Jill M. Ferdinands

Acute health effects after exposure to chlorine gas released after a train derailment

In January 2005, a train derailment on the premises of a textile mill in South Carolina released 42 to 60 tons of chlorine gas in the middle of a small town. Medical records and autopsy reports were reviewed to describe the clinical presentation, hospital course, and pathology observed in persons hospitalized or deceased as a result of chlorine gas exposure. Eight persons died before reaching medical care; of the 71 persons hospitalized for acute health effects as a result of chlorine exposure, 1 died in the hospital. The mean age of the hospitalized persons was 40 years (range, 4 months-76 years); 87% were male. The median duration of hospitalization was 4 days (range, 1-29 days). Twenty-five (35%) persons were admitted to the intensive care unit; the median length of stay was 3 days. Many surviving victims developed significant pulmonary signs and severe airway inflammation; 41 (58%) hospitalized persons met PO2/FiO2 criteria for acute respiratory distress syndrome or acute lung injury. During their hospitalization, 40 (57%) developed abnormal x-ray findings, 74% of those within the first day. Hypoxia on room air and PO2/FiO2 ratio predicted severity of outcome as assessed by the duration of hospitalization and the need for intensive care support. This community release of chlorine gas caused widespread exposure and resulted in significant acute health effects and substantial health care requirements. Pulse oximetry and arterial blood gas analysis provided early indications of outcome severity.

Innate Immune Function and Mortality in Critically Ill Children With Influenza: A Multicenter Study*

Objective:To prospectively evaluate relationships among serum cytokine levels, innate immune responsiveness, and mortality in a multicenter cohort of critically ill children with influenza infection. Design:Prospective, multicenter, observational study. Setting:Fifteen pediatric ICUs among members of the Pediatric Acute Lung Injury and Sepsis Investigators network. Patients:Patients ⩽18 yrs old admitted to a PICU with community-acquired influenza infection. A control group of outpatient children was also evaluated. Interventions:ICU patients underwent sampling within 72 hrs of ICU admission for measurement of a panel of 31 serum cytokine levels and quantification of whole blood ex vivo lipopolysaccharide-stimulated tumor necrosis factor-&agr; production capacity using a standardized stimulation protocol. Outpatient control subjects also underwent measurement of tumor necrosis factor-&agr; production capacity. Measurements and Main Results:Fifty-two patients (44 survivors, eight deaths) were sampled. High levels of serum cytokines (granulocyte macrophage colony-stimulating factor, interleukin-6, interleukin-8, interferon-inducible protein-10, monocyte chemotactic protein-1, and macrophage inflammatory protein-1&agr;) were associated with mortality (p < 0.0016 for each comparison) as was the presence of secondary infection with Staphylococcus aureus (p = 0.007), particularly methicillin-resistant S. aureus (p < 0.0001). Nonsurvivors were immunosuppressed with leukopenia and markedly reduced tumor necrosis factor-&agr; production capacity compared with outpatient control subjects (n = 21, p < 0.0001) and to ICU survivors (p < 0.0001). This association remained after controlling for multiple covariables. A tumor necrosis factor-&agr; response <250 pg/mL was highly predictive of death and longer duration of ICU stay (p < 0.0001). Patients with S. aureus coinfection demonstrated the greatest degree of immunosuppression (p < 0.0001). Conclusions:High serum levels of cytokines can coexist with marked innate immune suppression in children with critical influenza. Severe, early innate immune suppression is highly associated with both S. aureus coinfection and mortality in this population. Multicenter innate immune function testing is feasible and can identify these high-risk children.

Effectiveness of influenza vaccine against life-threatening RT-PCR-confirmed influenza illness in US children, 2010-2012

BACKGROUND No studies have examined the effectiveness of influenza vaccine against intensive care unit (ICU) admission associated with influenza virus infection among children. METHODS In 2010-2011 and 2011-2012, children aged 6 months to 17 years admitted to 21 US pediatric intensive care units (PICUs) with acute severe respiratory illness and testing positive for influenza were enrolled as cases; children who tested negative were PICU controls. Community controls were children without an influenza-related hospitalization, matched to cases by comorbidities and geographic region. Vaccine effectiveness was estimated with logistic regression models. RESULTS We analyzed data from 44 cases, 172 PICU controls, and 93 community controls. Eighteen percent of cases, 31% of PICU controls, and 51% of community controls were fully vaccinated. Compared to unvaccinated children, children who were fully vaccinated were 74% (95% CI, 19% to 91%) or 82% (95% CI, 23% to 96%) less likely to be admitted to a PICU for influenza compared to PICU controls or community controls, respectively. Receipt of 1 dose of vaccine among children for whom 2 doses were recommended was not protective. CONCLUSIONS During the 2010-2011 and 2011-2012 US influenza seasons, influenza vaccination was associated with a three-quarters reduction in the risk of life-threatening influenza illness in children.

