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1.  Outbreak of Antiviral Drug–Resistant Influenza A in Long-Term Care Facility, Illinois, USA, 2008 
Emerging Infectious Diseases  2009;15(12):1973-1976.
An outbreak of oseltamivir-resistant influenza A (H1N1) occurred in a long-term care facility. Eight (47%) of 17 and 1 (6%) of 16 residents in 2 wards had oseltamivir-resistant influenza A virus (H1N1) infections. Initial outbreak response included treatment and prophylaxis with oseltamivir. The outbreak abated, likely because of infection control measures.
doi:10.3201/eid1512.081644
PMCID: PMC3044511  PMID: 19961678
Influenza; outbreak; oseltamivir; drug resistance; viruses; nursing homes; infection control; Illinois; expedited; dispatch
3.  Asthma in patients hospitalized with pandemic influenza A(H1N1)pdm09 virus infection–United States, 2009 
Background
Asthma was the most common co-morbidity among patients hospitalized with pandemic influenza A(H1N1)pdm09 [pH1N1] infection. The objective was to compare characteristics of hospitalized pH1N1 patients with and without asthma and assess factors associated with severity among asthma patients.
Methods
Patient data were derived from two 2009 pandemic case-series of U.S. pH1N1 hospitalizations. A case was defined as a person ≥ 2 years old hospitalized with laboratory-confirmed pH1N1. Asthma status was determined through chart review.
Results
Among 473 cases, 29% had asthma. Persons with asthma were more likely to be 2–17 years old (39% vs. 30%, p = 0.04) and black (29% vs. 18%, p < 0.01), and have chronic obstructive pulmonary disease (13% vs. 9%, p = 0.04) but less likely to have pneumonia (37% vs. 47%, p = 0.05), need mechanical ventilation (13% vs. 23%, p = 0.02), and die (4% vs. 10%, p = 0.04) than those without asthma. Among patients with asthma, those admitted to an intensive care unit (ICU) or who died (n = 38) compared with survivors not admitted to an ICU (n = 99) were more likely to have pneumonia on admission (60% vs. 27%, p < 0.01) or acute respiratory distress syndrome (24% vs. 0%, p < 0.01) and less likely to receive influenza antiviral agents ≤ 2 days of admission (73% vs. 92%, p = 0.02).
Conclusions
The majority of persons with asthma had an uncomplicated course; however, severe disease, including ICU admission and death, occurred in asthma patients who presented with pneumonia. Influenza antiviral agents should be started early in hospitalized patients with suspected influenza, including those with asthma.
doi:10.1186/1471-2334-13-57
PMCID: PMC3585510  PMID: 23369034
Asthma; Influenza A virus; Hospitalization; ICU; H1N1pdm09
4.  Cluster of Oseltamivir-Resistant 2009 Pandemic Influenza A (H1N1) Virus Infections on a Hospital Ward among Immunocompromised Patients—North Carolina, 2009 
The Journal of Infectious Diseases  2011;203(6):838-846.
Background.  Oseltamivir resistance among 2009 pandemic influenza A (H1N1) viruses (pH1N1) is rare. We investigated a cluster of oseltamivir-resistant pH1N1 infections in a hospital ward.
Methods.  We reviewed patient records and infection control measures and interviewed health care personnel (HCP) and visitors. Oseltamivir-resistant pH1N1 infections were found with real-time reverse-transcription polymerase chain reaction and pyrosequencing for the H275Y neuraminidase (NA) mutation. We compared hemagglutinin (HA) sequences from clinical samples from the outbreak with those of other surveillance viruses.
Results.  During the period 6–11 October 2009, 4 immunocompromised patients within a hematology-oncology ward exhibited symptoms of pH1N1 infection. The likely index patient became febrile 8 days after completing a course of oseltamivir; isolation was instituted 9 days after symptom onset. Three other case patients developed symptoms 1, 3, and 5 days after the index patient. Three case patients were located in adjacent rooms. HA and NA sequences from case patients were identical. Twelve HCP and 6 visitors reported influenza symptoms during the study period. No other pH1N1 isolates from the hospital or from throughout the state carried the H275Y mutation.
