Pulmonary infections with nontuberculous mycobacteria (NTM) are recognized as a problem in immunodeficient individuals and are increasingly common in older people with no known immune defects. NTM are found in soil and water, but factors influencing transmission from the environment to humans are mostly unknown. Studies of the epidemiology of NTM disease have matched some clinical isolates of NTM with isolates from the patient's local environment. Definitive matching requires strain level differentiation based on molecular analyses, including partial sequencing, PCR-restriction fragment length polymorphism (RFLP) analysis, random amplified polymorphic DNA (RAPD) PCR, repetitive element (rep-) PCR and pulsed field gel electrophoresis (PFGE) of large restriction fragments. These approaches have identified hospital and residential showers and faucets, hot-tubs and garden soil as sources of transmissible pathogenic NTM. However, gaps exist in the literature, with many clinical isolates remaining unidentified within environments that have been tested, and few studies investigating NTM transmission in developing countries. To understand the environmental reservoirs and transmission routes of pathogenic NTM, different environments, countries and climates must be investigated.

Non-tuberculous mycobacteria (NTM) are environmental microbes that cause a variety of diseases both in immunocompromised and immunocompetent patients. Epidemiologic data indicate that there has been a global rise in the incidence of NTM infections. It has also been noted that NTM infections have a predilection to occur in postmenopausal women. In a recent study, it was demonstrated that in patients with non-CF bronchiectasis the probability of NTM isolation was significantly higher in elderly female patients and in those with a low body mass index. However, the mechanisms of causality of these gender differences and morpho-phenotypes remain enigmatic. The present study reviews the data and plausible mechanisms which might provide clues to this gender susceptibility and morpho-phenotypes of patients with bronchiectasis and NTM.

Background: Dihydrofolate reductase (DHFR) (dfrA gene) is an essential enzyme for cell survival and an unexplored target in Mycobacterium tuberculosis (Mtb). This study was carried out to analyze mutations in the dfrA gene amongst 20 clinical DNA samples from Mtb isolates obtained from Mumbai, India. Methods: Sequencing of the PCR amplified dfrA gene from these DNA isolates revealed a point mutation in one strain, leading to a glutamic acid to glycine change. in silico simulation studies revealed a surface alteration in the enzyme due to this E84G mutation. The amplified mutant gene was cloned and expressed. The mutant protein was assessed against known DHFR inhibitors: Methotrexate and Trimethoprim. Results: An increased affinity for inhibitor Trimethoprim and native substrate dihydrofolate was observed with the mutant. Methotrexate did not vary in its activity with both the enzyme forms. Conclusions: The Glu84Gly point mutation may lead to a variation in the strain which may cause resistance in the future.

Background and objectives: Bacterial DNA topoisomerases are unique in maintaining the DNA topology for cell viability. Mycobacterium tuberculosis (MTB) DNA gyrase, a sole type II topoisomerase has a larger scope as a target for developing novel therapeutics. In this study, an effort was made towards the design and synthesis of benzothiazinone-piperazine hybrid analogues to obtain the possibility of it to lead development through the molecular hybridization technique. Methods: A five-step scheme was followed to obtain a series of 36 benzothiazinone-piperazine derivatives and to evaluate them for Mtb DNA gyrase inhibition, antimycobacterial and cytotoxicity studies. Results: Compound N-(4-chlorophenyl)-4-(6-nitro-4-oxo-4H-benzo[e][1,3]thiazin-2-yl)piperazine-1-carbothioamide (18) showed greater inhibitory potential with an IC₅₀ of 0.51±0.16 μM in the DNA supercoiling assay of Mtb with a moderate anti-tubercular activity of 4.41 μM. The compound even passed the safety profile of eukaryotic cell cytotoxicity with a 1.81% inhibition in the RAW 264.7 cell line at 100 μM concentration. Conclusions: This study describes the discovery of benzothiazinone as gyrase inhibitors with potent Mtb MIC and inhibitory profiles of the gyrase enzyme with less cytotoxic effect. Furthermore, it is believed that this class of compounds has the potential to be further developed as an anti-TB drug candidate.

