Lauren J. Stockman

Respiratory syncytial virus-associated hospitalizations among infants and young children in the United States, 1997-2006.

Background: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract disease among young children in the United States. RSV-associated hospitalization increased among children in the United States during 1980 through 1996. In this study, we updated national estimates of RSV hospitalization rates among US children through 2006. Methods: We conducted a retrospective analysis of hospital discharges for lower respiratory tract illness (LRTI) in children <5 years old from the National Hospital Discharge Survey. LRTI hospitalizations were identified by using International Classification of Diseases, Ninth Revision, Clinical Modification codes. RSV-coded hospitalizations were International Classification of Diseases, Ninth Revision, Clinical Modification codes 466.11, 480.1, and 079.6. RSV-associated hospitalizations were the sum of RSV-coded hospitalizations and a proportion of hospitalizations coded as bronchiolitis and pneumonia during the RSV season. Results: RSV-coded hospitalizations accounted for 24% of an estimated 5.5 million LRTI hospitalizations among children <5 years of age during the 10 study years, 1997–2006. The RSV-coded hospitalization rate in infants <1 year old was 26.0 per 1000, with no significant difference between study years. The hospitalization rate was highest among infants <3 months old (48.9 per 1000), followed by infants 3 to 5 months old (28.4 per 1000), and lower among those >1 year old (1.8 per 1000). An estimated 132,000 to 172,000 RSV-associated hospitalizations occurred annually in children <5 years of age. Conclusion: RSV hospitalization rates remained steady during 1997 to 2006 and were a substantial burden in the United States, especially among infants and young children. A safe and effective RSV vaccine is needed.

SARS: Systematic review of treatment effects

Background The SARS outbreak of 2002–2003 presented clinicians with a new, life-threatening disease for which they had no experience in treating and no research on the effectiveness of treatment options. The World Health Organization (WHO) expert panel on SARS treatment requested a systematic review and comprehensive summary of treatments used for SARS-infected patients in order to guide future treatment and identify priorities for research. Methods and Findings In response to the WHO request we conducted a systematic review of the published literature on ribavirin, corticosteroids, lopinavir and ritonavir (LPV/r), type I interferon (IFN), intravenous immunoglobulin (IVIG), and SARS convalescent plasma from both in vitro studies and in SARS patients. We also searched for clinical trial evidence of treatment for acute respiratory distress syndrome. Sources of data were the literature databases MEDLINE, EMBASE, BIOSIS, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to February 2005. Data from publications were extracted and evidence within studies was classified using predefined criteria. In total, 54 SARS treatment studies, 15 in vitro studies, and three acute respiratory distress syndrome studies met our inclusion criteria. Within in vitro studies, ribavirin, lopinavir, and type I IFN showed inhibition of SARS-CoV in tissue culture. In SARS-infected patient reports on ribavirin, 26 studies were classified as inconclusive, and four showed possible harm. Seven studies of convalescent plasma or IVIG, three of IFN type I, and two of LPV/r were inconclusive. In 29 studies of steroid use, 25 were inconclusive and four were classified as causing possible harm. Conclusions Despite an extensive literature reporting on SARS treatments, it was not possible to determine whether treatments benefited patients during the SARS outbreak. Some may have been harmful. Clinical trials should be designed to validate a standard protocol for dosage and timing, and to accrue data in real time during future outbreaks to monitor specific adverse effects and help inform treatment.

WHO Rapid Advice Guidelines for pharmacological management of sporadic human infection with avian influenza A (H5N1) virus

Summary Recent spread of avian influenza A (H5N1) virus to poultry and wild birds has increased the threat of human infections with H5N1 virus worldwide. Despite international agreement to stockpile antivirals, evidence-based guidelines for their use do not exist. WHO assembled an international multidisciplinary panel to develop rapid advice for the pharmacological management of human H5N1 virus infection in the current pandemic alert period. A transparent methodological guideline process on the basis of the Grading Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to develop evidence-based guidelines. Our development of specific recommendations for treatment and chemoprophylaxis of sporadic H5N1 infection resulted from the benefits, harms, burden, and cost of interventions in several patient and exposure groups. Overall, the quality of the underlying evidence for all recommendations was rated as very low because it was based on small case series of H5N1 patients, on extrapolation from preclinical studies, and high quality studies of seasonal influenza. A strong recommendation to treat H5N1 patients with oseltamivir was made in part because of the severity of the disease. Similarly, strong recommendations were made to use neuraminidase inhibitors as chemoprophylaxis in high-risk exposure populations. Emergence of other novel influenza A viral subtypes with pandemic potential, or changes in the pathogenicity of H5N1 virus strains, will require an update of these guidelines and WHO will be monitoring this closely.

