Current tuberculosis (TB) treatment requires 6 months of combination therapy with isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol for active TB and 9 months of INH or 3 months of rifapentine (RFP) + INH for latent TB. The lungs of patients with active and latent TB contain heterogeneous mixtures of cellular and caseous granulomas harboring Mycobacterium tuberculosis bacilli ranging from actively replicating (AR) to nonreplicating (NR), phenotypically drug-resistant stages. Several in vitro models to obtain NR cells were reported, including exposure to hypoxia, nutrient starvation, acid + nitric oxide, and stationary phase. Overall, these models showed that RIF, RFP, PA-824 (PA), metronidazole (MZ), bedaquiline (BQ), and fluoroquinolones were the most active drugs against NR M. tuberculosis. In hypoxia at pH 5.8, some combinations killed AR plus NR cells, as shown by lack of regrowth in liquid media, whereas in hypoxia at pH 7.3 (the pH of the caseum), only RIF and RFP efficiently killed NR bacilli while several other drugs showed little effect. In conventional mouse models, combinations containing RFP, BQ, PA, PZA, moxifloxacin, sutezolid, linezolid, and clofazimine sterilized animals in ≤2 months, as shown by lack of viable bacilli in lung homogenates after 3 months without therapy. Drugs were less effective in C3HeB/FeJ mice forming caseous granulomas. Overall, in vitro observations and in vivo studies suggest that the search for new TB drugs could be addressed to low lipophilic molecules (e.g., new rpoB inhibitors with clogP < 3) killing NR M. tuberculosis in hypoxia at neutral pH and reaching high rates of unbound drug in the caseum.

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Every year >200,000 new leprosy cases are registered globally. This number has been fairly stable over the past 8 years. The World Health Organization has set a target to interrupt the transmission of leprosy globally by 2020. It is important, in terms of global action and research activities, to consider the eventuality of multidrug therapy (MDT) resistance developing. It is necessary to measure disease burden comprehensively, and contact-centered preventive interventions should be part of a global elimination strategy. Drug resistance is the reduction in effectiveness of a drug such as an antimicrobial or an antineoplastic in curing a disease or condition. MDT has proven to be a powerful tool in the control of leprosy, especially when patients report early and start prompt treatment. Adherence to and its successful completion is equally important. This paper has reviewed the current state of leprosy worldwide and discussed the challenges and also emphasizes the challenge beyond the elimination in leprosy.

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Background: National tuberculosis (TB) programmes globally rely heavily on passive case finding for detecting TB in the community as advocated by the World Health Organization (WHO). TB case detection is low in Nigeria despite improvement in TB services and coverage. Methods: A retrospective evaluation of an active case-finding intervention utilizing community-based approaches and targeted systematic TB screening in Ebonyi State, Nigeria was done. The analysis was performed using Epi Info. Results: Using community-based and health-facility-based systematic screening strategies, 218,751 persons were screened, with 19.7% of them being presumptive TB cases. Among these, 23,729 (55.1%) submitted sputum samples for microscopy, and 764 (3.2%) had smear-positive TB. In addition, 683 individuals were diagnosed with other forms of TB using X-ray and clinical evaluation giving a total of 1447 all forms of TB cases. The overall number needed to screen (NNS) to find one person with all forms of TB through the project was 151. The NNS was 53 for general outpatients, 88 through contact tracing, and 110 among HIV-infected persons. Conclusions: Active case-finding strategies achieved good yields though early loss to follow-up was high. Active case finding is recommended for integration into national TB control policy and practice.

