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Effect of intestinal resection on serum antibodies to the mycobacterial 45/48 kilodalton doublet antigen in Crohn's disease.

Interest in the role of mycobacterial infection in Crohn's disease has been revived by the cultural detection of Mycobacterium paratuberculosis in patients with Crohn's disease. This hypothesis was examined serologically using assays with high specificity for Crohn's disease. The effect of intestinal resection on serum antibodies specific for Crohn's disease was investigated with an immunoblot assay and an enzyme linked immunosorbent assay using the 45/48 kilodalton doublet antigen of Mycobacterium tuberculosis. Antibodies were detected in 64.7% of patients with Crohn's disease (n = 17), 10% of patients with ulcerative colitis (n = 10), 5% of patients with carcinoma of the colon (n = 20), and none of 10 healthy subjects with the immunoblot assay. Statistical comparison of the Crohn's disease patients with each control group resulted in p = 0.0000236. Immunoglobulin G was essentially unchanged 75 days (mean) after surgery. After more than 180 days, however, the antibody response was reduced in all of five patients studied, and was no longer demonstrable in two of them (40%). Simultaneously, the Crohn's disease activity index (CDAI) decreased. Both the high specificity of this assay for Crohn's disease and the diminished antibody response after intestinal resection in parallel with decreased CDAI support a mycobacterial aetiology of Crohn's disease.

Adolescent↗

Isoniazid hepatitis among pregnant and postpartum Hispanic patients.

On request of local health officials, the authors investigated isoniazid (INH) hepatitis morbidity and mortality among patients attending an Hispanic prenatal clinic. Among 3,681 women treated with INH during and after pregnancy to prevent tuberculosis (TB), 5 developed INH hepatitis, and 2 of the 5 women died. Comparison with previously collected Public Health Service data concerning 3,948 nonpregnant women, using the Cox proportional hazards model, revealed a 2.5-fold increased risk of INH hepatitis in the prenatal clinic group. The mortality rate was four times higher in the prenatal clinic group. However, statistical power was low because of the small number of cases, and neither of these findings was statistically significant (P greater than 0.05). In the absence of controlled studies, the issue of INH safety during the perinatal period remains unresolved. Nevertheless, current American Thoracic Society-Centers for Disease Control recommendations regarding TB screening, implementation of INH chemoprophylaxis programs, and adequate monitoring of individuals on INH should be adhered to. The results of this investigation raise concern that deviations from existing policy may contribute to unnecessary morbidity and mortality.

Adolescent↗

Tuberculosis skin test conversion among health care workers at a military medical center.

Health care workers (HCW) are at risk of occupationally acquiring Mycobacterium tuberculosis (TB) infection. The Centers for Disease Control and Prevention has published guidelines for health care facilities to protect HCW. One of the recommended elements is TB infection surveillance among HCW using purified protein derivative (PPD) skin testing and analysis of the data by occupational group and work location to determine areas of increased risk of infection. At the military medical center (MMC) we studied, occupational groups with statistically significant (p < 0.05) above-average PPD conversion risk (> 1.1%/year) included respiratory therapists (15.6%/year), nursing technicians (2.3%/year), and military personnel (1.6%/year). Maintenance and engineering workers (2.6%/year), food service workers (2.5%/year), laboratory workers (2.0%/year), custodial workers (1.8%/year), and practical nurses (1.7%/year) had above-average, but not statistically significant, risk. The fourth floor of the MMC had 39% (21/54) of the converters. The surveillance program also uncovered 235 individuals who had not completed adequate prophylactic therapy, and a case of active TB in a laboratory worker.

Allied Health Personnel↗

Influence of smoking on cutaneous delayed-type hyper sensitivity reaction by tuberculin skin test.

Tuberculin test (purified protein derivative) is currently accepted as a standard investigation used in the diagnosis of tuberculosis (TB). Although the sensitivity of the test is reliable, a substantial number of those subjected to screening for TB by such test are cigarette smokers. This study is designed to investigate the effect of smoking on cell-mediated delayed-type cellular hypersensitivity (DTH) reaction by PPD. Prospective, case-control study was conducted at the Chest and TB unit of Chest Hospital Kuwait. The study population consisted of 357 healthy volunteers serving as controls and 200 in-patients under direct medical supervision and treatment for tuberculosis as cases. The mean age was 33.69 +/- 8.6 SD; 286 were current smokers and 271 were lifetime non-smokers. PPD test was done using 2TU RT23 SSI-Denmark on all subjects. Median PPD was significant among the cases (P=0.03) between smokers and non-smokers and was highly significant among the healthy controls (P<0.001). No significant difference was seen between median pack years of smoking and PPD levels among the patient group (P=0.264) but the difference was significant among the control group (P<0.001). Univariate analysis of variance (ANOVA) on PPD, taking into account age, pack years of smoking, ethnic groups and BCG scar showed sufficient response but was not statistically significant to all these factors. Smoking habit does not appear to influence the cutaneous delayed type hypersensitivity reaction by tuberculin skin test.

