Background: Tuberculosis (TB) is a major global health problem, mainly in developing countries. Despite the availability of highly effective first-line antitubercular (ATT) drugs, ATT drug-induced liver injury (ATT DILI) leads to treatment interruption and consequently loss of therapeutic efficacy. Methods: In this prospective cohort study from India, all consecutive patients who met inclusion criteria and started on ATT were included. The incidence, risk factors, and outcome of ATT DILI were determined. A clinical prediction score for ATT DILI was derived. Results: A total of 393 patients were included. The incidence of ATT DILI was 9.7% (95% confidence interval 7%–13.2%). HIV infection, daily regimen, disseminated disease, and chronic liver disease were identified as significant risk factors (P < 0.05) for developing DILI. A prediction score derived from the risk factors showed that a score of >5 could predict DILI with a sensitivity of 74% and a specificity of 67%. All-cause mortality in DILI was 4.7%. Conclusion: The incidence of ATT DILI was 9.7% in our cohort with higher incidence among the patients on daily regimen. The study suggests that the combination of risk factors of extensive TB disease, HIV infection, chronic liver disease, and under nutrition increases the vulnerability to DILI, particularly with daily treatment regimen, emphasizing the role of acquired risk factors in the development of DILI.

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Introduction: Tuberculosis (TB) and diabetes mellitus (DM) are significant causes of morbidity and mortality in developing countries. This study aimed to explore the relationship between diabetes and TB. Methods: This was a prospective cohort study in which all newly diagnosed inpatients with TB above the age of 18 years during the study period (September 2018 to August 2020) were included. Fasting sugars and glycosylated hemoglobin (HbA1c) levels were recorded at the baseline, 3^rd month, and 6^th month in the diabetic patients on antitubercular therapy (ATT). Treatment outcomes were measured in both the diabetic and the nondiabetic groups. Results: The prevalence of diabetes in patients with TB admitted at our tertiary care hospital was found to be 38.5%. A favorable treatment outcome was seen in 96.3% of the patients with DM when compared to 95.6% in those without diabetes. A decreasing trend of HbA1c and fasting sugars was noticed in patients with DM during ATT. Conclusion: The screening of DM in patients with TB can help in early diagnosis and better glycemic control which may improve the possibility of favorable outcomes.

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Background: The emergence of drug-resistant tuberculosis (DRTB) has continued to pose a threat to public health in sub-Saharan Africa and globally. Despite the high burden of tuberculosis (TB) in Nigeria, there are paucity of data on the safety and efficacy of newer agents and repurposed drugs used in the treatment of DRTB. Methods: This prospective cohort study was conducted at a regional DRTB treatment center in Kano, Northwestern Nigeria. Descriptive statistics, Mann–Whitney U-test, and Chi-square or Fisher's exact test were used to analyze the data as appropriate. Results: The median age of the patients was 32 years (interquartile range 26–42 years). Of the 39 patients, 34 (87.18%) were males. The majority of the patients came from the rural areas 25 (64.10%). By 10 months of initiation of combination therapy, 25 (64.10%) of the patients were alive, culture negative and on treatment while 14 (35.90%) of the patients have died. Out of the 39 patients in the cohort, 26 (66.67%) patients had at least one serious adverse event. The most common serious adverse events were hematological disorders (13 [35.14%] of 37 events) and neurological disorders (11 [29.73%] of 37 events). Peripheral neuropathy (P < 0.0001), anemia (P = 0.029), and skin reaction (P = 0.021) occurred more frequently among linezolid interrupters. Conclusions: In conclusion linezolid-based combination therapy, with linezolid at a dose of 600mg daily is associated with satisfactory culture conversion rate by 10 months of therapy. However, linezolid may be associated with peripheral neuropathy that may warrant interruption of the drug.

