Alicia M. Fry

Hospitalized Patients with 2009 H1N1 Influenza in the United States, April–June 2009

BACKGROUND During the spring of 2009, a pandemic influenza A (H1N1) virus emerged and spread globally. We describe the clinical characteristics of patients who were hospitalized with 2009 H1N1 influenza in the United States from April 2009 to mid-June 2009. METHODS Using medical charts, we collected data on 272 patients who were hospitalized for at least 24 hours for influenza-like illness and who tested positive for the 2009 H1N1 virus with the use of a real-time reverse-transcriptase-polymerase-chain-reaction assay. RESULTS Of the 272 patients we studied, 25% were admitted to an intensive care unit and 7% died. Forty-five percent of the patients were children under the age of 18 years, and 5% were 65 years of age or older. Seventy-three percent of the patients had at least one underlying medical condition; these conditions included asthma; diabetes; heart, lung, and neurologic diseases; and pregnancy. Of the 249 patients who underwent chest radiography on admission, 100 (40%) had findings consistent with pneumonia. Of the 268 patients for whom data were available regarding the use of antiviral drugs, such therapy was initiated in 200 patients (75%) at a median of 3 days after the onset of illness. Data suggest that the use of antiviral drugs was beneficial in hospitalized patients, especially when such therapy was initiated early. CONCLUSIONS During the evaluation period, 2009 H1N1 influenza caused severe illness requiring hospitalization, including pneumonia and death. Nearly three quarters of the patients had one or more underlying medical conditions. Few severe illnesses were reported among persons 65 years of age or older. Patients seemed to benefit from antiviral therapy.

Pandemic 2009 Influenza A(H1N1) Virus Illness Among Pregnant Women in the United States

CONTEXT Early data on pandemic 2009 influenza A(H1N1) suggest pregnant women are at increased risk of hospitalization and death. OBJECTIVE To describe the severity of 2009 influenza A(H1N1) illness and the association with early antiviral treatment among pregnant women in the United States. DESIGN, SETTING, AND PATIENTS Surveillance of 2009 influenza A(H1N1) in pregnant women reported to the Centers for Disease Control and Prevention (CDC) with symptom onset from April through December 2009. MAIN OUTCOME MEASURES Severity of illness (hospitalizations, intensive care unit [ICU] admissions, and deaths) due to 2009 influenza A(H1N1) among pregnant women, stratified by timing of antiviral treatment and pregnancy trimester at symptom onset. RESULTS We received reports on 788 pregnant women in the United States with 2009 influenza A(H1N1) with symptom onset from April through August 2009. Among those, 30 died (5% of all reported 2009 influenza A[H1N1] influenza deaths in this period). Among 509 hospitalized women, 115 (22.6%) were admitted to an ICU. Pregnant women with treatment more than 4 days after symptom onset were more likely to be admitted to an ICU (56.9% vs 9.4%; relative risk [RR], 6.0; 95% confidence interval [CI], 3.5-10.6) than those treated within 2 days after symptom onset. Only 1 death occurred in a patient who received treatment within 2 days of symptom onset. Updating these data with the CDCs continued surveillance of ICU admissions and deaths among pregnant women with symptom onset through December 31, 2009, identified an additional 165 women for a total of 280 women who were admitted to ICUs, 56 of whom died. Among the deaths, 4 occurred in the first trimester (7.1%), 15 in the second (26.8%), and 36 in the third (64.3%); CONCLUSIONS Pregnant women had a disproportionately high risk of mortality due to 2009 influenza A(H1N1). Among pregnant women with 2009 influenza A(H1N1) influenza reported to the CDC, early antiviral treatment appeared to be associated with fewer admissions to an ICU and fewer deaths.

Infections with oseltamivir-resistant influenza A(H1N1) virus in the United States.

