Search results for: treatment of tuberculosis

Authors: Dwitya Elvira, Raveinal Masri, Rohayat Bilmahdi

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Human Immunodeficiency Virus (HIV) pandemic increased significantly worldwide. The rise in cases of HIV/AIDS was also followed by an increase in the incidence of opportunistic infection, with tuberculosis being the most opportunistic infection found in HIV/AIDS and the main cause of mortality in HIV/AIDS patients. Diagnosis of tuberculosis in HIV/AIDS patients is often difficult because of the uncommon symptom in HIV/AIDS patients compared to those without the disease. Thus, diagnostic tools are required that are more effective and efficient to diagnose tuberculosis in HIV/AIDS. CXCL-10/IP-10 is a chemokine that binds to the CXCR3 receptor found in HIV/AIDS patients with a weakened immune system. Tuberculosis infection in HIV/AIDS activates chemokine IP-10 in urine, which is used as a marker for diagnosis of infection. The aim of this study was to prove whether IP-10 urine can be a biomarker diagnosis of active lung tuberculosis in HIV-AIDS patients. Design of this study is a cross sectional study involving HIV/AIDS patients with lung tuberculosis as the subject of this study. Forty-seven HIV/AIDS patients with tuberculosis based on clinical and biochemical laboratory were asked to collect urine samples and IP-10/CXCL-10 urine being measured using ELISA method with 18 healthy human urine samples as control. Forty-seven patients diagnosed as HIV/AIDS were included as a subject of this study. HIV/AIDS were more common in male than in women with the percentage in male 85.1% vs. 14.5% of women. In this study, most diagnosed patients were aged 31-40 years old, followed by those 21-30 years, and > 40 years old, with one case diagnosed at age less than 20 years of age. From the result of the urine IP-10 using ELISA method, there was significant increase of the mean value of IP-10 urine in patients with TB-HIV/AIDS co-infection compared to the healthy control with mean 61.05 pg/mL ± 78.01 pg/mL vs. mean 17.2 pg/mL. Based on this research, there was significant increase of urine IP-10/CXCL-10 in active lung tuberculosis with HIV/AIDS compared to the healthy control. From this finding, it is necessary to conduct further research into whether urine IP-10/CXCL-10 plays a significant role in TB-HIV/AIDS co-infection, which can also be used as a biomarker in the early diagnosis of TB-HIV.

Keywords: chemokine, HIV/AIDS, IP-10 urine, tuberculosis

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Authors: Fasil Wagnew, Kerri Viney, Kefyalew Addis Alene, Matthew Kelly, Darren Gray

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Background: Undernutrition is a risk factor for tuberculosis (TB), including poor treatment outcomes. However, evidence regarding the effect of undernutrition on TB treatment outcomes is not well understood. We aimed to evaluate the effect of undernutrition on sputum culture conversion and treatment outcomes among people with multi-drug resistance (MDR)-TB. Methods: We searched for publications in the Medline, Embase, Scopus, and Web of Science databases without restrictions on geography or year of publication. We conducted a random-effect meta-analysis to estimate the effects of undernutrition on sputum culture conversion and treatment outcomes. Two reviewers independently assessed the study eligibility, extracted the necessary information, and assessed the risk of bias. Depending on the nature of the data, odds ratio (OR) and hazard ratio (HR) with 95% confidence intervals (CIs) were used to summarize the effect estimates. Potential publication bias was checked using funnel plots and Egger’s tests. Results: Of 2358 records screened, 59 studies comprising a total of 31,254 people with MDR-TB were included. Undernutrition was significantly associated with a lower sputum culture conversion rate (HR 0·7, 95% CI 0·6–0·9, I2=67·1%) and a higher rate of mortality (OR 2·9, 95%CI 2·1–3·8, I2=23·7%) and unfavourable treatment outcomes (OR 1·8, 95%CI 1·5–2·0, I2=72·7%). There was no statistically significant publication bias in the included studies. Three studies were low, forty-two studies were moderate, and fourteen studies were high quality. Interpretations: Undernutrition was significantly associated with unfavourable treatment outcomes, including mortality and lower sputum culture conversion among people with MDR-TB. These findings have implications for supporting targeted nutritional interventions alongside standardised second-line TB drugs.

Keywords: undernutrition, MDR-TB, sputum culture conversion, treatment outcomes, meta-analysis

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Authors: Saima Suleman, Kalsoom Sughra, Naeem Mahmood Ashraf

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Mycobacterium tuberculosis is a communicable chronic illness. This disease is being highly focused by researchers as it is present approximately in one third of world population either in active or latent form. The genetic makeup of a person plays an important part in producing immunity against disease. And one important factor association is single nucleotide polymorphism of relevant gene. In this study, we have studied association between single nucleotide polymorphism of CD-209 gene (encode DC-SIGN receptor) and patients of tuberculosis. Dry lab (in silico) and wet lab (RFLP) analysis have been carried out. GWAS catalogue and GEO database have been searched to find out previous association data. No association study has been found related to CD-209 nsSNPs but role of CD-209 in pulmonary tuberculosis have been addressed in GEO database.Therefore, CD-209 has been selected for this study. Different databases like ENSEMBLE and 1000 Genome Project has been used to retrieve SNP data in form of VCF file which is further submitted to different software to sort SNPs into benign and deleterious. Selected SNPs are further annotated by using 3-D modeling techniques using I-TASSER online software. Furthermore, selected nsSNPs were checked in Gujrat and Faisalabad population through RFLP analysis. In this study population two SNPs are found to be associated with tuberculosis while one nsSNP is not found to be associated with the disease.

Keywords: association, CD209, DC-SIGN, tuberculosis

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Authors: Anita, Sari Septiani Tangke, Rusdina Bte Ladju, Nasrum Massi

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New diagnostic tools are urgently needed to interrupt the transmission of tuberculosis and multidrug-resistant tuberculosis. The microscopic-observation drug-susceptibility (MODS) assay is a rapid, accurate and simple liquid culture method to detect multidrug-resistant tuberculosis (MDR-TB). MODS were evaluated to determine a lower and same concentration of isoniazid and rifampin for detection of MDR-TB. Direct drug-susceptibility testing was performed with the use of the MODS assay. Drug-sensitive control strains were tested daily. The drug concentrations that used for both isoniazid and rifampin were at the same concentration: 0.16, 0.08 and 0.04μg per milliliter. We tested 56 M. tuberculosis clinical isolates and the control strains M. tuberculosis H37RV. All concentration showed same result. Of 53 M. tuberculosis clinical isolates, 14 were MDR-TB, 38 were susceptible with isoniazid and rifampin, 1 was resistant with isoniazid only. Drug-susceptibility testing was performed with the use of the proportion method using Mycobacteria Growth Indicator Tube (MGIT) system as reference. The result of MODS assay using lower concentration was significance (P<0.001) compare with the reference methods. A lower and same concentration of isoniazid and rifampin can be used to detect MDR-TB. Operational cost and application can be more efficient and easier in resource-limited environments. However, additional studies evaluating the MODS using lower and same concentration of isoniazid and rifampin must be conducted with a larger number of clinical isolates.

