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RATIONALE: The goal for tuberculosis (TB) elimination in the United States is a TB disease incidence of less than 1 per million U.S. population by 2010, which requires that the latent TB infection (LTBI) prevalence be less than 1% and decreasing. OBJECTIVES: To estimate the prevalence of LTBI in the U.S. population. METHODS AND MEASUREMENTS: Interviews and medical examinations, including tuberculin skin testing (TST), of 7,386 individuals were conducted in 1999-2000 as part of the National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of the civilian, noninstitutionalized U.S. population. LTBI was defined as a TST measurement of >/=10 mm. Associations of age, race/ethnicity, sex, poverty, and birthplace were assessed. Results among the 24- to 74-year-old subgroup were compared with NHANES 1971-1972 data. MEASUREMENTS AND MAIN RESULTS: Estimated LTBI prevalence was 4.2%; an estimated 11,213,000 individuals had LTBI. Among 25- to 74-year-olds, prevalence decreased from 14.3% in 1971-1972 to 5.7% in 1999-2000. Higher prevalences were seen in the foreign born (18.7%), non-Hispanic blacks/African Americans (7.0%), Mexican Americans (9.4%), and individuals living in poverty (6.1%). A total of 63% of LTBI was among the foreign born. Among the U.S. born, after adjusting for confounding factors, LTBI was associated with non-Hispanic African-American race/ethnicity, Mexican American ethnicity, and poverty. A total of 25.5% of persons with LTBI had been previously diagnosed as having LTBI or TB, and only 13.2% had been prescribed treatment. CONCLUSIONS: In addition to basic TB control measures, elimination strategies should include targeted evaluation and treatment of individuals in high-prevalence groups, as well as enhanced support for global TB prevention and control. [ABSTRACT FROM AUTHOR]

Background: Patient-specific risk factors for acquisition of vancomycin-resistant enterococci (VRE) among hospitalized patients are becoming well defined. However, few studies have reported data on the institutional risk factors, including rates of antimicrobial use, that predict rates of VRE. Identifying modifiable institutional factors can advance quality-improvement efforts to minimize hospital-acquired infections with VRE.Objective: To determine the independent importance of any association between antimicrobial use and risk factors for nosocomial infection on rates of VRE in intensive care units (ICUs).Design: Prospective ecologic study.Setting: 126 adult ICUs from 60 U.S. hospitals from January 1996 through July 1999.Patients: All patients admitted to participating ICUs.Measurements: Monthly use of antimicrobial agents (defined daily doses per 1000 patient-days), nosocomial infection rates, and susceptibilities of all tested enterococci isolated from clinical cultures.Results: Prevalence of VRE (median, 10%; range, 0% to 59%) varied by type of ICU and by teaching status and size of the hospital. Prevalence of VRE was strongly associated with VRE prevalence among inpatient non-ICU areas and outpatient areas in the hospital, ventilator-days per 1000 patient-days, and rate of parenteral vancomycin use. In a weighted linear regression model controlling for type of ICU and rates of VRE among non-ICU inpatient areas, rates of vancomycin use (P < 0.001) and third-generation cephalosporin use (P = 0.02) were independently associated with VRE prevalence.Conclusions: Higher rates of vancomycin or third-generation cephalosporin use were associated with increased prevalence of VRE, independent of other ICU characteristics and the endemic VRE prevalence elsewhere in the hospital. Decreasing the use rates of these antimicrobial agents could reduce rates of VRE in ICUs. [ABSTRACT FROM AUTHOR]