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Background: Zinc deficiency is evident in chronic diseases, but little is known about its association with multi-drug resistant tuberculosis (MDRTB). We aimed to measure serum zinc level in MDRTB patients and explore its association with MDRTB compared to drug-sensitive tuberculosis (DSTB). Methods: We recruited 107 MDRTB and 87 DSTB patients from a tuberculosis referral hospital in Bangladesh. After overnight fasting, 5 ml venous blood was collected from each patient to measure serum zinc level through graphite furnace atomic absorption spectrophotometry method. Multivariate logistic regression was done to measure its association with MDRTB. Results: The mean age of all patients was 36 years, where 70% were male. About 27% MDRTB patients and 2.3% DSTB patients had low serum zinc level (P < 0.0001). An inverse correlation was observed between serum zinc level and duration of anti-TB therapy (r-value: −0.252, P < 0.01). Reduced serum zinc level (odds ratio, 0.957; 95% confidence interval 0.923–0.992) was found as a significant associating factor for MDRTB after adjusted with age, sex, occupation, residence, tobacco consumption, Bacillus Calmette–Guérin-vaccination, and duration of anti-TB therapy. Conclusion: A lower serum zinc level is significantly associated with MDRTB. The tuberculosis control program should address this in the MDRTB control strategy.

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Background: Project Extension for Community Healthcare Outcomes (Project ECHO) is a telementoring, case based virtual community of practice training and education model connecting experts to primary care clinicians (PCCs). Project ECHO has good evidence for favorable treatment outcomes on wide range of diseases. Since 2017, Tanzania hosts multidrug resistant tuberculosis (MDR TB) ECHO with hub at Kibong'oto Infectious Diseases Hospital. However, little is known on outcomes of MDR TB ECHO. This study aimed to describe the outcomes of MDR TB ECHO in managing MDR TB patients in Tanzania. Methods: Review of case studies was conducted at MDR TB ECHO hub in Tanzania. Up to June 2020, a total of 134 sessions and 60 patient cases were presented in MDR TB ECHO. This article describes outcomes of MDR TB ECHO in managing three selected complicated MDR TB patient cases presented. Case 1: Child with MDR TB, neck abscess, and anemia secondary to chronic illness. Case 2: Adult with MDR TB and end stage renal disease co morbidity. Case 3: Adult failing standard MDR TB treatment. Results: Anemia resolved in Case 1; surgical dressing was done to neck abscess and neck healed. Case 2 was initiated with end stage renal disease management; uremic encephalopathy and lower limb edema resolved. Case 3 was initiated with individualized MDR TB treatment. All three patients attained smear and culture conversion and continue with MDR TB treatment. Conclusions: To our knowledge, this is the first report on effectiveness of project ECHO in supporting PCCs in bringing favorable treatment outcomes to MDR TB patients. We advocate adaptation and scale up of ECHO model as an effective approach for strengthening management of MDR TB and other infectious diseases.

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A 75-year-old male presented with acute febrile respiratory illness with hypoxia and anorexia of longer duration; computed tomography (CT) of the thorax was suggestive of cavitary lung disease, with sputum smear positive for acid-fast bacilli and also having classical COVID-19 pneumonia patterns in the CT thorax; and COVID-19 rapid antigen test was positive. He was treated for COVID-19 pneumonia and antituberculosis treatment was initiated at the discharge. He was recovered of both conditions, and we have documented the crucial role of chest CT in managing this case in this pandemic period.

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The coronavirus disease-2019 (COVID-19) pandemic is one of the most devastating things that happened in the world which has taken the lives of millions of people and has brutally shattered the world economy. This pandemic has instigated an urgent need for a vaccine to reduce the ongoing morbidity and mortality. Bacillus Calmette-Guerin (BCG) apart from being used as an effective and old vaccine against tuberculosis has some known off-target protection effect and is getting more attention in this scenario. BCG confers nonspecific innate immune-boosting effects called trained immunity against secondary infection. Various recent publications have proposed the inverse relationship between the COVID-19 morbidity and mortality with that of BCG coverage of that country on the basis of epidemiological studies. However, these studies have not considered the confounding factors, and a lot of recent articles are contradicting these epidemiological and observational data. Several random control trials for BCG on health-care workers and elderly people are ongoing worldwide and could depict the actual relation between COVID-19 and BCG protection. Although a recent trial has found a protective function of BCG against COVID-19 in health-care workers, more results of the trials can only give approval on this. There has been a shortage of BCG worldwide due to its use in bladder cancer and vaccination in neonates, and hence, its use should be carefully regulated. In this review, we have tried to summarize the various issue and conflicts on BCG to be used as a temporary solution to COVID-19.

