The emergence of multidrug-resistant strains of Mycobacterium tuberculosis (MTB), the bacterium responsible for tuberculosis (TB), has rekindled the interest in the role of nutritional supplementation of micronutrients, such as vitamin D, as adjuvant treatment. Here, the growth of virulent MTB in macrophages obtained from the peripheral blood of patients with and without TB was studied. The H37Rv strain genetically modified to express Vibrio harveyi luciferase was used to determine the growth of MTB by luminometry in the human monocyte-derived macrophages (hMDMs) from study subjects. Determination of cytokine levels in culture supernatants was performed using a flow cytometry-based bead array technique. No differences in intracellular growth of MTB were observed between the different study groups. However, stimulation with 100nM 1,25-dihydroxyvitamin D significantly enhanced the capacity of hMDMs isolated from TB patients to control the infection. This effect was not observed in hMDMs from the other groups. The interleukin (IL)-1β and IL-10 release by hMDMs was clearly increased upon stimulation with 1,25-dihydroxyvitamin D. Furthermore, the 1,25-dihydroxyvitamin D stimulation also led to elevated levels of TNF-α (tumor necrosis factor-alpha) and IL-12p40. It was concluded that vitamin D triggers an inflammatory response in human macrophages with enhanced secretion of cytokines, as well as enhancing the capacity of hMDMs from patients with active TB to restrict mycobacterial growth.

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Tuberculosis continues to be a major health problem, and is among the leading causes of morbidity and mortality worldwide. Pulmonary tuberculosis is the commonest and epidemiologically the most important type of tuberculosis as the source of spread in the community. Some patients presenting with pulmonary tuberculosis also have associated multifocal extra-pulmonary tuberculosis and vice versa. Among these patients, some have predisposing factors for the development of disseminated tuberculosis, such as a heavy Mycobacterial load, weak or impaired innate or acquired immunity owing to diabetes, immune therapies, substance abuse or AIDS. Multifocal tuberculosis is characterized by the presence of large multifocal tuberculosis areas in the same or different adjacent or distant organs. This study presents a series of 20 patients with multifocal tuberculosis. Materials and methods: The patients' records were reviewed to locate those with multifocal tuberculosis as well as pulmonary tuberculosis during the period between 4/2003 and 12/2010. A total of 1,388 patients with confirmed open pulmonary tuberculosis were admitted at the tuberculosis center within the Dammam Medical Complex. Out of this group of patients, 20 cases (1.5%) were found to have multifocal tuberculosis. Conclusion: Multifocal tuberculosis is observed both in immunocompetent as well as in those with weak or compromised immune systems. A thorough physical examination is required even in those confirmed pulmonary cases of tuberculosis to suspect and find extra-pulmonary involvement, because it is important from the management and prognostic perspective. The ultimate outcome under DOTS (directly observed treatment short course) was good in the majority of these cases, and only a few of them required surgical intervention.

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Tuberculous meningitis (TBM) is the most severe form of tuberculosis and is commoner in those with immunsuppression. Diagnosis continues to be difficult particularly in resource limited settings, and this may be truer in the setting of pregnancy. We report the case of a pregnant Nigerian who was diagnosed late with atypical features of TBM complicated by cerebral infarction. High index of suspicion and early administration of anti-tuberculous medications as daily therapy according to the national treatment guidelines: 600 mg Rifampicin, 300 mg Isoniazid, 1.2g Pyrazinamide and 800 mg Ethambutol plus 50 mg pyridoxine and 0.4 mg/kg body weight/day dexamethasone which was tapered weekly led to a slow but sustained clinical improvement. The relationship between pregnancy, susceptibility to TBM and presenting features of TBM requires further exploration. Clinicians should also be aware of atypical presentation of TBM in pregnancy, and the suspicion of TBM may be sufficient grounds to initiate empirical anti-tuberculous therapy.

