bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical characteristics and outcome of tuberculous meningitis in the pediatric population- a cross sectional study at the aga khan university hospital
Authors: Qamar Farah , Ahmad Naveed , Mir Fatima 
Published: January 2021

Aims and Objectives:
The aim of this retrospective chart review was to determine the clinical characteristics and treatment outcome of the patients diagnosed with Tuberculous Meningitis (TBM) at a tertiary care hospital setting.

Methods:
This was a cross sectional study included children of either gender aged 1-18 years treated for suspected or confirmed diagnosis of TBM at the pediatric unit of Aga Khan University Hospital. The patients enrolled from January 2015 to June 2020 were identified through electronic medical record system. The data was collected on a predesigned paper-based questionnaire and results are presented as mean, standard deviation and interquartile ranges for continuous variables. Whereas, the qualitative variables presented as frequency and percentages.

Results:
There were 52 children included in the study with a mean age of 10.66 ± 6.21 years. Of these 27 (52%) were males and 25 (48%) females. Most of the patients 33 (63.5%) presented within ≤14 days of the onset of symptoms. Median length of stay at hospital was 10 days. The median time from admission to initiation of anti-tuberculous treatment (ATT) was 5 days however, the ATT was initiated before admission to hospital in 11 (21%). In 19 (35%) of patients. Cerebrospinal fluid (CSF) culture was positive for TBM in 5 (9%) patients. GeneXpert test performed on CSF sample in 40 (77%) children. Treatment was completed in half of the patients, seven each lost to follow up and died during treatment. A significant number of patients 33 (63%) developed mild to moderate disability in the initial phase followed by full recovery.

Conclusion:
The findings revealed that TBM is highly associated with morbidity and disability. Early initiation of treatment and diagnosis likely to play pivot role in outcomes.
Adolescent tuberculosis
Authors: Kranzer Katharine 
Published: January 2021

Aim and objectives:
Adolescence is characterised by a dramatic increase in the risk of developing tuberculosis, a fact that has been appreciated since the early 20th century. The majority of the world's adolescents live in low and middle-income countries where tuberculosis remains common. It is increasingly apparent that adolescents lie at the heart of the global tuberculosis epidemic, but they have not yet been addressed as a distinct population in tuberculosis policy or within tuberculosis treatment services.

Methods:
We will review the epidemiology of Mycobacterum tuberculosis (M.tb) infection among 10-24 year olds globally and in high tuberculosis burden countries.

Results:
We will discuss the management of M.tb infection and disease, including HIV co-infection and multidrug resistant tuberculosis.

Conclusions:
In addition, we will highlight special considerations regarding the tuberculosis continuum of care during adolescents.
Host-directed Therapy Alleviates Intracellular Mycobacterial Infection via Mediating Innate Immune Responses
Authors: Hussain Tariq , Zhao Deming , Ali Shah Syed Zahid , Sabir Naveed , Wang Jie , Song Yinjuan , Dong Haodi , Mangi Mazhar Hussain , Ni Jiamin , Lifeng Y , Zhou Xiangmei 
Published: January 2021

Aims and objectives:
Mycobacterium bovis (M. bovis) is the causative agent of bovine tuberculosis; however, it also causes infection in a wide range of hosts including human beings. Johne's disease (JD) is characterized by chronic granulomatous enteritis predominantly observed in ruminants, caused by Mycobacterium avium subsp. paratuberculosis (MAP). Autophagy is an innate immune defense mechanism for the control of intracellular bacteria, regulated by diverse signaling pathways. It plays a key role in the innate immune defense mechanism for controlling intracellular mycobacterium. Nilotinib, a tyrosine kinase inhibitor (TKI), has been studied extensively in various tumor models; however, no information exists about the pharmacological action of nilotinib in bacterial infections. We hypothesized to investigate the effect of nilotinib on the regulation of host innate immune responses against Mycobacterial infection. In addition, to devise best possible therapeutic remedy towards achieving the goal of mycobacterial diseases treatment based on molecular mechanism both in vitro and in vivo, which may provide useful strategy to treat animal's tuberculosis.

Methods:
In the current study, we conducted both in vitro and in vivo experiments to investigate the role of nilotinib in the regulation of autophagy. Western blot, confocal microscopy, electron microscopy and immunohistochemistry were performed to investigate the induction of autophagy upon nilotinib treatment during M. bovis infection. Gross and histological analysis were conducted to observe the effect of nilotinib on the development of lung's lesions in mice infected with M. bovis. CFU assay was performed to determine the effect of nilotinib on the intracellular growth of M. bovis.