Between 1993 and 1999, we monitored the efficacy of sulfadoxine-pyrimethamine in 1175 children aged <24 months receiving 2789 treatments for falciparum malaria in western Kenya using a widely deployed age-based dose regimen: infants, 125 plus 6.25 mg (sulfadoxine plus pyrimethamine); children aged 12 to 23 months; 250 plus 12.5 mg. Cumulative treatment failure by day 7, defined as early clinical failure by day 3 or presence of parasitemia on day 7, increased from 18% in 1993 to 1994 to 22% in 1997 to 1998 (P-trend test = 0.20). Based on body weight, the median dose received was 20 plus 1.00 mg/kg, and 73% of the treatments were given at lower than the recommended target dose of 25 plus 1.25 mg/kg. Underdosing accounted for 26% of cumulative treatment failures. After the dose was increased in 1998 (median, 36 plus 1.8 mg/kg), only 4.2% of patients received less than 25 plus 1.25 mg/kg and there was no association with treatment failure. However, the proportion of cumulative treatment failure continued to increase to 27% by 1999 (P-trend test = 0.03). These results raise concern about the longevity of sulfadoxine-pyrimethamine in these settings. Underdosing may have contributed to the rate at which sulfadoxine-pyrimethamine resistance developed in this area. Treatment guidelines should ensure that adequate doses are given from the initial deployment of antimalarials onward.

This study retrospectively studied amendable determinants of sulfadoxine-pyrimethamine (SP) efficacy involving 2869 treatments among 1072 Kenyan children <5 years old who had uncomplicated malaria. The dose was based on age: one-quarter tablet was given to infants <1 year old, one-half tablet was given to 1-3-year-old children, and a full tablet was given to 4-year-old children. Only 23.5% received the internationally recommended target dose of 25/1.25 mg of SP per kg of body weight. SP intake in the previous 15-35 days (adjusted relative risk, 1.67; 95% confidence interval, 1.35-2.07) and low SP dose (<27.5/1.375 mg/kg) (adjusted relative risk, 1.58; 95% confidence interval, 1.17-2.13) explained 38% of parasitological treatment failures by day 7. Patients with recent SP intake are likely to have recrudescent infections and may need close follow-up if treated with SP or alternative treatment. Applying our weight-for-age data to 31 existing age-based SP dose recommendations predicted that 22 of them would result in underdosing of >25% of children <5 years. Many age-based dose recommendations need urgent revision, because SP is increasingly used as first-line treatment in sub-Saharan Africa.

Polychlorinated biphenyls (PCBs) remain public health concerns because of their persistence in the environment and their potential health impact. We linked data from three mixed cross-sectional/longitudinal surveys of Michigan anglers conducted by the Michigan Department of Public Health in 1973-1974, 1979-1982, and 1989-1993 to examine the association between sport-caught fish consumption and serum PCBs. The reported weight of fish consumed declined over the three surveys (median 40, 38, and 31 lb/yr). Serum Aroclor 1260 levels were 2-3 times higher in fish-eaters than in nonfish-eaters in all three surveys in both men and women. In nonfish-eaters, serum PCB levels rose between 1973-1974 and 1979-1982 [adjusted change = 0.30 log(ppb), p = 0.01] and then declined between 1979-1982 and 1989-1993 [adjusted change = -0.16 log(ppb), p = 0.002]. Among fish-eaters, serum PCB levels also rose between 1973-1974 and 1979-1982 [adjusted change = 0.45 log(ppb), p < 0.001] but were unchanged between 1979-1982 and 1989-1993 [adjusted change = -0.09 log(ppb), p = 0.14]. Predictors of serum PCB levels included annual fish consumption, gender, and age. We conclude that background human serum levels of Aroclor 1260 had declined by 1989-1993 from earlier peak levels. Among consumers of sport-caught Great Lake fish, serum PCB levels did not significantly decrease, probably due to continued exposure and the long half-life of PCB.