CONTEXT During the 2007-2008 influenza season, oseltamivir resistance among influenza A(H1N1) viruses increased significantly for the first time worldwide. Early surveillance data suggest that the prevalence of oseltamivir resistance among A(H1N1) viruses will most likely be higher during the 2008-2009 season. OBJECTIVES To describe patients infected with oseltamivir-resistant influenza A(H1N1) virus and to determine whether there were any differences between these patients and patients infected with oseltamivir-susceptible A(H1N1) virus in demographic or epidemiological characteristics, clinical symptoms, severity of illness, or clinical outcomes. DESIGN, SETTING, AND PATIENTS Influenza A(H1N1) viruses that were identified and submitted to the Centers for Disease Control and Prevention by US public health laboratories between September 30, 2007, and May 17, 2008, and between September 28, 2008, and February 19, 2009, were tested as part of ongoing surveillance. Oseltamivir resistance was determined by neuraminidase inhibition assay and pyrosequencing analysis. Information was collected using a standardized case form from patients with oseltamivir-resistant A(H1N1) infections and a comparison group of patients with oseltamivir-susceptible A(H1N1) infections during 2007-2008. MAIN OUTCOME MEASURES Demographic and epidemiological information as well as clinical information, including symptoms, severity of illness, and clinical outcomes. RESULTS During the 2007-2008 season, influenza A(H1N1) accounted for an estimated 19% of circulating influenza viruses in the United States. Among 1155 influenza A(H1N1) viruses tested from 45 states, 142 (12.3%) from 24 states were resistant to oseltamivir. Data were available for 99 oseltamivir-resistant cases and 182 oseltamivir-susceptible cases from this period. Among resistant cases, median age was 19 years (range, 1 month to 62 years), 5 patients (5%) were hospitalized, and 4 patients (4%) died. None reported oseltamivir exposure before influenza diagnostic sample collection. No significant differences were found between cases of oseltamivir-resistant and oseltamivir-susceptible influenza in demographic characteristics, underlying medical illness, or clinical symptoms. Preliminary data from the 2008-2009 influenza season identified resistance to oseltamivir among 264 of 268 influenza A(H1N1) viruses (98.5%) tested. CONCLUSIONS Oseltamivir-resistant A(H1N1) viruses circulated widely in the United States during the 2007-2008 influenza season, appeared to be unrelated to oseltamivir use, and appeared to cause illness similar to oseltamivir-susceptible A(H1N1) viruses. Circulation of oseltamivir-resistant A(H1N1) viruses will continue, with a higher prevalence of resistance, during the 2008-2009 season.

Human Bocavirus: A Novel Parvovirus Epidemiologically Associated with Pneumonia Requiring Hospitalization in Thailand

Abstract Background. We detected human bocavirus (HBoV) infection in 4.5% of hospitalized patients with pneumonia in rural Thailand. However, the role of HBoV as a pathogen is unclear. Methods. We compared HBoV infection in patients with pneumonia with that in asymptomatic control patients enrolled between 1 September 2004 and 31 August 2005 in the same hospitals in Thailand.We examined outpatients with influenza-like illness for HBoV infection and tested for 13 additional respiratory viruses. Epidemiologic and clinical characteristics of HBoV infection are described. Results. HBoV infection was detected in 20 (3.9%) of 512 outpatients and 3 (1%) of 280 control patients. Coinfection with other viruses was detected in 83% of patients with pneumonia and in 90% of outpatients. Compared with control patients, HBoV infection was significantly associated with pneumonia requiring hospitalization (adjusted odds ratio, 3.56 [95% confidence interval, 1.06–11.91]; P = .04). Eighty-three percent of HBoV infections were detected in patients with pneumonia who were <5 years old. More patients with pneumonia associated with HBoV—respiratory syncytial virus (RSV) or human parainfluenza virus (HPIV) coinfections had wheezing than patients with RSV and HPIV infections alone (9 [53%] of 17 vs. 32 [23%] of 138]; P = .01). Conclusions. HBoV infection was epidemiologically associated with pneumonia among young children in rural Thailand, but infection and illness may be dependent on coinfection with other viruses.

Influenza-Associated Pediatric Mortality in the United States: Increase of Staphylococcus aureus Coinfection