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Background: Tuberculosis (TB) ranks as the second leading cause of death from an infectious disease worldwide. Early diagnosis of Mycobacterium tuberculosis in clinical samples becomes important in the control of TB both for the treatment of patients and for curbing of disease transmission to the others in the community. The study objective was to perform Ziehl–Neelsen (ZN) staining, fluorochrome staining, line probe assay (LPA), and loop-mediated isothermal amplification (LAMP) assay for rapid detection of pulmonary TB (PTB) and to compare the results of LPA and LAMP in terms of sensitivity, specificity, and turnaround time. Methods: A total of 891 sputum samples from clinically diagnosed/suspected cases of TB were subjected to ZN and fluorochrome staining. Smear positive samples were subjected to LPA, and smear negative were cultured on Lowenstein–Jensen media. A total of 177 samples were subjected to liquid culture and LAMP. Conventional culture was considered as “gold standard” for calculation of parameters. Results: Light-emitting diode fluorescence microscopy had the same sensitivity as ZN with similar high specificity. LPA was performed on 548 sputum samples which includes 520 smear positive and 28 smear negative culture positive samples and multidrug-resistant TB was detected in 32.64%. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TB-LAMP on direct sputum samples was found to be 98.96%, 95%, 96%, and 98.70%, respectively, when compared with ZN smear microscopy. By considering culture as “gold standard,” LAMP showed a sensitivity, specificity, PPV, and NPV of 98.94%, 96.34%, 96.90%, and 98.75%, respectively. The sensitivity and PPV of TB-LAMP were 98.97% and 96%, respectively, when compared with LPA. Conclusions: A successful rapid laboratory diagnosis of PTB is possible when one combines the available methodology of microscopy, culture as well as molecular techniques. The LAMP assay was found to be simple, self-contained, and efficacious for early diagnosis of suspected cases of PTB with advantages of having a high throughput, no requirements of sophisticated equipment, and complex biosafety facilities.

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Background: This study aimed to investigate the epidemiological characteristics of pulmonary tuberculosis (TB) in Heilongjiang province from 2008 to 2015 and provide scientific basis for the development of TB control. Methods: The TB patients were confirmed by chest radiography and sputum examination, and the TB incidence data were from the Chinese Tuberculosis Management Information System, population data were from the National Basic Information System. Results: By the SPSS statistics analysis, there was a total of 280,767 cases of TB registered in Heilongjiang province from 2008 to 2015; the average annual incidence rate was 91.60/100,000, the male incidence rate was 122.81/100,000; the female incidence rate was 59.39/100,000, and TB incidence increased as the growth of age. Farmers' incidence was higher than other occupations; Shuangyashan city incidence of 122.09/100,000 was highest during 13 cities in Heilongjiang province, all above factors existed significant difference. Conclusions: As a result, TB incidence was higher among the elderly, males and farmers, so it is important to promote the scientific knowledge about the prevention and treatment of TB. In particular, it is necessary to strengthen the health education of the elder aged people and improve the self-care awareness and ability to prevent TB.

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Background: The aim of this study was to evaluate the etiology of hemoptysis in patients presenting to emergency department of Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. Method: Prospectively 110 patients presenting to the emergency department with history of hemoptysis were screened for a period of one and half years. Out of these, 64 patients having true hemoptysis were enrolled in the study. The patients were clinically evaluated with detailed history. Radiological evaluation included chest x rays and computerized tomogram. Sputum examination and bronchoscopy was done to establish the etiology. All the patients were conservatively managed using intravenous fluids, antibiotics, anti-tussive and anti-fibrinolytic drugs. Bronchial/pulmonary artery embolization was performed for controlling ongoing bleeding/re-bleeding. All the patients were followed up till discharge or death. Results: The mean age was 41.8 ± 15.16 years with male preponderance. Pulmonary tuberculosis (active/ sequel) was the most common etiology (65%), followed by community acquired pneumonia (10.93%), bronchiectasis (9.3%), carcinoma lung (7.18%) and miscellaneous causes (8.6%). Almost all patients (98%) had severe hemoptysis (>100 ml in 24 hours). Abnormalities in bronchial circulation were present in 59.4% and 14% of patients had pulmonary circulation abnormalities. 65% patients responded to conservative treatment. 23.4% patients under went intervention out of which 73.3% underwent bronchial artery embolization (BAE) and remaining 26.6% underwent pulmonary artery embolization (PAE). One patient died during hospital stay due to necrotizing pneumonia and another left hospital against medical advice (outcome unknown). Conclusions: TB (active/sequel) remains the most common cause of hemoptysis in patients admitted in emergency department. Non-TB causes like primary bronchiectasis, carcinoma lung and pneumonia are other important causes. Conservative management suffices in majority patients for controlling active bleed.

