Tuberculin skin testing of physicians at a midwestern teaching hospital: a 6-year prospective study.

The epidemiology of tuberculin reactivity among physicians practicing in regions of moderate tuberculosis prevalence is unknown. We prospectively assessed the epidemiology of tuberculin skin test (TST) reactivity among physicians in training in St. Louis between 1992 and 1998. Of 1574 physicians who were tested, 267 (17%) had positive TST results. Older age, birth outside of the United States, prior bacille Calmette-Guérin (BCG) vaccination, and practice in the fields of medicine, anesthesiology, or psychiatry were associated with a positive TST result. Among physicians born in the United States, 63 (5.7%) had positive TST results. Among physicians with > or = 2 documented TSTs, 12 had conversion to a positive TST (1.6%; 1.03 conversions per 100 person-years). Physicians in this study had a high rate of tuberculin reactivity, despite a low conversion rate. The relationship between TST conversion and birth outside of the United States and BCG vaccination suggests a booster phenomenon rather than true new TST conversions.

Elevated lactate levels in hospitalized persons with HIV infection.

Lactic acidosis has been described in persons with HIV infection particularly in association with the use of nucleoside reverse transcriptase inhibitors (NRTIs). Little is known about the epidemiology of this problem. We reviewed the records of all HIV-infected adults with elevated lactate levels admitted to Barnes-Jewish hospital from 1996 to 1998. There were 37 patients identified with elevated lactate levels. The annual rate of elevated lactate levels was 22.6, 33.9, and 30.8 per 1,000 admissions in 1996, 1997, and 1998, respectively. The median age of the patients was 40.4 years; median CD4(+) count was 148 cells/mm(3); and the median HIV-1 RNA level was 4,401 copies/ml. The median lactate level was 4.5 mmol/liter (range, 2.2-19 mmol/liter). Twenty-nine patients (78%) had elevated lactate levels at admission. Elevated lactate levels were associated with sepsis (48.7%), pancreatitis (13.5%), liver failure (8.1%), multiorgan failure (8.1%), and other conditions. Five patients had lactic acidosis associated with the use of antiretroviral medications; one patient with unexplained lactic acidosis and four patients with pancreatitis. The mortality rate was 45.9% (17/37). Higher lactate levels were associated with increased mortality. In conclusion, elevated lactate levels were uncommon but not rare in hospitalized patients with HIV infection. Sepsis was the most commonly associated condition and antiretroviral medications were the second most frequently associated factor. There was no significant increase in the annual rate of lactic acidosis during this 3-year period.

Excretion of hepatitis A virus (HAV) in adults: comparison of immunologic and molecular detection methods and relationship between HAV positivity and infectivity in tamarins.

Fecal excretion of hepatitis A virus (HAV) in 18 patients with HAV infection was evaluated by enzyme immunoassay (EIA) to detect viral antigen and by reverse transcription-PCR amplification followed by ethidium bromide staining (PCR-ETBr) or nucleic acid hybridization (PCR-NA) to detect viral genetic material. A gradation of sensitivity was observed in the detection of virus by the three methods. In persons who had detectable virus, serial stool samples were found to be positive by EIA for up to 24 days after the peak elevation of liver enzymes. Viral genetic material could be detected by PCR-ETBr for up to 34 days and by PCR-NA for up to 54 days after the peak elevation of liver enzymes. After intravenous inoculation of tamarins with stool suspensions categorized as highly reactive for HAV (positive by EIA, PCR-ETBr, and PCR-NA), moderately reactive (positive by PCR-ETBr and PCR-NA), or weakly reactive (positive by PCR-NA), only tamarins infected with highly reactive stool suspensions (EIA positive) developed HAV infection. We conclude that positivity of stool specimens for HAV by PCR-ETBr or PCR-NA indicates a lower potential for infectivity, compared to that of EIA-positive stools.

Vancomycin use in a hospital with vancomycin restriction.

We evaluated vancomycin use in a hospital with endemic vancomycin-resistant enterococci and a vancomycin restriction program. Only 68% of vancomycin was prescribed appropriately. Inappropriate use was due primarily to empirical therapy. In the patients with a microbiological diagnosis following empirical therapy, 83% (25/30) had infections due to bacteria sensitive to an appropriate antibiotic other than vancomycin. However, only 60% (15/25) of these patients had their vancomycin orders changed.