Adult↗

Impact of an effective multidrug-resistant tuberculosis control programme in the setting of an immature HIV epidemic: system dynamics simulation model.

This study sought to determine the impact of an effective programme of multidrug resistant tuberculosis control (MDRTB) on a population that is witnessing an explosive HIV epidemic among injecting drug users (IDUs), where the prevalence of MDRTB is already high. A transmission model was constructed that represents the dynamics of the drug-susceptible tuberculosis (DSTB), MDRTB and HIV spread among the adult population of Samara Oblast, Russia: from official notifications of tuberculosis and of HIV infection, estimates of MDRTB derived from surveillance studies, population data from official regional statistics, data on transmission probabilities from peer-reviewed publications and informed estimates, and policy-makers' estimates of IDU populations. Two scenarios of programme effectiveness for MDRTB were modelled and run over a period of 10 years to predict cumulative deaths. In a population of 3.3 million with a high prevalence of MDRTB, an emerging epidemic of HIV among IDUs, and a functioning directly observed therapy-short course (DOTS) programme, the model predicts that under low cure rates for MDRTB the expected cumulative deaths from tuberculosis will reach 6303 deaths including 1900 deaths from MDRTB at 10 years. Under high cure rate for MDRTB 4465 deaths will occur including 134 deaths from MDRTB. At 10 years there is little impact on HIV-infected populations from the MDRTB epidemic, but as the HIV epidemic matures the impact becomes substantial. When the model is extended to 20 years cumulative deaths from MDRTB become very high if cure rates for MDRTB are low and cumulative deaths in the HIV-infected population, likewise, are profoundly affected. In the presence of an immature HIV epidemic failure to actively control MDRTB may result in approximately a third more deaths than if effective treatment is given. As the HIV epidemic matures then the impact of MDRTB grows substantially if MDRTB control strategies are ineffective. The epidemiological starting point for these scenarios is present in many regions within the former Soviet Union and this analysis suggests control of MDRTB should be an urgent priority.

AIDS-Related Opportunistic Infections↗

Control strategies for tuberculosis epidemics: new models for old problems.

Tuberculosis, although preventable and curable, causes more adult deaths than any other infectious disease. A theoretical framework for designing effective control strategies is developed and used to determine treatment levels for eradication, to assess the effects of noneradicating control, and to examine the global goals of the World Health Organization. The theory is extended to assess how suboptimal control programs contribute to the evolution of drug resistance. A new evaluation criterion is defined and used to suggest how control strategies can be improved. In order to control tuberculosis, treatment failure rates must be lower in developing countries than in developed countries.

Adult↗

[Serum adenosine deaminase in human immunodeficiency virus infection. Its relationship with CD4+ lymphocytes and beta 2-microglobulin].

BACKGROUND: The activity of the deaminase adenosine enzyme (ADA) has principally been related with the functionalism and replication of the T lymphocytes. Its serum behavior and possible clinical use in infection by the human immunodeficiency virus type 1 (HIV-1) was studied. METHODS: A multicenter study in which the serum values of ADA were examined and compared with those of two reference markers (CD4+ lymphocytes and beta 2-microglobulin) in 35 presumably healthy donors used as controls, in 60 intravenous drug users (IVDU) seronegative for HIV-1, in 69 HIV-1 asymptomatic seropositive intravenous drug users (HIV-1+) and in 48 patients with AIDS. RESULTS: The serum values of ADA were as follows: control group 10.9 +/- 4.2 U/I; IVDU group 17.6 +/- 7.4 U/I; asymptomatic HIV-1+ group 32.7 +/- 10.2 U/I, AIDS group 46.2 +/- 18.2 U/I. Differences between the different groups were statistically significant in themselves and in relation to the control group. A negative correlation was observed (r = 0.47, p < 0.01) with the number of CD4+ lymphocytes and a positive correlation was found with respect to beta 2-microglobulin (r = 0.76, p < 0.001). The values of serum ADA activity in patients with AIDS and tuberculosis (47.4 +/- 17.2 U/I) were not significantly higher (p < 0.05) to those of patients with AIDS without this second infection (45.9 +/- 19.3 U/I). CONCLUSIONS: Serum deaminase adenosine may be a useful evolutive marker for human immunodeficiency virus type 1 given that its activity increases significantly in infected patients in agreement with the grade of immunodeficiency and its values correlate well with those of reference markers (CD4+ lymphocytes and beta 2-microglobulin).