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Background: To investigate the factors affecting treatment outcome of extensively drug resistant tuberculosis (XDR-TB) in Gujarat, India. Methods: A prospective, observational study was conducted on patients with XDR TB from January 2012 to October 2016. Details of demography, clinical symptoms, sputum/culture and radiological examination, drug treatment, adverse drug reactions (ADRs) and treatment outcome were recorded in pretested case record form (CRF). Data was analyzed using Fisher's exact test and paired student's t test. Results: Out of 112 patients, 83 (74%) were men and 29 (26%) were women and majority of belonged to age group of 16 – 45 years. Majority of patients (79%) received standardized treatment. A total of 61 (54%) patients converted to sputum culture negative by 12 months and out of these, 49 turned sputum culture negative within initial 6 months of treatment. Successful treatment outcome was seen in 29 (25.89 %). Age ≤40 years (P<0.05), body mass index > 18.5 (P<0.05) and sputum/culture conversion at three month (P<0.001) were positive predictors for successful treatment outcome, while tobacco chewing habit (P<0.05) and alcohol consumption (P<0.05) were negative predictors for the successful treatment outcome. Out of 83 (74.1 %) patients with unsuccessful treatment outcome, 58 (51.78 %) died, 11 (9.82 %) were defaulter and 10 (8.92 %) were treatment failure. Factors positively associated with death were very low BMI (< 18.5), concomitant diseases and harmful personal habits. Conclusions: Treatment outcome of XDR TB patients is extremely poor with high mortality rate.

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Background: Health-care workers (HCWs) are at increased risk of acquiring tuberculosis (TB) than the general population. While national-level data on the burden of TB in general population is available from reliable sources, nationally representative data on latent tuberculosis infection (LTBI) burden in HCWs in the high burden countries is lacking. Methods: A prospective study was carried out to assess the risk of TB infection among HCWs who directly engage in medical duties. HCWs were recruited between January 2014 and December 2015. A structured questionnaire was used for risk assessment of TB infection among HCWs, including sociodemographic characteristics (e.g., age, gender, period of professional work, and employed position), knowledge of TB prevention and control, and history of professional work. A single-step tuberculin skin test (TST) using 5 international units (IU; 0.1 ml) of tuberculin (purified protein derivative from Mycobacterium bovis Bacillus Calmette–Guérin [BCG]). TB infection was determined using a TST induration ≥10 mm as a cutoff point for TST positivity. TST-positive participants were further subjected to detailed clinical evaluation and chest radiography to rule out active TB. The associations between TB infection and the sociodemographic characteristics, duration of possible exposure to TB while on medical duties, BCG vaccination, and knowledge about TB were estimated using Chi-square test. A two-sided P < 0.05 indicated statistical significance. Results: A total of 206 eligible HCWs signed the informed consent and completed the questionnaires between January 2014 and December 2015. The age of the participants ranged from 18 to 71 years, with a mean age of 27.13 years. TST induration size (mean 6.37 mm) the TST results suggested that 36.8% (76/206) were infected with TB using a TST induration ≥10 mm as a cut-off point. All 76 TST-positive HCWs showed no evidence of active TB in clinical evaluation and chest radiography. However, during the study, two HCWs developed pulmonary TB (both TST baseline test negative). Statistical analysis suggested that age, duration of employment as a health-care professional, literacy status, and working in medical wards/OP/Intensive Care Unit were significantly associated with TB infection. Conclusions: Many studies propose serial tests of LTBI as effective occupational protection strategies. However, practically, it is not feasible because it has to be done at frequent intervals, but how frequently to be done is not clear. Another concern is even if found to have LTBI, there are no clear consensus guidelines about the treatment in high prevalence settings. The prevalence of LTBI is so high in countries like India that affected HCWs could not be exempted from working in high-risk areas. The depth of knowledge of TB prevention and control among HCWs should be improved by regular infection control training.