Keywords: isoniazid, MODS assay, MDR-TB, rifampin

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Authors: Naima Nur, Safa Islam, Saeema Islam, Md. Faridul Alam

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Background: The worldwide increase in pediatric presumptive tuberculosis (TB) is the most life-threatening challenge in effectively controlling TB. The objective of this study was to determine the proportion of presumptive TB and the factors associated with it. Methods: A cross-sectional study was conducted between March and November 2013 at ICDDR-Bangladesh. Two hundred twelve pulmonary and extra-pulmonary specimens were collected from 84 suspected pediatric patients diagnosed with TB based on their clinical symptoms/radiological findings. Presumptive TB and confirmed TB were considered presumptive TB and non-presumptive TB and were isolated by smear-microscopy, culture, and GeneXpert. Logistic regression was used to analyze associations between outcome and predictor variables. Results: The proportion of presumptive TB was 85.7%, and 14.3% of non-presumptive TB. In presumptive TB, vaccine scars, family TB history, and school-going children were 16.6%, 33.3%, and 56.9%, respectively. In contrast, vaccine scars and family TB history were 8.3%, and school-going children were 58.3% in non-presumptive TB. Significant factors did not appear in the logistic regression analysis. Conclusion: Despite the high proportion of presumptive TB, there was no statistically significant between presumptive TB and non-presumptive TB.

Keywords: presumptive tuberculosis, confirmed tuberculosis, patient's characteristics, diagnosis

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Authors: Christy Rosaline, Rathankar Roa, Waheeta Hopper

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Persistence of tuberculosis, emergence of multidrug-resistance and extensively drug-resistant forms of the disease, has increased the interest in developing new antitubercular drugs. Developing inhibitors for 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis (MtbDAH7Ps), an enzyme involved in shikimate pathway, gives a selective target for antitubercular agents. MtbDAH7Ps was screened against ZINC database, and shortlisted compounds were subjected to induce fit docking. Prime/Molecular Mechanics Generalized Born Surface Area calculation was used to validate the binding energy of ligand-protein complex. Molecular Dynamics analysis for of the lead compounds–MtbDAH7Ps complexes showed that the backbone of MtbDAH7Ps in their complexes were stable. These results suggest that the shortlisted lead compounds ZINC04097114, ZINC15163225, ZINC16857013, ZINC06275603, and ZINC05331260 could be developed into novel drug leads to inhibit DAH7Ps in Mycobacterium tuberculosis.

Keywords: MtbDAH7Ps, Mycobacterium tuberculosis, HTVS, molecular dynamics

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Authors: M. F. Abreu, A. I. Aguiar, R. Gaio, R. Duarte

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Background: Prison establishments constitute high-risk environments for the transmission and spread of tuberculosis (TB), given their epidemiological context and the difficulty of implementing preventive and control measures. Guidelines for control and prevention of tuberculosis in prisons have been described as incomplete and heterogeneous internationally, due to several identified obstacles, for example scarcity of human resources and funding of prisoner health services. In Portugal, a protocol was created in 2014 with the aim to define and standardize procedures of detection and prevention of tuberculosis within prisons. Objective: The main objective of this study was to identify and describe barriers to tuberculosis detection in prisons of Porto and Lisbon districts in Portugal. Methods: A cross-sectional study was conducted from 2ⁿᵈ January 2018 till 30ᵗʰ June 2018. Semi-structured questionnaires were applied to health care professionals working in the prisons of the districts of Porto (n=6) and Lisbon (n=8). As inclusion criteria we considered having work experience in the area of tuberculosis (either in diagnosis, treatment, or follow up). The questionnaires were self-administered, in paper format. Descriptive analyses of the questionnaire variables were made using frequencies and median. Afterwards, a hierarchical agglomerative clusters analysis was performed. After obtaining the clusters, the chi-square test was applied to study the association between the variables collected and the clusters. The level of significance considered was 0.05. Results: From the total of 186 health professionals, 139 met the criteria of inclusion and 82 health professionals were interviewed (62,2% of participation). Most were female, nurses, with a median age of 34 years, with term employment contract. From the cluster analysis, two groups were identified with different characteristics and behaviors for the procedures of this protocol. Statistically significant results were found in: elements of cluster 1 (78% of the total participants) work in prisons for a longer time (p=0.003), 45,3% work > 4 years while 50% of the elements of cluster 2 work for less than a year, and more frequently answered they know and apply the procedures of the protocol (p=0.000). Both clusters answered frequently the need of having theoretical-practical training for TB (p=0.000), especially in the areas of diagnosis, treatment and prevention and that there is scarcity of funding to prisoner health services (p=0.000). Regarding procedures for TB screening (periodic and contact screening) and procedures for transferring a prisoner with this disease, cluster 1 also answered more frequently to perform them (p=0.000). They also referred that the material/equipment for TB screening is accessible and available (p=0.000). From this clusters we identified as barriers scarcity of human resources, the need to theoretical-practical training for tuberculosis, inexperience in working in health services prisons and limited knowledge of protocol procedures. Conclusions: The barriers found in this study are the same described internationally. This protocol is mostly being applied in portuguese prisons. The study also showed the need to invest in human and material resources. This investigation bridged gaps in knowledge that could help prison health services optimize the care provided for early detection and adherence of prisoners to treatment of tuberculosis.

Keywords: barriers, health care professionals, prisons, protocol, tuberculosis

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Authors: Mmamapudi Kubjane, Natacha Berkowitz, Rene Goliath, Naomi S. Levitt, Robert J. Wilkinson, Tolu Oni

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Background: South Africa remains a high tuberculosis (TB) burden country globally and the burden of diabetes – a TB risk factor is growing rapidly. As an infectious disease, TB also induces transient hyperglycaemia. Therefore, screening for diabetes in newly diagnosed tuberculosis patients may result in misclassification of transient hyperglycaemia as diabetes. Objective: The objective of this study was to determine and compare the prevalence of hyperglycaemia (diabetes and impaired glucose regulation (IGR)) in TB patients and to assess the cross-sectional association between TB and hyperglycaemia at enrolment and after three months of follow-up. Methods: Consecutive adult TB and non-TB participants presenting at a TB clinic in Cape Town were enrolled in this cross-sectional study and follow-up between July 2013 and August 2015. Diabetes was defined as self-reported diabetes, fasting plasma glucose (FPG) ≥ 7.0 mmol·L⁻¹ or glycated haemoglobin (HbA1c) ≥ 6.5%. IGR was defined as FPG 5.5– < 7.0 mmol·L⁻¹ or HbA1c 5.7– < 6.5%. TB patients initiated treatment. After three months, all participants were followed up and screened for diabetes again. The association between TB and hyperglycaemia was assessed using logistic regression adjusting for potential confounders including sex, age, income, hypertension, waist circumference, previous prisoner, marital status, work status, HIV status. Results: Diabetes screening was performed in 852 participants (414 TB and 438 non-TB) at enrolment and in 639 (304 TB and 335 non-TB) at three-month follow-up. The prevalence of HIV-1 infection was 69.6% (95% confidence interval (CI), 64.9–73.8 %) among TB patients, and 58.2% (95% CI, 53.5–62.8 %) among the non-TB participants. Glycaemic levels were much higher in TB patients than in the non-TB participants but decreased over time. Among TB patients, the prevalence of IGR was 65.2% (95% CI 60.1 - 69.9) at enrollment and 21.5% (95% CI 17.2-26.5) at follow-up; and was 50% (45.1 - 54.94) and 32% (95% CI 27.9 - 38.0) respectively, among non-TB participants. The prevalence of diabetes in TB patients was 12.5% (95% CI 9.69 – 16.12%) at enrolment and 9.2% (95% CI, 6.43–13.03%) at follow-up; and was 10.04% (95% CI, 7.55–13.24%) and 8.06% (95% CI, 5.58–11.51) respectively, among non-TB participants. The association between TB and IGT was significant at enrolment (adjusted odds ratio (OR) 2.26 (95% CI, 1.55-3.31) but disappeared at follow-up 0.84 (0.53 - 1.36). However, the TB-diabetes association remained positive and significant both at enrolment (2.41 (95% CI, 1.3-4.34)) and follow-up (OR 3.31 (95% CI, 1.5 - 7.25)). Conclusion: Transient hyperglycaemia exists during tuberculosis. This has implications on diabetes screening in TB patients and suggests a need for diabetes confirmation tests during or after TB treatment. Nonetheless, the association between TB and diabetes noted at enrolment persists at 3 months highlighting the importance of diabetes control and prevention for TB control. Further research is required to investigate the impact of hyperglycaemia (transient or otherwise) on TB outcomes to ascertain the clinical significance of hyperglycemia at enrolment.