Results:
We found that nilotinib improved the host immune responses by inhibiting intracellular survival and growth of both M. bovis and MAP. Nilotinib also attenuated PI3k/Akt/mTOR axis for the regulation of autophagic degradation of intracellular mycobacterium mediated by inhibition of Abelson (c-ABL) tyrosine kinase. In addition, nilotinib promoted ubiquitination of intracellular bacteria through activation of E3 ubiquitin ligase parkin. Similarly, lung tissue sections of nilotinib treated mice also showed high intensity of parkin protein post M. bovis infection. From in-vivo experiment, we found that nilotinib effectively controlled M. bovis growth and the severity of disease in infected mice.

Conclusions:
Altogether, our data shows that nilotinib regulates protective host innate immune responses against intracellular pathogen both in-vitro and in-vivo and can be exploited as a novel host-directed therapeutic agent in the control of M. bovis and MAP infections.
Hepatitis C Virus and Helicobacter pylori infections in Patients with Pulmonary Tuberculosis
Authors: Nasir Ammara , Rahim Kashif , Ameen Fuad , Ashraf Waqas , Rehman Asad ur , Shehzad Faisal , Alwakeel Suaad S. , Mansoor Muhammad Khalid , Hussian Firasat 
Published: January 2021

Aims and objectives:
The control of pulmonary tuberculosis (PTB) mainly depends upon prompt diagnosis and effective treatment which can be hindered by co-infections affecting organs like gastrointestinal system and liver involved in drug bioavailability and metabolism. Among those, Helicobacter pylori (H. pylori) causes chronic gastritis leading to peptic ulcer and related gastric malignancies and liver malfunctions induced by Hepatitis C virus (HCV) co-infections increase the risk of anti-tuberculosis drug-induced hepatotoxicity. The rates of Hepatitis C virus and Helicobacter pylori infections seem to increase day by day in pulmonary tuberculosis patients which need proper investigation followed by timely control and prevention form disease.

Methods:
The hospital-based study was performed in the area of Southern Punjab, Pakistan. The Tehsil Headquarter hospital in the area, where the study was conducted contained TB Clinic. Inclusion and exclusion criteria of suspected patients of pulmonary tuberculosis included in the study. A total of 132 subjects were screened for PTB, HCV and H. pylori infections for finding the role of co-infection. The positive PTB subjects were screened for HCV and H. pylori infections. Both infections (H. pylori and HCV) were also found among TB patients.

Results:
A total of 52.27% were positive for PTB in which 50.72% and 17.39% cases were found in H. pylori and HCV infections respectively. H. pylori had increased rate of infection among PTB cases when compared with that of non-TB cases. HCV was also found to be associated with PTB when compared with non-TB cases. Non-significant gender and age-based differences were present, among study population. Among all PTB patients, HCV and H. pylori coinfections were also found in 5.8% patients in current study.

Conclusions:
Our study showed a high prevalence of HCV and H. pylori infections among PTB patients, which suggest that PTB patients must be screened for the two infections which might be helpful in the control of further complications during the treatment of PTB.
Identification of Cytoplasmic and Conserved Hypothetical Mycobacterium tuberculosis proteins based on mass spectrometry and iedb analysis resource as potent biomarkers for therapeutic strategies or valuable new TB vaccine
Authors: Tasbiti Alireza Hadizadeh , Yari Shamsi , Khanipour Sharareh , Abdolrahimi Farid , Masoumi Morteza , Nematollahi Ali Noor , Ebrahimzadeh Nayyerh , poorazar Shahin , Ghazanfari Morteza , Davari Mehdi , Sakhaee Fatemeh , Siadat Seyed Davar 
Published: January 2021

Aims and objectives:
Tuberculosis (TB) remains a major challenge to public health. The disease burden caused by TB is falling globally, in all WHO regions, and in most countries, but not fast enough to reach the first, 2020, milestones of the End TB Strategy. By 2020, the TB incidence rate needs to be falling at 4–5% per year, and the proportion of people with Tuberculosis who die from the disease needs to fall to 10%. These deaths are in part due to late or missed diagnosis and could be prevented with appropriate treatment. The aim of this study was to identify new relevant cytoplasmic and conserved hypothetical protein biomarkers as TB diagnostic or therapeutic targets.