Active, Population-Based Surveillance for Severe Rotavirus Gastroenteritis in Children in the United States

OBJECTIVES. Routine vaccination of US infants against rotavirus was implemented in 2006, prompting the Centers for Disease Control and Prevention New Vaccine Surveillance Network to begin population-based acute gastroenteritis surveillance among US children <3 years of age. This surveillance system establishes baseline estimates of rotavirus disease burden and allows for the prospective monitoring of rotavirus vaccination impact. METHODS. Eligible children with acute gastroenteritis (≥3 episodes of diarrhea and/or any vomiting in a 24-hour period) who were hospitalized, were seen in emergency departments, or visited selected outpatient clinics in 3 US counties during the period of January through June 2006 were enrolled. Epidemiological and clinical information was obtained through parental interview and medical chart review, and stool specimens were tested for rotavirus with enzyme immunoassays. Rotavirus-positive specimens were genotyped by using reverse transcription-polymerase chain reaction assays. RESULTS. Stool specimens were collected from 516 of the 739 enrolled children with acute gastroenteritis (181 inpatient, 201 emergency department, and 134 outpatient) and 44% tested positive for rotavirus (227 of 516 specimens). The most common strain was P[8]G1 (84%), followed by P[4]G2 (5%) and P[6]G12 (4%). None of the 516 children had received rotavirus vaccine. The rotavirus detection rate was 50% for hospitalized acute gastroenteritis cases, 50% for emergency department visits, and 27% for outpatient visits. Rotavirus-related acute gastroenteritis cases were more likely than non–rotavirus-related acute gastroenteritis cases to present with vomiting, diarrhea, fever, and lethargy. Directly calculated, population-based rates for rotavirus hospitalizations and emergency department visits were 22.5 hospitalizations and 301.0 emergency department visits per 10 000 children <3 years of age, respectively. A sentinel outpatient clinic visit rate of 311.9 outpatient visits per 10 000 children <3 years of age was observed. CONCLUSIONS. Population-based, laboratory-confirmed rotavirus surveillance in the final rotavirus season before implementation of the US rotavirus vaccine program indicated a considerable burden of disease on the US health care system.

Prevalence of Acanthamoeba spp. and other free-living amoebae in household water, Ohio, USA—1990–1992

Knowledge of the prevalence of free-living amoebae (FLA) in US household water can provide a focus for prevention of amoeba-associated illnesses. Household water samples from two Ohio counties, collected and examined for amoebae during 1990–1992, were used to describe the prevalence of Acanthamoeba and other FLA in a household setting. Amoebae were isolated and identified by morphologic features. A total of 2,454 samples from 467 households were examined. Amoebae were found in water samples of 371 (79%) households. Sites most likely to contain amoeba were shower heads (52%) and kitchen sprayers (50%). Species of Hartmannella, Acanthamoeba, or Vahlkampfia were most common. Detection was higher in biofilm swab samples than in water samples. Detection of FLA and Acanthamoeba, at 79% and 51%, respectively, exceed estimates that have been published in previous surveys of household sources. We believe FLA are commonplace inhabitants of household water in this sample as they are in the environment.

Multidrug-Resistant Typhoid Fever With Neurologic Findings on the Malawi-Mozambique Border

BACKGROUND Salmonella enterica serovar Typhi causes an estimated 22 million cases of typhoid fever and 216 000 deaths annually worldwide. We investigated an outbreak of unexplained febrile illnesses with neurologic findings, determined to be typhoid fever, along the Malawi-Mozambique border. METHODS The investigation included active surveillance, interviews, examinations of ill and convalescent persons, medical chart reviews, and laboratory testing. Classification as a suspected case required fever and ≥1 other finding (eg, headache or abdominal pain); a probable case required fever and a positive rapid immunoglobulin M antibody test for typhoid (TUBEX TF); a confirmed case required isolation of Salmonella Typhi from blood or stool. Isolates underwent antimicrobial susceptibility testing and subtyping by pulsed-field gel electrophoresis (PFGE). RESULTS We identified 303 cases from 18 villages with onset during March-November 2009; 214 were suspected, 43 were probable, and 46 were confirmed cases. Forty patients presented with focal neurologic abnormalities, including a constellation of upper motor neuron signs (n = 19), ataxia (n = 22), and parkinsonism (n = 8). Eleven patients died. All 42 isolates tested were resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole; 4 were also resistant to nalidixic acid. Thirty-five of 42 isolates were indistinguishable by PFGE. CONCLUSIONS The unusual neurologic manifestations posed a diagnostic challenge that was resolved through rapid typhoid antibody testing in the field and subsequent blood culture confirmation in the Malawi national reference laboratory. Extending laboratory diagnostic capacity, including blood culture, to populations at risk for typhoid fever in Africa will improve outbreak detection, response, and clinical treatment.

Point-of-use water treatment and use among mothers in Malawi.