Keywords: diabetes, impaired glucose regulation, transient hyperglycaemia, tuberculosis

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Authors: Cherif Y., Ghariani R., Derbal S., Farhati S., Ben Dahmen F., Abdallah M.

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Introduction: Tuberculosis (TBC) is a frequent infection and is still a major public health problem in Tunisia. The aim of this work is to focus on diagnostic and therapeutic characteristics of TBC in patients referred to our internal medicine department. Patients and Methods: The study was retrospective and descriptive of a cohort of consecutive cases treated from January 2016 to December 2019, collecting patients with latent or patent TBC. Twenty-eight medical records of adults diagnosed with TBC were reviewed. Results: Twenty-eight patients, including 18 women and 10 men, were diagnosed with TBC. Their mean age is 48 years (range: 22-78 years). Five patients have a medical history of diabetes mellitus, 1 patient was followed for systemic lupus erythematosus treated with corticosteroids and immunosuppressant drugs, and another was treated with corticosteroids for Mac Duffy syndrome. The TBC is latent in 12 cases and patent in 16 cases. The most common symptoms were fever and weight loss and were found in 10 cases, a cough in 2 cases, sputum in 3 cases, lymph nodes in 4 cases, erythema nodosum in 2 cases, and neurological signs in 3 cases. Lymphopenia is noticed in 3 cases and a biological inflammatory syndrome in 18 of the cases. The purified protein derivate reaction was positive in 17 cases, anergic in 3 cases, negative in 5 cases, and not done in 3 cases. The acid-fast bacilli stain culture was strongly positive in one patient. The histopathological study was conclusive in 11 patients and showed granulomatosis with caseous necrosis. TBC was pulmonary in 7 patients, lymph node in 7 cases, peritoneal in 7 cases, digestive in 1 case, neuromeningeal in 3 cases, and thyroïd in 1 case. Seven patients had multifocal TBC. All the patients received anti-tuberculosis treatment with a mean duration of 8 months with no failure or relapse with an average follow-up time of 10.58 months. Conclusion: Diagnosis and management of TBC remain essential to avoid serious complications. The survey is necessary to ensure timely detection and treatment of infected adults to decrease its incidence. The best treatment remains preventive through vaccination and improving social and economic conditions.

Keywords: tuberculosis, infection, autoimmune disease, granulomatosis

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Authors: Shima Mahmoudi, Setareh Mamishi, Babak Pourakbari, Majid Marjani

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In the last years, the potential role of distinct T-cell subsets as biomarkers of active tuberculosis TB and/or latent tuberculosis infection (LTBI) has been studied. The aim of this study was to investigate the potential role of interleukin-2 (IL-2) in whole blood stimulated with M. tuberculosis-specific antigens in the QuantiFERON-TB Gold In Tube (QFT-G-IT) for the discrimination of active and latent tuberculosis. After 72-h of stimulation by antigens from the QFT-G-IT assay, IL-2 secretion was quantitated in supernatants by using ELISA (Mabtech AB, Sweden). Observing the level of IL-2 released after 72-h of incubation, we found that the level of IL-2 were significantly higher in LTBI group than in patients with active TB infection or control group (P value=0.019, Kruskal–Wallis test). The discrimination performance (assessed by the area under ROC curve) between LTBI and patients with active TB was 0.816 (95%CI: 0.72-0.97). Maximum discrimination was reached at a cut-off of 13.9 pg/mL for IL-2 following stimulation with 82% sensitivity and 86% specificity. In conclusion, although cytokine analysis has greatly contributed to the understanding of TB pathogenesis, data on cytokine profiles that might distinguish progression from latency of TB infection are scarce and even controversial. Our data indicate that the concomitant evaluation of IFN- γ and IL-2 could be instrumental in discriminating of active and latent TB infection.

Keywords: interleukin-2, discrimination, active TB, latent TB

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Authors: Windy Rakhmawati, Suryani Suryani, Sri Hendrawati, Nenden Nur Asriyani Maryam

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Tuberculosis (TB) is one of the leading causes of death in the world. Fear of COVID-19 has made people reluctant to visit health facilities, leading to disruptions to childhood TB control programs, which may increase household transmission and delay diagnosis and treatment. This study aimed to describe parents' knowledge, attitudes, and health-seeking behaviour towards childhood TB during the COVID-19 pandemic. This cross-sectional study was performed on 392 parents with TB children in three provinces with the highest proportion of TB cases in Indonesia. This study was conducted from February to December 2022. The inclusion criteria of respondents were parents with a child aged 0-14 years old with TB diagnosis who live with their parents. Data were collected using the Knowledge, Attitude, and Practice (KAP) survey guidelines from the World Health Organization and analyzed descriptively, as well as Spearman’s correlation. Overall, 392 parents of children with TB had poor knowledge (51.8%) including about causes, risk factors, transmission, symptoms, treatment, and prevention, which about 52.3%, 55.1%, 61.2%, 69.6%, 100%, 59.2%, respectively. Parents' health service-seeking behaviour towards Child TB was not normally distributed (P < 0.05) with knowledge test results (.000) and Seeking Health Services (.000). Health-seeking behaviour of parents in pediatric TB care was self-medication or self-treatment (86.2%), Traditional health seeking behaviour (4.8%), and modern health seeking behaviour (8.9%). The correlation between knowledge and seeking health services (Sig= .609) means there is no correlation between knowledge about TB and parents' health-seeking behaviour. Furthermore, 60.2% of the respondents would be shocked if their child had TB. More than half of the families in this study have poor knowledge and did self-medication or self-treatment regarding health-seeking behaviour for TB disease. Therefore, health workers, especially nurses, must provide TB-related education and health promotion and emphasize the importance of early detection. Health workers can also optimize their role in caring for and providing care to patients by increasing their trust in health workers, which will impact health-seeking behaviour in the future.