Methods:
TB Protein contents were prepared by detergent phase separation method. Two dimensional gel electrophoresis (2DE) was performed using the Ettan IPGphor 3 isoelecteric focusing (GE Healthcare). Comprehensive genomic and proteomic data were retrieved from MycoBrowser portal (http://www.mycobrowser.epfl.ch) followed by matrix assisted laser desorption ionization time-of flight Mass Spectrometry. The predictive of the MHC I peptide binding is carried out by the IEDB analysis resource (http://www.iedb.org).

Results:
At least six purified proteins with assigned putative functions were determined that corresponded to aldehyde dehydrogenase (Rv0147), iron regulated H-NS (Rv3597c), translocase SecE2 (Rv0379), methyltransferase (Rv3699), adenosylmethionin (Rv1392) and conserved hypothetical protein of Rv0443. Within the category of cytoplasm, membrane and conserved hypothetical patterns, six identified proteins were shown high expression during exponential growth in middlebrook 7H9 broth media. The MHC I peptide binding predictions of these protein spots on the SDS page gels were valued by the Immune Epitope Database tools. The IEDB-AR prediction result is given based on IC50nM value and percentile grad. Principally, a lower score, specified higher affinity. Peptides with IC50 estimation < 50 nM are regarded as high affinity.

Conclusions:
The output scores of the predicting peptides have been shown strong binding for each of identified peptides. Rank of the predicted output affinity of Rv0443 compared to the two others, Rv0147 and Rv0379, presumably leads to stronger binding affinity. The conserved hypothetical proteins, Rv3699 and Rv0443 displayed significant homology with several other TB proteins. These proteins can also be included in TB vaccine constructs or subunit vaccine mixtures combined with a potent adjuvant. We considered these protein profiles to represent reputed biomarker as a new TB vaccine or therapeutic strategies against TB.
Molecular characterization of Mycobacterium tuberculosis isolates using Spoligotyping method in Kurdistan province, iran
Authors: Ramazanzadeh Rashid , Shakib Pegah , Roohia Samaneh , Mohammadi Bahman , Mohajeri Parviz , Borji Soroush 
Published: January 2021

Aims and objectives:
Mycobacterium tuberculosis (M. tuberculosis) is one of the major threatening infectious diseases and public health in the world. Spoligotyping is a method for r genotyping assay and molecular epidemiology of M. tuberculosis strains. The aim of this study was to determine the molecular epidemiology of M. tuberculosis by spoligotype isolated from patients with tuberculosis at Kurdistan province, Iran.

Methods:
a total of 47 M. tuberculosis isolates were collected from TB patient at Kurdistan province, Iran. All sample cultures on Lowenstein-Jensen medium and were incubated at 37 °C and were kept for 8 weeks. Bacterial isolates were identified as M. tuberculosis using standard biochemical tests. Multi-drug resistance (MDR) were determined by using proportional method. Spoligotyping was performed.

Results:
Spoligotyping of 47 strains created 8 patterns. Out of 47 samples, 23 (48.94%) were new Spoligotype International Type (SIT). In preexisting shared pattern STI 2669 were highest degree 23.40% that belong to Ural family of M. tuberculosis spoligotypes. Frequency of MDR were 6.38%. Resistance to Isoniazid and Rifampin were 14.89% and 10.64%, respectively.

Conclusion:
In overall, half of isolated strains from patients showed new patterns that, indicated the dynamic transmission of tuberculosis. Therefore, highlights dominance of differ pattern of tuberculosis distribution in west Iran. The low frequency of resistance is very interested.
Kallikrein 12 regulates innate resistance of murine macrophages against Mycobacterium bovis infection by modulating autophagy and apoptosis
Authors: Sabir Naveed , Hussain Tariq , Zhou Xiangmei 
Published: January 2021

Aims and objectives:
Tuberculosis (TB) is a leading infectious cause of mortality worldwide and millions of people continue to develop active TB each year. Mycobacterium bovis (M. bovis) is a member of Mycobacterium tuberculosis (Mtb) complex causing bovine tuberculosis and imposing high zoonotic threat to human health. Kallikreins (KLKs) belong to a subgroup of secreted serine proteases and their role is established in various physiological and pathological processes. Since the KLKs expression has been linked to various cancerous, degenerative and infectious conditions, it is likely that KLKs expression may mediate host immune response against M. bovis infection.