Acquired Immunodeficiency Syndrome↗

The use of a computer in the organization of a large-scale co-operative controlled clinical trial of the treatment of pulmonary tuberculosis.

The organization of controlled clinical trials requires well-defined clerical procedures which, with large-scale studies, are so monotonous that it is difficult to attract and keep staff of a sufficiently high calibre. In a large-scale trial of pulmonary tuberculosis, a computer is being used to undertake much of the routine clerical work, including (1) the preparation of an appointments diary, which also specifies the exact requirements for the trial, and (2) the storage of all the data on magnetic tape so that periodic checks can be made for missing data and interim and final analyses can be produced rapidly. These arrangements reduce the time spent by clerical and statistical staff to a minimum. Although a strict evaluation of the effect of introducing the computer has not yet been made, this approach does appear to be sufficiently promising to warrant further investigations of a similar type.

Antitubercular Agents↗

A randomised controlled trial of lay health workers as direct observers for treatment of tuberculosis.

SETTING: Study conducted in a suburb of Cape Town, South Africa. OBJECTIVE: Comparison of successful tuberculosis treatment outcome rates between self supervision, supervision by lay health worker (LHW), and supervision by clinic nurse. METHODS: Open, randomised, controlled trial with intention-to-treat analysis. RESULTS: All groups (n = 156) achieved similar outcomes (LHW vs. clinic nurse: risk difference 17.2%, 95% confidence interval [CI] -0.1-34.5; LHW vs. self supervision 15%, 95%CI -3.7-33.6). New patients benefit from LHW supervision (LHW vs clinic nurse: risk difference 24.2%, 95%CI 6-42.5, LHW vs. self supervision 39.1%, 95%CI 17.8-60.3) as do female patients (LHW vs. clinic nurse 48.3%, 95%CI 22.8-73.8, LHW vs. self supervision 32.6%, 95%CI 6.4-58.7). CONCLUSIONS: LHW supervision approaches statistically significant superiority, but fails to reach it most likely due to the study's limitation, the small sample size. It is possible that subgroups (new and female patients) do well under LHW supervision. LHW supervision could be offered as one of several supervision options within TB control programmes.

Adult↗

[Retrospective evaluation of the effectiveness of the BCG vaccine campaign in newborns of Barcelona].

BACKGROUND: The aim of this study was to know the efficacy of the BCG vaccination campaign of the newborns of Barcelona carried out during the period from 1966-1974. METHODS: To achieve this aim an epidemiologic investigation was undertaken by an observational analytical study of paired cases and controls. Two hundred and fifty randomly selected cases were studied between 1978-1988 from between 4-21 years of age during the study period. The cases were paired with 750 controls (1:3) with identical conditions and age, sex and place of residence. Statistical analysis of data was performed by the specific methods for this type of study. RESULTS: The estimated gross odds ratio was 0.68; the interval of confidence 95% and 0.51-0.91 (p < 0.025). The efficacy of this vaccination campaign was estimated as weak at 32%, in the age group and investigation time being greater in males and diminished with time. The percentage of new cases of tuberculosis potentially prevented by this campaign was calculated at 13%. CONCLUSIONS: The weak efficacy of the BCG vaccination campaign may be attributed not only to the unforeseen effects of this vaccine but also to the deficient operative aspects of the campaign itself.

Age Factors↗

Cytokine transcripts in pediatric tuberculosis: a study with bronchoalveolar cells.

Pediatric tuberculosis (TB) differs from adult TB in many features. To date, cytokine expression has not been studied in children with TB. The relative amounts of the various cytokines released at the site of infection may be important determinants of TB disease development and pathology. We determined cytokine transcripts in bronchoalveolar cells (BACs) recovered from 9 children presenting with TB and from 9 children with pulmonary diseases other than TB. An RT-PCR-based method was developed to quantify the mRNAs encoding six cytokines (IFN- gamma, IL-12, TNF- alpha, IL-10, IL-4, TGF- beta 1) known to play key roles in mycobacterial infections. Expression of mRNA encoding TGF- beta, TNF- alpha and IFN- gamma was statistically significantly higher in BACs from children with TB than in BACs from children with other pulmonary diseases; whereas the levels of mRNA transcription for TGF- beta is high, the levels of mRNA transcription for IFN- gamma and TNF- alpha remain low. All children had low levels of mRNA for IL-12(p40). IL-4 was barely detectable in all cases. Children with miliary TB had high levels of IL-10 transcripts and low levels of mRNA encoding TGF- beta. The immunosuppressive cytokines TGF- beta and IL-10, are overproduced in children with non-miliary TB and miliary TB respectively and are probably involved in the progression of the disease. These data suggest that Th1 responses are reduced in children with TB.