Waning vaccine protection against influenza A (H3N2) illness in children and older adults during a single season

BACKGROUND Recent studies have suggested that vaccine-induced protection against influenza may decline within one season. We reanalyzed data from a study of influenza vaccine effectiveness to determine if time since vaccination was an independent predictor of influenza A (H3N2). METHODS Patients with acute respiratory illness were actively recruited during the 2007-2008 season. Respiratory swabs were tested for influenza, and vaccination dates were determined by a validated immunization registry. The association between influenza RT-PCR result and vaccination interval (days) was examined using multivariable logistic regression, adjusting for calendar time, age and other confounders. RESULTS There were 629 vaccinated participants, including 177 influenza A (H3N2) cases and 452 test negative controls. The mean (SD) interval from vaccination to illness onset was 101.7 (25.9) days for influenza cases and 93.0 (29.9) days for controls. There was a significant association between vaccination interval and influenza result in the main effects model. The adjusted odds ratio (aOR) for influenza was 1.12 (CI 1.01, 1.26) for every 14 day increase in the vaccination interval. Age modified the association between vaccination interval and influenza (p=0.005 for interaction). Influenza was associated with increasing vaccination interval in young children and older adults, but not in adolescents or non-elderly adults. Similar results were found when calendar week of vaccine receipt was assessed as the primary exposure variable. CONCLUSIONS Identification of influenza A (H3N2) was associated with increasing time since vaccination among young children and older adults during a single influenza season.

Resident cleanup activities, characteristics of flood-damaged homes and airborne microbial concentrations in New Orleans, Louisiana, October 2005

BACKGROUND Flooding in the greater New Orleans (GNO) area after the hurricanes caused extensive mold growth in homes resulting in public health concerns. OBJECTIVES We conducted an environmental assessment of homes to determine the extent and type of microbial growth. METHODS We randomly selected 112 homes, stratified by water damage, and then visually assessed mold growth. Air samples from a subset of 20 homes were analyzed for culturable fungi, fungal spores, and markers of mold ((1-->3, 1-->6)-beta-D-glucans) and bacteria (endotoxin). RESULTS Visible mold growth occurred in 49 (44%) homes; 18 (16%) homes had >50% mold coverage. Flood levels were >6 ft at 20 (19%), 3-6 ft at 20 (19%), and <3 ft at 28 (26%) homes out of 107; no flooding at 39 (36%) homes. The residents spent an average of 18 h (range: 1-84) doing heavy cleaning and of those, 22 (38%) reported using an N-95 or other respirator. Visible mold growth was significantly associated with flood height 3 ft and the predominant fungi indoors were Aspergillus and Penicillium species, which were in higher concentrations in homes with a flood level 3 ft. Geometric mean (GM) levels of endotoxin were as high as 40.2 EU/m(3), while GM glucan levels were as high as 3.5 microg/m(3) even when flooding was 3 ft. CONCLUSIONS Based on our observations of visible mold, we estimated that elevated mold growth was present in 194,000 (44%) homes in the GNO area and 70,000 (16%) homes had heavy mold growth. Concentrations of endotoxin and glucans exceeded those previously associated with health effects. With such high levels of microbial growth following flooding, potentially harmful inhalation exposures can be present for persons entering or cleaning affected homes. Persons exposed to water-damaged homes should follow the CDC recommendations developed following the 2005 hurricanes for appropriate respiratory precautions.

Intraseason Waning of Influenza Vaccine Protection: Evidence From the US Influenza Vaccine Effectiveness Network, 2011–2012 Through 2014–2015

Background Recent studies suggest that influenza vaccine effectiveness (VE) may wane over the course of an influenza season, leading to suboptimal VE during late influenza seasons. Methods We examined the association between influenza VE and time since vaccination among patients ≥9 years old with medically-attended acute respiratory illness in the US Influenza Vaccine Effectiveness Network using data pooled from the 2011-12 through 2014-15 influenza seasons. We used multivariate logistic regression with PCR-confirmed influenza infection as the outcome and vaccination status defined by days between vaccination and symptom onset as the predictor. Models were adjusted for calendar time and other potential confounding factors. Results We observed decreasing VE with increasing time since vaccination for influenza A(H3N2) (p=0.004), influenza A(H1N1)pdm09 (p=0.01), and influenza B viruses (p=0.04). Maximum VE was observed shortly after vaccination, followed by a decline in VE of about 7% (absolute) per month for influenza A(H3N2) and influenza B and 6% - 11% per month for influenza A(H1N1)pdm09 viruses. VE remained greater than zero for at least six months for influenza A(H1N1)pdm09 and influenza B and at least five months for influenza A(H3N2) viruses. Decline in VE was more pronounced among patients with prior season influenza vaccination. A similar pattern of increasing influenza risk with increasing time since vaccination was seen in analyses limited to vaccinees. Conclusions We observed decreasing influenza vaccine protection with increasing time since vaccination across influenza types/subtypes. This association is consistent with intraseason waning of host immunity, but bias or residual confounding could explain these findings.