Conclusions.  Geographic proximity, temporal clustering, presence of H275Y mutation, and viral sequence homology confirmed nosocomial transmission of oseltamivir-resistant pH1N1. Diagnostic vigilance and prompt isolation may prevent nosocomial transmission of influenza.
doi:10.1093/infdis/jiq124
PMCID: PMC3307091  PMID: 21343149
5.  Oseltamivir-Resistant Pandemic (H1N1) 2009 Virus Infections, United States, 2010–11 
Emerging Infectious Diseases  2012;18(2):308-311.
During October 2010–July 2011, 1.0% of pandemic (H1N1) 2009 viruses in the United States were oseltamivir resistant, compared with 0.5% during the 2009–10 influenza season. Of resistant viruses from 2010–11 and 2009–10, 26% and 89%, respectively, were from persons exposed to oseltamivir before specimen collection. Findings suggest limited community transmission of oseltamivir-resistant virus.
doi:10.3201/eid1802.111466
PMCID: PMC3310472  PMID: 22305467
influenza; influenza A; H1N1 virus; pandemic (H1N1) 2009; pandemic; antiviral drug resistance; oseltamivir; oseltamivir resistance; virus; United States
6.  Development of the Respiratory Index of Severity in Children (RISC) Score among Young Children with Respiratory Infections in South Africa 
PLoS ONE  2012;7(1):e27793.
Objective
Pneumonia is a leading cause of death in children worldwide. A simple clinical score predicting the probability of death in a young child with lower respiratory tract infection (LRTI) could aid clinicians in case management and provide a standardized severity measure during epidemiologic studies.
Methods
We analyzed 4,148 LRTI hospitalizations in children <24 months enrolled in a pneumococcal conjugate vaccine trial in South Africa from 1998–2001, to develop the Respiratory Index of Severity in Children (RISC). Using clinical data at admission, a multivariable logistic regression model for mortality was developed and statistically evaluated using bootstrap resampling techniques. Points were assigned to risk factors based on their coefficients in the multivariable model. A child's RISC score is the sum of points for each risk factor present. Separate models were developed for HIV-infected and non-infected children.
Results
Significant risk factors for HIV-infected and non-infected children included low oxygen saturation, chest indrawing, wheezing, and refusal to feed. The models also included age and HIV clinical classification (for HIV-infected children) or weight-for-age (for non-infected children). RISC scores ranged up to 7 points for HIV-infected or 6 points for non-infected children and correlated with probability of death (0–47%, HIV-infected; 0–14%, non-infected). Final models showed good discrimination (area under the ROC curve) and calibration (goodness-of-fit).
Conclusion
The RISC score incorporates a simple set of risk factors that accurately discriminate between young children based on their risk of death from LRTI, and may provide an objective means to quantify severity based on the risk of mortality.
doi:10.1371/journal.pone.0027793
PMCID: PMC3251620  PMID: 22238570
7.  Dual Resistance to Adamantanes and Oseltamivir Among Seasonal Influenza A(H1N1) Viruses: 2008–2010 
Two distinct genetic clades of seasonal influenza A(H1N1) viruses have cocirculated in the recent seasons: clade 2B oseltamivir-resistant and adamantane-susceptible viruses, and clade 2C viruses that are resistant to adamantanes and susceptible to oseltamivir. We tested seasonal influenza A(H1N1) viruses collected in 2008-2010 from the United States and globally for resistance to antivirals approved by the Food and Drug Administration. We report 28 viruses with both adamantane and oseltamivir (dual) resistance from 5 countries belonging to 4 distinct genotypes. Because of limited options for antiviral treatment, emergence of dual-resistant influenza viruses poses a public health concern, and their circulation needs to be closely monitored.
doi:10.1093/infdis/jiq005
PMCID: PMC3086447  PMID: 21148491
8.  Low usage of government healthcare facilities for acute respiratory infections in guatemala: implications for influenza surveillance 
BMC Public Health  2011;11:885.