Introduction: We have reported that men's lifetime sport-caught Great Lakes fish consumption was associated with lifetime prevalence of conception delay or failure. Those cross-sectional data were based on responses to a postal questionnaire. The present study was conducted to evaluate whether nonresponse bias could explain the cross-sectional findings., Methods: We conducted telephone interviews with 230 men and 38 women who did not respond to the original survey, and compared these individuals to the original responders with respect to key demographic, behavioral, and reproductive characteristics., Results: Nonresponders were approximately 1.5 years older at interview, were more likely to be Caucasian, and reported higher incomes than responders. Among men, nonresponders had fished fewer days in the past year (12% reported no fishing, compared to 4. 3% of responders). Almost one half of nonresponders reported no fish consumption in the past year, compared to one quarter of responders. Nonresponders were more likely than responders to have ever conceived a live-born child, had more children, and were less likely to intend to have additional children in the next 5 years. Among both responders and nonresponders there was an increased prevalence of a period of conception failure among men who reported consuming greater quantities of sport-caught Great Lakes fish., Discussion: Our study provides support for the cross-sectional analyses presented previously, insofar as nonresponse bias is unlikely to have a major role in the observed association., (Copyright 1999 Academic Press.)

Between 1993 and 1995, we surveyed 4931 licensed anglers aged 17-34 years residing in 10 Michigan counties bordering a Great Lake. Responses were received from 1443 anglers and 844 of their partners. Lifetime sport-caught fish consumption was estimated as the number of sport-caught fish meals consumed in the previous 12 months times years since 1970 in which sport-caught fish were consumed. Analysis was restricted to currently married couples (n=626). Lifetime sport-caught fish consumption was categorized in men as 0 (14%); 1-114 (27%); 115-270 (30%); 271-1127 (29%) meals; and in women as 0 (28%); 1-54 (26%); 55-138 (27%); fand 139-1127 (19%) meals, respectively. Conception delay (ever having failed to conceive after 12 months of trying) was reported by 13% of both men and women. Among men, the unadjusted odds ratios (OR) for conception delay were 1.2, 1.3, and 2.0 across the three increasing levels of sport-caught fish consumption compared to none (trend test P=0.06). After adjustment for age, race, region of Michigan, household income, educational attainment, smoking, alcohol consumption, and partner's sport fish consumption, the OR for conception delay in men were 1.4, 1.8, and 2.8, respectively. In women, unadjusted OR for conception delay were 0.9, 1.0, and 1.4 with increasing sport-caught fish consumption (trend test P=0.35). With the same covariates and the sport-caught fish consumption of the woman's partner included in the model, the OR were 0.8, 0.8, and 1.0, respectively. These data suggest a modest association, in men only, of sport-caught fish consumption with risk of conception delay., (Copyright 1999 Academic Press.)

Background: Traditional bowel preparation before colonoscopy involves lavage with approximately 4 L of polyethylene-glycol (PEG)-electrolyte solution. Using prokinetic agents in addition to PEG-electrolyte lavage may decrease the volume required and ease patient preparation., Methods: We conducted a blinded, placebo-controlled trial with the prokinetic agent, cisapride, in addition to standard PEG-electrolyte lavage. Patients were prospectively assigned to receive 20 mg of cisapride (n = 52) or placebo (n = 49) 30 minutes before drinking PEG-electrolyte solution. The volume consumed, time to clean bowel, side effects, and acceptance were recorded. Adequacy of colon cleaning was scored by a gastroenterologist blinded to group assignment., Results: Thirty-seven percent of patients assigned to cisapride required more than 3500 mL of PEG-electrolyte, compared with 75% of patients receiving placebo (p < 0.001). Median time to clean bowel was 95 minutes for the cisapride group and 120 minutes for those receiving placebo (p = 0.23). Side effects, patient acceptance, and quality of bowel preparation were not significantly different., Conclusion: We conclude that administration of 20 mg of cisapride reduces the required volume of PEG-electrolyte solution for bowel preparation. There were also favorable trends in the time required to achieve clean bowel, patient tolerance, and occurrence of side effects.

