Biomedical subjects
Publications and source records attributed to W R Jarvis.
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Age-related changes in human cell-specific cytokine responses to acute illness have not been well examined. We therefore evaluated age-related differences in T, B and natural killer (NK) peripheral blood lymphocyte cytokine responses of 309 acutely ill hospitalized people in Malawi, Africa, < 1 month-61 years of age. We used four-colour flow cytometry and performed Wilcoxon rank sum and Kruskal-Wallis tests, Pearson (rp) and Spearman (rs) correlations, and linear and logistic regression analyses to control for human immunodeficiency virus infection (HIV) status, the percentages of lymphocytes expressing CD4, and the nature of the acute infection. The percentages of CD8- and CD8+ T cells producing induced IL-8 decreased with age (rs = -0.44 and -0.53). The percentages of T cells producing TNF-alpha were higher, and the percentages producing IL-10 were lower, in those > or =13 than those < 13 years old (medians: 17.7 versus 10.5 and 1.4 versus 3.0, respectively). The percentages of CD8- T cells producing IFN-gamma were higher and stable in those > or =1 year old compared to infants (medians: 23.5 versus 10.4); the percentages of NK producing IFN-gamma were higher post-infancy and then declined to relatively low levels with increasing age. The percentages of T cells producing IL-2 were highest in those 5- <31 years old (median 5.6) and lowest in those > or =31 years old (median 1.9). The ratios of the percentages of T cells producing IL-4 to those producing IL-8 and to those producing IL-10 both increased with age. These data suggest that innate immunity, represented by NK IFN-gamma production, dominates in early life. A number of shifts occur after infancy and before adolescence, including a proinflammatory shift from IL-8 to TNF-gamma and a type 2 shift from IL-10 to IL-4 dominance. These findings suggest distinct age-related differences in the human response to acute illness and may be useful in directing future efforts at immunomodulatory therapies.
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To date, only 6 sporadic Microbacterium species (formerly coryneform Centers for Disease Control and Prevention [CDC] groups A-4 and A-5) infections have been reported. The source, mode of transmission, morbidity, mortality, and potential for nosocomial transmission of Microbacterium species remain unknown. From 26 July through 14 August 1997, 8 episodes of coryneform CDC group A-5 symptomatic bacteremia occurred in 6 patients on the oncology ward at the Maine Medical Center. One patient died. All isolates were identified at CDC as Microbacterium species and had identical DNA banding patterns by pulsed-field gel electrophoresis. To assess risk factors for Microbacterium species infection, a retrospective cohort study was conducted. The presence of a central venous catheter was the strongest risk factor (6/6 vs. 22/48; relative risk, 3.2; P<.0001). This outbreak demonstrates significant Microbacterium species-associated morbidity and mortality in immunocompromised populations and confirms the potential for epidemic nosocomial transmission.
From November 1996 through March 1997, presumptive active pulmonary tuberculosis (TB) was detected in 44 health care workers (HCWs) at a university hospital in Lima, Peru. To further assess the magnitude of the outbreak and determine risk factors for occupational Mycobacterium tuberculosis transmission, we identified HCWs in whom active pulmonary TB was diagnosed from January 1994 through January 1998, calculated rates by year and hospital work area, and conducted a tuberculin skin test (TST) survey. Thirty-six HCWs had confirmed active pulmonary TB. The rate of TB was significantly higher among the 171 HCWs employed in the laboratory than among HCWs employed in all other areas. In multivariate analysis, the only independent risk factor for HCW M. tuberculosis infection in HWCs employed in the laboratory was the use of common staff areas. Very high rates of active pulmonary TB were detected among HCWs at this hospital, and occupational acquisition in the laboratory was associated with HCW-to-HCW transmission.