Background
Sentinel surveillance for severe acute respiratory infections in hospitals and influenza-like illness in ambulatory clinics is recommended to assist in global pandemic influenza preparedness. Healthcare utilization patterns will affect the generalizability of data from sentinel sites and the potential to use them to estimate burden of disease. The objective of this study was to measure healthcare utilization patterns in Guatemala to inform the establishment of a sentinel surveillance system for influenza and other respiratory infections, and allow estimation of disease burden.
Methods
We used a stratified, two-stage cluster survey sample to select 1200 households from the Department of Santa Rosa. Trained interviewers screened household residents for self-reported pneumonia in the last year and influenza-like illness (ILI) in the last month and asked about healthcare utilization for each illness episode.
Results
We surveyed 1131 (94%) households and 5449 residents between October and December 2006 and identified 323 (6%) cases of pneumonia and 628 (13%) cases of ILI. Treatment for pneumonia outside the home was sought by 92% of the children <5 years old and 73% of the persons aged five years and older. For both children <5 years old (53%) and persons aged five years and older (31%) who reported pneumonia, private clinics were the most frequently reported source of care. For ILI, treatment was sought outside the home by 81% of children <5 years old and 65% of persons aged five years and older. Government ambulatory clinics were the most frequently sought source of care for ILI both for children <5 years old (41%) and persons aged five years and older (36%).
Conclusions
Sentinel surveillance for influenza and other respiratory infections based in government health facilities in Guatemala will significantly underestimate the burden of disease. Adjustment for healthcare utilization practices will permit more accurate estimation of the incidence of influenza and other respiratory pathogens in the community.
doi:10.1186/1471-2458-11-885
PMCID: PMC3267779  PMID: 22111590
9.  Influenza B Viruses with Mutation in the Neuraminidase Active Site, North Carolina, USA, 2010–11 
Emerging Infectious Diseases  2011;17(11):2043-2046.
Oseltamivir is 1 of 2 antiviral medications available for the treatment of influenza B virus infections. We describe and characterize a cluster of influenza B viruses circulating in North Carolina with a mutation in the neuraminidase active site that may reduce susceptibility to oseltamivir and the investigational drug peramivir but not to zanamivir.
doi:10.3201/eid1711.110787
PMCID: PMC3310577  PMID: 22099093
zanamivir; oseltamivir; peramivir; neuraminidase inhibitor; viruses; North Carolina; influenza; influenza B; mutation; United States
10.  Human Rhinovirus Infections in Rural Thailand: Epidemiological Evidence for Rhinovirus as Both Pathogen and Bystander 
PLoS ONE  2011;6(3):e17780.
Background
We describe human rhinovirus (HRV) detections in SaKaeo province, Thailand.
Methods
From September 1, 2003–August 31, 2005, we tested hospitalized patients with acute lower respiratory illness and outpatient controls without fever or respiratory symptoms for HRVs with polymerase chain reaction and molecularly-typed select HRVs. We compared HRV detection among hospitalized patients and controls and estimated enrollment adjusted incidence.
Results
HRVs were detected in 315 (16%) of 1919 hospitalized patients and 27 (9.6%) of 280 controls. Children had the highest frequency of HRV detections (hospitalized: <1 year: 29%, 1–4 year: 29%, ≥65 years: 9%; controls: <1 year: 24%, 1–4 year: 14%, ≥65 years: 2.8%). Enrollment adjusted hospitalized HRV detection rates were highest among persons aged <1 year (1038/100,000 persons/year), 1–4 years (457), and ≥65 years (71). All three HRV species were identified, HRV-A was the most common species in most age groups including children aged <1 year (61%) and all adult age groups. HRV-C was the most common species in the 1–4 year (51%) and 5–19 year age groups (54%). Compared to controls, hospitalized adults (≥19 years) and children were more likely to have HRV detections (odds ratio [OR]: 4.8, 95% confidence interval [CI]: 1.5, 15.8; OR: 2.0, CI: 1.2, 3.3, respectively) and hospitalized children were more likely to have HRV-A (OR 1.7, CI: 0.8, 3.5) or HVR-C (OR 2.7, CI: 1.2, 5.9) detection.