Objectives: To compare artemether (by intramuscular injection) and quinine (by intravenous infusion) as treatments for cerebral malaria in African children., Methods: An open, randomized trial conducted at the Queen Elizabeth Central Hospital in Blantyre, Malawi. This trial was part of a multicentre study designed to determine if treatment with artemether would significantly lower mortality rates compared with quinine. Data from 83 artemether recipients and 81 quinine recipients are reported here., Results: Overall mortality rates and coma resolution times were not significantly different in the two treatment groups. Parasite and fever clearance times were significantly more rapid in the artemether recipients. Analyses which took into account the possible confounding variables did not significantly alter the findings of these unadjusted analyses., Conclusion: These results do not suggest that treatment with artemether would confer a survival advantage in children with life-threatening malaria. The power and precision of the estimated treatment effects of artemether would be enhanced by a meta-analysis of all relevant clinical trials.

There has been considerable interest in the benefits and risks of eating Great Lakes fish, particularly with regard to reproductive health. We report the results of a survey conducted from 1993-1995 among Michigan anglers. The survey was designed to identify a reproductive-aged cohort of persons who consume high or low levels of Great Lakes fish in order to study the impact of polyhalogenated biphenyl (PHB) compounds and other toxins on human reproduction outcomes. Using fishing license data obtained from the Michigan Department of Natural Resources, we identified anglers of early reproductive age (18-34 years) in ten Michigan counties. The screening survey ascertained demographic, behavioral, fish consumption, and reproductive history information on anglers and their partners. Over 4,000 angler households were contacted. One thousand nine hundred fifty questionnaires were returned from 1,168 households. The median age of respondents was 30 years; 58% were male and 64% reported being married. Slightly more than one-half the respondents had attended or graduated from college, and less than 10% had not completed high school. In the past year, most respondents (46%) reported having eaten sport-caught fish 1-12 times, while 20% reported having eaten no sport-caught fish; 20% had consumed 13-24 meals. More sport-caught fish was consumed in the spring and summer than in the fall and winter, and males reported eating more fish than females. About 43% of our respondents reported that they intend to have one or more children in the next five years. Of these respondents, 287 couples had no identified impairments to reproduction and therefore would be eligible to participate in the future reproductive study.

The reproducibility of responses to the Behavioral Risk Factor Surveillance System questionnaire was examined across the demographic strata used by the Centers for Disease Control and Prevention and state health departments for reporting prevalence estimates (specifically age, sex, income, employment, and marital status), as well as race/ethnicity, which has been previously examined. The authors administered the questionnaire twice, 21-94 days apart, to randomly selected residents of Massachusetts (response rates: first administration, 68% of eligible households; second administration, 68% of persons who completed the first interview). Initial interviews were conducted in March and October 1992. Among 448 respondents to both interviews, group mean distributions of seven demographic characteristics and 19 risk factors were highly consistent across the two interviews. Discordance in individual risk factor status ranged from 1.2% to 21.8% (median, 7.8%) and was symmetric in direction, i.e., as many respondents were considered at increased risk on the basis of the first interview and at low risk on the basis of the second interview as the reverse. Kappas ranged from 0.30 to 0.90 (median, 0.75). Education, household income, and interval between administrations were not associated with prevalence of discordance for any risk factor. Sex, age, race/ethnicity, marital status, and employment status were each predictive of variation in discordance for one or more risk factors, but no consistent effect of any individual demographic characteristic across risk factors was observed. The questionnaire has relatively uniform and generally good reproducibility across all demographic strata used for monitoring the Health Objectives for Year 2000 and other chronic disease surveillance activities.

We have previously reported on development of a simple PCR-based method to detect Plasmodium falciparum in which patient blood samples are lysed and then filtered onto paper. The present studies, conducted in Thailand, were designed to identify factors contributing to differences between results from microscopy and PCR. To analyze microscope-positive, PCR-negative results, we demonstrated that using the lysis/filtration sample preparation method, target DNA degradation is not a significant factor. Similarly, we showed that sensitivity of PCR among patient samples did not differ using the lysis centrifugation method or organically extracted DNA. We further demonstrated that 7/13 samples which were negative by PCR for P. falciparum were positive by PCR when P. vivax-specific primers were used. Microscope-negative, P. falciparum PCR-positive samples were analyzed in two ways: the true rate of false-positivity for PCR (2%) was established by analyzing 498 samples from patients living in areas without transmission. We further showed that when microscope-negative, PCR-positive samples were amplified using an independent P. falciparum-specific PCR target sequence, 42/47 were PCR-positive. We conclude that the accuracy and reduced limit of detection of microscopy are major confounders when comparing this method to PCR.