To assess risk factors for development of candidal blood stream infections (CBSIs), a prospective cohort study was performed at 6 sites that involved all patients admitted to the surgical intensive care unit (SICU) for >48 h over a 2-year period. Among 4276 such patients, 42 CBSIs occurred (9.82 CBSIs per 1000 admissions). The overall incidence was 0.98 CBSIs per 1000 patient days and 1.42 per 1000 SICU days with a central venous catheter in place. In multivariate analysis, factors independently associated with increased risk of CBSI included prior surgery (relative risk [RR], 7.3), acute renal failure (RR, 4.2), receipt of parenteral nutrition (RR, 3.6), and, for patients who had undergone surgery, presence of a triple lumen catheter (RR, 5.4). Receipt of an antifungal agent was associated with decreased risk (RR, 0.3). Prospective clinical studies are needed to identify which antifungal agents are most protective and which high-risk patients will benefit from antifungal prophylaxis.
BACKGROUND: In a one month period, 10 Serratia liquefaciens bloodstream infections and 6 pyrogenic reactions occurred in outpatients at a hemodialysis center. METHODS: We performed a cohort study of all hemodialysis sessions on days that staff members reported S. liquefaciens bloodstream infections or pyrogenic reactions. We reviewed procedures and cultured samples of water, medications, soaps, and hand lotions and swabs from the hands of personnel. RESULTS: We analyzed 208 sessions involving 48 patients. In 12 sessions, patients had S. liquefaciens bloodstream infections, and in 8, patients had pyrogenic reactions without bloodstream infection. Sessions with infections or reactions were associated with higher median doses of epoetin alfa than the 188 other sessions (6500 vs. 4000 U, P=0.03) and were more common during afternoon or evening shifts than morning shifts (P=0.03). Sessions with infections or reactions were associated with doses of epoetin alfa of more than 4000 U (multivariate odds ratio, 4.0; 95 percent confidence interval, 1.3 to 12.3). A review of procedures revealed that preservative-free, single-use vials of epoetin alfa were punctured multiple times, and residual epoetin alfa from multiple vials was pooled and administered to patients. S. liquefaciens was isolated from pooled epoetin alfa, empty vials of epoetin alfa that had been pooled, antibacterial soap, and hand lotion. All the isolates were identical by pulsed-field gel electrophoresis. After the practice of pooling epoetin alfa was discontinued and the contaminated soap and lotion were replaced, no further S. liquefaciens bloodstream infections or pyrogenic reactions occurred at this hemodialysis facility. CONCLUSIONS: Puncturing single-use vials multiple times and pooling preservative-free epoetin alfa caused this outbreak of bloodstream infections in a hemodialysis unit. To prevent similar outbreaks, medical personnel should follow the manufacturer's guidelines for the use of preservative-free medications.
BACKGROUND: In late 1996, vancomycin-resistant enterococci were first detected in the Siouxland region of Iowa, Nebraska, and South Dakota. A task force was created, and in 1997 the assistance of the Centers for Disease Control and Prevention was sought in assessing the prevalence of vancomycin-resistant enterococci in the region's facilities and implementing recommendations for screening, infection control, and education at all 32 health care facilities in the region. METHODS: The infection-control intervention was evaluated in October 1998 and October 1999. We performed point-prevalence surveys, conducted a case-control study of gastrointestinal colonization with vancomycin-resistant enterococci, and compared infection-control practices and screening policies for vancomycin-resistant enterococci at the acute care and long-term care facilities in the Siouxland region. RESULTS: Perianal-swab samples were obtained from 1954 of 2196 eligible patients (89 percent) in 1998 and 1820 of 2049 eligible patients (89 percent) in 1999. The overall prevalence of vancomycin-resistant enterococci at 30 facilities that participated in all three years of the study decreased from 2.2 percent in 1997 to 1.4 percent in 1998 and to 0.5 percent in 1999 (P<0.001 by chi-square test for trend). The number of facilities that had had at least one patient with vancomycin-resistant enterococci declined from 15 in 1997 to 10 in 1998 to only 5 in 1999. At both acute care and long-term care facilities, the risk factors for colonization with vancomycin-resistant enterococci were prior hospitalization and treatment with antimicrobial agents. Most of the long-term care facilities screened for vancomycin-resistant enterococci (26 of 28 in 1998 [93 percent] and 23 of 25 in 1999 [92 percent]) and had infection-control policies to prevent the transmission of vancomycin-resistant enterococci (22 of 25 [88 percent] in 1999). All four acute care facilities had screening and infection-control policies for vancomycin-resistant enterococci in 1998 and 1999. CONCLUSIONS: An active infection-control intervention, which includes the obtaining of surveillance cultures and the isolation of infected patients, can reduce or eliminate the transmission of vancomycin-resistant enterococci in the health care facilities of a region.