Conclusions
HRV rates were high among hospitalized children and the elderly but asymptomatic children also had substantial HRV detection. HRV (all species), and HRV-A and HRV-C detections were epidemiologically-associated with hospitalized illness. Treatment or prevention modalities effective against HRV could reduce hospitalizations due to HRV in Thailand.
doi:10.1371/journal.pone.0017780
PMCID: PMC3066183  PMID: 21479259
11.  Characteristics of Patients with Oseltamivir-Resistant Pandemic (H1N1) 2009, United States 
Emerging Infectious Diseases  2011;17(2):255-257.
During April 2009–June 2010, thirty-seven (0.5%) of 6,740 pandemic (H1N1) 2009 viruses submitted to a US surveillance system were oseltamivir resistant. Most patients with oseltamivir-resistant infections were severely immunocompromised (76%) and had received oseltamivir before specimen collection (89%). No evidence was found for community circulation of resistant viruses; only 4 (unlinked) patients had no oseltamivir exposure.
doi:10.3201/eid1702.101724
PMCID: PMC3204784  PMID: 21291599
Oseltamivir; influenza; antimicrobial resistance; influenza A; H1N1 subtype; viruses; pandemic (H1N1) 2009; United States; expedited; dispatch
12.  A Comparison of the Epidemiology and Clinical Presentation of Seasonal Influenza A and 2009 Pandemic Influenza A (H1N1) in Guatemala 
PLoS ONE  2010;5(12):e15826.
Background
A new influenza A (H1N1) virus was first found in April 2009 and proceeded to cause a global pandemic. We compare the epidemiology and clinical presentation of seasonal influenza A (H1N1 and H3N2) and 2009 pandemic influenza A (H1N1) (pH1N1) using a prospective surveillance system for acute respiratory disease in Guatemala.
Methodology/Findings
Patients admitted to two public hospitals in Guatemala in 2008–2009 who met a pneumonia case definition, and ambulatory patients with influenza-like illness (ILI) at 10 ambulatory clinics were invited to participate. Data were collected through patient interview, chart abstraction and standardized physical and radiological exams. Nasopharyngeal swabs were taken from all enrolled patients for laboratory diagnosis of influenza A virus infection with real-time reverse transcription polymerase chain reaction. We identified 1,744 eligible, hospitalized pneumonia patients, enrolled 1,666 (96%) and tested samples from 1,601 (96%); 138 (9%) had influenza A virus infection. Surveillance for ILI found 899 eligible patients, enrolled 801 (89%) and tested samples from 793 (99%); influenza A virus infection was identified in 246 (31%). The age distribution of hospitalized pneumonia patients was similar between seasonal H1N1 and pH1N1 (P = 0.21); the proportion of pneumonia patients <1 year old with seasonal H1N1 (39%) and pH1N1 (37%) were similar (P = 0.42). The clinical presentation of pH1N1 and seasonal influenza A was similar for both hospitalized pneumonia and ILI patients. Although signs of severity (admission to an intensive care unit, mechanical ventilation and death) were higher among cases of pH1N1 than seasonal H1N1, none of the differences was statistically significant.
Conclusions/Significance
Small sample sizes may limit the power of this study to find significant differences between seasonal influenza A and pH1N1. In Guatemala, influenza, whether seasonal or pH1N1, appears to cause severe disease mainly in infants; targeted vaccination of children should be considered.
doi:10.1371/journal.pone.0015826
PMCID: PMC3012722  PMID: 21209850
13.  The Burden of Hospitalized Lower Respiratory Tract Infection due to Respiratory Syncytial Virus in Rural Thailand 
PLoS ONE  2010;5(11):e15098.
Background
We describe the epidemiology of hospitalized RSV infections for all age groups from population-based surveillance in two rural provinces in Thailand.