Methods:
In the current study, we investigated the expression of KLK12 in M. bovis infection in vivo and in vitro by using C57BL/6 mice and two types of murine macrophages, RAW264.7 cells and bone marrow derived macrophages (BMDMs). In this study, we used two strains of M. bovis, M. bovis C68004 strain and M. bovis N strain. To define the role of KLK12 in immune response regulation of murine macrophages, we produced KLK12 knockdown BMDMs by using siRNA transfection. We investigated the expression of various proteins through QRT-PCR, Immunoblot and ELISA. Apoptotic cells were detected by flow cytometry. Furthermore, cell viability and phagocytic ability of macrophages was also determined after transfection and infection. CFU assay was performed to know the intracellular survival of M. bovis.

Results:
Our results exhibited an increase in the expression of KLK12 in the lung and spleen of M. bovis infected mice. A dose (MOI) and time dependent up-regulation was also noticed in RAW264.7 and BMDMs. Then, we evaluated the role of KLK12 in innate immune response regulation against M. bovis. Interestingly, knockdown of KLK12 resulted into significant down regulation of autophagy and apoptosis in M. bovis infected BMDMs. Furthermore, we demonstrated that this KLK12 mediated regulation of autophagy and apoptosis involves mTOR/AMPK/TSC2 and BAX/Bcl-2/Cytochrome c/Caspase 3 pathways, respectively. Similarly, inflammatory cytokines IL-1β, IL-6, IL-12 and TNF-α were also significantly down regulated in KLK12 knockdown macrophages but difference in IL-10 and IFN-β expression was non-significant. Our finding also depicted that knockdown of KLK12 enhances the intracellular survival of M. bovis.

Conclusion:
Taken together, these findings suggest that up-regulation of KLK12 in M. bovis infected murine macrophages plays a substantial role in the protective immune response regulation by modulating autophagy, apoptosis and pro-inflammatory pathways. To our knowledge, this is the first report on expression and the role of KLK12 in M. bovis infection and the data may contribute to a new paradigm for diagnosis and treatment of bovine and human TB.
Successful management of multidrug-resistant tuberculosis with shorter treatment regimen in niger
Authors: Piubello Alberto , Souleymane Mahamadou Bassirou , Maman-Lawan Ibrahim , Attaher Sala , Boukary Ibrahim , Morou Soumaila , Hassane-Harouna Souleymane 
Published: January 2021

Aims and objectives:
Niger is a challenging environment, with limited resources for TB control. Health staff are scarce, access to care is limited due to long distances between communities and health facilities and security threats.

Methods:
Sputum specimens were collected before treatment initiation and monthly for smear and culture during treatment. Follow-up after cure continued up to one year after cure with smear and culture performed every 6 months.

Results:
Among 1,550 patients tested for rifampicin resistance, mainly previously treated patients, 411 (26.5%) were diagnosed with pulmonary RR-TB. The proportion of retreatment cases tested for RR-TB increased from 11.2% in 2008 to 60.5% in 2017. Of the 411 patients with confirmed RR-TB, 359 (87.3%) were enrolled on treatment and 324 (90.3%) started on STR. 24 patients received a modified STR mainly because of hearing loss at baseline or during treatment. Among 300 patients on standardised STR, 250 (83.3%) (IC95%: 78.7-87.1) were cured relapse-free, ten (3.3%) had failure, 28 (9.3%) died, eight (2.7%) were lost to follow-up and four (1.3%) relapsed. Among the 14 patients with bacteriological unfavourable outcome (failure and relapse), nine had initial resistance to fluoroquinolones (FQ) and five had susceptible strains. Among 251 patients with initial susceptibility to FQ there were 4 (1.6%) acquisition of resistance. Of 24 patients receiving a modified STR, 21 (87.5%) were cured relapse-free. Serious ototoxicity was reported in 6 of 120 patients (5%) with clinical monitoring, audiometry at the end of the intensive phase and switch from kanamycin to capreomycin and in 2 of 74 patients (2.8%) with bimonthly audiometry and reduction of kanamycin dose from daily to thrice a week.

Conclusions:
A comprehensive nationwide approach to multidrug-resistant tuberculosis management using the STR was feasible and successful. Hearing loss was manageable replacing the injectable with linezolid. Our study confirms the effectiveness and safety of the STR.
Mapping Mycobacterium tuberculosis genetic diversity in the gulf of guinea – africa
Authors: Thumamo Pokam Benjamin D. , Yeboah-Manu D. , Lawson L. , Guemdjom P. W. , Teyim P. M. , Okonu R. E. , Asuquo Anne E. 
Published: January 2021

Aims and objectives:
Tuberculosis (TB) worldwide re-emergence constitutes a major public health problem with multi-drug resistant (MDR) strains becoming a greater threat. Genotyping and drug susceptibility of Mycobacterium tuberculosis complex (MTBC) are important in order to improve the control of the disease. This study sought to determine drug susceptibility and genetic diversity of MTBC in three West/Central African countries, namely Cameroon, Nigeria and Ghana located in the Gulf of Guinea.

