks in US military deployments, but estimates of endemic disease burden among military personnel in garrison are lacking. Methods Diagnostic codes from gastroenteritis-associated medical encounters of active duty military personnel and their beneficiaries from July 1998–June 2011 were obtained from the Armed Forces Health Surveillance Center. Using time-series regression models, cause-unspecified encounters were modeled as a function of encounters for specific enteropathogens. Model residuals (representing unexplained encounters) were used to estimate norovirus-attributable medical encounters. Incidence rates were calculated using population data for both active duty and beneficiary populations. Results The estimated annual mean rate of norovirus-associated medically-attended visits among active duty personnel and their beneficiaries was 292 (95% CI: 258 to 326) and 93 (95% CI: 80 to 105) encounters per 10,000 persons, respectively. Rates were highest among beneficiaries <5 years of age with a median annual rate of 435 (range: 318 to 646) encounters per 10,000 children. Norovirus was estimated to cause 31% and 27% of all-cause gastroenteritis encounters in the active duty and beneficiary populations, respectively, with over 60% occurring between November and April. There was no evidence of any lag effect where norovirus disease occurred in one population before the other, or in one beneficiary age group before the others. Conclusions Norovirus is a major cause of medically-attended gastroenteritis among non-deployed US military active duty members as well as in their beneficiaries.

Inclusion of MERS-spike protein ELISA in algorithm to determine serologic evidence of MERS-CoV infection

The Centers for Disease Control and Prevention (CDC) algorithm for detecting presence of serum antibodies against Middle East Respiratory Syndrome coronavirus (MERS‐CoV) in subjects with potential infections with the virus has included screening by indirect ELISA against recombinant nucleocapsid (N) protein and confirmation by immunofluorescent staining of infected monolayers and/or microneutralization titration. Other international groups include indirect ELISA assays using the spike (S) protein, as part of their serological determinations. In the current study, we describe development and validation of an indirect MERS‐CoV S ELISA to be used as part of our serological determination for evidence of previous exposure to the virus.

Eosinophilic Appendicitis Attributable to Strongyloides Infection in a Pediatric Renal Transplant Patient

The patient was born in a town near Bogota, Colombia and was adopted in the United States at 2 years of age. At the time of adoption, there was a suspicion of renal disease with failure to thrive. Within a year of arriving in Alabama, she was diagnosed with hypoplastic-dysplastic syndrome. Her renal disease resulted in dialysis at age 16, and she received a living unrelated renal transplant from her adoptive mother at age 18. She was treated with an immunosuppressive regimen that included tacrolimus, mycophenolate, and prednisone. Her immediate posttransplant course was notable only for complaints of mild diarrhea that worsened when her regimen changed from tacrolimus to sirolimus in the 8th month after transplant for a research protocol. At 9 months posttransplant, she developed severe, constant, right lower quadrant abdominal pain. Her diarrhea worsened and she developed headaches, but she denied having fever, cough, difficulty breathing, vomiting, or bloody stools. A computerized tomography scan showed findings associated with appendicitis, which prompted appendectomy. Pathologic examination of the specimen identified intense transmural eosinophilic infiltration of the appendiceal wall consistent with eosinophilic appendicitis (Figure ​(Figure1).1). Biopsies of the terminal ileum, cecum, and colon at the hepatic flexure also revealed eosinophilic infiltrates. No parasitic forms were found in any of the tissue samples by direct visualization. A peripheral eosinophilia of up to 9.5%was documented, and a stool test was negative for ova and parasites (O&P). Figure 1. Pathology of appendix. Numerous eosinophils fill the lamina propria (left panel) and infiltrate the submucosa (right panel) of the appendix (hematoxylin and eosin stain, ×132). After appendectomy, the patients abdominal pain resolved and her diarrhea improved. However, her eosinophilia persisted, rising as high as 18.3% 3 months later, even after empiric treatment with 2 doses of mebendazole for “intestinal parasite” 1 month after appendectomy. Subsequent evaluation by the gastrointestinal and allergy/immunology services included negative immunoassays for food and upper respiratory allergens, negative screens for celiac disease, negative serology for Toxocara, and a Strongyloides immunoglobulin G (IgG) antibody by enzyme-linked immunosorbent assay (ELISA) that was positive (4.28, reference range <1.00, sensitivity and specificity of 90%; Focus Diagnostics, Cypress, CA). Based on these results, the eosinophilia and gastrointestinal findings were attributed to infection by Strongyloides. The patient was treated with a 4-day course of ivermectin (200 mcg/kg per day) 2 weeks before initial Infectious Diseases (ID) consultation. In ID clinic, additional history included a positive tuberculin skin test during pretransplant evaluation with a history of Bacillus Calmette-Guerin vaccination, which prompted a 9-month course of isoniazid. The patient reported intermittent “hive-like” rashes in “small red circles” mainly affecting her head, lower extremities, arms, and occasionally buttocks since early childhood, which she attributed to skin allergies. She lived with her parents and with 2 healthy dogs and cats. She reported walking outside barefoot frequently, but she denied any travel outside of the country since arriving in the United States. Investigation of the patients available records revealed negative human immunodeficiency virus status and negative serologies for Trympanosoma cruzi, but testing was not performed for Strongyloides or other parasites on pretransplant evaluation. Any medical evaluation performed in the international adoption process was not available in our patients medical record. However, her mother denied any medical issues at the time of adoption other than failure to thrive, a suspicion of renal disease, and bow-leggedness. One finding of particular interest was evidence of long-standing (up to 8 years before transplant) significant eosinophilia (>10%) that subsided with transplant but reappeared with the onset of her abdominal symptoms (Figure ​(Figure22). Figure 2. Eosinophil percentage from peripheral blood samples over a 10-year span. Time of transplant (a: 5/21/09), appendectomy (b: 2/18/10), and completion of first (c: 6/5/10) and second (d: 6/27/10) treatments with ivermectin are marked with arrows. On physical examination the patient was well-appearing and of short stature (143.5 cm, <3% for age), with a soft, nontender abdomen, palpable transplant kidney mass in the lower right quadrant, a well-healed surgical scar over her right abdomen, and no hepatomegaly. No rashes were observed. Although a single stool O&P before initial treatment had been negative, 3 daily stool O&P examinations were repeated and were negative. Serologies for human T-lymphotropic virus (HTLV) and filaria were likewise negative. A complete blood count after the first course of ivermectin revealed that her eosinophilia had improved (white blood cells of 6.27, 3.2% eosinophils). To ensure eradication in an immunocompromised patient, a second course of ivermectin was given (200 mcg/kg per day for 2 days). At a follow-up visit 6 months later the patient continued to do well with no new symptoms and no further reports of rashes. A repeat Strongyloides IgG level was undetectable.