The balance between pro- and antiinflammatory cytokines may be important in malaria presentation and outcome. Malaria tends to be more severe in children than in adults, presumably because partial immunity develops with age. However, the full nature of, and age-related differences in, anti-malarial immunity are unknown. We compared: (1) serum and cell-specific cytokines of patients with acute malaria to those of patients with other acute illnesses and to those of healthy adults and (2) the cytokine responses of parasitemic children and parasitemic adults. Flow cytometry was done on the peripheral blood mononuclear cells of 148 hospitalized children, 161 febrile hospitalized adults, and 20 healthy adults in Malawi, Africa, a malaria-endemic country. Serum cytokines were also assessed for 80 of these patients. Thirty-eight participants were parasitemic with Plasmodium falciparum. Serum interleukin (IL)-10 (an antiinflammatory, immunoregulatory, and type 2 cytokine) levels were higher in malaria patients than in other patients (medians 502 pg/mL vs 16 pg/mL, P = 0.002), and the percentages of various lymphocyte populations making IL-6 (a proinflammatory, type 2 cytokine regulating iron distribution) were lower in malaria patients than in other patients (e.g., for spontaneous production by children's CD8(+) T cells: medians 1.4% vs 33.1%, P = 0.004). For adult patients, the percentages of lymphocytes spontaneously making IL-4 (a type 2 cytokine) were significantly lower in those with malaria than in those without malaria (medians 0.9% vs 2.1%, P = 0.005). The percentages of monocytes spontaneously making IL-8 (a chemotactic, proinflammatory chemokine) were higher in parasitemic children than in parasitemic adults (medians 5.8% vs 1.7%, P = 0.003). A number of cellular proinflammatory, type 1 parameters were significantly higher in all children (with or without malaria) than in all adults; these included the percentages of various lymphocyte populations making IL-6, both IL-6 and interferon-gamma, or IL-8. These data support the importance of IL-10 in malaria parasitemia. Given the lack of an IL-4 (type 2) response, IL-10's primary role may be immunoregulatory rather than type 2 in nature. In this study, the immune response to malaria was more proinflammatory in children than in adults. This difference, if corroborated by other studies, could be related to malaria's greater severity in children.
OBJECTIVES: Published data suggest that Streptococcus pneumoniae, non-typhi Salmonella species, and Mycobacterium tuberculosis are the predominant causes of bloodstream infection (BSI) in hospitalized populations in sub-Saharan Africa. This study was conducted during the wet season to ascertain the etiology and prevalence of BSI among febrile inpatients in a hospital where the dry season BSI profile in a similar study population had already been documented. METHODS: In the period from March to May 1998, consecutive febrile (> or = 37.5 degrees C) adult (> or = 14 y) patients presenting to a Malawi hospital were enrolled after providing informed consent. Following clinical evaluation, blood was drawn for culture (bacteria, mycobacteria, and fungi), human immunodeficiency virus (HIV) testing, and malaria smears. RESULTS: Of 238 enrolled patients, 173 (73%) were HIV-positive and 67 (28%) had BSI. The predominant wet season BSI pathogens were non-typhi Salmonella species (41%), M. tuberculosis (19%), and Cryptococcus neoformans (9%) (cf. the predominant dry season pathogen was S. pneumoniae). Mycobacteremia was more likely in HIV-positive than in HIV-negative patients (13/173 vs. 0/65; P < 0.05). A logistic regression model yielded clinical predictors of BSI that included chronic fever, oral candidiasis, or acute diarrhea. CONCLUSION: Pathogens causing BSI in febrile inpatients in a Malawi teaching hospital vary by season. Season- and country-specific studies, such as this one, provide data that may facilitate empirical therapy of febrile illnesses whose etiologies vary by season.
