Multidrug -resistant tuberculosis (MDRTB) is a serious threat to mankind. India has the highest number of MDRTB cases, although majority remain undiagnosed due to inadequate diagnostic infrastructure, leading to increased community transmission and mortality. This one-year observational retrospective study highlighted the effectiveness of the National Tuberculosis Elimination Program (NTEP) for prompt detection of drug-resistant TB by GeneXpert MTB/RIF assay and revealed its associated clinico-epidemiological factors. The overall detection rates of MTB and RRTB were 20.70 % and 20.86 % respectively. The pediatric population had 7.69 % rifampicin resistance, and HIV was strongly associated with the development of TB and RRTB (P < 0.01).

Drug-resistant tuberculosis (DR-TB) epidemic is driven mainly by the effect of ongoing transmission. In high-burden settings such as South Africa (SA), considerable demographic and geographic heterogeneity in DR-TB transmission exists. Thus, a better understanding of risk-factors for clustering can help to prioritise resources to specifically targeted high-risk groups as well as areas that contribute disproportionately to transmission.
The study analyzed potential risk-factors for recent transmission in SA, using data collected from a sentinel molecular surveillance of DR-TB, by comparing demographic, clinical and epidemiologic characteristics with clustering and cluster sizes. A genotypic cluster was defined as two or more patients having identical patterns by the two genotyping methods used. Clustering was used as a proxy for recent transmission. Descriptive statistics and multinomial logistic regression were used.
The study identified 277 clusters, with cluster size ranging between 2 and 259 cases. The majority (81.6%) of the clusters were small (2-5 cases) with few large (11-25 cases) and very large (≥ 26 cases) clusters identified mainly in Western Cape (WC), Eastern Cape (EC) and Mpumalanga (MP). In a multivariable model, patients in clusters including 11-25 and ≥ 26 individuals were more likely to be infected by Beijing family, have XDR-TB, living in Nelson Mandela Metro in EC or Umgungunglovo in Kwa-Zulu Natal (KZN) provinces, and having history of imprisonment. Individuals belonging in a small genotypic cluster were more likely to infected with Rifampicin resistant TB (RR-TB) and more likely to reside in Frances Baard in Northern Cape (NC).
Sociodemographic, clinical and bacterial risk-factors influenced rate of Mycobacterium tuberculosis (M. tuberculosis) genotypic clustering. Hence, high-risk groups and hotspot areas for clustering in EC, WC, KZN and MP should be prioritized for targeted intervention to prevent ongoing DR-TB transmission.

UNASSIGNED: Drug-resistant tuberculosis (DR-TB) is a threat to tuberculosis (TB) control. Extra-pulmonary forms of DR-TB (DR-epTB) are not well characterized. This review summarizes the clinical features, resistance patterns and treatment outcomes of DR-epTB.
UNASSIGNED: We searched EMBASE to identify studies that reported drug-resistance among extra-pulmonary TB sites. All age groups were included in this review. Studies which did not describe drug-resistance patterns at extra-pulmonary TB sites were excluded. We summarized the proportion of resistance to individual anti-TB drugs as well as multi-drug resistant (MDR), pre-extensively drug resistant (pre-XDR) and extensively drug-resistant (XDR) TB.
UNASSIGNED: Eighteen studies with a total of 10,222 patients with extra-pulmonary TB of whom 1,236 (12.0%) had DR-epTB, were included in this review. DR-epTB was mostly reported in young people aged 28 to 46 years. While TB meningitis is the most commonly studied form, adenitis is the commonest form of DR-epTB reported in 21% to 47%. Central nervous system TB (3.8% to 51.6%), pleural TB (11.3% to 25.9%), skeletal TB (9.4% to 18.1%), abdominal TB (4.3% to 6.5%), and disseminated TB (3.8%) are also encountered. The HIV co-infection rate is reported to be 5.0% to 81.3% while 2.6% to 25.4 % have diabetes mellitus. Clinical symptoms of DR-epTB are consistent with morbidity in the affected body system. Among patients with DR-epTB, the proportion of MDR TB was 5% to 53% while that for pre-XDR TB and XDR TB was 3% to 40% and 4% to 33%, respectively. Treatment success is achieved in 26% to 83% of patients with DR-epTB while death, treatment loss-to-follow up, and treatment failure occur in 2% to 76%, 7% to 15%, and 0% to 4% respectively. Patients with DR-epTB were reported to have poorer outcomes than those with pulmonary DR-TB and extra-pulmonary drug-susceptible TB.
UNASSIGNED: Clinical features of DR-epTB are similar to those observed among people with drug-susceptible EPTB but patients with DR-epTB post worse treatment outcomes.

