Tuberculosis: an update.

Purified protein derivatives (PPD) prepared in the USA were compared with those prepared in Australia by a private company (CSL Veterinary) for use with a commercial gamma interferon (gamma-IFN) assay for diagnosis of bovine tuberculosis. The effect of skin testing on results of the gamma-IFN assay was determined, and results were compared when blood samples were stimulated with PPD within 2 hours and after 24 hours of sample collection. Twenty cattle that were sensitized by subcutaneous injection of heat-killed Mycobacterium bovis were randomly divided into 3 groups. Cattle in group A were tested with the caudal fold skin test (CFT) on day 0 and the comparative cervical skin test (CCT) on day 7. Cattle in group B were tested with the CFT on day 0 and the CCT on day 63, and group C cattle were not skin tested. Blood samples for the gamma-IFN assay were collected at various times throughout the study period. Optical density (OD) values for the gamma-IFN assay were not significantly different when blood samples were stimulated with US avian PPD and CSL avian PPD. However, OD values were significantly higher for US bovine PPD than for CSL bovine PPD. However, the final interpretation of the gamma-IFN assay was usually the same when using either US or CSL PPD. In addition, OD values for the gamma-IFN assay were significantly higher for blood samples collected after sensitized cattle were skin tested than for samples collected from the same cattle before skin testing or from cattle not skin tested. The OD values for blood samples stimulated within 2 hours of sample collection were significantly higher than for samples stimulated 24 hours after sample collection. However, OD values for all PPD-stimulated samples from sensitized cattle were significantly higher in samples collected 3 days after skin testing and stimulated 24 hours after collection than for samples from the same animals collected before skin testing and stimulated within 2 hours of sample collection. Results of this study indicate that PPD prepared in the USA or Australia can be used to stimulate blood samples for the gamma-IFN assay. Skin testing cattle prior to collection of blood for the gamma-IFN assay boosts production of gamma-IFN by lymphocytes from cattle that have had prior exposure to M. bovis antigens. Use of the gamma-IFN assay in conjunction with skin testing may improve detection of cattle infected with M. bovis. In addition, the increase in production of gamma-IFN after skin testing will permit greater flexibility in conducting the assay because samples can be stimulated after they have been shipped overnight rather than only on the day of sample collection.

The diagnosis of tuberculosis: what's old, what's new.

Prompt diagnosis and early treatment of Tuberculosis (TB) cases is an important strategy in TB prevention and control. Thus, passive case finding of TB suspects, sputum examination for diagnosis, and prompt treatment using Directly Observed Treatment Short Course (DOTS) are key elements in the national guideline for TB control programme. The aim of this study is to determine the time interval between diagnosis of smear-positive TB cases and the commencement of treatment in DOTS facilities in southern Nigeria. The study was carried out in 20 healthcare facilities supported by TB Control Assistance Program (TB-CAP) involved in TB management in southern Nigeria, which comprised tertiary, secondary, and primary healthcare facilities including public and private facilities. Data were collected through review of clients' and facility records covering July-September 2009. Data collected were sociodemographic characteristics, sputum-smear result, date of diagnosis, and date of commencement of treatment. Data were analyzed using SPSS version 15.0 software. Of the total 2,507 TB suspects examined for Acid-Fast Bacillus (AFB), 323 were diagnosed to be Sputum-Smear-Positive (SS+ve), However, 269 new smear positive cases were commenced on treatment within the period, thus 54 (17.0%) of the new SS+ve cases defaulted initially. One hundred and two (38%) of them commenced TB treatment within 3 days of smear examination for diagnosis, while 59 (22%) commenced 4-6 days after diagnosis. The study revealed significant delay in commencement of TB treatment for most new smear positive TB cases in southern Nigeria and underlines the need to further explore factors responsible for delay in commencement of TB treatment following diagnosis.

Background The presence of latent tuberculosis is routinely assessed by tuberculin skin test (TST), which detects a cell mediated immune response to the injected tuberculin purified protein derivative (PPD). Although TST has been in use for over a century, its limitations include poor specificity (i.e. numerous false positive results), the need to examine the site 48-72 hours after injection and the subjective interpretation of results (i.e. estimation of the diameter of induration). Recently, an in vitro assay has been investigated as an alternative to overcome limitations posed by TST. This assay, also known as gamma interferon release assay (GIRA) detects the release of gamma interferon from sensitized lymphocytes upon exposure to mycobacterium TB antigen coated tubes.