Worldwide, over 40% of children have iron deficiency anaemia, frequently associated with infections. Certain cytokines are involved in both immune activation/response to infection and iron transport/metabolism. We therefore assessed the relations among iron deficiency, cytokine production and lymphocyte activation markers in 142 hospitalized Malawian children. We examined peripheral blood lymphocyte antigens/cytokine production using four- colour flow cytometry and serum transferrin receptor (TfR) levels, an inverse measure of iron status unaffected by acute illness or infection, with an enzyme-linked immunosorbent assay. Wilcoxon rank sum tests and logistic regression analyses (LRA) were performed. Iron deficiency (TfR > or = 10 microg/ml) versus TfR < 10 microg/ml, was associated with higher percentages of lymphocytes producing: (a) induced or spontaneous IL-6 (medians: induced, 15.9% for iron-deficient children versus 8.8% for iron-replete children, P = 0.002; spontaneous, 24.4% versus 13.0%, P < 0.001) and (b) induced IFN-gamma (medians:18.4% versus 12.4%, P = 0.006). The percentages of CD8(+) T cells spontaneously producing IL-6 and of all lymphocytes producing induced TNF-alpha and IFN-gamma in the same cell had the strongest relationships to iron deficiency (b = + 0.0211, P = 0.005 and b = + 0.1158, P = 0.012, respectively, LRA) and were also positively related to the co-expression of the T cell activation markers HLA DR and CD38. Severe iron deficiency (TfR > or = 30 microg/ml) was associated with the percentage of lymphocytes producing induced IL-4 (medians: 0.5% versus 1.6%, P < 0.010). The cytokine patterns associated with iron deficiency in our study would preserve iron stores but also preferentially retain the activation capabilities of T cells, albeit not necessarily other immune cells, until a critical level of iron depletion is reached.
BACKGROUND: Vancomycin-resistant enterococci (VRE) are increasing in prevalence at many institutions, and are often reported in dialysis patients. We studied the prevalence of and risk factors for VRE at seven outpatient hemodialysis centers (three in Baltimore, MD, USA, and four in Richmond, VA, USA). METHODS: Rectal or stool cultures were performed on consenting hemodialysis patients during December 1997 to April 1998. Consenting patients were recultured during May to July 1998 (median 120 days later). Clinical and laboratory data and functional status (1 to 10 scale: 1, normal function; 9, home attendant, not totally disabled; 10, disabled, living at home) were recorded. RESULTS: Of 478 cultures performed, 20 (4.2%) were positive for VRE. Among the seven centers, the prevalence of VRE-positive cultures varied from 1.0 to 7.9%. Independently significant risk factors for a VRE-positive culture were a functional score of 9 to 10 (odds ratio 6.9, P < 0.001), antimicrobial receipt within 90 days before culture (odds ratio 6.1, P < 0.001), and a history of injection drug use (odds ratio 5.4, P = 0.004). CONCLUSIONS: VRE-colonized patients were present at all seven participating centers, suggesting that careful infection-control precautions should be used at all centers to limit transmission. In agreement with previous studies, VRE colonization was more frequent in patients who had received antimicrobial agents recently, underscoring the importance of judicious antimicrobial use in limiting selection for this potential pathogen.