Tubercular lymphadenitis (TBLA), the most common form of extrapulmonary tuberculosis, is a diagnostic challenge.
Truenat MTB Plus (TruPlus) along with Truenat Rif assay (TruRif) was evaluated for detection of TBLA and rifampicin resistance and compared with GeneXpert Ultra (Xpert Ultra).
100 fine-needle aspirated specimens [50 confirmed by culture/smear/cytology, 20 clinically suspected, and 30 controls], processed in the mycobacteriology division of department of microbiology were subjected to TruPlus and TruRif, Xpert Ultra and multiplex PCR. The results of TBLA detection were compared against composite reference standard (CRS) and those of rifampicin resistance were compared against phenotypic drug susceptibility testing and rpoB gene sequencing.
In comparison to CRS, the diagnostic yield of TruPlus, Xpert Ultra and MPCR was 77.14%, 59.18% and 84.28%, respectively; with substantial agreement for TruPlus (k = 0.66) and MPCR (k = 0.76) and moderate for Xpert Ultra (k = 0.60). TruRif reported four cases as RifR and Xpert Ultra reported two. On comparing with phenotypic DST and gene sequencing, only two cases of RifR were confirmed, hence TruRif reported false-RifR in two cases.
TruPlus could be used as a reliable tool for diagnosing TBLA. The reporting of RifR by TruRif should be confirmed by phenotypic DST or gene sequencing.

The dynamics of DNA gyrase and mutants of DNA gyrA such as G88A, A90V, S91P, D94A, D94G, D94N, D94Y; and double-point mutant (S91P-D94G), are meticulously investigated using computational approaches. Molecular dynamics (MD) and hydration thermodynamics have shed light on the fundamental, mechanistic basis of mutations on the conformational stability of Quinolone Binding Pocket (QBP) of DNA gyrase. Analysis of MD results revealed the displacement of a single crystal water molecule (HOH201) from the catalytic site of wild-type (WT) and mutants of DNA gyrA. This prompted our research group to probe the five crystal water molecules present in the QBP of the enzyme using water thermodynamics. Hydration thermodynamics analysis revealed the displacement of HOH201 due to unstable thermodynamic signatures. Further, the analysis highlighted significant changes in thermodynamic signatures and locations of five crystal water hydration sites upon mutation. Integrated MD simulations and water thermodynamics provided promising insights into the conformational changes and inaccessibility of the catalytic water molecule that can influence the design of DNA gyrase inhibitors.Communicated by Ramaswamy H. Sarma.

Mycobacterium tuberculosis complex (MTBC) is divided into 9 whole genome sequencing (WGS) lineages. Among them, lineages 1−4 are widely distributed. Multi-drug resistant tuberculosis (MDR-TB) is a major public health threat. For effective TB control, there is a need to obtain genetic information on lineages of Mycobacterium tuberculosis (Mtb) and to understand distribution of lineages and drug resistance. This study aimed to describe the distribution of major lineages and drug resistance patterns of Mtb in Upper Myanmar. This was a cross-sectional study conducted with 506 sequenced isolates. We found that the most common lineage was lineage 2 (n = 223, 44.1%). The most common drug resistance mutation found was streptomycin (n = 44, 8.7%). Lineage 2 showed a higher number of MDR-TB compared to other lineages. There were significant associations between lineages of Mtb and drug resistance patterns, and between lineages and geographical locations of Upper Myanmar (p value < 0.001). This information on the distribution of Mtb lineages across the geographical areas will support a lot for the better understanding of TB transmission and control in Myanmar and other neighboring countries. Therefore, closer collaboration in cross border tuberculosis control is recommended.

BACKGROUND: Zambia is one of the TB high-burden countries. It is important to track the progress being made towards enhancing case finding and reducing mortality. We reviewed routine TB notifications and mortality trends, over a decade from all facilities in Zambia.
METHODS: A 10-year retrospective study of TB notifications and mortality trends was performed using a Joint Point Analysis version 4.9.0.0, NCI. We extracted the annual national TB program data for the period under review.
RESULTS: There was a decline in annual point average for notification between 2010 and 2020 in both males and females, but the females notification rates had a higher rate of decline (AAPC = -6.7, 95%CI:-8.3 to -5.0), p<0.001) compared to the decline in males notification rate (AAPC = -4.1, 95%CI:-4.1 to -5.1, P<0.001). We found a significant growth rate in the proportion of TB patients that were bacteriologically confirmed (AAPC = 6.1, 95% CI: 3.6 to 8.7, p< 0.001), while the proportion of clinically diagnosed patients declined (AAPC= -0.1, 95%CI: -2.3 to 2.1, p<0.001). Notification of drug-resistant TB increased exponentially (AAPC=27.3, 95% CI: 13 to 41), p< 0.001) while mortality rate declined from 21.3 in 2011 to 12.7 in 2019 per 100,000 population (AAP=-5.6, 95%CI: -9.6 to -1.5, p=0.008).
CONCLUSIONS: This study has illustrated the importance of reviewing and analyzing routinely collected TB data by national programs. The study revealed areas of improvement in terms of TB control and underscores the need for increased and sustained investment in case detection and diagnostics.