Adolescent↗

Analysis of environmental carcinogens associated with the incidence of lung cancer.

It is presumed that carcinogens present in human lungs contribute to the incidence of lung cancer. Most of the carcinogens are inhaled in lung alveoli with particulate matter through the respiratory tract. On the basis of chemical analysis of 256 lung specimens with carcinomas resected in the period 1991 1996, the concentration of 1-nitropyrene (1-NP) was 19.7+/-10.5 pg/g of dry weight, and that of the dinitropyrenes (DNP) was 3.50+/-0.14-6.26+/-1.76. In addition, 2-nitrofluoranthene (NF) and 3-NF were detected at a higher level of 38.6+/-17.2 and 39.1+/-14.2, respectively, pg/g of dry weight. Concentrations of benzo[a]pyrene, benzo[e]pyrene, benzo[k]fluoranthene and benzo[ghi]perylene in 37 specimens collected in the period 1991 1996, were in the range of 138+/-82-399+/-220 pg/g of dry weight. No difference was found in the concentration of chemicals deposited in lung specimens from patients with lung cancer and tuberculosis as a control. By following the prognosis of 112 patients with carcinomas, we found that the deposition of 1-NP, 1,3-DNP, and 3-NF in lung tissues influenced their 5-year-survival after determination of chemicals. Lung specimens were divided into two groups of higher and lower chemical concentrations at the levels of 18 pg/g for 1-NP, 15 for 1,3-DNP, and 35 for 3-NF, and the findings were statistically analyzed by adjusting for age, gender, smoking status and cell type. The 5-year-survival of patients was markedly lower in the higher concentration group than the lower group.

Adult↗

Periodontal indices of patients taking isoniazid and rifampin: a pilot study.

A significant reduction in the incidence of tuberculosis (TB) has resulted from the use of medications such as isoniazid (INH) and rifampin. Unfortunately, there has been a resurgence of TB since the mid 1980s. The purpose of this pilot study was to evaluate the effects of INH and rifampin on periodontal indices of patients with positive tuberculin skin tests (PPD). The gingival index, plaque index, and periodontal scoring and recording were recorded in PPD-positive patients at baseline and 1 month. Control patients received no medications during the study and were evaluated at baseline and 1 month. Mean values for each patient were obtained and analyzed using unpaired t tests (N = 8). Statistically, within the limits of this study, it was found that patients taking INH and/or rifampin had a significant decreased (p < 0.05) in gingival inflammation from baseline.

Adult↗

Comparison of outcomes from a district tuberculosis control programme in the Pacific: before and after the implementation of DOTS.

Outcomes are compared for a district tuberculosis (TB) control programme, before and after DOTS (directly observed therapy short-course) and a computerized register were introduced. There were significant improvements in case holding associated with the interventions. The successful treatment rate was 13.6% [95% CI (confidence interval), 4.9-23.0] higher and the default rate 9.6% (95% CI, 3.6-17.3) lower following the introduction of DOTS and the computerized register. There was no difference in cure rates or death rates, the notification of new cases, the proportion of pulmonary cases or sputum positives. Additional benefits associated with the computerized register were improvements in supervision, reporting and statistical analysis. The short-course chemotherapy permitted flexibility and was well accepted by both health staff and patients. This study demonstrates that computerization of TB registration using appropriate software is feasible in district TB programmes in resource poor countries and can contribute to improving their performance.

Antitubercular Agents↗

Daily single-dose regimen and alternate-two-week triple-dose/day regimen of oral ofloxacin for the prophylaxis and control of exacerbations of chronic respiratory tract infections.

Two different oral ofloxacin regimens, a daily single-dose regimen with 200 mg (Regimen I) and an every-two-week multidose regimen with 3 x 200 mg/day (Regimen II) was compared as to the efficacy in controlling repeated acute exacerbations of chronic respiratory tract infections. Fifty-eight patients consisting of 19 patients each of bronchiectasis and pulmonary emphysema, 10 patients of chronic bronchitis, 5 patients of old pulmonary tuberculosis, 4 patients of diffuse panbronchiolitis and 1 patient of multiple pulmonary bullae were evaluated: 32 patients in Regimen I and 26 patients in Regimen II. The corrected mean incidence of exacerbations per case decreased from pre-study 2.47 to intra-study 0.59 in Regimen I, and from pre-study 2.66 to intra-study 0.95 in Regimen II, respectively, with a statistically significant difference (p < 0.05, respectively). Only one of 12 persistent isolates of Pseudomonas aeruginosa acquired a certain degree of resistance to ofloxacin. Adverse reactions were found in six of 66 patients. We conclude that long-term administration of an new-quinolone, especially a daily single-dose regimen with ofloxacin, is useful to control acute exacerbations of chronic respiratory tract infections.