Colonization with vancomycin-resistant enterococci in chronic hemodialysis patients.

Vancomycin-resistant enterococcus (VRE) has been identified with increased frequency in dialysis populations, but the risk factors for VRE colonization are not well defined in hemodialysis patients. Patients from a university-affiliated outpatient dialysis center had surveillance stool or rectal cultures for VRE during April 1994 and January 1996. The combined cohort of 168 patients was followed-up for all-cause mortality, subsequent hospitalization, and VRE infection. Demographic and risk factor information, including age, gender, race, diabetes, coronary artery disease (CAD), and human immunodeficiency virus (HIV) infection, were collected on all patients. Sixteen patients had surveillance cultures grow vancomycin-resistant Enterococcus faecium or E faecalis (VREF), and nine additional patients had clinical cultures positive for VREF. The median follow-up time for patients with positive surveillance or clinical cultures for VREF was 421 days versus 423 days for those without VREF. Patients with positive surveillance cultures for VREF had less time on hemodialysis before screening (median = 207 days v 822 days; P < 0.01), and more hospitalization in the year before screening (median = 19 days v 3 days, P < 0.01) compared with those without VREF. Patients with VREF colonization were more likely to develop infection with VREF (25% v 1%, P < 0.01) than those without VREF colonization. However, adjusting for age, diabetes, coronary artery disease, and acquired immune deficiency syndrome (AIDS) using Cox-proportional hazards models, the presence of VREF on screening culture was not associated with increased risk of death (RR = 1.1, P = 0.86). Thus after adjusting for other comorbidities, VREF colonization was not associated with increased mortality. Patients with end-stage renal disease (ESRD) on hemodialysis who are hospitalized are more likely to have VREF, but longer duration on hemodialysis was not associated with presence of this organism. This suggests that VRE transmission occurs predominantly in the inpatient setting.

Hospital-based evaluation of programs to prevent perinatal hepatitis B virus transmission.

OBJECTIVE: To evaluate the frequency of hepatitis B surface antigen (HBsAg) screening of pregnant women in the United States and factors associated with the lack of screening. DESIGN: A random sample of 200 hospitals with 100 or more births per year was surveyed with regard to policy and practices. Each hospital was also asked to provide maternal screening and infant follow-up data for the first 25 infants who were born on or after March 1, 1993. RESULTS: Of 183 participating hospitals, 137 (75%) had maternal HBsAg screening policies, and 102 (56%) had standing orders for HBsAg testing of pregnant women who were admitted without prior screening. Hospitals that were located in states with laws that required maternal HBsAg screening were more likely to have a written screening policy (prevalence ratio [PR], 1.7; 95% confidence interval [CI], 1.2-2.4) and a standing order (PR, 1.7; 95% CI, 1.4-2.2). A lack of screening was related to delivery in hospitals without screening policies (PR, 3.4; 95% CI, 1.3-8.9) or standing orders (PR, 2.8; 95% CI, 1.2-6.2), and to the infant's provider being a family practitioner (PR, 1.7; 95% CI, 1.1-2.7). Among the 3982 infants for whom data were available, 3342 (84%) were born to mothers who had undergone screening for HBsAg. CONCLUSIONS: These findings suggest that hospitals should develop specific policies for HBsAg screening, states should enact laws that require maternal screening, and additional education of health care providers is needed with regard to the screening of all pregnant women for HBsAg.

Enterococci resistant to multiple antimicrobial agents, including vancomycin. Establishment of endemicity in a university medical center.