A national household survey was conducted in Malawi to determine awareness and use of a socially marketed water treatment product. In all, 64% of mothers were aware of the product, and 7% were using it. Both poor and rural mothers had lower awareness and use rates. Targeting promotion to rural populations could enhance program effectiveness.

Comparison of fast-track diagnostics respiratory pathogens multiplex real-time RT-PCR assay with in-house singleplex assays for comprehensive detection of human respiratory viruses

Abstract Fast-track Diagnostics respiratory pathogens (FTDRP) multiplex real-time RT-PCR assay was compared with in-house singleplex real-time RT-PCR assays for detection of 16 common respiratory viruses. The FTDRP assay correctly identified 26 diverse respiratory virus strains, 35 of 41 (85%) external quality assessment samples spiked with cultured virus and 232 of 263 (88%) archived respiratory specimens that tested positive for respiratory viruses by in-house assays. Of 308 prospectively tested respiratory specimens selected from children hospitalized with acute respiratory illness, 270 (87.7%) and 265 (86%) were positive by FTDRP and in-house assays for one or more viruses, respectively, with combined test results showing good concordance (K =0.812, 95% CI=0.786–0.838). Individual FTDRP assays for adenovirus, respiratory syncytial virus and rhinovirus showed the lowest comparative sensitivities with in-house assays, with most discrepancies occurring with specimens containing low virus loads and failed to detect some rhinovirus strains, even when abundant. The FTDRP enterovirus and human bocavirus assays appeared to be more sensitive than the in-house assays with some specimens. With the exceptions noted above, most FTDRP assays performed comparably with in-house assays for most viruses while offering enhanced throughput and easy integration by laboratories using conventional real-time PCR instrumentation.

Outbreak of Pneumonia Associated with Emergent Human Adenovirus Serotype 14—Southeast Alaska, 2008

BACKGROUND In September 2008, an outbreak of pneumonia associated with an emerging human adenovirus (human adenovirus serotype 14 [HAdV-14]) occurred on a rural Southeast Alaska island. Nine patients required hospitalization, and 1 patient died. METHODS To investigate the outbreak, pneumonia case patients were matched to control participants on the basis of age, sex, and community of residence. Participants in the investigation and their household contacts were interviewed, and serum samples and respiratory tract specimens were collected. Risk factors were evaluated by means of conditional logistic regression. RESULTS Among 32 pneumonia case patients, 21 (65%) had confirmed or probable HAdV-14 infection. None of 32 matched control participants had evidence of HAdV-14 infection (P<.001 for the difference). Factors independently associated with pneumonia included contact with a known HAdV-14-infected case patient (odds ratio [OR], 18.3 [95% confidence interval {CI}, >or=2.0]), current smoking (OR, 6.7 [95% CI, >or=0.9]), and having neither traveled off the island nor attended a large public gathering (OR, 14.7 [95% CI, >or=2.0]). Fourteen (67%) of 21 HAdV-14-positive case patients belonged to a single network of people who socialized and often smoked together and infrequently traveled off the island. HAdV-14 infection occurred in 43% of case-patient household contacts, compared with 5% of control-participant household contacts (P = .005). CONCLUSIONS During a community outbreak in Alaska, HAdV-14 appeared to have spread mostly among close contacts and not widely in the community. Demographic characteristics and illness patterns among the case patients were similar to those observed in other recent outbreaks of HAdV-14 infection in the United States.

Use of Respiratory Syncytial Virus Surveillance Data to Optimize the Timing of Immunoprophylaxis

OBJECTIVE: For children in the United States who are at high risk for severe respiratory syncytial virus (RSV) infection, the American Academy of Pediatrics (AAP) recommends administering immunoprophylaxis during the RSV season. We present an approach to using surveillance data to help guide application of AAP recommendations for immunoprophylaxis to local patterns of RSV outbreaks. METHODS: We analyzed data from laboratories that report consistently to the National Respiratory and Enteric Virus Surveillance System from 1992 to 2007. Local RSV seasons were defined and an immunoprophylaxis schedule was determined by using the median onset dates from each laboratory during 2002–2007. We applied these dates to 10 preceding years of RSV detection data. We compared how well the 5-year median-based method and a fixed date method were able to match the timing of immunoprophylaxis to the RSV season. RESULTS: Nineteen laboratories met our inclusion criteria and generally experienced only 1 RSV outbreak per season. Five years of data gave similar median onset/offset dates and season duration, as did 10 years and 15 years of data. The 5-year median schedule increased the number of seasons that children were protected at the season onset by 15% compared with a fixed start date of November 1 and identified communities that experienced RSV seasons with extended durations. CONCLUSIONS: The 5-year median method can be used to characterize timing of RSV seasons and optimally apply the current AAP recommendations for timing of palivizumab prophylaxis to the local community.