OBJECTIVE. Pediatric influenza-associated death became a nationally notifiable condition in the United States during 2004. We describe influenza-associated pediatric mortality from 2004 to 2007, including an increase of Staphylococcus aureus coinfections. METHODS. Influenza-associated pediatric death is defined as a death of a child who is younger than 18 years and has laboratory-confirmed influenza. State and local health departments report to the Centers for Disease Control and Prevention demographic, clinical, and laboratory data on influenza-associated pediatric deaths. RESULTS. During the 2004–2007 influenza seasons, 166 influenza-associated pediatric deaths were reported (n = 47, 46, and 73, respectively). Median age of the children was 5 years. Children often progressed rapidly to death; 45% died within 72 hours of onset, including 43% who died at home or in an emergency department. Of 90 children who were recommended for influenza vaccination, only 5 (6%) were fully vaccinated. Reports of bacterial coinfection increased substantially from 2004–2005 to 2006–2007 (6%, 15%, and 34%, respectively). S aureus was isolated from a sterile site or endotracheal tube culture in 1 case in 2004–2005, 3 cases in 2005–2006, and 22 cases in 2006–2007; 64% were methicillin-resistant S aureus. Children with S aureus coinfection were significantly older and more likely to have pneumonia and acute respiratory distress syndrome than those who were not coinfected. CONCLUSIONS. Influenza-associated pediatric mortality is rare, but the proportion of S aureus coinfection identified increased fivefold over the past 3 seasons. Research is needed to identify risk factors for influenza coinfection with invasive bacteria and to determine the impact of influenza vaccination and antiviral agents in preventing pediatric mortality.

The Influence of Chronic Illnesses on the Incidence of Invasive Pneumococcal Disease in Adults

Pneumococcal disease is more frequent and more deadly in persons with certain comorbidities. We used 1999 and 2000 data from the Active Bacterial Core surveillance (ABCs) and the National Health Interview Survey (NHIS) to determine rates of invasive pneumococcal disease in healthy adults (> or =18 years old) and in adults with various high-risk conditions. The risks of invasive pneumococcal disease in persons with specific chronic illnesses was compared with that in healthy adults, controlling for age, race, and the other chronic illnesses. Overall incidence rates, in cases/100,000 persons, were 8.8 in healthy adults, 51.4 in adults with diabetes, 62.9 in adults with chronic lung disease, 93.7 in adults with chronic heart disease, and 100.4 in adults who abused alcohol. Among the high-risk groups evaluated, risk was highest in adults with solid cancer (300.4), HIV/AIDS (422.9), and hematological cancer (503.1). Incidence rates increased with advancing age in adults with chronic lung disease, diabetes, and solid cancer. Black adults had higher incidence rates than white adults, both in healthy adults and in adults with chronic illnesses. These data support recommendations to provide pneumococcal vaccine to persons in these at-risk groups and underscore the need for better prevention strategies for immunocompromised persons.

Morbid Obesity as a Risk Factor for Hospitalization and Death Due to 2009 Pandemic Influenza A(H1N1) Disease

Background Severe illness due to 2009 pandemic A(H1N1) infection has been reported among persons who are obese or morbidly obese. We assessed whether obesity is a risk factor for hospitalization and death due to 2009 pandemic influenza A(H1N1), independent of chronic medical conditions considered by the Advisory Committee on Immunization Practices (ACIP) to increase the risk of influenza-related complications. Methodology/Principal Findings We used a case-cohort design to compare cases of hospitalizations and deaths from 2009 pandemic A(H1N1) influenza occurring between April–July, 2009, with a cohort of the U.S. population estimated from the 2003–2006 National Health and Nutrition Examination Survey (NHANES); pregnant women and children <2 years old were excluded. For hospitalizations, we defined categories of relative weight by body mass index (BMI, kg/m2); for deaths, obesity or morbid obesity was recorded on medical charts, and death certificates. Odds ratio (OR) of being in each BMI category was determined; normal weight was the reference category. Overall, 361 hospitalizations and 233 deaths included information to determine BMI category and presence of ACIP-recognized medical conditions. Among ≥20 year olds, hospitalization was associated with being morbidly obese (BMI≥40) for individuals with ACIP-recognized chronic conditions (OR = 4.9, 95% CI 2.4–9.9) and without ACIP-recognized chronic conditions (OR = 4.7, 95%CI 1.3–17.2). Among 2–19 year olds, hospitalization was associated with being underweight (BMI≤5th percentile) among those with (OR = 12.5, 95%CI 3.4–45.5) and without (OR = 5.5, 95%CI 1.3–22.5) ACIP-recognized chronic conditions. Death was not associated with BMI category among individuals 2–19 years old. Among individuals aged ≥20 years without ACIP-recognized chronic medical conditions death was associated with obesity (OR = 3.1, 95%CI: 1.5–6.6) and morbid obesity (OR = 7.6, 95%CI 2.1–27.9). Conclusions/Significance Our findings support observations that morbid obesity may be associated with hospitalization and possibly death due to 2009 pandemic H1N1 infection. These complications could be prevented by early antiviral therapy and vaccination.

