Snapshot of Mycobacterium tuberculosis Phylogenetics from an Indian State of Arunachal Pradesh Bordering China

Uncontrolled transmission of Mycobacterium tuberculosis (M. tuberculosis, MTB) drug resistant strains is a challenge to control efforts of global tuberculosis programme. Due to increasing multi-drug resistant (MDR) cases in Arunachal Pradesh, a northeastern state of India, the tracking and tracing of these resistant MTB strains is crucial for infection control and spread of drug resistance. This study aims to correlate the phenotypic DST, genomic DST (gDST) and phylogenetic analysis of MDR-MTB strains in the region. Of total 200 suspected MDR-MTB isolates, 125(62.5%) were identified as MTB. MGIT-960 SIRE DST detected 71/125(56.8%) isolates as MDR/RR-MTB of which 22(30.9%) were detected resistant to second line drugs. Whole genome sequencing of 65 isolates and their gDST found Ser315Thr mutation in katG (35/45;77.8%) and Ser531Leu mutation in rpoB (21/41;51.2%) associated with drug resistance. SNP barcoding categorized the dataset with Lineage2 (41;63.1%) being predominant followed by Lineage3 (10;15.4%), Lineage1 (8;12.3%) and Lineage4 (6;9.2%) respectively. Phylogenetic assignment by cgMLST gave insights of two Beijing sub-lineages viz; 2.2.1 (SNP difference < 19) and 2.2.1.2 (SNP difference < 9) associated with recent ongoing transmission in Arunachal Pradesh. This study provides first insight in identifying the ongoing transmission of two virulent Beijing sub-lineages associated with TB drug resistance.

Addressing Constraints to Informal Health Service Providers’ Involvement in Tuberculosis Control: a Qualitative Study of Patent Medicine Dealers and Tuberculosis Programme Managers in Ebonyi State Nigeria

Background: A major constraint to tuberculosis control is low case finding with under-reporting to national authorities. Evidence shows that Patent Medicine Dealers are first port of call for most people with symptoms of tuberculosis, yet there is poor referral of such clients to tuberculosis treatment facilities for further evaluation. This study investigated constraints to involvement of Patent Medicine Dealers in tuberculosis control.Methods: This was a cross-sectional qualitative study among Patent Medicine Dealers and Tuberculosis Programme Managers in Ebonyi State Nigeria. Sixty-four Patent Medicine Dealers and five Tuberculosis Programme Managers were interviewed using Focus Group Discussion and In-Depth Interview respectively. Data was collected with electronic audio-recording device and analyzed using thematic approach. Results: There are some knowledge gaps about tuberculosis signs, symptoms, free-treatment policy and mode of operation of care service among Patent Medicine Dealers. Patent Medicine Dealers and Tuberculosis Programme Managers are willing to collaborate in tuberculosis control effort but constant demand for incentives by Patent Medicine Dealers and inability of National Tuberculosis Programme to keep up with such demands are obvious constraints. Conclusions: Knowledge gaps in tuberculosis, its control, constant demand for incentives by Patent Medicine Dealers and inability of National Tuberculosis Programme to satisfy such demands are constraints to involvement of Patent Medicine Dealers in tuberculosis control. More robust engagement of Patent Medicine Dealers in tuberculosis control with clear job description through tuberculosis education and provision of incentives to support them are recommended policy approaches to improve linkage of clients to tuberculosis treatment facilities.

Level of Mycobacteria in Pre-Treatment Sputum and Susceptibility of M. tuberculosis Strains Isolated from Patients with non-Multidrug-Resistant Pulmonary Tuberculosis AFB (+) and Factors Influencing MGIT Results after the First 8 Weeks of Anti-Tuberculosi

