Introduction: Tuberculosis (TB) is a disease of public health importance globally. The incidence of pulmonary TB is rising in sub-Saharan Africa. Bilateral adrenal destruction and the use of medications such as rifampicin are possible mechanisms by which TB cause adrenal insufficiency. Failure to promptly recognize adrenal insufficiency may lead to a medical crisis causing death. This systematic review aimed to identify the frequency of adrenal insufficiency, the clinical presentation and its predictors in patients with pulmonary TB in sub-Saharan Africa. Methods: The study was a systematic review. Medical databases and the grey literature were searched. Literature search and studies selection were done following the PRISMA guidelines. Results: The total sample size was 809. The frequency of adrenal insufficiency among patients with pulmonary TB in sub-Saharan Africa was 0.9%–59.8%. Patients with adrenal insufficiency had symptoms such as nausea, vomiting, darkening of the skin, salt craving, and weight loss. Other symptoms were dry, itchy skin, abdominal pain, and muscle pain. The predictors of adrenal insufficiency among patients with pulmonary TB in sub-Saharan Africa were low blood pressure, low blood glucose, presence of multidrug-resistant TB, and low CD4 count. Other predictors were abdominal pain and generalized skin hyperpigmentation. Conclusion: The frequency of adrenal insufficiency in patients with pulmonary TB can be as high as 50%. The presence of low blood pressure, low blood glucose, multidrug-resistant TB, and generalized skin hyperpigmentation is a pointer to the possibility of adrenal insufficiency in these patients.

Background: Early detection of an outbreak is a role of disease surveillance systems; however, tuberculosis (TB) surveillance systems were underutilized to detect the outbreaks. In mid-2015, a local health office of central Japan noticed the number of TB cases of city in 2012–2014 were well above the expected numbers. This study was conducted to determine whether and when a community TB outbreak could be detected and characterize the cases using the national surveillance data. Method: The surveillance data of the A city and surrounding areas were retrospectively reviewed and analyzed for 2006–2018. Results: The TB notification rates of the A city from 2012 to 2014 were 28.0 (95% confidence interval [CI]: 20.3–38.4), 26.0 (95%CI: 18.6–36.0), 28.2 (95%CI: 20.3–38.4) per 100,000 population, respectively, higher than that of the entire prefecture (13.6, 13.0, 13.3, respectively). Similarly, in the neighboring B city, the rates of 2012 and 2014 were 51.0 (95%CI: 27.2–87.2) and 51.2 (95%CI: 27.3–87.5), respectively, higher than that of its parent prefecture (13.4 and 12.7, respectively). By the end of July 2012 (A city) or August 2012 (B city), the accumulated numbers of TB cases exceeded the previous annual TB cases. The average TB notification rates of A and B cities for 2012–2014 were higher than the surrounding areas. Conclusion: A community TB outbreak without well-defined setting could be detected by monitoring TB surveillance data.

Background: Polyphenols have been studied for their potential involvement in the prevention of various chronic diseases as well as for their antimicrobial potential. The crude extracts of arecanut have been reported to have antiinfective properties. We aimed to explore the endosperm of Areca catechu (arecanut) for the extraction of polyphenol components and to study the antituberculosis activity of these polyphenol against Mycobacterium tuberculosis H37Rv. Method: A comparative extraction was performed using microwave and Soxlet apparatus. High performance liquid chromatography (HPLC) technique was used for the estimation of the extracted polyphenols. The minimum inhibitory concentration (MIC) values against M.tuberculosis H37Rv stain, Staphylococcus aureus and Escherichia coli were estimated by resazurin microtiter assay. Results: There was a 11-fold increase in the total phenolic content by microwave assisted extraction compared to the Soxhlet extraction. The powdered extract was found to be active with MIC value of 0.975 ± 0.02 μg/mL. Fractionation and HPLC-based estimation of the extract revealed catechin, epicatechin, and epigallocatechin gallate to be the polyphenol components in the ethanol fraction. Conclusions: The bioactivity of these polyphenols confirmed their presence and complementary effect in the extract form. Because the toxic alkaloid arecoline, known to be present in arecanut, did not show any activity individually, the bioactivity of the extract was attributed to the nontoxic polyphenols present. This extract also showed selective inhibition of M. tuberculosis over other gram positive and gram-negative bacteria, thereby establishing that arecanut is an exploitable selective source of polyphenols acting against M. tuberculosis.