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Background: Myeloperoxidase (MPO), in the presence of hydrogen peroxide and a halide represent an efficient microbicidal mechanism of phagocytic cells. MPO is abundant in neutrophils which also respond to infection by producing large amounts of reactive oxygen species (ROS). MPO, ROS and halide constitute a very toxic antimicrobial system (called the Klebanoff system or KS). Resting mature macrophages do not contain granular MPO and thus are unable to kill pathogenic mycobacteria and some other microorganisms by this system. Experimental: Under the hypothesis that transforming macrophages into peroxidase-positive (PO+) cells, these cells would be able to kill Mycobacterium tuberculosis, in this study, mature macrophages were loaded with exogenous peroxidase and were tested for their capacity to kill the Mycobacterium in the presence or in the absence of hydrogen peroxide. Results: It was found that PO-loaded macrophages eagerly ingest M. tuberculosis, but do not show a significant mycobactericidal activity on this microorganism despite that it is highly susceptible to the Klebanoff system in vitro. Failure of PO-loaded macrophages to kill M. tuberculosis may obey either to an inappropriate location of the exogenous PO in these cells or more likely, to the presence of efficient detoxifying mechanisms in the bacteria. On the contrary, MPO-loaded or unloaded macrophages efficiently killed Listeria monocytogenes. Conclusion: The lack of granular MPO in mature macrophages, and the predilection of mycobacteria to infect these cells are two situations that favor the development of tuberculosis and related diseases, such as leprosy and Buruli ulcer.

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Objective: This study aimed to evaluate the factors associated with pulmonary tuberculosis (TB) among individuals aged 15 years or more in urban Karachi, Pakistan. Design and setting: A case–control design was implemented in three major tertiary-care hospitals to select cases (n = 342) with active pulmonary TB (i.e. two sputum smears positive for Mycobacterium tuberculosis with clinical and radiographic evidence of current pulmonary TB and diagnosed between August 2002 and October 2003. Selected controls (n = 342) were surgery patients from the same hospitals at time of recruitment of the cases, without clinical and radiographic evidence of pulmonary TB. Results: Multivariable logistic regression model showed that daily contact with a pulmonary TB patient (adjusted odds ratio [OR_adj])= 5.07; 95% CI: 3.31, 7.78), and poor housing affordability (i.e. rented vs. owned) (OR_adj= 1.59; 95% CI: 1.13, 2.26) were significantly associated with pulmonary TB status. The overall adjusted summary population attributable risk (%) for both the risk factors together was 38.7. Conclusion: Reaching out to underprivileged TB patients for delivery of DOTS and focused education of patients and their contacts about M. tuberculosis transmission mode may substantially minimize pulmonary TB risk in this and similar settings.

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The following report highlights the case of a 55-year-old female with nasal and middle ear tuberculosis. The diagnosis was confirmed using imagery, histopathological biopsy reports, and Polymerase chain reaction (TB-PCR). The patient was treated with rifampicin (10 mg/kg), isoniazid (5 mg/kg) and pyrazinamide (25 mg/kg) for 9 months. No recurrence was observed after one year of follow-up examination. Both nasal tuberculosis and tuberculous otitis media are currently considered rare diseases, yet if they are evaluated rapidly, there will be a good response to therapy without the need for surgery.

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Objective: Determine the prevalence of latent TB infection in HIV-infected people. Method: Using a cross-sectional study on HIV-infected persons monitored in the Department of Lung and Infectious Diseases of CHU Sylvanus Olympio of Lomé from August 10, 2010 to November 10, 2010. All patients are receiving anti-retroviral therapy and have no clinical or radiological symptoms of TB, and had never received tuberculin skin test (TST) in the last 3 months. The CD4 rate of all patients was more than 200cells/ μl. The diagnosis of latent TB infection is based on the measurement of at least 5 mm of skin induration, 72 h after a subcutaneous injection of 5IU of purified tuberculin. Results: One hundred and fifty four persons were included in the study, of which 107 were female and 47 were male. The median age was 40 years old. Eleven patients were exposed to a risk of TB and only 70.7% of patients had a BCG scar. A suspicion of former TB was found in 18.8% of patients and approximately 45% of patients were very immunocompromised with a CD4 rate between 200 and 350; 117 patients had a positive TST. This represents an overall prevalence of 76% of latent TB infection. Conclusion: The prevalence of latent TB infection obtained with the TST is high in this study. A similar study using the interferon-gamma release assay, which is more specific, would be more helpful to obtain more reliable epidemiological data on patient outcomes and to determine the appropriateness of the use of chemoprophylaxis with isoniazid.