Aims: The current study was designed to document medicinal plant species that are traditionally used to treat tuberculosis (TB) by Ghanaian communities. Methods: The medicinal plants used against TB or its signs and symptoms were selected using library and online published data searches. A guided questionnaire interview was also conducted with a botanist involved in plant collection at the Centre for Scientific Research into Plant Medicine (CSRPM) at Mampong. Data obtained were entered in Excel and summarized into means and frequencies using SPSS 12.0.1 for windows, and expressed as tables and bar graphs. Results: A total of 15 medicinal plant species distributed between 13 genera and 13 families were documented. The following medicinal plant species were found to be used against TB in Greater Accra and Eastern parts of Ghana: Azadirachta indica A. Juss. Stem bark (Meliaceae), Hygrophila auriculata Heine, whole plant (Acanthaceae), Chenopodium ambrosioides L. leaves (Amaranthaceae), Coix lacryma-jobi L. glumes (Poaceae), Solanum torvum Sw. unripe fruits (Solanaceae), Solanum torvum Sw. leaves (Solanaceae), Bidens pilosa L. whole plant (Asteraceae), Phyllanthus fraternus G.L. Webster leaves (Phyllanthaceae), Dissotis rotundifolia (Sm.) Triana, leaves (Melastomataceae), Cymbopogon giganteus Chiov. Leaves (Poaceae), Cyperus articulatus L. roots (Cyperaceae), Allium sativum L. bulb (Amaryllidaceae), Zingiber officinale Roscoe, rhizomes (Zingiberaceae), Allium cepa L. bulbs (Amaryllidaceae), Allium cepa L. leaves (Amaryllidaceae), Aloe vera var. barbadensis aqueous extract from leaves (Xanthorrhoeaceae), Aloe vera var. barbadensis organic extract from leaves (Xanthorrhoeaceae), Cocos nucifera Linn, water (Arecaceae) and Cocos nucifera Linn. Husk (Arecaceae). Conclusions: The collected plant species could be a source of a new class of drugs against TB. Bioactivity guided fractionation is recommended to identify lead compounds for antimycobacterial activity. The current paper documents for the first time medicinal plant species used by Ghanaian communities to treat TB. These results are a basis for selection of plants for further pharmacological, toxicological and phytochemical studies in developing new plant-based antimycobacterial drugs.

Tuberculous meningitis (TBM) is a serious form of disease of the central nervous system. Early and accurate diagnosis of the disease and effective treatment are key important factors to contain the disease. The disease presents as chronic meningitis where other partners such as fungal meningitis, neurosyphilis, cysticercal meningitis, carcinomatous meningitis and partially treated pyogenic meningitis share a similar clinical picture making the diagnosis complicated. Culturing of the pathogen Mycobacterium tuberculosis (MTB) from the cerebrospinal fluid (CSF) sample has shown a poor response. The main immunological method for the immunodiagnosis of TBM is the detection of an antibody response in the CSF. In the present study, total Mtb sonicated extract antigen was used for ELISA and Western blot. ELISA shows overall immune response of the test sample, whereas Western blotting reveals the specific reactivity to a particular molecular weight antigen. This would also reveal the immunodominant antigen. A total of 300 CSF samples were analyzed by both ELISA and Western blotting. Of the 240 clinically suspected TBM cases, 111 samples were positive by ELISA and 81 samples by Western blot. A total of 76 CSF samples were positive by both ELISA and Western blot. None of the control samples showed positivity either by ELISA or by Western blot. TBM patients revealed major antibody reactivity to 30–40kD region, followed by 14kD region. ELISA is sensitive with mild non-specific binding, but Western blot is specific in detecting the immune response. The findings will be useful in definitive immunodiagnosis of TBM.