Background: The aim of this study was the validation of AYC.2.2 agar and AYC.2.1 broth for the breakpoint values of first- and second-line drugs for Mycobacterium tuberculosis. Method: A total of 12 isolates including 5 reference strains and 7 well-defined clinical isolates were tested for their antituberculosis susceptibilities. Inhibitory effects of first- and second-line antituberculous drugs including isoniazid, rifampicin, streptomycin, ethambutol, amikacin, capreomycin, kanamycin, para-aminosalicylic acid, ethionamide, rifabutin, ofloxacin, levofloxacin, and moxifloxacin were tested. Results: According to the minimal inhibitory concentration values obtained in 7H10 agar, 7H9-S broth, AYC.2.2 agar, and AYC.2.1 broth, category agreement is 100%, and very major discrepancy (MAD), MAD, and minor discrepancy ratios were determined as 0 for all drugs. Conclusion: It was concluded that breakpoint values by CLSI recommendation for 7H10 agar can be also used for AYC.2.2 agar and AYC.2.1 broth. In addition, further multicenter studies are needed to use the new medium in routine mycobacteriology laboratories.

Objective: The objective of the study was to study the clinico-radiological profile of patients of pulmonary tuberculosis (TB) with deep vein thrombosis (DVT). Method: This is a prospective cross-sectional observational study from September 2017 to March 2019 on diagnosed patients of pulmonary TB who attended the outpatient department or presented with signs and symptoms of DVT. Results: A total of forty patients were included, out of them 57.5% were males. Nearly 45% of the patients belonged to the upper lower class. Nearly 77.5% of cases were undernourished and did not have any comorbid conditions. Sputum smear was reported positive in 92.5% of cases. Bilateral disease was seen in 95% of cases. Far advanced chest X-ray involvement was seen in 72.5% of cases. Newly diagnosed cases of TB were 87.5%. Maximum thrombus formation was seen 97.5% in superficial femoral vein and 92.5% in the common femoral and popliteal vein. Hypoxia was reported in 62.5% of cases. Interval between diagnosis of TB and the development of DVT was 2–3 weeks in a maximum of 35% of cases. Conclusion: The clinical profile of TB with DVT shows a male predominance with upper lower class more prone to develop disease and its complications. Poor physical built is seen in the majority of patients with TB and DVT. New cases of TB are still on rise. Single comorbid condition cannot define the increased risk of DVT in TB. Superficial venous system of lower limb is more prone to develop thrombus. Time interval between TB and development of DVT is variable and cannot be predicted.

Background: “Quality of life (QOL)” is relatively a new concept, which originates from the World Health Organization (WHO) “health” definition. The WHO defines “health” as a state of complete physical, mental, and social well-being and not merely an absence of disease or infirmity. It introduces a word, “well-being,” which has two components, one the objective component and the second subjective component. The objective component mainly includes all the material possession by an individual, whereas the subjective component includes the perception of health by an individual, i.e., “QoL.” It has been observed that most of the persons affected by Hansen's Disease (leprosy) have good economic conditions, but they continue to suffer from social, psychological, and physical problems which makes their life miserable. Hence, an attempt has been made to assess their QOL and factors determining them. Method: A convenient sampling technique was used and 114 persons affected with Hansen's disease were studied. The study was conducted for a period of 1 year from November 2012 to October 2013. QOL was assessed using the WHO QOL-BREF Questionnaire and mental health status by the Self-Reporting Questionnaire. The results were obtained using SPSS 17.0 software, statistical tests such as Chi-square test, ANOVA, and standard multiple logistic regression analysis were used. Results: Quality of leprosy patients was poor. The mean WHOQOL-BREF total score was below average (mean score <65). Physical QOL of leprosy was more affected in females (mean WHOQOL-BREF score = 20.80). Mental distress was more prevalent in males (74.6%) compared to females (25.4%). Presence of deformities, female sex of the patient, and advanced age of the patient showed the greatest association with adverse QOL. Conclusion: Presence of physical disabilities or deformities and advanced age of leprosy patients adversely affect QOL of leprosy patients, whereas low level of education and poor socioeconomic status do not have a significant effect on QOL.