Methods
From September 1, 2003 through December 31, 2007, we enrolled hospitalized patients with acute lower respiratory tract illness, who had a chest radiograph ordered by the physician, from all hospitals in SaKaeo and Nakhom Phanom Provinces. We tested nasopharyngeal specimens for RSV with reverse transcriptase polymerase chain reaction (RT-PCR) assays and paired-sera from a subset of patients with IgG enzyme immunoassay. Rates were adjusted for enrollment.
Results
Among 11,097 enrolled patients, 987 (8.9%) had RSV infection. Rates of hospitalized RSV infection overall (and radiographically-confirmed pneumonia) were highest among children aged <1 year: 1,067/100,000 (534/100,000 radiographically-confirmed pneumonia) and 1–4 year: 403/100,000 (222/100,000), but low among enrolled adults aged ≥65 years: 42/100,000. Age <1 year (adjusted odds ratio [aOR]  = 13.2, 95% confidence interval [CI] 7.7, 22.5) and 1–4 year (aOR = 8.3, 95% CI 5.0, 13.9) were independent predictors of hospitalized RSV infection.
Conclusions
The incidence of hospitalized RSV lower respiratory tract illness among children <5 years was high in rural Thailand. Efforts to prevent RSV infection could substantially reduce the pneumonia burden in children aged <5 years.
doi:10.1371/journal.pone.0015098
PMCID: PMC2994907  PMID: 21152047
14.  Estimating the Disease Burden of Pandemic (H1N1) 2009 Virus Infection in Hunter New England, Northern New South Wales, Australia, 2009 
PLoS ONE  2010;5(3):e9880.
Introduction
On May 26, 2009, the first confirmed case of Pandemic (H1N1) 2009 virus (pH1N1) infection in Hunter New England (HNE), New South Wales (NSW), Australia (population 866,000) was identified. We used local surveillance data to estimate pH1N1-associated disease burden during the first wave of pH1N1 circulation in HNE.
Methods
Surveillance was established during June 1-August 30, 2009, for: 1) laboratory detection of pH1N1 at HNE and NSW laboratories, 2) pH1N1 community influenza-like illness (ILI) using an internet survey of HNE residents, and 3) pH1N1-associated hospitalizations and deaths using respiratory illness International Classification of Diseases 10 codes at 35 HNE hospitals and mandatory reporting of confirmed pH1N1-associated hospitalizations and deaths to the public health service. The proportion of pH1N1 positive specimens was applied to estimates of ILI, hospitalizations, and deaths to estimate disease burden.
Results
Of 34,177 specimens tested at NSW laboratories, 4,094 (12%) were pH1N1 positive. Of 1,881 specimens from patients evaluated in emergency departments and/or hospitalized, 524 (26%) were pH1N1 positive. The estimated number of persons with pH1N1-associated ILI in the HNE region was 53,383 (range 37,828–70,597) suggesting a 6.2% attack rate (range 4.4–8.2%). An estimated 509 pH1N1-associated hospitalizations (range 388–630) occurred (reported: 184), and up to 10 pH1N1-associated deaths (range 8–13) occurred (reported: 5). The estimated case hospitalization ratio was 1% and case fatality ratio was 0.02%.
Discussion
The first wave of pH1N1 activity in HNE resulted in symptomatic infection in a small proportion of the population, and the number of HNE pH1N1-associated hospitalizations and deaths is likely higher than officially reported.
doi:10.1371/journal.pone.0009880
PMCID: PMC2848017  PMID: 20360868
15.  Avian Influenza Virus A (H5N1), Detected through Routine Surveillance, in Child, Bangladesh 
Emerging Infectious Diseases  2009;15(8):1311-1313.