Keywords: attitude, child, health seeking behaviour, knowledge, tuberculosis

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Authors: Shubhita Mathur, Ritika Kar Bahal, Priyanka Chauhan, Anil K. Tyagi

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Mycobacterium tuberculosis, the causative agent of human tuberculosis, is a major cause of mortality. Bacillus Calmette-Guérin (BCG), the only licensed vaccine available for protection against tuberculosis confers highly variable protection ranging from 0%-80%. Thus, novel vaccine strains need to be evaluated for their potential as a vaccine against tuberculosis. We had previously constructed a triple gene mutant of M. tuberculosis (MtbΔmms), having deletions in genes encoding for phosphatases mptpA, mptpB, and sapM that are involved in host-pathogen interaction. Though vaccination with Mtb∆mms strain induced protection in the lungs of guinea pigs, the mutant strain was not able to control the hematogenous spread of the challenge strain to the spleens. Additionally, inoculation with Mtb∆mms resulted in some pathological damage to the spleens in the early phase of infection. In order to overcome the pathology caused by MtbΔmms in the spleens of guinea pigs and also to control the dissemination of the challenge strain, MtbΔmms was genetically modified by disrupting bioA gene to generate MtbΔmmsb strain. Further, in vivo attenuation of MtbΔmmsb was evaluated, and its protective efficacy was assessed against virulent M. tuberculosis challenge in guinea pigs. Our study demonstrates that Mtb∆mmsb mutant was highly attenuated for growth and virulence in guinea pigs. Vaccination with Mtb∆mmsb mutant generated significant protection in comparison to sham-immunized animals at 4 and 12 weeks post-infection in lungs and spleens of the infected animals. Our findings provide evidence that deletion of genes involved in signal transduction and biotin biosynthesis severely attenuates the pathogen and the single immunization with the auxotroph was able to provide significant protection as compared to sham-immunized animals. The protection imparted by Mtb∆mmsb fell short in comparison to the protection observed in BCG-immunized animals. This study nevertheless indicates the importance of attenuated multiple gene deletion mutants of M. tuberculosis in generating protection against tuberculosis.

Keywords: Mycobacterium tuberculosis, BCG, MtbΔmmsb, bioA, guinea pigs

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Authors: Fasil Wagnew, Kefyalew Addis Alene, Setegn Eshetie, Tom Wingfield, Matthew Kelly, Darren Gray

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Introduction: Undernutrition is a major and under-appreciated risk factor for TB, which is estimated to be responsible for 1.9 million TB cases per year globally. The effectiveness of micronutrient supplementation on TB treatment outcomes and its prognostic markers such as sputum conversion and serum zinc, retinol, and hemoglobin levels has been poorly understood. This systematic review and meta-analysis aimed to determine the association between zinc and vitamin A supplementation and TB treatment outcomes and its prognostic markers. Methods: A systematic literature search for randomized controlled trials (RCTs) was performed in PubMed, Embase, and Scopus databases. Meta-analysis with a random effect model was performed to estimate risk ratio (RR) and mean difference (MD), with a 95% confidence interval (CI), for dichotomous and continuous outcomes, respectively. Results: Our search identified 2,195 records. Of these, nine RCTs consisting of 1,375 participants were included in the final analyses. Among adults with pulmonary TB, zinc (RR: 0.94, 95%CI: 0.86, 1.03), vitamin A (RR: 0.90, 95%CI: 0.80, 1.01), and combined zinc and vitamin A (RR: 0.98, 95%CI: 0.89, 1.08) supplementation were not significantly associated with TB treatment success. Combined zinc and vitamin A supplementation was significantly associated with increased sputum smear conversion at 2 months (RR: 1.16, 95%CI: 1.03, 1.32), serum zinc levels at 2 months (MD of 0.86umol/l, 95% CI: 0.14, 1.57), serum retinol levels at 2 months (MD: 0.06umol/l, 95 % CI: 0.04, 0.08) and 6 months (MD: 0.12umol/l, 95 % CI: 0.10, 0.14), and serum hemoglobin level at 6 months (MD: 0.29 ug/dl, 95% CI: 0.08 to 0.51), among adults with TB. Conclusions: Providing zinc and vitamin A supplementation to adults with pulmonary TB during treatment may increase early sputum smear conversion, serum zinc, retinol, and hemoglobin levels. However, the use of zinc, vitamin A, or both were not associated with TB treatment success.

Keywords: zinc and vitamin A supplementation, tuberculosis, treatment outcomes, meta-analysis, RCT

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Authors: Muhammad Younas, Zimal Naveed

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Introduction : TB is caused by the bacillus Mycobacterium tuberculosis, which is spread when people who are sick with TB expel bacteria into the air (e.g. by coughing). The 30 high TB burden countries accounted for 87% of all estimated incident cases worldwide, and eight of these countries accounted for more than two thirds of the global total: India (27%), Indonesia (10%), China (7.1%), the Philippines (7.0%), Pakistan (5.7%), Nigeria (4.5%), Bangladesh (3.6%) and the Democratic Republic of the Congo (3.0%). Objective : To analyze prevalence of tuberculosis among the people who presented at THQ hospital Bhalwal between April 2024 to June 2024. Method : Total of 9200 patients presented in the OPD of THQ hospital Bhalwal were included in the study. These presumed cases underwent diagnostic testing by sputum for AFB, Gene expert and chest x rays. The data was then classified based Pulmonary and Extra-pulmonary TB disease and further classified on the basis of bacteriology positive and clinically diagnosed TB. The registered TB cases were then classified in 8 age groups in years and according to the gender. All the registered TB cases were then tested for HIV to observe the relation between Tuberculosis and HIV. Results : The total of 9200 patients presented to OPD during the period of 3 months between April 2024 to June 2024. Total registered cases of Tuberculosis were 161 (comprising 153 new cases and 8 cases after treatment failure). Out of the new cases 83 were males and 70 female cases were identified. The majority of males that were identified lies between age 55-64 and 65 and above while the majority of females that were diagnosed lies in the age group of 5-14 and 15-24. All the registered cases were then tested for HIV but none of them were found to be positive. Conclusion : According to World Health Organisation Global Tuberculosis Report, the incidence of Tubeculosis per 100000 people was 258, equivalent to 0.258 %. However, the study reveals an exceptionally high frequency of TB cases. The prevalence of Tuberculosis per 100000 people was found to be 1750 which is equivalent to 1.75 %. The study revealed that larger proportion of the population is currently affected by TB compared to the global average incidence reported by the WHO. The findings of the study indicates that the prevalence of tuberculosis (TB) among females is most common in the younger population, specifically between the ages of 5 to 24, and particularly within the peak fertility age group of 15 to 24 years. The health of women in their peak fertility years is crucial for maternal and child health outcomes. This highlights the need for targeted public health interventions in this area to manage and reduce the burden of TB.

Keywords: AGE, AFB, female, male

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Authors: Muhammad Shahbaz Akhtar

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Background; Tuberculosis remains a significant public health challenge in Pakistan, with high incidence and prevalence rates, particularly among vulnerable populations. Addressing the TB burden requires comprehensive efforts to improve healthcare infrastructure, increase access to quality diagnosis and treatment services, raise public awareness, and address socioeconomic determinants of health. Objective; To assess the knowledge and practices of healthcare workers and patients regarding prevention of tuberculosis at a tertiary care hospital of Southern Punjab.Material and methods; Data will be collected from 135 healthcare workers and 135 TB patients visiting Nishtar Hospital, Multan in this descriptive cross – sectional study using non – probability consecutive sampling technique. Proper approval will be taken from Hospital authorities to conduct this study. Study participants will be recruited after taking informed written consent, describing them objectives of this study. The study participants will be ensured of their confidentiality of the data and interviewed to assess their knowledge and practices regarding prevention of tuberculosis. Data Analysis Procedure; Data will be entered and analyzed by using SPSS version 25 to calculated mean and standard deviation for the numerical data such as age, duration of disease and duration of experience. Frequencies and percentages will be calculated for gender, age groups, level of knowledge, qualification, designation and practices. Impact of confounders like gender, age groups, duration of experience, disease duration, years of experience and designation will be assessed by stratification. Post stratification chi – square test will be applied at 0.05 level of significance at 95 % CI.