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Evaluation of newer methods and optimization of existing methods for the susceptibility testing of second-line drugs, especially ethionamide, are essential when treatment of multidrug-resistant tuberculosis (MDR-TB) is warranted. The ideal method must clearly demarcate sensitive from resistant strains. Hence, optimization of the conventional minimum inhibitory concentration (MIC) method was attempted using diluted inoculum. The optimized MIC method was evaluated using 206 Mycobacterium tuberculosis strains isolated from new and previously treated tuberculosis patients and were compared with the conventional MIC method and proportion sensitivity (PST) method. The sensitivity and specificity of the optimized MIC method in comparison with the PST method was 74% and 90%. Assessment of the optimized MIC method with the conventional MIC method gave a sensitivity of and specificity of 73% and 98%. Overall agreement between the methods was found to be ≥ 80%. Endowed with the ability to identify the resistant strains precisely, the optimized MIC method can be used for screening resistance to ethionamide.

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Among the disadvantages of smear microscopy for detection of tuberculosis cases is its inability to differentiate between Mycobacterium tuberculosis (MTB) and non-tuberculous mycobacteria (NTM). This study evaluated two, new immunochromatographic assays – Capilia TB-Neo and SD Bioline – on unheated and heated cultures at 80 °C for 30 min respectively for their ability to discriminate between MTB complex and NTM as compared with the molecular Genotype assay. Mycobacteria used in the study were obtained from smear-positive specimens collected from patients at four major hospitals in Cross River State, Nigeria. Capilia TB-Neo and SD Bioline showed sensitivities of 98.8% and 93.8% respectively and 100% specificity for both assays. Heating the isolates did not significantly impact the test performance. Both tests are recommended for use in rapid differentiation of strains isolated in Nigeria.

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Oral vaccination with BCG provides protective systemic immunity against pathogenic mycobacterial challenge. In this study, the anatomical distribution of Mycobacterium bovis BCG following oral vaccination was investigated. Replicating bacteria in the Peyer's patches and mesenteric lymph nodes were present as solitary rods or clusters of two to three bacteria, the majority of which were isolated ex vivo as extracellular forms. Only a minority were shown to be associated with typical antigen-presenting cells. Acid-fast staining of mast cell granules in lymphoid tissues revealed a potential pitfall for these analyses and may explain previous reports of acid-fast ‘coccoid’ forms of mycobacteria in tissues.

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Drug susceptibility testing (DST) of Mycobacterium tuberculosis is a crucial procedure to determine the effective drug regimen for patients' treatment. Reporting of erroneous DST results to the treating physician has adulterous effects on patients. As a first study of its type, the inconsistencies in reporting DST results of rifampicin and isoniazid from Saudi Arabia were assessed. An automated liquid culture-based DST and a molecular mutation detection technique were used. Performance of first-line drug susceptibility testing of 1904 clinical isolates showed 44 inconsistent results. The majority of the cases reported as MDR-TB from the referral laboratories could not reproduce the same results at a different site (Mycobacteriology Research Section). Of the 44 cases, 16 (36.3%) showed false resistance to isoniazid and rifampicin and on the other hand, 14 (31.8%) cases showed false susceptibility to the same drugs. The possible causes for the inconsistencies and recommendations to overcome the biases based on this experience are discussed.

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