Ionic determinants of exhaled breath condensate pH before and after exercise in adolescent athletes

The pH of exhaled breath condensate (EBC) of adolescent athletes engaged in vigorous physical activity is low compared to healthy controls; however, the ionic determinants of EBC pH and the acute effects of exercise on those determinants have not been definitively established.

Comparative Effectiveness of High-Dose Versus Standard-Dose Influenza Vaccines Among US Medicare Beneficiaries in Preventing Postinfluenza Deaths During 2012-2013 and 2013-2014.

Background Recipients of high-dose vs standard-dose influenza vaccines have fewer influenza illnesses. We evaluated the comparative effectiveness of high-dose vaccine in preventing postinfluenza deaths during 2012-2013 and 2013-2014, when influenza viruses and vaccines were similar. Methods We identified Medicare beneficiaries aged ≥65 years who received high-dose or standard-dose vaccines in community-located pharmacies offering both vaccines. The primary outcome was death in the 30 days following an inpatient or emergency department encounter listing an influenza International of Classification of Diseases, Ninth Revision, Clinical Modification code. Effectiveness was estimated by using multivariate Poisson regression models; effectiveness was allowed to vary by season. Results We studied 1039645 recipients of high-dose and 1683264 recipients of standard-dose vaccines during 2012-2013, and 1508176 high-dose and 1877327 standard-dose recipients during 2013-2014. Vaccinees were well-balanced for medical conditions and indicators of frail health. Rates of postinfluenza death were 0.028 and 0.038/10000 person-weeks in high-dose and standard-dose recipients, respectively. Comparative effectiveness was 24.0% (95% confidence interval [CI], .6%-42%); there was evidence of variation by season (P = .12). In 2012-2013, high-dose was 36.4% (95% CI, 9.0%-56%) more effective in reducing mortality; in 2013-2014, it was 2.5% (95% CI, -47% to 35%). Conclusions High-dose vaccine was significantly more effective in preventing postinfluenza deaths in 2012-2013, when A(H3N2) circulation was common, but not in 2013-2014.

Magnitude of Potential Biases in a Simulated Case-Control Study of the Effectiveness of Influenza Vaccination

BACKGROUND Many influenza vaccine effectiveness estimates have been made using case-control methods. Although several forms of bias may distort estimates of vaccine effectiveness derived from case-control studies, there have been few attempts to quantify the magnitude of these biases. METHODS We estimated the magnitude of potential biases in influenza vaccine effectiveness values derived from case-control studies from several factors, including bias from differential use of diagnostic testing based on influenza vaccine status, imperfect diagnostic test characteristics, and confounding. A decision tree model was used to simulate an influenza vaccine effectiveness case-control study in children. Using probability distributions, we varied the value of factors that influence vaccine effectiveness estimates, including diagnostic test characteristics, vaccine coverage, likelihood of receiving a diagnostic test for influenza, likelihood that a child hospitalized with acute respiratory infection had influenza, and others. Bias was measured as the difference between the effectiveness observed in the simulated case-control study and a true underlying effectiveness value. RESULTS AND CONCLUSIONS We found an average difference between observed and true vaccine effectiveness of -11.9%. Observed vaccine effectiveness underestimated the true effectiveness in 88% of model iterations. Diagnostic test specificity exhibited the strongest association with observed vaccine effectiveness, followed by the likelihood of receiving a diagnostic test based on vaccination status and the likelihood that a child hospitalized with acute respiratory infection had influenza. Our findings suggest that the potential biases in case-control studies that we examined tend to result in underestimates of true influenza vaccine effects.

Inactivated influenza vaccines for prevention of community-acquired pneumonia: the limits of using nonspecific outcomes in vaccine effectiveness studies.

Background: One to 4 million cases of community-acquired pneumonia (CAP) occur annually in the United States, resulting in 600,000 hospitalizations and 45,000 deaths. Influenza infection facilitates secondary bacterial infections, and influenza vaccination may prevent CAP directly by preventing influenza pneumonia or indirectly by preventing secondary bacterial CAP. Methods: We investigated how influenza vaccination could affect incidence of CAP using deterministic probability and stochastic simulation models. The models included likely influential factors, including vaccine effectiveness (VE) against influenza, rates of influenza in the unvaccinated, vaccination coverage, and the relative risk (RR) of pneumonia, given influenza infection. To estimate effectiveness of influenza vaccine against CAP, we assumed mean VE against influenza of 55% and vaccine coverage of 38%. Results: Given our baseline parameters, influenza vaccine had a mean effectiveness against CAP of 7% (95% confidence interval = 0–25%). Effectiveness of influenza vaccine against CAP increased as its effectiveness against influenza increased, as RR of pneumonia after influenza infection increased, and as rates of influenza among unvaccinated persons increased. Conclusions: No matter how effective vaccine may be in preventing influenza infection, it is only modestly effective at preventing CAP. Because of the large annual burden of CAP, a vaccine that is only moderately effective in preventing influenza infection has the potential to prevent a substantial number of CAP cases. This modeling approach may be useful for planning influenza vaccine-probe studies and evaluating the effectiveness of other interventions targeted against infections that manifest in nonspecific outcomes.