OBJECTIVES: To determine the distribution of and risk factors for colonization and infection with vancomycin-resistant enterococci; to evaluate the molecular epidemiology of these strains; and to assess the effect of interventions, including 1) strict adherence to infection control procedures and 2) restricted use of vancomycin. DESIGN: Problem identification based on descriptive studies, point-prevalence surveys, and case-control studies and followed by specific interventions and evaluation of the response to these interventions. SETTING: University medical center. PARTICIPANTS: All patients hospitalized between May 1992 and June 1994 (59,196 admissions). MAIN RESULTS: 75 active infections attributed to vancomycin-resistant enterococci were identified. Thirty-one patients (41%) had bloodstream infections and 6 (8%) died. The incidence of active infection was highest in the organ transplantation unit (13.2 infections/1000 admissions). In the point-prevalence studies, vancomycin-resistant enterococci were isolated from 20% of a random sample of hospitalized patients in July, August, and September 1993 (adjusted prevalence, 16.9%). Case-control studies showed significant associations between colonization and infection and 1) receipt of antimicrobial agents, particularly vancomycin, and 2) severity of illness. Although several small case clusters had isolates with identical banding patterns on pulsed field gel electrophoresis, at least 45 different banding patterns were noted among medical center isolates. Interventions took place in November and December 1993. Vancomycin restriction policies resulted in a 59% decrease in intravenous vancomycin use and an 85% decrease in oral vancomycin use. Point-prevalence surveys done in April, May, and June 1994 showed a consistent 20% level of colonization with vancomycin-resistant enterococci strains (adjusted prevalence, 18.7%). No significant changes were seen in rates of vancomycin-resistant enterococci infection. CONCLUSIONS: Vancomycin-resistant enterococci are an important cause of illness and death in the study institution, particularly among organ transplant recipients and other seriously ill persons; they have also become a common intestinal colonizer among hospitalized patients. The diversity of isolates (based on molecular typing studies) suggests that resistant organisms have been introduced from multiple sources. Interventions that effectively lower the overall level of colonization with vancomycin-resistant enterococci must still be identified.

Routine hepatitis B vaccination in a clinic for sexually transmitted diseases.

Patients were assigned to one of two vaccine schedules to assess the feasibility of vaccinating a sexually transmitted disease clinic population against hepatitis B virus. Of 1386 patients entering an inner-city clinic between June and July 1990, 611 (44%) accepted a first dose of vaccine. Twenty-one percent of all susceptible patients received at least two doses of vaccine. Annualizing these findings shows that an ongoing program could prevent 636 hepatitis B virus infections per year. Although a significant proportion of sexually transmitted disease clinic patients can be successfully vaccinated, strategies for preventing hepatitis B virus infections in this high-risk population must consider patient behavior as well as vaccine efficacy.

Impact of the bloodborne pathogens standard on vaccination of healthcare workers with hepatitis B vaccine.

OBJECTIVES: To evaluate the impact of Occupational Safety and Health Administration (OSHA) regulations on the vaccination of healthcare workers (HCWs), to assess interpretation of these regulations, and to evaluate changes in hospital vaccination policies. DESIGN: Between June 1, 1992, and August 15, 1992, a telephone survey was conducted among 150 hospitals selected randomly from participants in the American Hospital Association 1991 annual survey. RESULTS: Of the 150 hospitals, 96 (64%) provided information on hepatitis B vaccination coverage of their employees. Of the 103,419 employees in these hospitals, 77,302 (75%) were eligible to receive the hepatitis B vaccine, and 38,850 (51%) of these were vaccinated completely (had received 3 doses of vaccine). Following issuance of the final regulations, 73% of hospitals reported greater employee acceptance of hepatitis B vaccine, and hospitals were more likely to offer hepatitis B vaccine to maintenance workers, security personnel, dietary staff, and clerical personnel. Seventy-five hospitals (50%) reported conducting postvaccination serologic testing on all hospital employees, 12 (8%) as a result of OSHA regulations. Twenty-three hospitals (16%) reported administering routine booster doses of hepatitis B vaccine at 3, 5, or 7 years. CONCLUSIONS: The new OSHA standard resulted in a greater awareness of risk for HBV infection among HCWs and an increase in the number of HCWs receiving hepatitis B vaccine; however, vaccination coverage remained suboptimal. Postvaccination serologic testing of employees with negligible risk and the routine administration of vaccine booster doses may be diverting resources and preventing comprehensive coverage of high-risk employees.

Enzyme immunoassay for the detection of antibody to hepatitis E virus based on synthetic peptides.