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Background: Detection of latent tuberculosis infection (LTBI) in children, exposed to tuberculosis (TB) infections, followed by appropriate treatment, could be instrumental in reducing TB burden. Interferon Gamma release assays (IGRA) have higher specificity than tuberculin skin tests (TST), hence are more effective option for diagnosis. Hence, the present study was aimed to diagnose the presence of latent TB in children with the help of a new Standard E TB-Feron Enzyme-Linked Immunosorbent Assay (TBF) and evaluating its efficiency as compared to TST and Quantiferon TB Gold plus (QFT Plus). Methods: Diagnosis of LTBI in participants, <18 years old, who were the close household contacts of patients with active TB was carried out employing techniques such as TST, QFT Plus, and TBF. Results: Higher positive results were obtained with IGRA assays QFT Plus and TBF than TST. The perfect agreement was observed between QFT Plus and TBF assays with a Kappa value of 0.9176 whereas TST and TBF assay showed moderate agreement with a Kappa value of 0.42365. The level of cytokines secreted as a result of stimulation by the antigens from QFT Plus tubes was lower in comparison to antigens from TBF tubes. Conclusion: Hence, TBF, which showed similar efficiency as the widely used QFT Plus, can be a useful detection technique for LTBI in children. Moreover, it could prove to be an efficient alternative to expensive IGRAs like QFT Plus.

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Background: Tubercular lymphadenitis (TBLN) remains the most frequent manifestation for extrapulmonary TB despite advancements in diagnostics and management over the years. Our study intends to explore five-year trend of TBLN in a tertiary care centre from south India, and aims to study clinico-demographic and diagnostic factors in the management of TBLN. Methods: All the adult patients (≥18 years) diagnosed and confirmed for TB lymphadenitis between January 2015 to December 2019 were retrospectively evaluated. Demographic factors, clinical manifestations, and different diagnostic approaches used in the management of TBLN were analysed using SPSS ver. 16. Results: A total of 164 patients with confirmed TBLN were included. Patients aged 18-45 years were the most affected (63.41%) with female dominancy. The most affected lymph nodes were cervical lymph nodes (84.1%) presenting with single palpable enlarged lymph node (80.5%). Majority (78.7%) of the lymph nodes were non-matted and 68.9% of enlarged lymph nodes were >3cm size. Excisional biopsy was performed for the majority of the patients 99 (60.4%) and 60.4% of the cases were managed with a combination of surgical excision and anti-tubercular treatment (ATT). Conclusions: The declining trend of TBLN observed in this study highlights the outcome of good public health policies; however, young females and high-risk groups like HIV infected or AIDS (affected more in the study) demand further attention. Overall, the advanced diagnostic tools along with surgical management and ATT can lead us to earlier diagnosis and successful treatment outcomes

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Background: Treatment of the patients with multidrug-resistant tuberculosis (MDR-TB)/HIV coinfection in a state of severely suppressed immune system remains unsatisfactory. Methods: The study involved 52 HIV-positive patients with MDR-TB and CD4+ lymphocyte cells below 50 cells/μCL. Patients in control group (Group 1) and in basic group (Group 2) received standard treatment with second-line antituberculosis agents and antiretroviral agents. In addition, the patients in basic group were treated by immunoglobulin G (IgG) intravenously. Immunological diagnostics with the determination of the level of lymphocytes subgroups (CD3+, CD4+, CD8+, CD4+/CD8+) was carried out using an AQUIOS™ CL flow cytometry device at the beginning and after 3–20 months of treatment. Statistical analysis was performed using the Statistica 10.0 software (Stat. Soft Inc., USA). Results: In the patients of Group 2, the absolute number of CD3+ and CD4+ cells at the end of the 20th month of the treatment normalized in 26.9% (absolute amount) and 42.3% (relative amount) of subjects, while in Group 1, this indicator remained below the normal level (P < 0.05). The addition of IgG into standard therapy caused normalization of CD8+ count in 76.9% of patients, while in the control group-only in 46.2% of patients (P < 0.05). Conclusions: The administration of IgG in combination with standard anti-tuberculosis and antiretroviral therapy (ART) contributes to the normalization of the cellular immunity status in patients with MDR-TB/HIV coinfection and severe immunosuppression and allows you to start ART earlier than in patients with single standard therapy