Background: Japan has successfully reduced the burden of tuberculosis (TB) in the past seven decades; however, there are still some issues in eliminating TB. Its presence in immigrants, particularly multidrug-resistant (MDR) TB, is one of them. In mid-September 2019, a teenage Chinese male student in a morning class of a Japanese language school in Tokyo, Japan, was diagnosed with sputum smear-positive pulmonary MDR-TB. Method: The outbreak cases were analyzed in a cohort study. Results: We investigated 138 students and 18 teachers, of whom 81 (51.9%) were male, 115 (73.7%) were aged from 20 to 29 years, and 124 (76.9%) were from China. Four other students in the same classroom and another in a different classroom from the index patient in the morning classes were also diagnosed with MDR-TB disease by the end of November 2020. In addition, 31 cases of latent TB infection (LTBI) were detected among the students and teachers. Students in the same classroom had the highest risk of TB infection (78.9%, 95% confidence interval [CI]: 54.4%–93.9%) with a relative risk of 8.6 (95% CI: 3.9–19.0), followed by students in the other classrooms of the morning classes (25.9%, 95% CI: 15.0%–39.7%) with a relative risk of 2.8 (95% CI: 1.2–6.8), compared with the afternoon class students (9.2%, 95% CI: 3.5–19.0) who had minimal contact with the index patient. Conclusion: National TB programs should adopt prophylaxis regimens for MDR-TB LTBI cases and provide prophylaxis to them, particularly if related to an outbreak. The Japanese government should screen immigrants for TB, particularly those from TB-endemic areas.

Background: Nontuberculous mycobacteria (NTM) form two types of biofilms: Bottom biofilm and pellicle. The spatial distribution of cells between these types of biofilms and their dispersion into the liquid medium depends on the ratio of the nutrient components of the growth medium. The inhibition of biofilm formation by NTM can be achieved through the use of lipophilic compounds, such as essential oils (EOs). Method: The biofilm and pellicle formation of Mycobacterium smegmatis and Mycobacterium avium on four nutrient media under static conditions and in the vapors of six EOs was evaluated by conventional method. The antimycobacterial effect of EOs was also studied by the disc diffusion method. Results: The bottom biofilm and pellicle formation of NTM largely depended on the composition and availability of nutrients. Nutrient media in which NTM form powerful bottom biofilm or pellicle or both have been determined. The growth of studied NTM strains on agar was highly sensitive to the EOs of Scots pine, Atlas cedar, bergamot, and a mixture of EO of different plants. The cultivation of bacteria in the EO vapors also resulted in total suppression of the pellicle for all studied NTM strains. Conclusions: Our data clearly indicate that the carbon-nitrogen ratio is involved in the regulation of the spatial distribution of the biofilm. The preventing effect of EOs vapors, especially the synergistic action of mixture of EOs on the biofilm and pellicle formation by NTMs can be observed.

Background: Paratuberculosis is an enteric disease caused by Mycobacterium avium sp. paratuberculosis (MAP) that affects mainly ruminant producing losses to the livestock industry. Many molecular epidemiological methods have been used to discriminate MAP isolates. Method: The aim of this study was to describe the genetic diversity of the Argentinean MAP isolates using a combination of two molecular systems, the mycobacterial interspersed repetitive unit–variable number tandem repeat (MIRU-VNTR) (“automated and “non-automated”) and the multi-locus short-sequence repeat (MLSSR) system. Results: Thirty-two isolates were identified as MAP of C type by IS900 polymerase chain reaction (PCA) and IS1311 PCA-restriction enzyme analysis. The main patterns found by both MIRU-VNTR systems were INMV1 (54.5%), INMV2 (24.2%) and INMV11 (9.1%). The INMV5, INMV8 and INMV16 were represented with one isolate each (3.0%). Only 4 MIRU-VNTR loci were polymorphic. Conclusion: Those isolates sharing the same INMV patterns were analyzed by MLSSR, being locus 2 the most polymorphic one showing isolates with 9, 10, 11, and more than 11 “G” repeats. Besides, the global discriminatory power among isolates could be increased using both techniques. Based on these results, a short version of the “automated” MIRU-VNTR could be used as a screening tool to group isolates genetically related and subsequently perform the SSR using locus 2 on those isolates sharing the same INMV pattern.