Keywords: tuberculosis, data analysis, HIV/AIDS, preventable

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Authors: R. K. Yadav, S. Baral, H. R. Paudel, R. Basnet

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The Public-Private Mix (PPM) approach is a strategic initiative that involves engaging all private and public healthcare providers in the fight against tuberculosis using international healthcare standards. For tuberculosis control in Nepal, the PPM approach could be a milestone. This study aimed to explore the barriers to a public-private mix approach in the management of tuberculosis cases in Nepal. A total of 20 respondents participated in the study. Barriers to PPM were identified in the following three themes: 1) Obstacles related to TB case detection, 2) Obstacles related to patients, and 3) Obstacles related to the healthcare system. PPM implementation was challenged by following subthemes that included staff turnover, low private sector participation in workshops, a lack of training, poor recording and reporting, insufficient joint monitoring and supervision, poor financial benefit, lack of coordination and collaboration, and non-supportive TB-related policies and strategies. The study concludes that numerous barriers exist in the way of effective implementation of the PPM approach, including TB cases detection barriers such as knowledge of TB diagnosis and treatment, HW attitude, workload, patient-related barriers such as knowledge of TB, self-medication practice, stigma and discrimination, financial status, and health system-related barriers such as staff turnover and poor engagement of the private sector in workshops, training, recording, and re-evaluation. Government stakeholders must work together with private sector stakeholders to perform joint monitoring and supervision. Private practitioners should receive training and orientation, and presumptive TB patients should be given adequate time and counseling as well as motivation to visit a government health facility.

Keywords: barrier, tuberculosis, case finding, PPM, nepal

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Authors: Elena G. Salina, Laurent R. Chiarelli, Maria R. Pasca, Vadim A. Makarov

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Tuberculosis is one of the most challenging threats to human health, confronted by the problem of drug resistance. Evidently, new drugs for tuberculosis are urgently needed. Thienopyrimidine TP053 is one of the most promising new antitubercular prodrugs. Mycothiol-dependent reductase Mrx2, encoded by rv2466c, is known to be a TP053 activator; however, the precise mode of action of this compound remained unclear. Being highly active against both replicating and non-replicating tuberculosis bacilli, TP053 also revealed dose-escalating activity for M. tuberculosis-infected murine macrophages. The chemical structure of TP053 is characterized by the presence of NO₂ group which was suggested to be responsible for the toxic effects of the activated compound. Reduction of a nitroaromatic moiety of TP53 by Mrx2 was hypothesized to result in NO release. Analysis of the products of enzymatic activation of TP053 by Mrx2 by the Greiss reagent clearly demonstrated production of nitric oxide in a time-dependent manner. Mass-spectra of cell lysates of TP-treated M. tuberculosis bacilli demonstrated the transformation of TP053 to its non-active metabolite with Mw=261 that corresponds NO release. The mechanism of NO toxicity for bacteria includes DNA damage and degradation of iron-sulfur centers, especially under oxygen depletion. Thus, TP-053 drug-like scaffold is prospective for further development of novel anti-TB drug. This work was financially supported by the Russian Foundation for Basic Research (Grant 17-04-00342).

Keywords: drug discovery, M. tuberculosis, nitric oxide, NO donors

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Authors: Vadim Makarov, Stewart T.Cole

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PBTZ169 is novel drug candidate with high efficacy in animals models, and its combination treatment of PBTZ169 with BDQ and pyrazinamide was shown to be more efficacious than the standard treatment for tuberculosis in a mouse model. The target of PBTZ169 is famous DprE1, an essential enzyme in cell wall biosynthesis. The crystal structure of the DprE1-PBTZ169 complex reveals formation of a semimercaptal adduct with Cys387 in the active site and explains the irreversible inactivation of the enzyme. Furthermore, this drug candidate demonstrated during preclinical research ‘drug like’ properties what made it an attractive drug candidate to treat tuberculosis in humans. During first clinical trials several cohorts of the healthy volunteers were treated by the single doses of PBTZ169 as well as two weeks repeated treatment was chosen for two maximal doses. As expected PBTZ169 was well tolerated, and no significant toxicity effects were observed during the trials. The study of the metabolism shown that human metabolism of PBTZ169 is very different from microbial or animals compound transformation. So main pathway of microbial, mice and less rats metabolism connected with reduction processes, but human metabolism mainly connected with oxidation processes. Due to this difference we observed several metabolites of PBTZ169 in humans with antitubercular activity, and now we can conclude that animal antituberculosis activity of PBTZ169 is a result not only activity of the drug itself, but it is a result of the sum activity of the drug and its metabolites. Direct antimicrobial plasma activity was studied, and such activity was observed for 24 hours after human treatment for some doses. This data gets high chance for good efficacy of PBTZ169 in human for treatment TB infection. Second phase of clinical trials was started summer of 2017 and continues to the present day. Available data will be presented.

Keywords: clinical trials, DprE1, PBTZ169, metabolism

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Authors: Lok Raj Joshi, Naveen Prakash Shah, Sharad Kumar Sharma, I. Ratna Bhattarai, Rajendra Basnet, Deepak Dahal, Bahagwan Maharjan, Seraphine Kaminsa

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Context: Tuberculosis (TB) is a significant health issue in Nepal, a country with a high burden of the disease. Despite efforts to control TB, there is still a gap in the notification of TB cases, which hinders effective control and treatment. This paper aims to address this notification gap and proposes strategies to improve TB control in Nepal. Research Aim: The aim of this research is to understand and address the tuberculosis notification gap in Nepal. The focus is on enhancing the healthcare system, involving the private sector and communities, raising awareness, and addressing social determinants to achieve sustainable TB control. Methodology: The research methodology involved a review of existing epidemiological data and research studies related to TB in Nepal. Additionally, consultation with an expert group from the TB control program in Nepal provided insights into the current state of TB control and challenges in addressing the notification gap. Findings: The findings reveal that only 55% of TB cases were reported in 2022, indicating a significant notification gap. Of the reported cases, only 32% and 19% were referred by the private sector and community, respectively. Furthermore, 20% of diagnosed cases were not treated in the initial phase. The estimated number of cases of multidrug-resistant TB (MDR TB) was 2,800, suggesting a low diagnosis rate. Among the diagnosed MDR TB cases, only 60% were receiving treatment. Additionally, it was observed that 20% of diagnosed MDR TB cases were from India and not enrolling in TB treatment in Nepal, indicating a high rate of defaulters. Theoretical Importance: The study highlights the importance of adopting a holistic strategy to address the notification gap in TB cases in Nepal. It emphasizes the need to enhance healthcare infrastructure, raise awareness, involve the private sector and local communities, establish effective methods to trace initial defaulters, implement TB interventions in border regions, and mitigate the social stigma associated with the disease. Data Collection and Analysis Procedures: Data for this study was collected through a review of existing epidemiological data and research studies. The data were then analyzed to identify patterns, trends, and gaps in TB case notification in Nepal.