Timing of Respiratory Syncytial Virus and Influenza Epidemic Activity in Five Regions of Argentina, 2007-2016

Within‐country differences in the timing of RSV and influenza epidemics have not been assessed in Argentina, the eighth largest country in the world by area.

Respiratory Syncytial Virus-Associated Hospitalizations in Young Children in the United States, 2015–2016

Abstract Background Respiratory syncytial virus (RSV) is a major cause of severe acute respiratory illness (ARI) among young children. With several vaccines and immunoprophylaxis agents for RSV currently in development, updated estimates of severe RSV disease in young children in the United States (US) are needed. Methods Prospective active surveillance for hospitalized ARI was conducted from 11/1/2015 to 6/30/2016 among children <5 years of age at seven pediatric hospital sites participating in the New Vaccine Surveillance Network. Demographic and clinical information for enrolled subjects were gathered through parent interviews and medical chart reviews. Mid-turbinate nasal and throat flocked swabs (combined for testing when available) and/or tracheal aspirates (when pertinent) were collected for respiratory pathogen testing. Specimens were tested for RSV using molecular diagnostic assays at each site. Results In preliminary data analyses, 2,948 hospitalized children with a median age of 11 months were enrolled during the study period, of whom 1,030 (35%) tested positive for RSV. Most RSV-detections occurred in children <2 years of age (87%; n = 893), with 340 (33%) RSV-positive children aged 0–2 months, 184 (18%) aged 3–5 months, 174 (17%) aged 6–11 months, and 195 (19%) aged 12–23 months. The majority of RSV-positive children (75%; n = 776) had no chart-documented comorbid conditions. Among 893 RSV-positive children <2 years of age, 161 (18%) reported a history of preterm birth, with 99 (11%) reporting birth at 34–36 weeks gestational age (WGA), 33 (4%) at 30–33 WGA, 20 (2%) at <30 WGA, and 9 (1%) with no further gestational age information available. Among all RSV-positive subjects, the median length of stay was 2 days; 706 (69%) received supplemental oxygen during hospitalization, 226 (22%) were admitted to an intensive care unit, and 28 (3%) required mechanical ventilation. Conclusion During the 2015–16 season, RSV was associated with one-third of ARI hospitalizations in young children, the majority of which occurred in children aged <2 years. Most RSV-positive children were previously healthy, and nearly one fifth of those <2 years of age reported a history of preterm birth. RSV continues to be a major cause of morbidity among young children in the US. Disclosures N. B. Halasa, sanofi pasteur: Research Contractor, Research support; Astra Zeneca: Research Contractor, Grant recipient; J. Englund, Gilead: Consultant and Investigator, Research support; Chimerix: Investigator, Research support; Alios: Investigator, Research support; Novavax: Investigator, Research support; MedImmune: Investigator, Research support; GlaxoSmithKline: Investigator, Research support; J. V. Williams, Quidel: Scientific Advisor, Consulting fee; GlaxoSmithKline: Scientific Advisor, Consulting fee; F. M. Munoz, Novavax: Investigator, Research support; Regeneron: Investigator, Research support; GSK: Investigator, Research support