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Immune reconstitution inflammatory syndrome (IRIS) is a common complication following the initiation of antiretroviral therapy (ART). The most commonly associated pathogens include Mycobacterium tuberculosis and Cryptococcus spp.^[1] IRIS following nontuberculosis mycobacteria (NTM) infection is uncommon, particularly, IRIS following NTM conjunctivitis.^[2] Herein, we present a case of Mycobacterium scrofulaceum conjunctivitis with peripheral ulcerative keratitis and orbital cellulitis in a 45-year-old patient with AIDS who developed IRIS 1 month after starting ART therapy. A combination of both systemic and topical antibiotics together with corticosteroids were used and resulted in a satisfactory outcome with no early recurrence. This case demonstrated a rare ocular IRIS manifestation involving both the external eye and orbit and to the author's knowledge is the first case in the literature in which M. scrofulaceum has been found to be involved in the eye.

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Objectives: The study aimed to understand the organism spectrum and antibiotic sensitivity profile of acute bacterial meningitis in pediatric population. Methods: A cross-sectional study was conducted at the department of microbiology of a tertiary care center for a period of 18 months. Suspected cases of meningitis between 1 and 60 months of age were considered for the study. All cases underwent cerebrospinal fluid tap for direct microscopy (DM), Gram staining, and culture sensitivity. Results: The mean age of the study patients was 10.42 months, with 61.7% of males and 38.3% of females. DM and culture were positive in 22.90% and 28.00% of the patients, respectively. On Gram stain, there were 29 (59.18%) cases of Gram positivity and 20 (40.82%) cases of Gram negativity. The culture growth showed that Acinetobacter spp. was isolated in 15 (30.6%) of the cases. Enterococcus spp. was isolated in 9 (18.4%) of the cases. Klebsiella pneumoniae was isolated in 8 (16.3%) of the cases. Staphylococcus aureus was isolated in 8 (16.3%) of the cases. Enterobacter spp. was isolated in 3 (6.12%) of the cases. Pseudomonas aeruginosa was isolated in 3 (6.12%) of the cases. Streptococcus pneumoniae was isolated in 3 (6.1%) of the cases. The antibiogram of different agents showed wide variation, with colistin being 100% sensitive for Acinetobacter, Enterobacter, K. pneumoniae, and P. aeruginosa. Conclusion: The present study revealed that Acinetobacter, Enterococcus, K. pneumoniae, and S. aureus were the most common bacterial etiologic agents of ABM. The 100% antibiotic sensitivity of the organisms to some antibiotics may suggest the use of such antibiotics while awaiting for culture sensitivity reports.

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Background: Mycobacterium leprae was considered the only causal agent of leprosy until Mycobacterium lepromatosis was identified' which it has been suggested has greater pathogenicity and is linked to diffuse lepromatous leprosy (DLL) and Lucio's phenomenon (LPh). Our objective is to identify Mycobacterium spp. in an endemic area of leprosy in Colombia. Methods: The study included cases with a diagnosis of leprosy by clinical and histopathological analysis. DNA extraction and two specific rounds of semi-nested polymerase chain reaction (PCR) were performed in paraffin biopsies skin to identify M. leprae and M. lepromatosis. Demographic, clinical, and histopathological data were extracted and tabulated for analysis. Results: Forty-one cases of leprosy were analyzed. The most frequent clinical diagnosis was lepromatous leprosy (36.6%); there was one case with DLL and two with LPh. The most common histopathological finding was tuberculoid leprosy (36.59%); three cases had negative histopathology. M. lepromatosis was not detected; all cases corresponded to M. leprae including cases with negative histopathology' DLL, and LPh. Conclusion: In this study, M. leprae was the causative agent of leprosy, encompassing even its most severe phenotypic forms. It is appropriate to consider PCR as an indispensable tool for the diagnosis of leprosy and to continue to carry out the active search for M. lepromatosis.