Keywords: TB, tuberculosis, private sector, community, migrants, nepal

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Authors: Aneta Nitsch-Osuch, Beata Pawlus, Maria Pawlak

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Introduction: Recently, the number of parents who refuse to vaccinate their children or present so-called hesitant behaviors has increased in many developed countries. The study aimed to analyze the completeness and timeliness of vaccinations against hepatitis B and tuberculosis in neonates in a single maternity hospital in Warsaw (Poland). Material and Methods: We analyzed medical records of children born in the hospital between 1st January 2015 and 31st December 2016 and calculated the proportion of newborns not vaccinated on time. Results: The percentage of unvaccinated newborns was similar in the analyzed years: 7.2% in 2015 and 6.7% in 2016. Parental decisions rather than medical contraindications caused non-immunization (4.3% vs. 2.9% in 2015, and 4.7% vs. 2% in 2016). Most parents refused both vaccinations (81%-84%), whereas 7-8% refused only hep B vaccination, and 9-11% refused alone tuberculosis vaccination. The majority of hesitant parents decided to delay both vaccinations (70-80%), while 10-11% of parents chose to delay only one vaccination (hep B). In consecutive years, an increase in the percentage of parents delaying tuberculosis vaccination was reported (10 vs. 19%). Discussion: The increase in the number of newborns who are not correctly vaccinated just after birth due to their parents' decision should be considered non-gradual, both for hepatitis B and tuberculosis. It is necessary to implement effective educational and informative measures targeted at future parents to reinforce positive attitudes towards vaccinations and to dispel doubts about them among parents who are hesitant.

Keywords: hepatitis B, tuberculosis, immunization, new-borns, coverage rate

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Authors: Vasundhara Arora, Anupam Jhobta, Suresh Thakur, Sanjiv Sharma

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Aims and Objectives: Intracranial tuberculosis (TB) is one of the most devastating manifestations of TB and a challenging public health issue of considerable importance and magnitude world over. This study elaborates on the imaging spectrum of neurotuberculosis on magnetic resonance imaging (MRI) in 29 clinically suspected cases from a tertiary care hospital. Materials and Methods: The prospective hospital based evaluation of MR imaging features of neuro-tuberculosis in 29 clinically suspected cases was carried out in Department of Radio-diagnosis, Indira Gandhi Medical Hospital from July 2017 to August 2018. MR Images were obtained on a 1.5 T Magnetom Avanto machine and were analyzed to identify any abnormal meningeal enhancement or parenchymal lesions. Microbiological and Biochemical CSF analysis was performed in radio-logically suspected cases and the results were compared with the imaging data. Clinical follow up of the patients started on anti-tuberculous treatment was done to evaluate the response to treatment and clinical outcome. Results: Age range of patients in the study was between 1 year to 73 years. The mean age of presentation was 11.5 years. No significant difference in the distribution of cerebral tuberculosis was noted among the two genders. Imaging findings of neuro-tuberculosis obtained were varied and non specific ranging from lepto-meningeal enhancement, cerebritis to space occupying lesions such as tuberculomas and tubercular abscesses. Complications presenting as hydrocephalus (n= 7) and infarcts (n=9) was noted in few of these patients. 29 patients showed radiological suspicion of CNS tuberculosis with meningitis alone observed in 11 cases, tuberculomas alone were observed in 4 cases, meningitis with parenchymal tuberculomas in 11 cases. Tubercular abscess and cerebritis were observed in one case each. Tuberculous arachnoiditis was noted in one patient. Gene expert positivity was obtained in 11 out of 29 radiologically suspected patients; none of the patients showed culture positivity. Meningeal form of the disease alone showed higher positivity rate of gene Xpert (n=5) followed by combination of meningeal and parenchymal forms of disease (n=4). The parenchymal manifestation of disease alone showed least positivity rates (n= 3) with gene xpert testing. All 29 patients were started on anti tubercular treatment based on radiological suspicion of the disease with clinical improvement observed in 27 treated patients. Conclusions: In our study, higher incidence of neuro- tuberculosis was noted in paediatric population with predominance of the meningeal form of the disease. Gene Xpert positivity obtained was low due to paucibacillary nature of cerebrospinal fluid (CSF) with even lower positivity of CSF samples in parenchymal form of the manifestation. MRI showed high accuracy in detecting CNS lesions in neuro-tuberculosis. Hence, it can be concluded that MRI plays a crucial role in the diagnosis because of its inherent sensitivity and specificity and is an indispensible imaging modality. It caters to the need of early diagnosis owing to poor sensitivity of microbiological tests more so in the parenchymal manifestation of the disease.

Keywords: neurotuberculosis, tubercular abscess, tuberculoma, tuberculous meningitis

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Authors: Rachel Fanelwa Ajayi, Anovuyo Jonnas, Emmanuel I. Iwuoha

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Tuberculosis (TB) is an infectious disease caused by the bacterium (Mycobacterium tuberculosis) which has a predilection for lung tissue due to its rich oxygen supply. The mycobacterial cell has a unique innate characteristic which allows it to resist human immune systems and drug treatments; hence, it is one of the most difficult of all bacterial infections to treat, let alone to cure. At the same time, multi-drug resistance TB (MDR-TB) caused by poorly managed TB treatment, is a growing problem and requires the administration of expensive and less effective second line drugs which take much longer treatment duration than fist line drugs. Therefore, to acknowledge the issues of patients falling ill as a result of inappropriate dosing of treatment and inadequate treatment administration, a device with a fast response time coupled with enhanced performance and increased sensitivity is essential. This study involved the synthesis of electroactive platforms for application in the development of nano-biosensors suitable for the appropriate dosing of clinically diagnosed patients by promptly quantifying the levels of the TB drug; Isonaizid. These nano-biosensors systems were developed on gold surfaces using the enzyme N-acetyletransferase 2 coupled to the cysteamine modified poly(8-anilino-1-napthalene sulphonic acid)/zinc oxide nanocomposites. The morphology of ZnO nanoparticles, PANSA/ZnO nano-composite and nano-biosensors platforms were characterized using High-Resolution Transmission Electron Microscopy (HRTEM) and High-Resolution Scanning Electron Microscopy (HRSEM). On the other hand, the elemental composition of the developed nanocomposites and nano-biosensors were studied using Fourier Transform Infra-Red Spectroscopy (FTIR) and Energy Dispersive X-Ray (EDX). The electrochemical studies showed an increase in electron conductivity for the PANSA/ZnO nanocomposite which was an indication that it was suitable as a platform towards biosensor development.

Keywords: N-acetyletransferase 2, isonaizid, tuberculosis, zinc oxide

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Authors: Seyed Davar Siadat, Samira Tarashi, Abolfazl Fateh, Arfa Moshiri

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Background: The global health issue of tuberculosis (TB) still affects patients in every country. TB control may not be as effective as it should be, especially when resistant strains are involved. In this regard, mycobacterial MTases play a major role in tuberculosis, but the mechanisms underlying their function have yet to be fully deciphered. Methods: Five resistant isolates of M.tb were accumulated. As a reference strain, M.tb H37Rv (ATCC 27249) was used. For this analysis, seven putative mycobacterial MTase genes (Rv0645c, Rv1694, Rv2966c, Rv3919c, Rv2756c, Rv1988, and Rv3263), as well as Rv1392 as SAM synthase, were selected. Comparing mutations and expression levels of MTases in different strains was accomplished by PCR-sequencing and qRT-PCR. The relative expression levels of these genes were calculated using the 2 -ΔΔCt method. Results: The Rv3919c gene (T to G in codon 341) and Rv1392 gene (G to A in codon 97) were the only mutations found in the INHR strain. In all sensitive and resistant isolates, Rv0645c, Rv3263, Rv2756c, and Rv2966c were overexpressed. However, the expression of Rv1988 and Rv3919c decreased in the sensitive strains, whereas the expression of Rv1694 increased. There was also a decreased expression of Rv1392 in the INHR isolate. Conclusion: The presence of mycobacterial MTases as well as resistance to antibiotics were found to be correlated in M.tb strains. Undoubtedly, there are some MTases that are associated with the virulence process. It is necessary to conduct additional studies to fully explore the impact of mycobacterial MTases within specific strains of M.tb to develop novel diagnostic and treatment strategies.