Background: Buruli ulcer (BU) is a neglected tropical disease caused by the Mycobacterium ulcerans. BU is an endemic disease in many communities in sub-Saharan Africa where population have long history of using medicinal plants for treatment. Indeed, several medicinal plants have been documented against BU and related conditions. The present study was undertaken to prove the efficacy of seven medicinal plants documented for the treatment of mycobacterial infections and related symptoms in Ghana. Method: Antimycobacterial activity of the stem bark extracts and reference control drugs were conducted using the resazurin microtiter assay (REMA) assay method in clear round bottom 96-well microtiter plates. The extracts that showed anti-mycobacterium ulcerans activity were assessed for cytotoxicity using the Alamar blue assay. Results: Overall, The Cryptolepis sanguinolenta root aqueous extract exhibited the highest antimycobacterial activity (MIC=64 μg/mL) followed by Cleistopholis patens (MIC=256 μg/mL). Based on the marked activity of the Cryptolepis sanguinolenta extracts, pure cryptolepine, its major metabolite recorded a MIC value of 32 μg/mL. These extracts with considerable antimycobacterial activity showed 50% cytotoxic concentration (CC50) ranging from 94 to 384 μg/mL. Conclusions: Thus, Cleistopholis patens and Cryptolepis sanguinolenta are primed for further studies and could afford novel drugs for the mitigation of buruli ulcer disease.

Background: Female genital tuberculosis (FGTB) is an underobserved clinical entity owing to diagnostic challenges stemming from difficulty of obtaining diagnostic specimens and paucibacillary nature of the disease. Yet, FGTB is a cause of infertility, pelvic pain, or menstrual irregularities in high-burden countries. To assess laboratory and microbiology diagnostic utilization for FGTB in Pakistan, we have collected data from 2007 to 2016 to inform the need for improved laboratory diagnostics. The objectives of this study were to determine the proportion of FGTB as culture-confirmed extrapulmonary tuberculosis (EPTB) and to describe the characteristics of women with culture-confirmed FGTB in a nationwide laboratory network in Pakistan. Method: A retrospective database was established by accessing laboratory archives and analyzed by sex and source to determine extrapulmonary cases among women. Data were checked for quality, and after removing patient identifiers and duplicate samples, frequencies were calculated in MS Excel. Clinical characteristics of patients were derived from a linked hospital database for those patients who were diagnosed and managed at the affiliated university hospital in Karachi, Pakistan. Results: Over 10 years, 410,748 mycobacterial cultures were received from multiple geographic sites throughout Pakistan and processed at the study laboratory. The overall mean culture positivity rate was 5.9% ± 3.5%, while the mean culture positivity rate among females was 2.8% ± 0.8%. Among female culture-confirmed tuberculosis cases, the pulmonary-to-EPTB ratio of infection was 5. Over 10 years, a total of 32 FGTB cases were reported on the basis of positive cultures for Mycobacterium tuberculosis; 3 (9.4%) were rifampin resistant. Conclusions: FGTB currently constitutes a small but significant proportion of culture-confirmed EPTB. A fewer number of laboratory requisitions suggest the need to increase awareness and testing. The advent of high-sensitivity molecular testing on extrapulmonary specimens has the potential to improve diagnostic accuracy and improved detection of FGTB cases in high-burden regions.

Background: Tuberculosis (TB) is a major cause of ill-health and death globally but a serious challenge to its control is low case notification. In low- and middle-income countries, most patients with symptoms of the disease first seek care from patent medicine vendors (PMVs) who are not formerly trained to manage TB. The practices of PMVs toward presumptive TB are pivotal to control of TB. Aim: The aim of this study was to describe the pattern of practices toward presumptive TB and assess their determinants among PMVs. Method: The study was carried out in Ebonyi State Nigeria using descriptive cross-sectional design. Through a multistage sampling, 250 PMVs were selected and interviewed. Data were collected using pretested interviewer-administered questionnaire and analyzed with IBM SPSS Statistics for Windows, version 22 (IBM Corp., Armonk, N.Y., USA). Chi-square test and binary logistic regression were used to determine factors associated with practices toward presumptive TB with P value set at 0.05 for statistical significance. Results: Almost half (48.8%) of the respondents engaged in poor practices by inadequate referral of clients (45.2%), delayed referral (69.6%), and unstandardized treatment with antibiotics (56.4%). There was no statistically significant association between independent variables and practice and none of the variables significantly predicted practice. Conclusions: There were poor practices toward presumptive TB shown in inadequate referral, delayed referral, and unstandardized treatment of clients. We recommend that PMVs should be trained and regularly sensitized about TB to improve their practices and that regulatory authorities should enforce policies on antibiotics distribution and sale.