Objective: To analyze determinants of success and death in multidrug-resistant tuberculosis patients (MDR-TB; resistance to, at least, isoniazid and rifampicin) placed on treatment in Bulgaria during the period September 2009 to March 2010 using logistic regression. Results: Fifty MDR-TB patients started treatment. Male:Female ratio was 2.3:1; mean age 43 years (range: 18–77); 19 patients (38%) were new; median duration of disease before treatment was 5 years (range: 1–13). All patients tested negative for HIV. Eight cases had XDR-TB (MDR-TB plus resistance to any fluoroquinolone and any second-line injectable). Twenty-four months after starting treatment, 24 patients (48%) had a successful outcome, in 6 (12%) treatment failed, 19 (38%) died, and one (2%) interrupted treatment. XDR-TB cases experienced higher mortality than others (75% vs. 30.9%, respectively, P < 0.05). Sputum smear positivity at start of treatment and weight loss or no weight gain were positively associated with death (adjusted Odds ratio: 5.16; 95% confidence interval: 1.16–22.84 and 5.61; 1.48–21.20, respectively) and negatively with success (0.13; 0.02–0.94 and 0.02; 0.00–0.19). No previous TB treatment increased likelihood of success (7.82; 1.09–56.15). Discussion and conclusions: Most MDR-TB patients in this first treatment cohort using WHO-recommended norms had advanced disease explaining the high mortality and low success. Early, adequate treatment of MDR-TB patients can improve outcomes and avert transmission.

Background: Mycobacterium ulcerans (MU) produces mycolactone toxin when infected with a plasmid. Toxin is cytotoxic and immunosuppressive, causing extensive destruction of tissues, leading to large ulcers on exposed parts of the body. Spontaneous healing by secondary intention leads to contractures, subluxation of joints, disuse atrophy, distal lymphedema and other complications. The disease is endemic in some communities within the middle belt of Ghana. Objective: To document the clinical and epidemiological features of MU disease in the middle belt of Ghana and the outcome of treatment. Patients and methods: Patients with lesions suspected to MU disease were screened by community workers. Lesions were confirmed by any of the following: direct smear examination, culture, polymerase chain reaction (PCR), or histopathology. Patients were treated with rifampicin (10 mg/kg orally) and streptomycin (15 mg/kg IM) combination for eight weeks. Patients selected for surgical treatment included cases where medical treatment had failed, cases where medical treatment is contraindicated, cases presenting late with complications and recurrent cases. Results: 258 patients were seen in the Ahafo Ano, Amansie Central, Amansie West, Asunafo, Asutifi, and Upper Denkyira districts of Ghana between 2005 and 2012. Their ages ranged from 1 year 3 months to 98 years, with a mean age of 29.8 (SD 20.4). The clinical forms of MU disease seen were: papule (0.5%), nodule (1.5%), chronic osteomyelitis (1.5%), contracture (1.5%), edematous lesion (3%), and ulcer (92%). Uncommon complications include subluxation of knee joint, salivary gland fistula and Marjolin's ulcer. The lesions were distributed as follows: head and neck (6.8%), upper limb (20.3%), trunk (1.7%), and lower limb (71.2%). Conclusion: MU disease in the middle belt of Ghana can be controlled by early case detection and adequate curative treatment.