We have previously reported on development of a DNA probe-based method for diagnosing Plasmodium falciparum infection directly from patient blood samples. In the present studies, we sought to examine applicability of the method to large epidemiological surveys, comparing sensitivity, specificity, time required to obtain results, and costs with those of conventional microscopic examination. Results of DNA probe hybridization were also compared between laboratories in the US and Thailand, to assess transferability of the DNA probe technology. Five separate surveys of approximately 5000 villagers each were performed between December 1987 and June 1989 (26,176 samples total). Sensitivity ranged from 61% to 92% for both US and Thai laboratories, while specificity ranged from 98.2% to 99.9%. Agreement between the US and Thai laboratories was good, with kappa coefficients between 0.62 and 0.78 for different surveys. Between 4 and 8 person-days were required to obtain results from each set of 5000 samples by DNA hybridization, whereas microscopic examination required 150 person-days. Approximate costs were US 0.17 per sample for DNA probe analysis, and US$0.36 for microscopic examination. We conclude that the DNA probe method offers significant advantages when large numbers of samples must be surveyed for P. falciparum.

Previously a cloned emetine-resistant mutant of the protozoal parasite Entamoeba histolytica was shown to overexpress a gene for an ameba homolog of the mammalian P-glycoprotein, a plasma membrane pump that removes hydrophobic drugs from multidrug-resistant tumor cells. Three sets of experiments were performed to better characterize the multidrug-resistant phenotype of the emetine-resistant amebae. First, the emetine resistance of the mutant amebae was reversed by concentrations of calcium and sodium channel blockers effective in reversing drug resistance by multidrug-resistant tumor cells, but it was reversed only in the presence of very high concentrations of the tricyclic antidepressants. Second, the mutant amebae showed cross-resistance to antiamebic drugs used to treat luminal infection (iodoquinol and diloxanide) but were not cross-resistant to drugs used to treat invasive disease (chloroquine and metronidazole). Third, when amebae were loaded with radiolabeled emetine, the mutant parasites released the drug at approximately 1.6 times the rate of the wild-type organisms. We conclude that the emetine-resistant E. histolytica parasites have some but not all the features of the multidrug-resistant phenotype.

We have developed a simple method for treating blood samples permitting direct detection of Plasmodium falciparum parasites using the P. falciparum-specific DNA probe pPF14 after polymerase chain reaction (PCR) amplification of target DNA sequences, and have compared this method with microscopic examination of thick blood smears. For PCR amplification, blood samples were lysed, then filtered onto filter paper. After drying, a piece of the filter paper was added directly to the PCR mixture for amplification. The presence of PCR products was detected using nonisotopically labeled probe. This method permits detection of less than than 10 parasites in a 20-microliters sample, and minimizes the effects of PCR inhibitors generally found in blood. Samples were collected from patients presenting at malaria clinics in Mae Sod and Mae Ramat, Thailand, and 626 were analyzed both by the PCR method and by conventional microscopy. Of these, 157 were positive both by microscopy and by PCR, while 297 were negative by both methods. PCR detected 131 samples that were negative by microscopy, and failed to detect 41 samples identified as positive by microscopy. All discordant samples were re-analyzed by microscopy and by PCR. Upon re-examination at a higher sensitivity, microscopy identified five additional positive cases, while six previously positive cases were found to be negative. This method of treating blood samples for PCR may also be useful in other diagnostic assays.