Five synthetic peptides were prepared based on the nucleotide sequence of open reading frames 2 and 3 encoded in the hepatitis E virus (HEV) genome and were used to develop an enzyme immunoassay (EIA) for the detection of anti-HEV activity in sera. Three different approaches were employed to ascertain the optimal preparation of these peptides as an immunodiagnostic reagent, including (1) a mixture of unconjugated peptides, (2) conjugating individual peptides to bovine serum albumin (BSA) followed by mixing each conjugate at various concentrations, and (3) mixing the peptides before conjugation with BSA to create an artificial antigen complex. The third method was superior in discriminating anti-HEV activity in sera previously tested by Western blot (WB). A frequency distribution of optical density values demonstrated that the peptide-based EIA was able to readily discriminate anti-HEV positive sera from sera devoid of anti-HEV activity. To confirm anti-HEV activity a neutralization test was developed using a mixture of 5 unconjugated peptides. With the exception of sera containing high levels of anti-HEV activity, all sera were neutralized greater than 50%. Strong sera required a higher dilution before a 50% neutralization was achieved. The sensitivity of the WB compared to EIA was 89.5% with and overall concordance of 94.8%. The peptide-EIA was used to determine anti-HEV activity in sera collected from various populations worldwide. In six outbreaks of ET-NANB hepatitis in various geographic regions, anti-HEV activity was demonstrated in 78-100% of cases. The peptide-EIA also detected anti-HEV activity in 14 out of 14 follow-up sera obtained 4-6 months after onset of disease and in 2 of 2 of these patients 5 yr after the acute episode. Anti-HEV activity was found in 8.5% of sera obtain from a healthy population residing in an HEV endemic region and 0.5% in two non-endemic regions (P < 0.001). These data demonstrate that a synthetic peptide-based EIA is sensitive for detecting anti-HEV activity in the sera of patients with acute hepatitis E, convalescents, and among healthy individuals.

Risk factors for hepatitis C virus infection among health care personnel in a community hospital.

OBJECTIVE: To determine the prevalence of and risk factors for antibody to the hepatitis C virus in hospital employees. METHODS: Retrospective testing of serum samples obtained from 1677 hospital employees during a prehepatitis B vaccination program in a private teaching community hospital. RESULTS: Twenty-three employees (1.4%) were found to have antibody to hepatitis C virus. The prevalence of antibody to hepatitis C virus was higher in blacks (3.4%) than in whites (1.1%, p = 0.03) and Hispanics (2.6%, p = 0.88). In a logistic regression model, factors significantly associated with antibody to hepatitis C virus seropositivity included antibody to hepatitis B core antigen (p = 0.002), a history of blood transfusion (p = 0.03), and needlestick injuries (p = 0.04). CONCLUSION: Although the prevalence of antibody to hepatitis C virus in health care workers was not high, needlestick injuries were associated with an increased risk for acquiring hepatitis C virus infection.

Delta hepatitis: molecular biology and clinical and epidemiological features.

Hepatitis delta virus, discovered in 1977, requires the help of hepatitis B virus to replicate in hepatocytes and is an important cause of acute, fulminant, and chronic liver disease in many regions of the world. Because of the helper function of hepatitis delta virus, infection with it occurs either as a coinfection with hepatitis B or as a superinfection of a carrier of hepatitis B surface antigen. Although the mechanisms of transmission are similar to those of hepatitis B virus, the patterns of transmission of delta virus vary widely around the world. In regions of the world in which hepatitis delta virus infection is not endemic, the disease is confined to groups at high risk of acquiring hepatitis B infection and high-risk hepatitis B carriers. Because of the propensity of this viral infection to cause fulminant as well as chronic liver disease, continued incursion of hepatitis delta virus into areas of the world where persistent hepatitis B infection is endemic will have serious implications. Prevention depends on the widespread use of hepatitis B vaccine. This review focuses on the molecular biology and the clinical and epidemiologic features of this important viral infection.

Results of screening for tuberculosis in foreign-born persons applying for adjustment of immigration status.