Is the BCG test of diagnostic value in tuberculosis?

We studied tuberculin reactivity and clinical course after starting chemotherapy in patients with active pulmonary tuberculosis divided by four age-groups less than 29, 30-49, 50-69 and 70 years and more. The skin test to tuberculin purified protein derivative (PPD) was examined in 178 cases of active pulmonary tuberculosis, 120 cases of lung cancer, 25 cases of atypical mycobacteriosis and 466 cases of the other respiratory diseases. The average size of tuberculin reaction in pulmonary tuberculosis decreased with age, but significantly higher than that in patients with other nontuberculous pulmonary diseases of the same age-group. The size of PPD skin test in the group of 70 years and more was significantly lower than other age-groups in pulmonary tuberculosis. We compared the time required for negative conversion of sputum by culture after primary chemotherapy among the different age-groups in pulmonary tuberculosis. It revealed that the time for negative conversion tended to be longer with age, and the time in the group 70 years and more was significantly longer than that of the group less than 29 years of age, although no significant differences in the radiographic severity and conditions of chemotherapy were observed. Finally, the PPD-induced lymphocyte proliferation test in vitro was done in newly diagnosed patients with pulmonary tuberculosis. The patients were divided into two groups by the size of PPD skin test (high responder more than 16 mm and low responder less than 15 mm of erythema induced by PPD).(ABSTRACT TRUNCATED AT 250 WORDS)

To investigate whether an unrecognised diagnosis of tuberculosis (TB) at the start of antiretroviral therapy (ART) influences subsequent CD4+ T cell (CD4) count recovery in an urban HIV clinic in Uganda. In a retrospective cohort study, a multivariable polynomial mixed effects model was used to estimate CD4 recovery in the first 96 weeks of ART in two groups of patients: prevalent TB (started ART while on TB treatment), unrecognised TB (developed TB within 6 months after start ART). Included were 511 patients with a median baseline CD4 count of 57 cells/mm(3) (interquartile range: 22-130), of whom 368 (72%) had prevalent TB and 143 (28%) had unrecognised TB. Compared with prevalent TB, unrecognised TB was associated with lower CD4 count recovery at 96 weeks: -22.3 cells/mm(3) (95% confidence interval -43.2 to -1.5, P = 0.036). These estimates were adjusted for gender, age, baseline CD4 count and the use of zidovudine-based regimen. Unrecognised TB at the time of ART initiation resulted in impaired CD4 recovery compared with TB treated before ART initiation. More vigilant screening with more sensitive and rapid TB diagnostics prior to ART initiation is needed to decrease the risk of ART-associated TB and sub-optimal immune reconstitution.

Shortening tuberculosis (TB) treatment duration is a research priority. We tested the efficacy and safety of 3- and 4-month regimens containing moxifloxacin in a randomised clinical trial in pulmonary TB (PTB) patients in South India. New, sputum-positive, adult, HIV-negative, non-diabetic PTB patients were randomised to 3- or 4-month moxifloxacin regimens [moxifloxacin (M), isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E)] or to a control regimen (2H3 R3 Z3 E3 /4R3 H3 ) [C]. The 4 test regimens were 3R7 H7 Z7 E7 M7 [M3], 2R7 H7 Z7 E7 M7 /2R7 H7 M7 [M4], 2R7 H7 Z7 E7 M7 /2R3 H3 M3 [M4-I] or 2R7 H7 Z7 E7 M7 /2R3 H3 E3 M3 [M4-IE]. Treatment was directly observed. Clinical and bacteriological assessments were done monthly during treatment and for 24months post-treatment. The primary end point was TB recurrence post-treatment. Of 1371 patients, randomised, modified intention-to-treat (ITT) analysis was done in 1329 and per-protocol (PP) analysis in 1223 patients. Regimen M3 was terminated due to high TB recurrence rates. 'Favourable' response at end of treatment was 96-100% in the moxifloxacin regimensand 93% in the control regimen. Among these, the TB recurrence occurred in 4.1% in the M4 regimen and in 4.5% in the control regimen and demonstrated equivalence within a 5% margin (95% CI -3.68, 4.55). Similar findings were observed in modified ITT analysis. The TB recurrence rates in the M4-I and M4-IE regimens did not show equivalence with the control regimen. Sixteen (1.4%) of 1087 patients in the moxifloxacin regimens required treatment modification. The 4-month daily moxifloxacin regimen [M4] was found to be equivalent and as safe as the 6-month thrice-weekly control regimen.