Opioid substitution therapy (OST) is one of the pillars of harm reduction strategies for People Who Inject Drugs (PWID). It should be an integral part of tuberculosis (TB) care to increase the uptake, compliance and effectiveness of treatment and also curtail risk behaviors. We aimed to compare TB treatment outcomes in relation to OST among PWID in six regions of Ukraine.
A retrospective cohort study using routine programmatic data from centers offering integrated TB and OST (December 2016 - May 2020). OST involved use of methadone or buprenorphine. TB treatment outcomes were standardized.
Of 228 PWID (85% male) diagnosed with TB, 104 (46%) had drug-sensitive and 124 (64%) drug-resistant TB. The majority had pulmonary TB (95%), 64 (28%) were HCV-positive and 179 (78%) were HIV-positive, 91% of the latter were also on antiretroviral therapy. There were 114 (50%) PWID with TB on OST. For drug-sensitive TB (n=104), treatment success was significantly higher (61%) in those on adjunctive OST than those not on OST (42%, P<0.001). Similarly, for drug-resistant TB (n=124) treatment success was also significantly higher when individuals were on OST (43%) compared to when not on OST (26%, P<0.001).
This operational research study shows that OST is associated with significantly improved treatment success in PWID and can contribute to achieving Universal Health Coverage and the WHO Flagship Initiative \"Find.Treat.All. #End TB\". We advocate for the scale-up of this intervention in Ukraine.

The current write-up is for Dr P.K.Sen TAI Gold Medal Oration Award for 2020 conferred to Dr Rupak Singla and delivered on 19 th December 2020. The title chosen for the oration was \"Introduction and scale up of new anti-TB drugs in India: role of NITRD.ˮ However, in the oration the role this institute has played for overall scale up of Drug-resistant TB services in India under National Tuberculosis Elimination Programme (NTEP) at different times from the beginning of national TB programme has also been presented. National Institute of TB and Respiratory Diseases has travelled with our country from beginning of DR-TB care. It demonstrated for the first time use of a Standardized Treatment Regimen with second line drugs for MDR-TB in field conditions. NITRD assisted NTEP for the concept of DST guided treatment. This institute guided NTEP for the management of MDR-TB failure patients with Pre-XDR and XDR-TB. Also, NITRD assisted India for the introduction of newer DR-TB drugs and scale up of newer drugs across the country. The strength of NITRD include clinical expertise, laboratory support and training division. NITRD commitment is strong and will continue to support NTEP for all endeavors in future also.

Tuberculosis (TB) is a common infectious pathology especially in low-income countries, which may complicate pregnancy. Although pulmonary TB is more common in pregnancy than extra pulmonary TB (EPTB), EPTB is becoming more common especially in those living with human deficiency virus (HIV) co infection or have other comorbidities. The diagnosis of TB may be delayed in pregnancy due to the masking of its symptoms by those of pregnancy. If diagnosed and treated on time both pulmonary TB and EPTB are associated with excellent maternal and perinatal outcome. If, however, there is delay in diagnosis and treatment then there could be adverse maternal and fetal consequences like preterm labour, fetal growth restriction and even stillbirths. Similarly severe forms of TB like disseminated disease (miliary TB) or multi drug resistant TB (MDR TB) are associated with poor outcome. Diagnosis and management is same as in non-pregnant patients. Both drug sensitive pulmonary TB and EPTB are treated with four drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) orally daily for 2 months followed by three drugs (isoniazid, rifampicin and ethambutol) orally daily for 4 months. Drug resistant TB is treated with second line drugs with caution, as some of these drugs are teratogenic. Optimum antenatal care and nutrition therapy along with anti-tuberculosis drugs provide for optimum maternal and perinatal outcome. This review discusses maternal and perinatal outcomes, diagnosis and management of pulmonary TB and extrapulmonary TB as well as perinatal tuberculosis.