Keywords: mycobacterium tuberculosis, drug resistance, methyltransferases, s-adenosylmethionine

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Authors: Christi Jackson, Chuka Onaga

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Introduction: We report a case of delayed diagnosis of extra-pulmonary INH-mono-resistant Tuberculosis (TB) in a South African patient with drug-resistant HIV. Case Presentation: A 36-year old male was initiated on 1st line (NNRTI-based) anti-retroviral therapy (ART) in September 2009 and switched to 2nd line (PI-based) ART in 2011, according to local guidelines. He was following up at the outpatient wellness unit of a public hospital, where he was diagnosed with Protease Inhibitor resistant HIV in March 2016. He had an HIV viral load (HIVVL) of 737000 copies/mL, CD4-count of 10 cells/µL and presented with complaints of productive cough, weight loss, chronic diarrhoea and a septic buttock wound. Several investigations were done on sputum, stool and pus samples but all were negative for TB. The patient was treated with antibiotics and the cough and the buttock wound improved. He was subsequently started on a 3rd-line ART regimen of Darunavir, Ritonavir, Etravirine, Raltegravir, Tenofovir and Emtricitabine in May 2016. He continued losing weight, became too weak to stand unsupported and started complaining of abdominal pain. Further investigations were done in September 2016, including a urine specimen for Line Probe Assay (LPA), which showed M. tuberculosis sensitive to Rifampicin but resistant to INH. A lymph node biopsy also showed histological confirmation of TB. Management and outcome: He was started on Rifabutin, Pyrazinamide and Ethambutol in September 2016, and Etravirine was discontinued. After 6 months on ART and 2 months on TB treatment, his HIVVL had dropped to 286 copies/mL, CD4 improved to 179 cells/µL and he showed clinical improvement. Pharmacy supply of his individualised drugs was unreliable and presented some challenges to continuity of treatment. He successfully completed his treatment in June 2017 while still maintaining virological suppression. Discussion: Several laboratory-related factors delayed the diagnosis of TB, including the unavailability of urine-lipoarabinomannan (LAM) and urine-GeneXpert (GXP) tests at this facility. Once the diagnosis was made, it presented a treatment dilemma due to the expected drug-drug interactions between his 3rd-line ART regimen and his INH-resistant TB regimen, and specialist input was required. Conclusion: TB is more difficult to diagnose in patients with severe immunosuppression, therefore additional tests like urine-LAM and urine-GXP can be helpful in expediting the diagnosis in these cases. Patients with non-standard drug regimens should always be discussed with a specialist in order to avoid potentially harmful drug-drug interactions.

Keywords: drug-resistance, HIV, line probe assay, tuberculosis

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Authors: Sonam Kumari

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Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, possesses a remarkable feature of entering into and emerging from a persistent state. The mechanism by which Mtb switches from the dormant state to the replicative form is still poorly characterized. Proteome studies have given us an insight into the role of certain proteins in giving stupendous virulence to Mtb, but numerous dotsremain unconnected and unaccounted. The WhiB family of proteins is one such protein that is associated with developmental processes in actinomycetes.Mtb has seven such proteins (WhiB1 to WhiB7).WhiB proteins are transcriptional regulators; their conserved C-terminal HTH motif is involved in DNA binding. They regulate various essential genes of Mtbby binding to their promoter DNA. Biophysical Analysis of the effect of DNA binding on WhiB proteins has not yet been appropriately characterized. Interaction with DNA induces conformational changes in the WhiB proteins, confirmed by steady-state fluorescence and circular dichroism spectroscopy. ITC has deduced thermodynamic parameters and the binding affinity of the interaction. Since these transcription factors are highly unstable in vitro, their stability and solubility were enhanced by the co-expression of molecular chaperones. The present study findings help determine the conditions under which the WhiB proteins interact with their interacting partner and the factors that influence their binding affinity. This is crucial in understanding their role in regulating gene expression in Mtbandin targeting WhiB proteins as a drug target to cure TB.

Keywords: tuberculosis, WhiB proteins, mycobacterium tuberculosis, nucleic acid binding

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Authors: Vandna Raghuvanshi, Vikrant Thakur, Anupam Jhobta

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Objective: To design HRCT criterion to forecast the threat of pulmonary tuberculosis. Material and methods: This was a prospective study of 69 patients with clinical suspicion of pulmonary tuberculosis. We studied their medical characteristics, numerous separate HRCT-results, and a combination of HRCT findings to foresee the danger for PTB by utilizing univariate and multivariate investigation. Temporary HRCT diagnostic criteria were planned in view of these outcomes to find out the risk of PTB and tested these criteria on our patients. Results: The results of HRCT chest were analyzed, and Rank was given from 1 to 4 according to the HRCT chest findings. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. Rank 1: Highly suspected PTB. Rank 2: Probable PTB Rank 3: Nonspecific or difficult to differentiate from other diseases Rank 4: Other suspected diseases • Rank 1 (Highly suspected TB) was present in 22 (31.9%) patients, all of them finally diagnosed to have pulmonary tuberculosis. The sensitivity, specificity, and negative likelihood ratio for RANK 1 on HRCT chest was 53.6%, 100%, and 0.43, respectively. • Rank 2 (Probable TB) was present in 13 patients, out of which 12 were tubercular, and 1 was non-tubercular. • The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of the combination of Rank 1 and Rank 2 was 82.9%, 96.4%, 23.22, and 0.18, respectively. • Rank 3 (Non-specific TB) was present in 25 patients, and out of these, 7 were tubercular, and 18 were non-tubercular. • When all these 3 ranks were considered together, the sensitivity approached 100% however, the specificity reduced to 35.7%. The positive likelihood ratio and negative likelihood ratio were 1.56 and 0, respectively. • Rank 4 (Other specific findings) was given to 9 patients, and all of these were non-tubercular. Conclusion: HRCT is useful in selecting individuals with greater chances of pulmonary tuberculosis.

Keywords: pulmonary, tuberculosis, multivariate, HRCT

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Authors: Juan Santos Garcia

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Introduction: Tuberculosis is a chronic granulomatous disease caused by a microorganism called Mycobacterium tuberculosis, it has the capacity to spread from the lungs to other parts of the body. Globally, the rate per 100 thousand inhabitants has varied from 136 in 2007 to 122 in 2012; while in the region of the Americas has been much lower: 32 cases per 100,000 in 2007, to 29 in 2012. In El Salvador have also varied incidence rates from 2007 to 2012, from 27.4 cases per 100 000 population to 32 in the period indicated. Methods: Screening was performed with smear and chest X-ray at 80 military personnel from Military Brigade # 5 of El Salvador. Besides HIV tests were taken at the positive cases, which are also made interview, investigating demographic, clinical, laboratory and risk factors data. Frequencies, percentages and rates were calculated using Excel page. The rates were calculated for each of the 5 military bedrooms (called A, B, C, D, and E). Results: Attack rate was 18.75% in the bedroom C. the index case was identified and two secondary cases, with an exposure period of 59 days. Only the index case presented symptoms: cough, fever and weight loss. The other two cases had no symptoms. Discussion: We found a rate of tuberculosis 526 times higher than the national rate. He was also 12.5 times higher than that found in other studies in closed populations such as school facilities. It was not possible to make association analysis.