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This report describes parotid gland tuberculosis in a 38-year-old female patient that presented with a firm, painless, progressively increasing swelling over the right preauricular region. Diagnostic workup including contrast enhanced computerized tomography neck and subsequent fine needle aspiration cytology of the swelling made the final diagnosis. The patient responded favorably with anti-tubercular therapy.

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Background: An increase in NTM diseases in the international scenario has been observed in recent years. Aims: To analyze the epidemiological and laboratory profiles of patients with isolation of nontuberculous mycobacteria (NTM) over one decade. A retrospective analysis of records of a mycobacterial reference laboratory found 135 cases with isolation of NTM. Methods: Clinical and epidemiological data were collected from the records of government health clinics and from the State notification system (TBWEB). The cases were geocoded by location based on the street address in the Mercator Transverse Universal projection, Datum SAD/69 and MapInfo software. Results: Most patients were male (66.7%), older than 50 years (40%) and had only completed elementary schooling (38.5%). Associated health problems were found in 71.8% of the subjects, with 43.7% being HIV positive and 25.9% having had tuberculosis in the past. Hospitals were the most able institutions to diagnose cases (45.2%). Sputum was the most common material tested (63.0%) with the bacilloscopy being positive in 33.3% of cases. The most common mycobacteria species in the region were Mycobacterium avium and M. abscessus/M. massiliense/M. bolletii. When the regional reference municipality was analyzed, M. avium and M. fortuitum were the most common species isolated in the urban area. Conclusions: In the study region, mycobacteriosis most affected adult males with low schooling. Most patients presented comorbidities in particular co-infection with the HIV virus. M. avium is the most prevalent species in the region with the M. abscessus/M. massiliense/M. bolletii species being the main cause of nosocomial infections.

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Background: In Colombia, epidemiological and clinical information related to pediatric tuberculosis (TB) is scarce. Data are needed to define the impact of the disease and to strengthen measures for detection and treatment. It is proposed to analyze the pediatric population diagnosed with pulmonary TB in a national reference institution. Methods: Retrospective observational study including pediatric patients with pulmonary and miliary TB, and pulmonary and extrapulmonary involvement, treated between January 1, 2008 and December 31, 2016. A descriptive analysis of the selected variables was done. Results: A total of 93 cases of diagnosed TB were identified, of which 61 cases were classified as pulmonary (65.6%). The location of TB occurred only in lungs in 51 patients (83.6%), was miliar in 3 (4.9%), pulmonary and extrapulmonary involvement in 7 patients (11.5%). The mean age was 7.5 years (0.5–18 years). Clinical criteria used for diagnosis was related to 98.3% of the cases, whereas radiological criteria in 90.2%. Bacteriological criterion was met in 42.6% of the cases. The most frequent symptoms were coughing (83.6%), fever (63.9%), and weight loss (26.2%); human immunodeficiency virus co-infection occurred in 3 cases (4.9%). During treatment, 5 mortality cases were recorded, although they were not attributable to TB. Conclusions: The epidemiological characterization of pediatric patients with pulmonary TB helps to achieve a better diagnostic approach in this population. Improving monitoring and follow-up activities in children with pulmonary TB, as well as promoting actions for adequate prevention and treatment is highly necessary.