We identified avian influenza virus A (H5N1) infection in a child in Bangladesh in 2008 by routine influenza surveillance. The virus was of the same clade and phylogenetic subgroup as that circulating among poultry during the period. This case illustrates the value of routine surveillance for detection of novel influenza virus.
doi:10.3201/eid1508.090283
PMCID: PMC2815980  PMID: 19751601
H5N1; influenza; avian influenza; human; surveillance; Bangladesh; viruses; dispatch
16.  Coronavirus Antibodies in Bat Biologists 
Emerging Infectious Diseases  2008;14(6):999-1000.
doi:10.3201/eid1406.070964
PMCID: PMC2600275  PMID: 18507931
coronavirus; mammologists; severe acute respiratory syndrome; letter
17.  Outbreaks of Short-Incubation Ocular and Respiratory Illness Following Exposure to Indoor Swimming Pools 
Environmental Health Perspectives  2006;115(2):267-271.
Objectives
Chlorination destroys pathogens in swimming pool water, but by-products of chlorination can cause human illness. We investigated outbreaks of ocular and respiratory symptoms associated with chlorinated indoor swimming pools at two hotels.
Measurements
We interviewed registered guests and companions who stayed at hotels X and Y within 2 days of outbreak onset. We performed bivariate and stratified analyses, calculated relative risks (RR), and conducted environmental investigations of indoor pool areas.
Results
Of 77 guests at hotel X, 47 (61%) completed questionnaires. Among persons exposed to the indoor pool area, 22 (71%) of 31 developed ocular symptoms [RR = 24; 95% confidence interval (CI), 1.5–370], and 14 (45%) developed respiratory symptoms (RR = 6.8; 95% CI, 1.0–47) with a median duration of 10 hr (0.25–24 hr). We interviewed 30 (39%) of 77 registered persons and 59 unregistered companions at hotel Y. Among persons exposed to the indoor pool area, 41 (59%) of 69 developed ocular symptoms (RR = 24; 95% CI, 1.5–370), and 28 (41%) developed respiratory symptoms (RR = 17; 95% CI, 1.1–260) with a median duration of 2.5 hr (2 min–14 days). Four persons sought medical care. During the outbreak, the hotel X’s ventilation system malfunctioned. Appropriate water and air samples were not available for laboratory analysis.
Conclusions and relevance to professional practice
Indoor pool areas were associated with illness in these outbreaks. A large proportion of bathers were affected; symptoms were consistent with chloramine exposure and were sometimes severe. Improved staff training, pool maintenance, and pool area ventilation could prevent future outbreaks.
doi:10.1289/ehp.9555
PMCID: PMC1817713  PMID: 17384776
chloramines; cyanuric acid; disease outbreaks; indoor air pollution; swimming pools; trihalomethanes
18.  Real-Time PCR Assays for Detection of Bocavirus in Human Specimens 
Journal of Clinical Microbiology  2006;44(9):3231-3235.
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.
doi:10.1128/JCM.00889-06
PMCID: PMC1594719  PMID: 16954253
19.  Genetically Diverse Group A Streptococci from Children in Far-Western Nepal Share High Genetic Relatedness with Isolates from Other Countries 
Journal of Clinical Microbiology  2006;44(6):2160-2166.
The genetic diversity of group A streptococci (GAS) throughout much of the world has not been adequately explored. To assess genetic variation among GAS in western Nepal, 120 noninvasive GAS, collected from eight different villages, were genetically characterized using emm typing, sof sequencing, and multilocus sequence typing (MLST). A high level of genetic diversity was observed among these isolates, with 51 genotypes based upon 51 multilocus sequence types (STs), 45 emm sequence types, and 28 sof sequence types. On the basis of shared ST-emm and sof-emm associations, 40 of the 51 genotypes were identical or highly related to genotypes characterized from locations outside of Nepal, even though most of the emm sequence and clonal types are rare among GAS within the United States. When analyzing all known STs highly related to Nepal STs, only one example of similar STs shared between a sof PCR-positive strain and a sof PCR-negative strain was observed. Since previous data indicate free exchange of MLST loci between sof-positive and sof-negative strains, there is possibly selection against the expansion of subclones resulting from horizontal transfers of sof or emm genes between sof-positive and sof-negative strains. All 45 emm types encountered in Nepal have also been documented from other countries. These data, together with data encompassing the past decade of emm type surveillance, support the possibility that most existing GAS emm types have been discovered. Similarly, since most (40/51) strain types were highly related to strains found elsewhere, it is likely that a major fraction of the existing GAS clonal complexes have been discovered.
doi:10.1128/JCM.02456-05
PMCID: PMC1489425  PMID: 16757615
20.  Multidrug-resistant Tuberculosis Detection, Latvia 
Emerging Infectious Diseases  2005;11(9):1461-1463.