Vietnam is among 30 high TB ​​burden countries even though the Vietnam National TB Program has made great efforts to detect and treat tuberculosis. Objectives: Assessment of Mycobacterial level in sputum before treatment, and susceptibility to the first line anti-TB drugs of M. tuberculosis strains isolated from TB patients with AFB (+) and non-multidrug-resistant. Moreover, factors influencing MGIT outcome after the first 8 weeks of first-line anti-TB drugs therapy in patients with pulmonary tuberculosis was also analysed. Methodology: An observational, analytical study was performed in 128 patients with non-multidrug-resistant pulmonary tuberculosis AFB (+) for evaluating the level of Mycobacteria in sputum before treatment by smear microscopy method; the susceptibility of M. tuberculosis isolated from sputum of the patient was analysed by Lowenstein - Jensen method. Factors affecting positive MGIT results after 2 months of treatment were determined by multivariate logistics regression. Results: The patients had AFB 3+ were 28% in new cases and 24,5% retreatment patients. The rate of M. tuberculosis strains was susceptible to the first line anti-TB drugs in new cases was higher than retreatment patients. The percentage of any anti-TB drug resistance in retreatment tuberculosis was 59,6%, higher than that of new case TB (23,6%). There was high rate of M. tuberculosis strains resistant to Streptomycin and Isoniazid (12,5% and 16,8% for new cases; 42,3% and 36,5% for retreatment cases, respectively). Large radiographic chest lesions and high AFB levels in pre-treatment sputum were factors associated with a positive MGIT result after the first 8 weeks of treatment. Conclusion: Most of TB patients had high level of Mycobacteria in sputum samples collected before treatment. The percentage of M. tuberculosis strains isolated from sputum of pulmonary non MDR-TB patients had any anti-TB drug resistance were high. High Mycobacteria level in pre-treatment sputum and radiographic chest lesions related to positive MGIT result after the first 8 weeks of treatment. Keywords Pulmonary tuberculosis, first-line anti-TB drugs, anti-TB drug resistance, susceptibility, M. tuberculosis. References [1] World Health Organization, Global Tuberculosis Report 2020. Tuberculosis profiles: Viet Nam (2020) Available: https://worldhealthorg.shinyapps.io/tb_profiles/?_inputs_&entity_type=%22country%22&lan=%22EN%22&iso2=%22VN%22 (accessed 10 April 2020).[2] L.T. Luyen, N.V. Hung, Methods for Diagnosis in Tuberculosis, in Le Thi Luyen (Ed), Tuberculosis - Textbook for General Medical Students. Vietnam National University Press, Hanoi, 2020, pp: 47-69 (in Vietnamese).[3] Ministry of Health - National Tuberculosis Programme Guideline for Standard Operating Procedures of Microbiology Laboratory Methods for Mycobacteria. Vietnam National Tuberculosis Programme, Hanoi (2013) (in Vietnamese).[4] Ministry of Health (2018) Guideline for Management, Diagnosis and Treatment for Tuberculosis. (in Vietnamese) Available: https://kcb.vn/vanban/quyet-dinh-so-3216-qd-byt-ngay-23-5-2018-ve-viec-ban-hanh-huong-dan-chan-doan-dieu-tri-va-du-phong-benh-lao (Accessed 12 January 2019)[5] A.P. Ralph, M. Ardian, A. Wiguna et al. A simple, valid, numerical score for grading chest x-ray severity in adult smear-positive pulmonary tuberculosis. Thorax 2010 Oct;65(10):863-869. https://doi.org/10.1136/thx.2010.136242[6] C.T. Minh, L.T. Luyen, N.T.L. Huong et al. Plasma concentration of anti-tubeculosis drugs in pulmonary tuberculosis patients, who treatment in National Tuberculosis and Lung Diseases Hospital 2008 Journal of Practical Medicine 651(2009) 50-53 (in Vietnamese).[7] N.V. Nhung, N.B. Hoa, D.N. Sy, C.M. Hennig, A.S. Dean (2015) The fourth national anti-tuberculosis drug resistance survey in Viet Nam. Int J Tuberc Lung Dis. Jun 2015 19(6) 670-675. https://doi.org/10.5588/ijtld.14.0785[8] N.T. Hang, S. Maeda, L.T. Lien, et al. Primary drug-resistant tuberculosis in Hanoi, Viet Nam: present status and risk factors. PloS one 8(8) (2013) e71867. https://doi.org/10.1371/journal.pone.0071867[9] R. Hafner, J.A. Cohn, D.J. Wright, et al. Early bactericidal activity of isoniazid in pulmonary tuberculosis. Optimization of methodology. The DATRI 008 Study Group. Am J Respir Crit Care Med 156 (1997) 918–923. https://doi.org/10.1164/ajrccm.156.3.9612016[10] A. Jindani, V.R. Aber, E.A. Edwards, D.A. Mitchison. The early bactericidal activity of drugs in patients with pulmonary tuberculosis. Am J Respir Crit Care Med. 121(1980)(6) 939-949. Available: https://www.atsjournals.org/doi/10.1164/arrd.1980.121.6.939 (Accessed 12 January 2019).[11] H.L. Rieder. Intervention for Tuberculosis Control and Elimination. International Union of Tuberculosis and Lung Diseases, Paris, France, 2002.