OBJECTIVES: To determine the frequency of and risk factors for colonization of skilled-care unit residents by several antimicrobial-resistant bacterial species, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus (VRE), or extended-spectrum-beta-lactamase-producing (ESBL-producing) (ceftazidime resistant) Klebsiella pneumoniae or Escherichia coli. DESIGN: Point-prevalence survey and medical record review. SETTING: The skilled-care units in one healthcare facility. PARTICIPANTS: 120 skilled-care unit residents. MEASUREMENTS: Colonization by each of the four antimicrobial-resistant pathogens during a point-prevalence survey, using rectal, nasal, gastrostomy-tube site, wound, and axillary cultures, June 1-3, 1998; 117 (98%) had at least one swab collected and 114 (95%) had a rectal swab collected. Demographic and clinical characteristics were evaluated as risk factors for colonization. All isolates were strain typed by pulsed-field gel electrophoresis of total genomic deoxyribonucleic acid. RESULTS: Of 117 participants, 50 (43%) were culture positive for > or =1 antimicrobial-resistant pathogen: MRSA (24%), ESBL-producing K. pneumoniae (18%) or E. coli (15%), and VRE (3.5%). Of 50 residents culture positive for any of these four antimicrobial-resistant species, 13 (26%) were colonized by more than one resistant species; only three (6%) were on contact-isolation precautions at the time of the prevalence survey. Risk factors for colonization varied by pathogen: total dependence on healthcare workers (HCWs) for activities of daily living (ADLs) and antimicrobial receipt for MRSA, total dependence on HCWs for ADLs for ESBL-producing K. pneumoniae, and antimicrobial receipt for VRE. No significant risk factors were identified for colonization by ESBL-producing E. coli. Among colonized patients, there was a limited number of strain types for MRSA (24 patients, 4 strain types) and ESBL-producing K. pneumoniae (21 patients, 3 strain types), and a high proportion of unique strain types for VRE (4 patients, 4 strain types) and FSBL-producing E. coli (17 patients, 10 strain types). CONCLUSION: A large unrecognized reservoir of skilled-care-unit residents was colonized by antimicrobial-resistant pathogens, and co-colonization by more than one target species was common. To prevent transmission of antimicrobial-resistant pathogens in long-term care facilities in which residents have high rates of colonization, infection-control strategies may need to be modified. Potential modifications include enhanced infection-control strategies, such as universal gloving for all or high-risk residents, or screening of high-risk residents, such as those with total dependence on HCWs for ADLs or recent antimicrobial receipt, and initiation of contact-isolation precautions for colonized residents.
BACKGROUND: The transfusion of blood components contaminated with bacteria may have serious clinical consequences, but few data are available on the incidence of these events. A national effort to assess the frequency of blood component bacterial contamination associated with transfusion reaction (the BaCon Study) was initiated to better estimate their occurrence. STUDY DESIGN AND METHODS: Standard reporting criteria, data collection forms, and a standardized reporting protocol were developed in collaboration with the American Red Cross, AABB, and the Department of Defense. Episodes reported to the BaCon Study were compared with those reported to the FDA's national reporting systems to estimate the extent to which all serious reactions associated with bacterial contamination were captured. RESULTS: During the first 2 years, 38 episodes meeting study criteria were reported; 21 were laboratory-confirmed. The estimated proportion of episodes reported to the BaCon Study (i.e., completeness of coverage) was lower than that reported to the FDA during the same period (0.33 vs. 0.68), but the positive predictive value was higher (0.66 vs.0.28). CONCLUSION: Despite the complexity of obtaining reports from a large number of United States hospitals and transfusion centers, the feasibility and usefulness of the BaCon Study were shown. This study was the only national study in the United States to monitor adverse clinical events associated with bacterial contamination of blood components. By building on hospital-based reporting of transfusion-related adverse events, the BaCon Study serves as a model for the study of other complications associated with blood and blood components.