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Background: Rapidly growing mycobacteria (RGM) are a group of nontuberculous mycobacteria (NTM) implicated in difficult-to-treat pulmonary and extrapulmonary diseases, possibly associated with invasive procedures and failures in sterilization of materials and equipment. Methods: We report our experience with the laboratory identification of RGM in a routine work and give an overview of the RGM isolated in our setting. Laboratorial data from all RGM mycobacterial isolates received at Adolfo Lutz Institute of São José do Rio Preto were analyzed from January 2000 to December 2015. Results: Five hundred and seventy-nine isolates were identified with NTM, of which 193 were RGM, which affected 113 patients. Among the 113 patients, the female gender was more frequent (55%) and the average age was 50 years. Pulmonary samples were the most frequent (79%), and 54.9% of the cases were isolated from sputum. Twelve different species were found and the most identified were group Mycobacterium abscessus and Mycobacterium fortuitum, making up 77.9% of all identified RGM. The most frequent comorbidities were smoking (n = 21), alcoholism (n = 12), and human immunodeficiency virus (n = 16). Drug susceptibility test was performed for nine patients and all showed susceptibility to amikacin and seven resistances to doxycycline. Conclusions: This study showed the experience of mycobacterial diagnosis in a routine laboratory, revealing that failure to meet the bacteriological criteria generates losses in the establishment of cases of RGM and consequently its correct treatment.

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Background: In last years, few attention has given to the patient's prediagnostic costs when evaluating the introduction of new technologies for tuberculosis (TB) and in this context, this study evaluated patient's costs and cost-effectiveness incurred with TB diagnosis comparing Bactec^TMMGIT^TM960 system (MGIT) to the Löwestein–Jensen (LJ) culture in a health center and in a university hospital, in Rio de Janeiro City, Brazil. Methods: Patient's mean costs were evaluated during the diagnosis process and cost-effectiveness based on mean time in days for the adoption of appropriate clinical anti-TB treatment in two health units comparing culture by means LJ and MGIT. Results: The mean cost of LJ and MGIT in the health center was U. S. dollars (US$) 26.6 and US$ 45.13, respectively, and in university hospital was US$ 206.87 and US$ 285.48, respectively. Comparing the two approaches for TB diagnosis incurred by the patients, the incremental cost-effectiveness of MGIT compared to LJ was US$ 0.88 and US$ 4.03 per patient, respectively, to reduce the average time to adopt appropriate treatment. Conclusions: The culture method directly impacts patient costs while waiting for the correct diagnosis and contributing to aggravating costs with patients with TB.

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Objective: Nontuberculous mycobacteria (NTM) have been recognized as a diverse group of organisms that are ubiquitous in environmental sources. In most regions of the world, NTM are not reportable as a public health disease, so epidemiological data are not easily available. However, data in published studies note increasing trends at the rate of NTM isolation from different geographic regions of the world. Increasing NTM isolation may have important public health implications. The aim of our study is the investigation of NTM from water resources and networks in Düzce, Turkey. Methods: NTM are common in water resources and water networks. They can cause waterborne infections in humans. A total of 120 water samples measured of chlorine and pH levels were decontaminated and filtered. Then, the filters were placed in the culturing media. Statistical Analysis Used: Chi-square and t-test were used for the statistical analysis. Results: NTM were detected in 20 (16.6%) samples. Nine of them (45%) were Mycobacterium fortuitum, three (15%) were Mycobacterium gordonae, three (15%) were Mycobacterium szulgai, two (10%) were Mycobacterium lentiflavum, two (10%) were Mycobacterium chelonae, and one (5%) was Mycobacterium peregrinum. Conclusions: These environmental bacteria can cause serious illnesses in both immunocompetent and especially immunocompromised individuals. For the correct treatment of these patients, it is important to determine NTM in clinical samples. Surveillance is necessary to know the source of NTM infection, to identify and type the strains, and to establish effective control measures such as disinfection, maintenance, and modernization of water systems.

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Epidermodysplasia verruciformis (EDV) is a rare, autosomal recessive, genetic disorder of immune dysregulation characterized by increased susceptibility to cutaneous human papilloma virus infections. It was first described by Lewandowsky and Lutz in 1922 as a form of epidermal nevus. Its association with skin cancers was proposed by Sullivan and Ellis in 1939. Initial lesions often occur in childhood and are of two types; lifelong eruptions of pityriasis versicolor like lesions and flat wart like papules. The latter is characterized by malignant transformation in 35%–50% of patients especially after 40–50 years of age. Bowen disease is the most common tumor followed by invasive squamous cell carcinoma, however, metastasis is rarely encountered.