Administration, Oral↗

[A survey on nosocomial tuberculosis infection control in hospitals in Osaka City].

PURPOSE: To ascertain nosocomial tuberculosis (TB) infection control practice in hospitals in Osaka City. METHOD: A questionnaire was distributed in the orientation meeting and collected at the occasion of medical inspection in all 196 hospitals in Osaka City in 2003. RESULTS: TB patients were diagnosed in about half of hospitals in the past 3 years. Basic TB infection control measures were taken in the majority of hospitals; such as chest X-ray screening for all inpatients, health check for employees, tuberculin skin test (TST) for newly employed staff, and nomination of a person in charge of TB infection control. Control measures were practiced more often in hospitals where TB patients were diagnosed, such as "fiberoptic bronchoscopy is to be conducted last in the working hours to avoid contamination of TB bacilli in a room," "TST (including two-step method) for all newly employed staff," "Staff wear N95 mask when they deal with TB patients/suspects," and the differences were statistically significant. DISCUSSION: It is necessary in hospitals in Osaka City to strengthen nosocomial TB infection control as TB patients were diagnosed in about half of hospitals in the past 3 years. Low cost infection control measures were undertaken more often among hospitals where TB patients were diagnosed. Introduction of high cost equipment or improvement of facilities should be considered in hospitals of high TB risk. Guidelines formulated based on analysis of the survey should facilitate all hospitals to introduce at least low cost effective tuberculosis infection control measures.

Cross Infection↗

Prevalence of human immunodeficiency virus (HIV) antibodies in tuberculosis patients in Lagos, Nigeria.

To establish the prevalence of HIV antibodies in patients with pulmonary tuberculosis, 536 new cases presenting with symptoms of bronchopulmonary disorders were randomly selected from the six referral chest clinics in Lagos and screened for tuberculosis and HIV infections. Sputum and serum samples were obtained from all the patients. The sputum samples were examined for acid-fast bacilli (AFB) by both microscopy and culture. The sera were screened for HIV-1 and HIV-2 antibodies by ELISA and confirmed by Western blot (WB). Of the 536 cases studied, 188 (35%) were positive for AFB while 13 (2.4%) were seropositive for HIV. Correlation between the AFB and HIV results revealed that 10 (5.3%) of the 188 AFB positives were also seropositive for HIV as compared to 3 (0.9%) in the 348 AFB negative cases. The difference in the HIV seroprevalence rates in the two groups was statistically significant (P < 0.001). The recorded higher frequency of HIV infections in the AFB positives strongly suggested some level of interaction between TB and HIV infections in Lagos. Infections with HIV-2 were more prevalent than HIV-1 in the patients with HIV and TB. No case of dual infection with HIV-1 and HIV-2 was recorded in this group of patients. However, in the 3 HIV-seropositive patients within the control group (non-tuberculosis patients), 2 (67%) were positive for both HIV-1 and HIV-2 while 1 (33%) was positive for HIV-2 only. Mycobacterium tuberculosis (70%), M. avium (20%) and M. kansasii (10%) were the mycobacteria strains isolated from the HIV/TB infected patients.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗

Seroepidemiological associations between tuberculosis, malaria, hepatitis B, and AIDS in West Africa.

Serum samples from 51 patients with malaria, 35 patients with hepatitis B virus infection, 111 patients with tuberculosis, and 166 healthy controls were studied to determine any associations between tuberculosis, malaria, hepatitis B, and AIDS in Nigeria, West Africa. All serum samples were examined for the presence of HIV-1/HIV-2, hepatitis B virus surface antigen (HBsAg), and malaria antibodies. Only one patient was HIV-1 antibody-positive and none HIV-2 antibody-positive. Statistical associations were found between the presence of malaria antibody titres on the one hand and a diagnosis of hepatitis B virus infection (P < 0.05) or tuberculosis (P < 0.05). A stronger association (P < 0.001) was found between the presence of HBsAg and tuberculosis suggesting that HBsAg carriers are at higher risk of contracting tuberculosis.

Acquired Immunodeficiency Syndrome↗