SERIOUS MORBIDITY DUE TO ACUTE RESPIRATORY DISEASE ASSOCIATED WITH EPIDEMIC INFLUENZA

Current measures of the health impact of epidemic influenza are focused on analyses of death certificate data which may underestimate the true health effect. Previous investigations of influenza-related morbidity have either lacked virologic confirmation of influenza activity in the community or were not population-based. Community virologic surveillance in Houston has demonstrated that influenza viruses have produced epidemics each year since 1974. This study examined the relation of hospitalized for Acute Respiratory Disease (ARD) to the occurrence of influenza epidemics. Considering only Harris County residents, a total of 13,297 ARD hospital discharge records from hospitals representing 48.4% of Harris County hospital beds were compiled for the period July 1978 through June 1981. Variables collected from each discharge included: age, sex, race, dates of admission and discharge, length of stay, discharge disposition and a maximum of five diagnoses. This three year period included epidemics caused by Influenza A/Brazil (H1N1), Influenza B/Singapore, Influenza A/England (H1N1) and Influenza A/Bangkok (H3N2).^ Correlations of both ARD and pneumonia or influenza hospitalizations with indices of community morbidity (specifically, the weekly frequency of virologically-confirmed influenza virus infections) are consistently strong and suggest that hospitalization data reflect the pattern of influenza activity derived from virologic surveillance.^ While 65 percent of the epidemic period hospital deaths occurred in patients who were 65 years of age or older, fewer than 25 percent of epidemic period ARD hospitalizations occurred in persons of that age group. Over 97 percent of epidemic period hospital deaths were accompanied by a chronic underlying illness, however, 45 percent of ARD hospitalizations during epidemics had no mention of underlying illness. Over 2500 persons, approximately 35 percent of all persons hospitalized during the three epidemics, would have been excluded in an analysis for high risk candidates for influenza prophylaxis.^ These results suggest that examination of hospitalizations for ARD may better define the population-at-risk for serious morbidity associated with epidemic influenza. ^

Characterization of Staphylococcus aureus adhesins important for respiratory tract infection

Staphylococcus aureus is a leading cause of lower respiratory tract infections in both adult and pediatric populations. In the past two decades, reports have described emergent incidence of severe necrotizing pneumonia in previously healthy individuals, frequently caused by antibiotic resistant strains. Additionally, S. aureus remains the most common cause of ventilator-associated pneumonia, contributing morbidity and mortality in intensive care units. As treatment of infection is made more difficult by the resistance to multiple antibiotics including vancomycin, there is a pressing need for novel strategies to prevent and treat S. aureus infections. Targeting essential mechanisms that promote infection such as adhesion, colonization, invasion, evasion of immune system and signaling may lead to inhibition of pathogenic surge. Staphylococcal adhesins of the MSCRAMM family (microbial surface components recognizing adherent matrix molecules) represent viable targets for such investigations. Understanding the molecular mechanism of binding is the first step toward the development of such therapies. Analysis of bacterial strains isolated from patients with staphylococcal pneumonia show increased expression of protein A, SdrD, SdrC and ClfB, cell surface proteins members of the MSCRAMM family. In this study the interaction of these MSCRAMMs with candidate ligands has been examined. We found that SdrD mediates S. aureus adherence to the lung epithelial cell line A549. Consistently, bacteria expressing SdrD have increased persistence in the lungs of infected mice after bronchoalveolar lavage in comparison with bacteria lacking this protein. Inhibition studies revealed that bacterial attachment can be abolished using neutralizing antibodies against SdrD. Using phage display, neurexin β isoforms were identified as SdrC binding partners. Previous reports postulated that MSCRAMMS bind their ligands by a 'dock, lock and latch' mechanism of interaction. Our data suggested that ClfB, an MSCRAMM responsible for nasal colonization, binds cytokeratin 10 by a 'dock and lock' variant of this model, in which the 'latching' event is not necessary. In summary, we have characterized aspects of molecular interaction between several MSCRAMMS and host components. We hope that continued delineation of these interactions will lead to identification of novel therapeutic targets or preventive strategies against S. aureus infections. ^