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Background: Myanmar, one of the high tuberculosis (TB) burden countries, is in serious need of research work to develop strategies aiming to tackle the problem. Conducting a study on the knowledge of the population will help understand the flaws in the National TB Control Program (NTP), and how to correct them, and further strategic planning to reach the goals of Sustainable Development Goals. Aims: The aim of the study was to access sociodemographic characteristics, knowledge, and behavioral practice of TB among the community members in Ngar Syu Taung Village, Hlegu Township. This is a cross-sectional descriptive study. The number of defined person was 200. Methods: Nonprobability convenience sampling method was used. Data collection method used was face-to-face interviewing method using questionnaires. They were collected by house officers as a part of the community medicine training program. Results: Less than half of the respondents were not aware of TB meningitis (41%) and TB osteomyelitis (49%) and they are not aware that diabetic patients are one of the commonly infected people (41.5%). Furthermore, less than one-third of the patients know that TB can infect the gut (23%) and cause bowel obstruction (30.5%). Conclusions: Wrong ideas should be tackled, and lacking knowledge should be enlightened. Nationwide studies using stronger study designs are also urgently needed. Implementing these evidence into NTP is necessary for Myanmar, to escape from being a TB high-burden country.

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Pediatric tuberculosis (TB) is known to have a wide range of presentations, and if left untreated, primary TB may lead to bone and joint involvement. The literature on this topic is very scarce, and no comprehensive systematic review or meta-analysis of the current knowledge is available to date. The aim of this study is to identify and analyze the literature with highest impact based on citation rate analysis. All databases of the Thomson and Reuters “Web of Knowledge” were used to conduct our search of the 100 most cited articles on this topic published between 1950 and 2014. The included articles were analyzed in terms of citation rate, age, study type, area of research, level of evidence (LOE), and more. All 100 articles were published between 1967 and 2011 in 51 different journals. The average citation rate was 74.26, all articles were on average 23.1 years, and most studies were originated from India (n = 22), followed by the USA (n = 21). The majority of publications were review articles (42%), described clinical course (n = 48), and assigned an LOE IV (44%). TB infection is a high burden disease in low-income countries but widely studied in a fi rst world setup. This research gap between the geographic distribution of disease burden and origin of publications could initiate possibilities for high-burden countries to share their opinion. Their experience is of a high level of importance and relevance which furthermore is necessary to create a more accurate picture of pediatric musculoskeletal TB burden in literature.

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Background: We aimed to study the antigen-specific antibody responses in mice immunized with recombinant DNA vaccines constructs of pUMVC6 and pUMVC7, containing RD1 and RD9 genes of Mycobacterium tuberculosis. Methods: We immunized mice with the parent and recombinant plasmids and sera were collected and tested for antibodies against pure recombinant proteins of RD1 (PE35, PPE68, EsxA, EsxB) and RD9 (EsxV), peptide mixtures of each protein and their individual peptides using enzyme-linked immunosorbent assays. The optical density (OD) values were measured at 405 nm. E/C (OD in antigen-coated wells/OD in antigen uncoated wells) were calculated, and the values of E/C>2 were considered positive. Results: RD1 and RD9 antigen-specific antibodies were detected in sera of mice immunized with the recombinant DNA vaccine constructs (E/C >2.0). With respect to peptide mixtures and single peptides, only PE35_mixand P6 of PE35; PPE68_mixand P19, P24 of PPE68 showed antibody reactivity with sera of mice immunized with the corresponding recombinant pUMVC6 and/or pUMVC7 DNA vaccine constructs. Conclusions: The results confirm in vivo expression and immunogenicity of all the five RD1 and RD9 genes cloned in both of the DNA vaccine vectors.

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Background: It is of critical importance to improve and maintain the quality of chest radiography (CXR) to avoid faulty diagnosis of respiratory diseases. The study aims to determine the effectiveness of a training program in improving the quality of CXR among radiological technologists (RTs) in Laos. Design: This was a cross-sectional study, conducted through on-site investigation of X-ray facilities, assessment of CXR films in Laos, both before and after a training course in November 2013. Methods: Each RT prospectively selected 6 recent CXR films, taken both before and within approximately 6 months of attending the training course. Consequently, 12 CXR films per RT were supposed to be collected for assessment. The quality of the CXR films was assessed using the “Assessment Sheet for Imaging Quality of Chest Radiography.” Results: Nineteen RTs from 19 facilities at 16 provinces in Laos participated in the training course. Among them, 17 RTs submitted the required set of CXR films (total: 204 films). A wide range of X-ray machine settings had been used as tube voltage ranged from 40 to 130 kV. The assessment of the CXR films indicated that the training was effective in improving the CXR quality regarding contrast (P = 0.005), sharpness (P = 0.004), and the total score on the 6 assessment factors (P = 0.009). Conclusions: The significant improvement in the total score on the 6 assessment factors, in contrast, and in sharpness, strongly suggests that the training course had a positive impact on the quality of CXR among a sample trainees of RTs in Laos.