Methods:
A collection of 498 isolates (150 from Cameroon, 202 from Nigeria and 146 from Ghana) obtained from culture using Lowenstein–Jensen medium, Middlebrook 7H9 Broth and/or Xpert MTB/RIF and Line Probe Assay (LPA) were included in the study and some isolates tested for drug susceptibility using the proportion method. Isolates were further subjected to IS6110 typing, region of difference 1, 4, 9, 12, 702, 711, spoligotyping and hsp65 gene sequencing analysis.

Results:
The LAM10_CAM was the most prevalent genetic family [128/202 (63.4%) in Nigeria, 46/123 (37.4%) in Ghana and 54/150 (36%) in Cameroon] and SIT 61 the largest cluster with 111/202 (55%) and 43/150 (27%) isolates in Nigeria and Cameroon respectively. Multidrug resistance (MDR) was observed in 29/202 (14.4%) cases in Nigeria, and HIV positivity [37/202 (18.3%) patients] was associated with rifampicin 9/37 (24.3%) resistance (p=0.012), as well as gender (p=0.009). In Cameroon, 13/147 (8.8 %) were resistant to rifampicin (RIF), with 6 (46.2%) of the 13 RIF resistant isolates associated with UgandaI sub-lineage (p=0.0007). Other sublineages such as Haarlem, Ghana, West African 1 were recorded in the three countries.

Conclusion:
Rifampicin resistance in TB/HIV co-infected patient and its association with a sublineage calls for a reinforced surveillance strategy to curb drug resistance development in the Gulf of Guinea.
Implementation of biomedical and social support for people affected by multidrug resistant tuberculosis in guinea
Authors: Hassane H S , Chérif G , Camara S , Diallo D B , Alberto Piubello , Bangoura A , Gutierrez N 
Published: January 2021

Aims and objectives:
In 2016, Guinea had an estimated notification rate of 177 new tuberculosis (TB) cases per 100.000 population, with 360 estimated-number of rifampicin-resistant (RR) TB cases. In 2014, Damien Foundation and the National Tuberculosis Programme (NTP) of Guinea started a biomedical-social-support to people treated by multidrug-resistant TB (MDR-TB) in one-pilot health-facility. The aim of this study is to analysis effectiveness of biomedical-social-support on MDR-TB-care.

Methods:
All MDR-TB-cases treated during 2016 to 2017 were analysed. Treatment-outcomes were compared according to the provision of biomedical-social-support in one pilot-health-facility to two-health-facilities without it. In biomedical-social-support, all biological-tests, ancillary drugs were provided free of charge and a nutritional-kit and transport-refunds were monthly provided during the whole treatment. Treatment regimen included 20-month treatment regimen with Kanamycin (Km), Levofloxacin (Lfx), Cycloserine (Cs), Pyrazinamide (Z) and Prothionamide (Pto) during 6-month in the intensive-phase, followed by 12-18-month of same drugs but Km.

Results:
We included 75 MDR-TB cases, 7(9%) HIV-positive. Mean-age was 26years (IQR 15-49). All cases were pulmonary-TB, from which 10(13%) were new-cases. There were 27 MDR-TB cases with biomedical-social support and 48 without it. Mean delay of treatment-start in days was 20(IQR 9-110) in the pilot health-facility compared to 34(IQR 9-111). Treatment outcomes in the group with biomedical-social support were: cured 22(82%), treatment-completion 0(0%), death 2(7%), failure 1(4%) and 2(7%) lost-to-follow-up compared to those without biomedical-social support 23(48%), 2(4%), 9(19%), 2(4%) and 12(25%) respectively. Treatment success to unfavourable- outcomes (failure, death and lost-to-follow-up) in the pilot health-facility was 82% and 18% respectively compared to 52% and 48% respectively in those health-facilities without biomedical-social support (p<0.01).

Conclusions:
The introduction of biomedical-social support to people affected by MDR-TB was successful in Guinea. People who benefited from this strategy had more favourable treatment-outcomes. The biomedical-social support could improve treatment-success if extended to all MDR-TB people under treatment.