Clinical and economic outcomes of serious postoperative infections following resection of common respiratory and gastrointestinal solid tumors

Unlike infections occurring during periods of chemotherapy-induced neutropenia, postoperative infections in patients with solid malignancy remain largely understudied. The purpose of this population-based study was to evaluate the clinical and economic burden, as well as the relationship of hospital surgical volume and outcomes associated with serious postoperative infection (SPI) – i.e., bacteremia/sepsis, pneumonia, and wound infection – following resection of common solid tumors.^ From the Texas Discharge Data Research File, we identified all Texas residents who underwent resection of cancer of the lung, esophagus, stomach, pancreas, colon, or rectum between 2002 and 2006. From their billing records, we identified ICD-9 codes indicating SPI and also subsequent SPI-related readmissions occurring within 30 days of surgery. Random-effects logistic regression was used to calculate the impact of SPI on mortality, as well as the association between surgical volume and SPI, adjusting for case-mix, hospital characteristics, and clustering of multiple surgical admissions within the same patient and patients within the same hospital. Excess bed days and costs were calculated by subtracting values for patients without infections from those with infections computed using multilevel mixed-effects generalized linear model by fitting a gamma distribution to the data using log link.^ Serious postoperative infection occurred following 9.4% of the 37,582 eligible tumor resections and was independently associated with an 11-fold increase in the odds of in-hospital mortality (95% Confidence Interval [95% CI], 6.7-18.5, P < 0.001). Patients with SPI required 6.3 additional hospital days (95% CI, 6.1 - 6.5) at an incremental cost of $16,396 (95% CI, $15,927–$16,875). There was a significant trend toward lower overall rates of SPI with higher surgical volume (P=0.037). ^ Due to the substantial morbidity, mortality, and excess costs associated with SPI following solid tumor resections and given that, under current reimbursement practices, most of this heavy burden is borne by acute care providers, it is imperative for hospitals to identify more effective prophylactic measures, so that these potentially preventable infections and their associated expenditures can be averted. Additional volume-outcomes research is also needed to identify infection prevention processes that can be transferred from higher- to lower-volume providers.^

SEVERITY OF IRON DEFICIENCY ANEMIA AND ITS RELATIONSHIP TO GROWTH AND MORBIDITY IN A POPULATION OF PRE-SCHOOLERS IN RURAL GUATEMALA (IRON DEFICIENCY, MORBIDITY, GROWTH)

The objectives of this study were to determine the nature of the relationship between severity of iron deficiency anemia, response to iron treatment, respiratory and gastrointestinal illness and weight change. Seventy-five pre-school children from rural Guatemala received daily oral iron therapy for an eleven week period, and were classified into one of three groups having different degrees of iron deficiency anemia. Anthropometric and biochemical data were collected prior and after iron treatment; morbidity data were collected throughout the period of treatment. The outcome variables were percentage weight change, percentage of total days ill with any type of symptom, percentage of total days ill with gastrointestinal symptoms, percentage of total days ill with respiratory symptoms, percentage of total days ill with combination syndrome symptoms. Age, sex and socio-economic status, were independent of any of the independent or outcome variables used. On the other hand, the level of hemoglobin covaried with the height of the children, the smallest children were the most severely anemic. The relationships between hemoglobin levels and weight change, frequency of morbidity (gastrointestinal, respiratory and combination syndrome) and total number of days ill with any symptomatology were investigated. No statistical significance was found in these analyses except when contrasting children with normal hemoglobin levels to iron deficient children, where the findings indicated the normal children experienced more gastrointestinal morbidity. The same relationship were again analyzed but including delta hemoglobin as covariate in the analysis, this latter one was found to be significant at 7% when the percentage of days ill from gastrointestinal morbidity was tested against the hemoglobin groups. The relationship found indicates that, all other covariates accounted for, the percentage of days ill from gastrointestinal morbidity will decrease approximately 1% for each 1% increase in delta of hemoglobin. ^