Human coronavirus infections in rural thailand : A comprehensive study using real-time reverse-transcription polymerase chain reaction assays

Abstract Background. We sought to determine whether infections with human coronaviruses (HCoVs) 229E, OC43, HKU1, and NL63 are associated with pneumonia and to define the epidemiology of HCoV infection in rural Thailand. Methods. We developed a real-time reverse-transcription polymerase chain reaction (RT-PCR) assay panel for the recognized HCoV types and compared HCoV infections in patients hospitalized with pneumonia, outpatients with influenza-like illness, and asymptomatic control patients between September 2003 and August 2005. Results. During study year 1, 43 (5.9%) of 734 patients with pneumonia had HCoV infections; 72.1% of the infections were with OC43. During study year 2, when control patients were available, 21 (1.8%) of 1156 patients with pneumonia, 12 (2.3%) of 513 outpatients, and 6 (2.1%) of 281 control patients had HCoV infections. Compared with infection in control patients, infection with any HCoV type or with all types combined was not associated with pneumonia (adjusted odds ratio for all HCoV types, 0.67 [95% confidence interval, 0.26–1.75]; P= .40 ). HCoV infections were detected throughout both study years; 93.6% of OC43 infections in the first year occurred from January through March. Conclusions. HCoV infections were infrequently detected in rural Thailand by use of sensitive real-time RTPCR assays. We found no association between HCoV infection and illness. However, we noted year-to-year variation in the prevalence of HCoV strains, which likely influenced our results.

Real-Time PCR Assays for Detection of Bocavirus in Human Specimens

ABSTRACT The recently discovered human bocavirus (HBoV) is the first member of the family Parvoviridae, genus Bocavirus, to be potentially associated with human disease. Several studies have identified HBoV in respiratory specimens from children with acute respiratory disease, but the full spectrum of clinical disease and the epidemiology of HBoV infection remain unclear. The availability of rapid and reliable molecular diagnostics would therefore aid future studies of this novel virus. To address this, we developed two sensitive and specific real-time TaqMan PCR assays that target the HBoV NS1 and NP-1 genes. Both assays could reproducibly detect 10 copies of a recombinant DNA plasmid containing a partial region of the HBoV genome, with a dynamic range of 8 log units (101 to 108 copies). Eight blinded clinical specimen extracts positive for HBoV by an independent PCR assay were positive by both real-time assays. Among 1,178 NP swabs collected from hospitalized pneumonia patients in Sa Kaeo Province, Thailand, 53 (4.5%) were reproducibly positive for HBoV by one or both targets. Our data confirm the possible association of HBoV infection with pneumonia and demonstrate the utility of these real-time PCR assays for HBoV detection.

Influenza Vaccine Effectiveness in the United States During 2012–2013: Variable Protection by Age and Virus Type

Background. During the 2012–2013 influenza season, there was cocirculation of influenza A(H3N2) and 2 influenza B lineage viruses in the United States. Methods. Patients with acute cough illness for ≤7 days were prospectively enrolled and had swab samples obtained at outpatient clinics in 5 states. Influenza vaccination dates were confirmed by medical records. The vaccine effectiveness (VE) was estimated as [100% × (1 − adjusted odds ratio)] for vaccination in cases versus test-negative controls. Results. Influenza was detected in 2307 of 6452 patients (36%); 1292 (56%) had influenza A(H3N2), 582 (25%) had influenza B/Yamagata, and 303 (13%) had influenza B/Victoria. VE was 49% (95% confidence interval [CI], 43%–55%) overall, 39% (95% CI, 29%–47%) against influenza A(H3N2), 66% (95% CI, 58%–73%) against influenza B/Yamagata (vaccine lineage), and 51% (95% CI, 36%–63%) against influenza B/Victoria. VE against influenza A(H3N2) was highest among persons aged 50–64 years (52%; 95% CI, 33%–65%) and persons aged 6 months–8 years (51%; 95% CI, 32%–64%) and lowest among persons aged ≥65 years (11%; 95% CI, −41% to 43%). In younger age groups, there was evidence of residual protection from receipt of the 2011–2012 vaccine 1 year earlier. Conclusions. The 2012–2013 vaccines were moderately effective in most age groups. Cross-lineage protection and residual effects from prior vaccination were observed and warrant further investigation.