As part of the required screening process of illegal aliens applying for adjustment of status by the Immigration and Naturalization Service, 7,573 persons were evaluated for tuberculous infection by the Denver Department of Health and Hospitals from May 1987 through December 1988. Applicants were screened with tuberculin skin testing, chest radiographs, or both. Review of 6,520 charts that were available found that 4,840 applicants had tuberculin skin tests, of which 2,039 (42 percent) were > or = 10 mm and 1,528 had further evaluation at the Denver Metro Tuberculosis Clinic. Seventy-five percent of the applicants were between the ages of 15 and 34 years, and 91 percent were from Mexico. Evidence of past or current tuberculous infection on chest radiograph was present in 273 (17 percent) and 16 (7 percent) had sputum cultures obtained that identified four new cases of active tuberculosis. Isoniazid preventive therapy (IPT) was recommended to 1,029 applicants, of whom 29 (3 percent) were 35 years of age or older; 716 (70 percent) completed at least six months of treatment. We conclude that there is a high prevalence of tuberculous infection in foreign-born persons applying for adjustment of immigration status, but a low prevalence of clinically apparent tuberculosis. This population is an excellent target for IPT, which can be achieved with good success. Proactive screening and preventive therapy is likely to significantly reduce tuberculosis reactivation and morbidity, prevent secondary infection of contacts, and be cost-effective.

Epitope mapping in proteins of hepatitis E virus.

A series of synthetic peptides derived from proteins encoded by open reading frames 2 and 3 (ORF2 and ORF3) of the hepatitis E virus was used in an enzyme immunoassay to determine the localization of epitopes in these proteins. Five peptides spanning almost the entire ORF3 protein sequence and 12 peptides from the ORF2 protein were synthesized. Serum samples collected from outbreaks in three different regions of the world (Turkmenistan, Kenya, and Mexico) were analyzed by a peptide-based enzyme immunoassay. Primary analysis of the peptides was accomplished with the use of serum samples obtained from Middle Asia. Four of 5 peptides from the ORF3 protein and 4 of 12 peptides from the ORF2 protein specifically reacted with antibody from sera of HEV-infected patients. Peptides representing immunodominant epitopes were used for the analysis of serum samples from outbreaks in Kenya and Mexico. The data indicate that these synthetic peptides may be used to develop a diagnostic test to detect antibody to the hepatitis E virus.

Hepatitis A post-viral encephalitis.

We report a seven-year-old girl who developed a hepatitis A viral infection and encephalitis. The patient developed fever, abdominal pains and jaundice. Five days later she became delirious, combative, and did not respond to verbal commands. Laboratory studies showed elevated liver enzymes and elevated serum immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies to hepatitis A virus. Cerebrospinal fluid contained IgG antibodies to hepatitis A virus but not IgM antibodies. Polymerase chain reaction, which amplifies a portion of the hepatitis A virus genome, did not demonstrate viral nucleic acid in cerebrospinal fluid. These studies suggest that the patient may have suffered from a post-viral hepatitis A encephalitis from which she fully recovered.

Hepatitis C virus infection among patients attending a clinic for sexually transmitted diseases.

OBJECTIVE: To evaluate the association between hepatitis C virus (HCV) infection and sexual behavior in a sexually active population. DESIGN: Cross-sectional study. SETTING: Inner-city clinic for sexually transmitted diseases. SUBJECTS: The study included 1292 patients attending the clinic for care during a 1-month period and having syphilis serologic tests performed. OUTCOME MEASURES: Antibody to HCV (anti-HCV) positivity as defined by a repeatedly-reactive enzyme immunoassay and a positive neutralization enzyme immunoassay (Abbott Laboratories, Chicago, Ill). RESULTS: Of 1292 patients screened for anti-HCV, 99 (7.7%) were positive. Logistic regression analysis found that patients who reported intravenous drug use, were positive for antibody to hepatitis B core antigen, reported a history of a blood transfusion, were black, or reported crack cocaine use were more likely to be anti-HCV-positive. Forty-five percent of patients who were anti-HCV-positive reported intravenous drug use. Sex with an intravenous drug user and a history of gonorrhea and syphilis were associated with anti-HCV positivity in a univariate analysis, but after controlling for confounding variables, no such associations remained. While having multiple sexual partners in the previous 3 months, being homosexual or bisexual, and engaging in receptive anal intercourse were associated with being positive for antibody to hepatitis B core antigen, those behaviors were not associated with anti-HCV positivity. CONCLUSIONS: While these results cannot exclude a role for the sexual transmission of HCV, they do suggest that, in this sexually active population, the sexual transmission of HCV occurs infrequently and that HCV is largely associated with intravenous drug use.

Multistate outbreak of hepatitis A associated with frozen strawberries.