To improve multidrug-resistant tuberculosis (MDR-TB) detection, we successfully introduced the rpoB gene mutation line probe assay into the national laboratory in Latvia, a country with epidemic MDR-TB. The assay detected rifampin resistance with 91% sensitivity and 96% specificity within 1 to 5 days (vs. 12–47 days for BACTEC).
doi:10.3201/eid1109.041236
PMCID: PMC3310615  PMID: 16229783
TB/HIV control; developing countries; multidrug-resistant TB, tuberculosis, TB diagnosis, dispatch
21.  Trachoma Decline and Widespread Use of Antimicrobial Drugs 
Emerging Infectious Diseases  2004;10(11):1895-1899.
Widespread use of antimicrobial drugs may be contributing to trachoma decline.
Trachoma is disappearing in many parts of the world, even in the absence of specific control programs. Following mass antimicrobial drug treatments for trachoma in western Nepal, the prevalence of trachoma declined far more rapidly than could be attributed to the control program alone. Pharmacy surveys in the same region found that children received more antichlamydial drugs from sources outside the trachoma program than they did from the program itself. We demonstrate that high background antimicrobial drug use may be responsible for much of the observed decline in trachoma and discuss its potential role in eliminating this infectious disease.
doi:10.3201/eid1011.040476
PMCID: PMC3329000  PMID: 15550197
trachoma; chlamydia; azithromycin; elimination; antibiotics; perspective
22.  Adherence to Antimicrobial Inhalational Anthrax Prophylaxis among Postal Workers, Washington, D.C., 2001 
Emerging Infectious Diseases  2002;8(10):1138-1144.
In October 2001, two envelopes containing Bacillus anthracis spores were processed at the Washington, D.C., Processing and Distribution Center of the U.S. Postal Service; inhalational anthrax developed in four workers at this facility. More than 2,000 workers were advised to complete 60 days of postexposure prophylaxis to prevent inhalational anthrax. Interventions to promote adherence were carried out to support workers, and qualitative information was collected to evaluate our interventions. A quantitative survey was administered to a convenience sample of workers to assess factors influencing adherence. No anthrax infections developed in any workers involved in the interventions or interviews. Of 245 workers, 98 (40%) reported full adherence to prophylaxis, and 45 (18%) had completely discontinued it. Experiencing adverse effects to prophylaxis, anxiety, and being <45 years old were risk factors for discontinuing prophylaxis. Interventions, especially frequent visits by public health staff, proved effective in supporting adherence.
doi:10.3201/eid0810.020331
PMCID: PMC2730315  PMID: 12396929
adherence; Bacillus anthracis; bioterrorism; antimicrobial prophylaxis; compliance
23.  Inhalational Anthrax Outbreak among Postal Workers, Washington, D.C., 2001 
Emerging Infectious Diseases  2002;8(10):1066-1072.
In October 2001, four cases of inhalational anthrax occurred in workers in a Washington, D.C., mail facility that processed envelopes containing Bacillus anthracis spores. We reviewed the envelopes’ paths and obtained exposure histories and nasal swab cultures from postal workers. Environmental sampling was performed. A sample of employees was assessed for antibody concentrations to B. anthracis protective antigen. Case-patients worked on nonoverlapping shifts throughout the facility. Environmental sampling showed diffuse contamination of the facility, suggesting multiple aerosolization events. Potential workplace exposures were similar for the case-patients and the sample of workers. All nasal swab cultures and serum antibody tests were negative. Available tools could not identify subgroups of employees at higher risk for exposure or disease. Prophylaxis was necessary for all employees. To protect postal workers against bioterrorism, measures to reduce the risk of occupational exposure are necessary.
doi:10.3201/eid0810.020330
PMCID: PMC2730301  PMID: 12396917
bioterrorism; Bacillus anthracis; postal facility; inhalational anthrax
24.  Population-Based Incidence of Severe Acute Respiratory Virus Infections among Children Aged <5 Years in Rural Bangladesh, June–October 2010 
PLoS ONE  2014;9(2):e89978.