Background: Tuberculosis (TB) infection and spread are preventable, and TB disease is curable depending on individual and community knowledge of causes of the disease, mode of prevention and cure. An earlier educational intervention carried out in Akwa Ibom State (AKS) of Nigeria in 2006 created awareness of the disease and improved utilization of orthodox medical facilities of residents in 34 communities who had symptoms of TB. Objective: The overall aim of this program is to reduce the burden of TB disease in 18 communities of AKS through educational intervention, TB case detection and integration into the State National Tuberculosis and Leprosy Control Programme (NTBLCP), as well as build laboratory capacity to improve TB case detection and control. Methods: Prior to the educational intervention in each community, standard pretested questionnaires were administered to residents to test their knowledge, attitudes and practices concerning TB. Information about causes, symptoms and prevention of TB was disseminated in community town halls, churches, markets and schools. Individuals who were coughing for three weeks or more were investigated for TB following clinical examination by a physician. Three sputum samples (spot-morning-spot) were obtained from each individual and examined microscopically for the presence of acid-fast bacilli (AFB) using the Ziehl–Neelson staining technique. Those with positive AFB results were integrated into the existing NTBLCP treatment facilities for immediate commencement of Directly-Observed Therapy Short Course (DOTS). Treatment outcome was monitored by retesting patients' sputum after two, five and seven months. Two new laboratories were facilitated while existing laboratory capacity was built by providing higher resolution microscopes, power generating plants, refrigerators, locally-fabricated incinerators and furnishing of staff offices. The program was facilitated by a public–private partnership. Effective Health Care Alliance Research Programme (EHCARP-Nigeria), in collaboration with Nigeria National Petroleum Cooperation and Mobil Producing Nigeria Unlimited (NNPC/MPN) Joint Venture, utilized health personnel from the Akwa Ibom State NTBLCP who conducted laboratory testing and supervised the treatment. Results: The 916 responses to the questionnaires showed that 65.3% (549/841) correctly identified that TB is airborne, and 86% (749/871) were aware that TB could be cured by anti-TB medication. Responses to care-seeking attitudes were provided by 123 respondents. Of this number, fear of stigmatization was the reason for 31% (38) seeking care in unorthodox facilities, while 43.1% (53) did not believe that orthodox medicine could cure their symptoms. Of the 374 detected cases, 9 did not commence treatment. Hence, 365 were placed on DOTS; 36 defaulted, while 11 either died or failed to convert after the seventh month. At the end of month 8, cure was achieved for 87.1% (318). Conclusion: Although the previous intervention may have contributed to the good knowledge about TB and care-seeking attitudes displayed by respondents in the communities, sustaining active case finding through public–private partnership can go a long way to reduce TB burden, especially in rural communities where healthcare systems are generally weak or inadequate. Adequate funding of TB control activities is critical in eliminating TB as a public health problem, and the private sector participation such as this is a welcome development.

This case report introduces a 26-year-old male IV drug abuser with fever, abdominal pain and distension referred to the emergency ward. According to these findings, abdominal tenderness and involuntary guarding, an explorative laparotomy was performed. Multiple biopsies of omentum, peritoneum and liver were taken. Pathologic assessment of multiple biopsies confirmed intra-abdominal TB infection.

Endobronchial tuberculosis (EBTB) is a tuberculous infection of the tracheobronchial tree with microbiological and histopathological evidence, with or without parenchymal involvement. EBTB commonly presents as acute or insidious onset cough, wheeze, low grade fever, and constitutional symptoms. In elderly patients, other differentials like malignancy and pneumonia may lead to misdiagnosis. Hence, bronchoscopy is essential for confirmation of EBTB. Here we report a rare presentation of EBTB in a 65 year old patient who presented with 3 months history of fever and cough and have multiple endobronchial vesicular lesions on bronchoscopy.

In order to assess the confusion attendant with current definitions of extrapulmonary tuberculosis, pleural and miliary disease, a set of 37 papers published which analyzed disease states were assessed for how the terms adhered to official definitions of the American Thoracic Society, the World Health Organization, and the Centers for Disease Control. The findings showed uncertainties in the classification of extrapulmonary disease, a frequent inconsistency in the inclusion of pleural disease within pulmonary rather than extrapulmonary disease, and the ambivalent use of the terms pleural and disseminated tuberculosis. Further attention by editors and authors is needed in the use of tuberculosis definitions.

The tuberculosis of the hand and the wrist is a rare entity. Affecting the scapholunate joint is exceptional. It is usually diagnosed at an advanced stage of carpal destruction, due to slowly development of the symptoms. We report the case of a 58-year-old female, presenting as wrist pain for 3 months. Clinical study showed a local swelling in the left wrist, the mobility of the wrist was normal but painful at the end of motion. The diagnosis of osteoarticular tuberculosis was suspected after radiological and biological study then confirmed after histological study. Antibacillary chemotherapy during 12 months promoted healing and good outcome.