Keywords: tuberculosis, outbreak, military brigade, chronic granulomatous disease

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Authors: Rithika Sriram, Kiran M. Bhojwani

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Introduction : Tuberculosis of the head and neck has proved to be a diagnostic challenge for otorhinolarynologists around the world. These lesions are often misdiagnosed as cancer. So in order to contribute to a better understanding of these lesions, we have conducted our study among patients affected by TB in the head and neck region with the objective of assessing the various manifestations, presentations, diagnostic techniques, risk factors such as smoking and alcohol consumption, coexisting illnesses and treatment modalities. Materials and Methods: This was a retrospective study conducted over a three year period (2012-2014) in 2 hospitals affliated to Kasturba Medical College in Mangalore, South India. A semi structured proforma was used to capture information from the medical records pertaining to the various objectives of the study such as clinical features and history of smoking. Data was analysed using SPSS version 16.0 and results obtained were depicted as percentages. Chi square test was used to find association between the variables and p<0.05 was considered statistically significant. Results: 104 patients were found to have TB of the head and neck and among them,the most common manifestation was found to be Tubercular Lymphadenitis (86.53%), followed by laryngeal TB (4.8%), submandibular gland TB (3.8%), deep neck space abscess(3.8%) and adenotonsillar TB. FNAC was found to be the gold standard for the diagnosis of TB disease of the lymph node.26% of the patients had coexisting HIV infection and 16.3% of the patients had associated pulmonary TB. More than 20% of the patients were smokers. Most patients were treated using ATT. Conclusion: Tuberculosis affecting regions of head and neck is no longer uncommon. Sufficient knowledge and appropriate diagnostic means is required while dealing with these lesions and must be included in the differential diagnosis of pathological lesions of head and neck.

Keywords: FNAC, Mangalore, smoking, tuberculosis

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Authors: Theophilus Asante, Comfort Nyarko, Daniel Antwi

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Drug-resistant tuberculosis, together with the associated comorbidities like pulmonary fibrosis and silicosis, has been one of the most serious global public health threats that requires immediate action to curb or mitigate it. This prolongs hospital stays, increases the cost of medication, and increases the death toll recorded annually. Crinum asiaticum bulb (CAE) and betulin (BET) are known for their biological and pharmacological effects. Pharmacological effects reported on CAE include antimicrobial, anti-inflammatory, anti-pyretic, anti-analgesic, and anti-cancer effects. Betulin has exhibited a multitude of powerful pharmacological properties ranging from antitumor, anti-inflammatory, anti-parasitic, anti-microbial, and anti-viral activities. This work sought to investigate the anti-tuberculosis and resistant modulatory effects and also assess their effects on mitigating pulmonary fibrosis and silicosis. In the anti-tuberculosis and resistant modulatory effects, both CAE and BET showed strong antimicrobial activities (31.25 ≤ MIC ≤ 500) µg/ml against the studied microorganisms and also produced significant anti-efflux pump and biofilm inhibitory effects (ρ < 0.0001) as well as exhibiting resistance modulatory and synergistic effects when combined with standard antibiotics. Crinum asiaticum bulbs extract and betulin were shown to possess anti-pulmonary fibrosis effects. There was an increased survival rate in the CAE and BET treatment groups compared to the BLM-induced group. There was a marked decrease in the levels of hydroxyproline and collagen I and III in the CAE and BET treatment groups compared to the BLM-treated group. The treatment groups of CAE and BET significantly downregulated the levels of pro-fibrotic and pro-inflammatory cytokine concentrations such as TGF-β1, MMP9, IL-6, IL-1β and TNF-alpha compared to an increase in the BLM-treated groups. The histological findings of the lungs suggested the curative effects of CAE and BET following BLM-induced pulmonary fibrosis in mice. The study showed improved lung functions with a wide focal area of viable alveolar spaces and few collagen fibers deposition on the lungs of the treatment groups. In the anti-silicosis and pulmonoprotective effects of CAE and BET, the levels of NF-κB, TNF-α, IL-1β, IL-6 and hydroxyproline, collagen types I and III were significantly reduced by CAE and BET (ρ < 0.0001). Both CAE and BET significantly (ρ < 0.0001) inhibited the levels of hydroxyproline, collagen I and III when compared with the negative control group. On BALF biomarkers such as macrophages, lymphocytes, monocytes, and neutrophils, CAE and BET were able to reduce their levels significantly (ρ < 0.0001). The CAE and BET were examined for anti-oxidant activity and shown to raise the levels of catalase (CAT) and superoxide dismutase (SOD) while lowering the level of malondialdehyde (MDA). There was an improvement in lung function when lung tissues were examined histologically. Crinum asiaticum bulbs extract and betulin were discovered to exhibit anti-tubercular and resistance-modulatory properties, as well as the capacity to minimize TB comorbidities such as pulmonary fibrosis and silicosis. In addition, CAE and BET may act as protective mechanisms, facilitating the preservation of the lung's physiological integrity. The outcomes of this study might pave the way for the development of leads for producing single medications for the management of drug-resistant tuberculosis and its accompanying comorbidities.

Keywords: fibrosis, crinum, tuberculosis, antiinflammation, drug resistant

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Authors: Yassir Adam Shuaib, Stefan Niemann, Eltahir Awad Khalil, Ulrich Schaible, Lothar Heinz Wieler, Mohammed Ahmed Bakhiet, Abbashar Osman Mohammed, Mohamed Abdelsalam Abdalla, Elvira Richter

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Tuberculosis (TB) is a chronic bacterial disease of humans and animals and it is characterized by the progressive development of specific granulomatous tubercle lesions in affected tissues. In a six-month study, from June to November 2014, a total of 2,304 carcasses of cattle, camel, sheep, and goats slaughtered at East and West Gaash slaughterhouses, Kassala, were investigated during postmortem, in parallel, 101 sputum samples from TB suspected patients at Kassala and El-Gadarif Teaching Hospitals were collected in order to investigate tuberculosis in animals and humans. Only 0.1% carcasses were found with suspected TB lesions in the liver and lung and peritoneal cavity of two sheep and no tuberculous lesions were found in the carcasses of cattle, goats or camels. All samples, tissue lesions and sputum, were decontaminated by the NALC-NaOH method and cultured for mycobacterial growth at the NRZ for Mycobacteria, Research Center Borstel, Germany. Genotyping and molecular characterization of the grown strains were done by line probe assay (GenoType CM and MTBC) and 16S rDNA, rpoB gene, and ITS sequencing, spoligotyping, MIRU-VNTR typing and next generation sequencing (NGS). Culture of the specimens revealed growth of organisms from 81.6% of all samples. Mycobacterium tuberculosis (76.2%), M. intracellulare (14.2%), mixed infection with M. tuberculosis and M. intracellulare (6.0%) and mixed infection with M. tuberculosis and M. fortuitum and with M. intracellulare and unknown species (1.2%) were detected in the sputum samples and unknown species (1.2%) were detected in the samples of one of the animals tissues. From the 69 M. tuberculosis strains, 25 (36.2%) were showing either mono-drug-resistant or multi-drug-resistant or poly-drug-resistant but none was extensively drug-resistant. In conclusion, the prevalence of TB in animals was very low while in humans M. tuberculosis-Delhi/CAS lineage was responsible for most cases and there was an evidence of MDR transmission and acquisition.

Keywords: animal, human, slaughterhouse, Sudan, tuberculosis

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