Background
Better understanding the etiology-specific incidence of severe acute respiratory infections (SARIs) in resource-poor, rural settings will help further develop and prioritize prevention strategies. To address this gap in knowledge, we conducted a longitudinal study to estimate the incidence of SARIs among children in rural Bangladesh.
Methods
During June through October 2010, we followed children aged <5 years in 67 villages to identify those with cough, difficulty breathing, age-specific tachypnea and/or danger signs in the community or admitted to the local hospital. A study physician collected clinical information and obtained nasopharyngeal swabs from all SARI cases and blood for bacterial culture from those hospitalized. We tested swabs for respiratory syncytial virus (RSV), influenza viruses, human metapneumoviruses, adenoviruses and human parainfluenza viruses 1–3 (HPIV) by real-time reverse transcription polymerase chain reaction. We calculated virus-specific SARI incidence by dividing the number of new illnesses by the person-time each child contributed to the study.
Results
We followed 12,850 children for 279,029 person-weeks (pw) and identified 141 SARI cases; 76 (54%) at their homes and 65 (46%) at the hospital. RSV was associated with 7.9 SARI hospitalizations per 100,000 pw, HPIV3 2.2 hospitalizations/100,000 pw, and influenza 1.1 hospitalizations/100,000 pw. Among non-hospitalized SARI cases, RSV was associated with 10.8 illnesses/100,000 pw, HPIV3 1.8/100,000 pw, influenza 1.4/100,000 pw, and adenoviruses 0.4/100,000 pw.
Conclusion
Respiratory viruses, particularly RSV, were commonly associated with SARI among children. It may be useful to explore the value of investing in prevention strategies, such as handwashing and respiratory hygiene, to reduce respiratory infections among young children in such settings.
doi:10.1371/journal.pone.0089978
PMCID: PMC3934972  PMID: 24587163
25.  Prevalence of Seropositivity to Pandemic Influenza A/H1N1 Virus in the United States following the 2009 Pandemic 
PLoS ONE  2012;7(10):e48187.
Background
2009 pandemic influenza A/H1N1 (A(H1N1)pdm09) was first detected in the United States in April 2009 and resulted in a global pandemic. We conducted a serologic survey to estimate the cumulative incidence of A(H1N1)pdm09 through the end of 2009 when pandemic activity had waned in the United States.
Methods
We conducted a pair of cross sectional serologic surveys before and after the spring/fall waves of the pandemic for evidence of seropositivity (titer ≥40) using the hemagglutination inhibition (HI) assay. We tested a baseline sample of 1,142 serum specimens from the 2007–2008 National Health and Nutrition Examination Survey (NHANES), and 2,759 serum specimens submitted for routine screening to clinical diagnostic laboratories from ten representative sites.
Results
The age-adjusted prevalence of seropositivity to A(H1N1)pdm09 by year-end 2009 was 36.9% (95%CI: 31.7–42.2%). After adjusting for baseline cross-reactive antibody, pandemic vaccination coverage and the sensitivity/specificity of the HI assay, we estimate that 20.2% (95%CI: 10.1–28.3%) of the population was infected with A(H1N1)pdm09 by December 2009, including 53.3% (95%CI: 39.0–67.1%) of children aged 5–17 years.
Conclusions
By December 2009, approximately one-fifth of the US population, or 61.9 million persons, may have been infected with A(H1N1)pdm09, including around half of school-aged children.
doi:10.1371/journal.pone.0048187
PMCID: PMC3485186  PMID: 23118949

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