Gamma interferon assay as an alternative to PPD skin testing in selected patients with granulomatous intraocular inflammatory disease

Mycobacterium tuberculosis Infections in Solid Organ Transplantation

Management and transference of patients diagnosed with tuberculosis in a rural hospital in Southern Ethiopia

Directly Observed Treatment (DOT) is the key element of DOTS (directly observed treatment, short course), part of the internationally recommended control strategy for tuberculosis (TB). The evaluation of DOT has not been widely evaluated in rural areas in developed settings. The aim of this pilot study was to evaluate a modified DOT program (MDOT) by a general practitioner (GP) in a rural area of southwest Greece, where there is substantial underreporting of TB cases. Thirteen new TB cases with 30 close contacts were compared with 41 past-treated TB subjects (controls) with 111 close contacts in this observational, case-control study. Home visits by a GP were conducted and comparison of various data (laboratory findings, treatment outcomes, questionnaire-based parameters, on-site recorded conditions) was performed in both newly detected pulmonary TB cases and previously treated TB cases managed without DOT intervention. MDOT by GP implementation revealed that 11 cases (84.6%) were successfully treated, one (7.7%) case died, and one (7.7%) was lost to follow up. None of the close contacts of new TB cases was infected with active TB, while 6.3% of previously-treated TB subjects were infected with active TB and had to receive a complete anti-TB regimen. Chemoprophylaxis was administered to 13.3% of close contacts of new cases; whereas 12.6% of close contacts of previously-treated patients received chemoprophylaxis. This pilot study revealed that a GP is able to implement a program based on DOT resulting in high treatment adherence and prevention of TB compared with the conventional self-administration of treatment.

Tuberculosis (TB) clinic, Douala Laquintinie Hospital, Douala, Cameroon. To describe the clinical characteristics of TB and to investigate predictors of poor treatment outcomes. A registry-based, retrospective cohort study of all TB cases recorded from 2007 to 2013 was conducted. Multinomial logistic regression models were used to identify predictors of poor outcomes. Of 8902 TB cases included, 5110 (57.4%) were males. The median age was 33 years. The prevalence of human immunodeficiency virus (HIV) infection was 37.6%, with a significant decline over the study years (P = 0.000). The main clinical form of TB was smear-positive TB (50.5%). The treatment success rate was 75.2%, while the mortality rate was 8.1%. The year of TB diagnosis, retreatment cases, sputum non-conversion at the end of month 2, HIV infection and HIV testing not done were associated with death. Retreatment and non-conversion of sputum were associated with treatment failure, while male sex, age, sputum non-conversion, HIV infection and HIV testing not done were associated with loss to follow-up. TB management objectives may be attained by focusing specifically on higher risk groups to prevent poor treatment outcomes.

This study aimed to describe the prevalence of drug-resistant tuberculosis (TB) among pulmonary TB patients in rural China and to determine the extent of multidrug-resistant TB (MDR-TB) circulating in areas with varied duration of Directly Observed Treatment, Short Course (DOTS) implementation. A cross-sectional study was conducted in two rural counties in eastern China: Deqing with over 10 years' DOTS implementation and Guanyun under its second year of DOTS. The subjects were all culture-positive pulmonary TB patients newly diagnosed or re-treated during 12 months of 2004-2005. The proportion method was used for drug susceptibility testing. Among the 399 subjects, 283 were new TB cases and 116 were previously treated. The rates of overall resistance (i.e., resistance to at least one drug) in new cases were 50.4% (67) and 63.4% (95), respectively, in Deqing and Guanyun (p = 0.028), and 67.3% (33) and 83.6% (56), respectively, in previously treated cases (p = 0.0410). The rates of MDR-TB in new cases were 3.8% (5) in Deqing and 14.7% (22) in Guanyun (p = 0.0018), and 16.3% (8) and 34.3% (23) in previously treated cases (p = 0.0305). Newly diagnosed and previously treated TB patients from the short-term DOTS-covered county were at higher risk for overall drug-resistance TB and MDR-TB. Standardized diagnosis and treatment strategies for drug-resistant TB are urgently needed for effective control of MDR-TB in rural China.

The anergy panel: An ineffective tool to validate tuberculin skin testing