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Background: Nontuberculous mycobacteria (NTM) cause opportunistic infections with increasing frequency in immunocompromised humans. Water is one of the natural sources for transmission of NTM and plays a major role in the epidemiology of NTM infections. This study evaluated the efficacy of calcium hypochlorite and ultraviolet irradiation (UV) to eliminate potentially zoonotic NTM species such as M. marinum and M. fortuitum. Materials and Methods: Bacterial suspensions containing1-4 × 10⁵ CFU/ml were exposed to 5, 50, 100, 1,000 and 10,000 mg/L of Ca (OCl)₂for 1, 5, 10, 15, 20, 30 and 60 minutes, and 6,000 μW/cm² UV dose for 5, 10, 20, 30, 60 and 120 seconds. Results: Of the two methods tested, UV irradiation was more effective than chlorine in achieving three log reduction in viable bacterial count (UV dose 6,000 μW/cm², exposure time 60 S) as well as in eliminating the organisms (UV dose 17,000 μW/cm², exposure time: 30 S). When 10,000 mg/L of chlorine was used, 10 and 20 min contact times were required to achieve three log inactivation and complete elimination of M. fortuitum respectively. Conclusion: Our study suggest that initial disinfection of water by chlorine at the water treatment plant followed by UV irradiation at the household level would minimise the spread of NTM to the susceptible population via drinking water.

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Initially diagnosed with cervical lymphadenitis, a 15-year-old boy was started with category I anti-tuberculosis (TB) drugs. Follow-up investigations led to isolation and identification of Mycobacterium lentiflavum by multiple diagnostic and identification approaches. Observation of this rare pathogen from human origin urges cautious diagnosis while attending TB cases.

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Background: Bacterial meningitis is still one of the major causes of deaths, disabilities, and mental retardation in children in Morogoro region. To study the current meningitis burden, we evaluated the common bacterial isolates and clinical outcome of the disease in the region. Methods: We conducted a hospital-based prospective study on 1352 children aged between 7 days and 12 years admitted in pediatric wards at Morogoro Regional Referral Hospital for 7 months. Cerebrospinal fluid (CSF) for laboratory microbiological examination was collected by lumbar puncture in 72 children with signs and symptoms of meningitis. Latex agglutination test was used to confirm the bacterial colonies in the culture. Chi-square test was used for relative risk with 95% confidence intervals; statistical analysis and tests were considered statistically significant when P < 0.05. Results: Among 72 CSF samples, 23 (31.9%) were positive for Streptococcus pneumoniae, 6 (8.3%) for Haemophilus influenzae, 5 (6.9%) for Group B Streptococcus, 3 (4.2%) for Escherichia coli, and 1 (1.4%) was positive for Mycobacterium tuberculosis. Furthermore, 34 CSF samples showed no bacteria growth in the culture media. In addition, 39 children (54.2%) did not respond to the treatment, whereas 79.5% (n = 39) of them died, while 20.5% (n = 39) of them were referred to a tertiary hospital. Nevertheless, the incidence of meningitis infection was 5.3% (n = 1352) among the admitted children. Conclusions: S. pneumoniae was the major laboratory-confirmed bacterial isolate associated with meningitis in children. We report for the first time the presence of tuberculous meningitis in Morogoro region. Ziehl–Neelsen staining for acid-fast bacilli should be mandatory for any case clinically suspected for meningitis.

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