Childhood TB in China: notification, characteristics and risk factors for outcomes, 2010–2017

SETTING: China National Tuberculosis Programme, 2010–2017.OBJECTIVE: To describe the epidemiology of childhood (age < 15 years) TB, including treatment outcomes and risk factors for unfavourable outcomes and death.DESIGN: We used a cross-sectional design for the descriptive component and a cohort design for treatment outcomes and their risk factors (assessed using log binomial regression).RESULTS: Of 40 561 children, 77.7% (n = 31 529) were aged 10–14 years and 19.6% (n = 7931) were bacteriologically confirmed. Around 14% (n = 5827) belonged to migrant families (internal migration) and 4.0% (n = 1,642) were actively detected. Over 8 years, annual notification was consistently very low (<1%), and notification of bacteriologically confirmed TB decreased by half. Unfavourable outcomes were seen in 6% and deaths in 0.4%; there were no significant changes over the years. The independent predictors of unfavourable outcomes were active case finding and extrapulmonary TB. Children belonging to migrant family were more likely to die. Independent predictors of unfavourable outcomes as well as death were age < 5 years and previous treatment.CONCLUSION: China needs to address the issue of under-detection of childhood TB, especially in younger age groups. The risk factors identified require attention if China is to attain zero child TB deaths.

Completeness of TB notification in Portugal, 2015: an inventory and capture-recapture study

BACKGROUND: Despite the steady decline in the last few decades, Portugal remains the Western European country with the highest TB notification rates. The aim of this study was to estimate the completeness of notification to the National Tuberculosis Programme (NTP) Surveillance System (SVIG-TB) in 2015.METHODS: We implemented an inventory study and a three-source log-linear capture-recapture analysis using two additional data sources that were deterministic and probabilistically linked: the national notifiable diseases surveillance system (Sistema Nacional de Vigilância Epidemiológica SINAVE) and the national hospital discharge database (Grupos de Diagnósticos Homogéneos GDH).RESULTS: We identified 2328 unique probable/confirmed TB cases across the three data sources. We found a positive dependency between SVIG-TB and SINAVE (incidence rate ratio IRR 8.9, 95%CI 6.6–12.0) and between GDH and SINAVE (IRR 2.6, 95%CI 2.0–3.4). After adjusting for these dependencies, we estimated that 266 cases (95%CI 198–358) were not reported, indicating a notification (to SVIG-TB) completeness rate of 77.0%.CONCLUSION: True incidence rate of TB in Portugal in 2015 could have been as high as 26.1 per 100 000. This could be an overestimation because of false-positive cases recorded in both SINAVE and GDH or on a smaller scale, false non-matches. Studies aimed at validating potentially false-positive cases should be implemented to address these limitations.

Completeness of TB notification in Portugal, 2015: an inventory and capture-recapture study

BACKGROUND: Despite the steady decline in the last few decades, Portugal remains the Western European country with the highest TB notification rates. The aim of this study was to estimate the completeness of notification to the National Tuberculosis Programme (NTP) Surveillance System (SVIG-TB) in 2015.METHODS: We implemented an inventory study and a three-source log-linear capture-recapture analysis using two additional data sources that were deterministic and probabilistically linked: the national notifiable diseases surveillance system (Sistema Nacional de Vigilância Epidemiológica SINAVE) and the national hospital discharge database (Grupos de Diagnósticos Homogéneos GDH).RESULTS: We identified 2328 unique probable/confirmed TB cases across the three data sources. We found a positive dependency between SVIG-TB and SINAVE (incidence rate ratio IRR 8.9, 95%CI 6.6–12.0) and between GDH and SINAVE (IRR 2.6, 95%CI 2.0–3.4). After adjusting for these dependencies, we estimated that 266 cases (95%CI 198–358) were not reported, indicating a notification (to SVIG-TB) completeness rate of 77.0%.CONCLUSION: True incidence rate of TB in Portugal in 2015 could have been as high as 26.1 per 100 000. This could be an overestimation because of false-positive cases recorded in both SINAVE and GDH or on a smaller scale, false non-matches. Studies aimed at validating potentially false-positive cases should be implemented to address these limitations.