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Hansen's disease is one of the ancient skin diseases known to humankind, still foxes even trained physician leading to delay in its diagnosis and unusual health burden. India followed by Brazil constitutes the highest number in newly diagnosed cases. Even though the World Health Organization and individual country have done much to contain the spread of leprosy, the findings of systemic complications, grade 2 deformity, and childhood leprosy reflect some shortcomings of the worldwide public health program. Renal involvement, particularly glomerulonephritis, is a known common systemic complication of the leprosy, but introduction of multidrug therapy and early case detection have reduced the chances of systemic complication significantly over the last three decades. Here, we report a case who presented in the emergency department with rapidly progressive swelling of the body, on evaluation found to have leprosy and glomerulonephritis having tubuloreticular inclusions in glomerular endothelial cell cytoplasm on electron microscopy.

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Background: The microbiology of cystic fibrosis (CF) is complicated by the presence of several species, including Mycobacterium abscessus, which are highly resistant to antibiotics. Conventional selective bacteriological methods employ antibiotics which favor the growth of one bacterial component over others in a mixed population. For in vitro studies examining multiple species, for example, in dual biofilm models, it is difficult to successfully separate M. abscessus from nontuberculous mycobacterial (NTM) species. Therefore, it was the aim of this study to develop a selective agar medium that was able to isolate M. abscessus from a pool of other highly-resistant Gram-negative organisms, which would be useful to microbiologists performing co-culture experiments and which require re-isolation of the NTM organism. Methods: Wylie-Stanley agar (WSA) was developed consisting of glucose, 16 g/l; yeast extract, 30 g/l; peptone, 6.8 g/l; and agar, 20 g/l along with selective supplements including chloramphenicol, 50 mg/l; ceftazidime, 32 mg/l; colistin, 24 mg/l; trimethoprim, 21.3 mg/l; sulfamethoxazole, 106.7 mg/l; and novobiocin, 50 mg/l. This medium was (i) challenged with 10 non-NTM species (27 isolates) of common Gram-negative and Gram-positive organisms associated with CF and (ii) compared to Columbia Blood Agar and Middlebrook 7H10 Agar for the isolation of M. abscessus organisms from mixed cultures of NTM organisms and Pseudomonas aeruginosa and Stenotrophomonas maltophilia. Results: This medium was highly specific for the growth of M. abscessus organisms and grew all NTM organisms. WSA medium did not allow the growth of any of the non-NTM species. When mixed cultures of M. abscessus species and P. aeruginosa and S. maltophilia were inoculated onto WSA medium, only the NTM organism could be grown successfully, highlighting the specificity of this medium. In contrast, both Columbia Blood Agar and Middlebrook 7H10 Agar allowed the growth of both NTM and non-NTM organisms. Conclusion: While the specificity was high, the sensitivity of WSA was low, and therefore, we do not advocate employment of WSA medium for the primary isolation of M. abscessus organisms from CF sputum, rather for the purposes of separating M. abscessus populations of organisms from other highly-resistant organisms, including P. aeruginosa and S. maltophilia, which would be useful to microbiologists performing co-culture experiments and which require re-isolation of the pure M. abscessus organism.

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Background: Bacillus Calmette–Guérin (BCG) vaccination programs were introduced in Czechoslovakia more than 60 years ago under a quite different epidemiological situation than that of today. Compulsory mass BCG vaccination was abolished in November 2010 and changed to a selective vaccination program for infants at high risk of contracting tuberculosis (TB). Methods: This work sets out to ascertain the risk of TB and nontuberculous mycobacterial (NTM) infection in the 10-year period following the change to the vaccination program and to compare this with the same period of time when mass BCG vaccination was compulsory. Descriptive study. Statistical analysis of the incidence of tuberculosis and non-tuberculous mycobacteriosis as reported in the TB register in years 2001-2020. Conclusions: The incidence trend of TB in children in both monitored time periods is identical and statistically significantly decreasing (P < 0.001). In the first monitored period, the incidence trend of NTM cervical lymphadenitis in children is degressive and is not statistically significant (P = 0.561). However, in the second monitored period, the trend increases and is statistically significant (P < 0.001); in every compared 2-consecutive year period, there is an increase of 8%. These findings indicate that the change from mass BCG vaccination to selective vaccination of high-risk newborns and the abolishment of BCG revaccination can be recommended, so long as a keen eye is kept on NTM caused lymphadenitis.

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