A multistate outbreak of hepatitis A was traced to frozen strawberries processed at a single plant. Among 827 students and 60 teachers at an elementary school in Georgia during a 2-week period, 15 developed hepatitis A. Three months later, among 174 residents and 467 staff in an institution for the developmentally disabled in Montana during a 3-week period, 13 developed hepatitis A. Primary attack rates were 10% in the school and 8% in the institution. Cohort analysis in the school implicated consumption of strawberry shortcake in hepatitis A virus (HAV) infection (relative risk, 7.6; 95% confidence interval, 1.04-55.6). In the institution, such analysis implicated desserts and uncooked strawberries as the most biologically plausible vehicle of HAV transmission. Molecular analysis of HAV from patients in the two outbreaks revealed that the viral genomes were genetically identical and distinct from other known US strains. Contamination of food products before retail distribution is rare but should be considered in investigating common-source outbreaks of hepatitis A.

Nosocomial transmission of hepatitis B virus associated with the use of a spring-loaded finger-stick device.

BACKGROUND AND METHODS: From June 1989 through March 1990, 26 patients, of whom 23 had diabetes, contracted acute hepatitis B virus (HBV) infection in a hospital in California. All 26 patients and one HBV carrier (also a diabetic) had been admitted to a single medical ward during the six months before the case patients became infected with HBV. To determine the source of the infection, we conducted a retrospective cohort study of the 72 patients with diabetes who had been admitted to the ward from January through December 1989 and a case-control study comparing the 3 nondiabetic patients who contracted hepatitis with 20 nondiabetic controls. RESULTS: The retrospective cohort study of all the patients with diabetes who were admitted to the ward during 1989 found that those who underwent capillary blood sampling by finger stick with a spring-loaded lancet device were more likely to contract HBV infection than those who did not have finger sticks (attack rate, 42 percent vs. 0 percent; P = 0.08). In addition, a dose-response relation was observed between the number of finger sticks received and the frequency of hepatitis B (P = 0.002). The case-control study found that all 3 of the nondiabetic patients who contracted hepatitis underwent finger-stick blood sampling with the device, as compared with none of the 20 nondiabetic controls (P = 0.0006). A review of nursing procedures indicated that the platform of the device was not routinely changed after each use; this finding suggested that contamination of the platform by HBV-infected blood was the mechanism of percutaneous transmission of HBV. CONCLUSIONS: Proper use of finger-stick devices as well as strict adherence to universal precautions to avoid contamination by blood are required to decrease the possibility of transmission of blood-borne pathogens among hospitalized patients.

Characterization of risk factors for Helicobacter pylori infection among men attending a sexually transmitted disease clinic: lack of evidence for sexual transmission.

The mechanism of transmission of Helicobacter pylori is unknown. To investigate the role of sexual behavior and demographic factors in the acquisition of H. pylori infection, we evaluated the seroprevalence of antibody to H. pylori in 370 men attending an urban sexually transmitted diseases clinic. Sera from the following three groups were analyzed by enzyme-linked immunosorbent assay for H. pylori-specific immunoglobulin G: 78 human immunodeficiency virus (HIV)-seropositive homosexual men, 102 HIV-seronegative homosexual men, and 190 HIV-seronegative heterosexual men. Overall, the seroprevalence of H. pylori was 100 of 370 men (27%), with rates of 18% in HIV-seropositive homosexual men and 20% in HIV-seronegative homosexual men versus 35% in heterosexual men (P less than 0.005, chi 2 test). By ethnic group, 21 (12%) of 181 Caucasian men, 40 (41%) of 97 black men, and 37 (43%) of 87 Hispanic men were seropositive (P less than 0.001, chi 2 test). Multivariate analysis revealed that race was associated with H. pylori seropositivity independent of HIV status, sexual preference, or age. There was no relationship between H. pylori seropositivity and the number of lifetime sexual partners or previous sexually transmitted diseases. Three HIV-seropositive men with H. pylori immunoglobulin G had essentially identical antibody titers over 8 to 16 months of follow-up. In conclusion, black and Hispanic men have significantly higher H. pylori seroprevalence rates than do Caucasian men, but neither sexual behavior nor HIV infection influences the presence or persistence of H. pylori antibody. Further evaluation of the factors associated with these ethnic differences may lead to a better understanding of H. pylori acquisition and transmission.