BACKGROUND: Bacterial contamination of blood components can result in transfusion-transmitted infection, but the risk is not established. STUDY DESIGN AND METHODS: Suspected cases of transfusion-transmitted bacteremia were reported to the CDC by participating blood collection facilities and transfusion services affiliated with the American Red Cross, AABB, or Department of Defense blood programs from 1998 through 2000. A case was defined as any transfusion reaction meeting clinical criteria in which the same organism species was cultured from a blood component and from recipient blood, with the organism pair confirmed as identical by molecular typing. RESULTS: There were 34 cases and 9 deaths. The rate of transfusion-transmitted bacteremia (in events/million units) was 9.98 for single-donor platelets, 10.64 for pooled platelets, and 0.21 for RBC units; for fatal reactions, the rates were 1.94, 2.22, and 0.13, respectively. Patients at greatest risk for death received components containing gram-negative organisms (OR, 7.5; 95% CI, 1.3-64.2; p = 0.009). CONCLUSION: Bacterial contamination of blood is an important cause of transfusion-transmitted infection; infection risk from platelet transfusion is higher compared with that from RBCs, and, overall, the risk of infection from bacterial contamination now may exceed that from viral agents. Recipients of components containing gram-negative organisms are at highest risk for transfusion-related death. The results of this study may help direct efforts to improve transfusion-related patient safety.
Vascular access infections are a major cause of morbidity and mortality in hemodialysis patients, and the use of antimicrobials to treat such infections contributes to the emergence and spread of antimicrobial-resistant bacteria. To determine the incidence of and risk factors for vascular access infections, we studied hemodialysis patients at 7 outpatient dialysis centers (4 in Richmond, VA, and 3 in Baltimore, MD) during December 1997 to July 1998. Vascular access infections were defined as local signs (pus or redness) at the vascular access site or a positive blood culture with no known source other than the vascular access; and hospitalization or receipt of an intravenous (IV) antimicrobial. A total of 796 patients were followed for 4,134 patient-months. The vascular access infection rate was 3.5/100 patient-months, ie, patients had a 3.5% risk of infection each month. Independent risk factors were the specific dialysis unit where the patient was treated (relative hazard varying from 1.0 to 4.1 among the 7 centers), catheter access (relative hazard, 2.1 v implanted access), albumin level (relative hazard, 2.4 for lowest v highest quartile), urea reduction ratio (relative hazard, 2.2 for lowest v highest quartile), and hospitalizations during the previous 90 days (relative hazard, 4.9 for >/=6 v zero hospitalizations). These data confirm that vascular access infections are common in hemodialysis patients and that infection rates differ substantially among different centers. Catheter use should be minimized to reduce these infections. Additionally, the possibility that improved serum albumin and urea reduction ratio could reduce vascular access infections should be evaluated.
BACKGROUND: In April 1997, vancomycin-resistant enterococci (VRE) emerged in several health care facilities in the Siouxland region and a VRE Task Force was formed. From 1997 through 1999, an evaluation of VRE prevalence at 30 facilities was performed. METHODS: In 1999, we conducted a survey and focus groups of health care workers to address initial reactions to VRE, feasibility of the Task Force recommendations, and lessons learned. RESULTS: Personnel at 29 (97%) facilities surveyed completed the questionnaire, and 15 health care workers from 11 facilities participated in 5 focus groups. The outcomes of expanded education and improved awareness of VRE for patients and health care workers were ranked the No. 1 priority overall and by long-term care facility personnel. Respondents agreed that Task Force recommendation adherence had significantly improved infection control (83%) and that the Task Force was an appropriate mechanism to coordinate infection control efforts (90%). Focus groups commented that it was most difficult to educate family members about VRE; they expressed concern about variation between VRE policies, especially between acute care and long-term care facilities, and about the quality of life of isolated patients. CONCLUSIONS: Our data illustrate that this intervention has been far-reaching and include the development of a health care infrastructure that may be used as a model to address additional health care issues (eg, emerging pathogens or biological threats).