Addison's disease is primary adrenal insufficiency which is most commonly due to an autoimmune disease. Patients usually presents with fatigue, anorexia, gastrointestinal complaints, salt craving, and orthostatic hypotension. Rare manifestations during presentation can result in diagnostic dilemma. A 53-year-old male presented with cerebellar ataxia and bipolar disorder secondary to Addison's disease (due to tuberculous adrenalitis) which improved following treatment with steroids. We describe a patient with Addison's disease who presented with two rare manifestations which to our knowledge is the first such report.

Mycobacterium chimaera has been described in postoperative cardiovascular procedures in patients after an outbreak of contaminated 3T heater–cooler units. Immune reconstitution inflammatory syndrome (IRIS) has been mostly reported in immunocompromised patients, especially HIV after starting therapy. Our case is a 52-year-old immunocompetent male who was diagnosed with M. chimaera mediastinitis a year after Type A dissection repair and was started on quadruple antimicrobial therapy. He clinically improved but 8 months into therapy he presented with a declining kidney function, pancytopenia, and hypercalcemia which after bone marrow and kidney biopsies were attributed to IRIS. Our patient's diagnosis spared him subsequent surgery. IRIS during the treatment of nontuberculous mycobacteria must be suspected even in immunocompetent patients as reaching the diagnosis is very helpful in preventing additional diagnostic and therapeutic measures.

Cutaneous tuberculosis is uncommon, comprising 1%–2% of all extrapulmonary manifestations. It has a wide clinical spectrum. The clinical presentation depends on the route of the infection, the pathogenicity of the bacteria, and the immune status of the host. Association of multiple forms in a same patient is uncommon. We report a case of disseminated tuberculosis with polymorphous cutaneous lesions in an immunocompetent woman, combining scrofuloderma, gummas, and sporotrichoid lesions, along with tuberculous adenitis and bone tuberculosis.

Background: Clinical characteristics of endobronchial tuberculosis (EBTB) patients whose sputum smears were negative have not been elucidated yet. Method: EBTB patients with negative sputum smears were documented retrospectively at the outpatient pulmonary clinic from late 2015 to early 2019. Results: We described the characteristics of 31 EBTB patients with negative sputum smears. The median age was 36 years (range 18–81 years). The male-to-female ratio is 1:1.58. The “peripheral” lesion group included 16 cases with opacity/consolidation, 2 cases with atelectasis, 1 case with cavitary lesion, and 1 case with pleural effusion. The “central” lesion group included four cases with normal chest X-ray and seven cases with only unilateral hilar enlargement. EBTB patients with “central” lesion were more common the presence of cough, the positive rate of bronchial lavage acid-fast bacilli smear, and the rate of misdiagnosis as pharyngitis, bronchitis, or asthma than that with “peripheral” lesion. Conclusions: EBTB with negative sputum smears was found in adult patients at any age and predominant in females. The diagnosis of EBTB with “central” lesion was more difficult than that with “peripheral” lesion. The location of the lesion could play a role in inducing cough among EBTB patients.

Pulmonary disease due to Mycobacterium abscessus (Mab) has become an increasing cause of health concern, particularly among individuals infected with nontuberculous mycobacteria. Since Mab is intrinsically resistant to many antibiotics, it is very challenging to treat patients with symptomatic disease. In this case series, we report four patients with symptomatic pulmonary Mab who had prior history of antituberculosis treatment intake and declared cured at the end of treatment. The current episode was confirmed to be due to Mab infection by molecular and clinical diagnosis and received species specific-antibiotics therapy. All were periodically monitored for the sputum smear and culture conversions throughout the treatment period. The clinical course was variable though all received similar antibiotic regimen and showed varied treatment outcomes. The time of diagnosis and the treatment outcome indicate that a better understanding of host-pathogen interactions is essential for the successful treatment of pulmonary Mab infection.

Symphysis pubis tuberculosis (TB) is extremely rare in the reported literature. The diagnosis of pelvic TB is confounded by close differentials such as osteomyelitis as well as the low yield of TB bacilli in microbiological sampling in the initial stages of the disease. Pelvic TB should be suspected early on in areas with high TB burden, and prompt treatment with antitubercular treatment may help prevent disability associated with the disease. Here, we present a 49-year-old diabetic man with pubic symphysis TB which was diagnosed on the basis of clinical and radiological aspects, with near-total resolution following 9 months of anti-tubercular treatment.