Conference Material > Video
Kalon S, Iyer AS, Zarli K
MSF Scientific Days Asia 2021. 25 August 2021
Journal Article > ResearchFull Text
PLOS One. 18 February 2021; Volume 16 (Issue 2); e0246639.; DOI:10.1371/journal.pone.0246639
Dhakulkar S, Das M, Sutar N, Oswal V, Shah D, et al.
PLOS One. 18 February 2021; Volume 16 (Issue 2); e0246639.; DOI:10.1371/journal.pone.0246639
BACKGROUND
Childhood and adolescent drug-resistant TB (DR-TB) is one of the neglected infectious diseases. Limited evidence exists around programmatic outcomes of children and adolescents receiving DR-TB treatment. The study aimed to determine the final treatment outcomes, culture conversion rates and factors associated with unsuccessful treatment outcome in children and adolescents with DR-TB.
METHODS
This is a descriptive study including children (0-9 years) and adolescents (10-19 years) with DR-TB were who were initiated on ambulatory based treatment between January 2017-June 2018 in Shatabdi hospital, Mumbai, India where National TB elimination programme(NTEP) Mumbai collaborates with chest physicians and Médecins Sans Frontières(MSF) in providing comprehensive care to DR-TB patients. The patients with available end-of-treatment outcomes were included. The data was censored on February 2020.
RESULT
A total of 268 patients were included; 16 (6%) of them were children (0-9 years). The median(min-max) age was 17(4-19) years and 192 (72%) were females. Majority (199, 74%) had pulmonary TB. Most (58%) had MDR-TB while 42% had fluoroquinolone-resistant TB. The median(IQR) duration of treatment (n = 239) was 24(10-25) months. Median(IQR) time for culture-conversion (n = 128) was 3(3-4) months. Of 268 patients, 166(62%) had successful end-of-treatment outcomes (cured-112; completed treatment-54). Children below 10 years had higher proportion of successful treatment outcomes (94% versus 60%) compared to adolescents. Patients with undernutrition [adjusted odds-ratio, aOR (95% Confidence Interval, 95%CI): 2.5 (1.3-4.8) or those with XDR-TB [aOR (95% CI): 4.3 (1.3-13.8)] had higher likelihood of having unsuccessful DR-TB treatment outcome.
CONCLUSIONS
High proportion of successful treatment outcome was reported, better than global reports. Further, the nutritional support and routine treatment follow up should be strengthened. All oral short and long regimens including systematic use of new TB drugs (Bedaquiline and Delamanid) should be rapidly scaled up in routine TB programme, especially for the paediatric and adolescent population.
Childhood and adolescent drug-resistant TB (DR-TB) is one of the neglected infectious diseases. Limited evidence exists around programmatic outcomes of children and adolescents receiving DR-TB treatment. The study aimed to determine the final treatment outcomes, culture conversion rates and factors associated with unsuccessful treatment outcome in children and adolescents with DR-TB.
METHODS
This is a descriptive study including children (0-9 years) and adolescents (10-19 years) with DR-TB were who were initiated on ambulatory based treatment between January 2017-June 2018 in Shatabdi hospital, Mumbai, India where National TB elimination programme(NTEP) Mumbai collaborates with chest physicians and Médecins Sans Frontières(MSF) in providing comprehensive care to DR-TB patients. The patients with available end-of-treatment outcomes were included. The data was censored on February 2020.
RESULT
A total of 268 patients were included; 16 (6%) of them were children (0-9 years). The median(min-max) age was 17(4-19) years and 192 (72%) were females. Majority (199, 74%) had pulmonary TB. Most (58%) had MDR-TB while 42% had fluoroquinolone-resistant TB. The median(IQR) duration of treatment (n = 239) was 24(10-25) months. Median(IQR) time for culture-conversion (n = 128) was 3(3-4) months. Of 268 patients, 166(62%) had successful end-of-treatment outcomes (cured-112; completed treatment-54). Children below 10 years had higher proportion of successful treatment outcomes (94% versus 60%) compared to adolescents. Patients with undernutrition [adjusted odds-ratio, aOR (95% Confidence Interval, 95%CI): 2.5 (1.3-4.8) or those with XDR-TB [aOR (95% CI): 4.3 (1.3-13.8)] had higher likelihood of having unsuccessful DR-TB treatment outcome.
CONCLUSIONS
High proportion of successful treatment outcome was reported, better than global reports. Further, the nutritional support and routine treatment follow up should be strengthened. All oral short and long regimens including systematic use of new TB drugs (Bedaquiline and Delamanid) should be rapidly scaled up in routine TB programme, especially for the paediatric and adolescent population.
Journal Article > LetterSubscription Only
N Engl J Med. 27 November 2008; Volume 359 (Issue 22); 2398-400.; DOI:10.1056/NEJMc0805644
Cox HS, Sibilia C, Feuerriegel S, Kalon S, Polonsky JA, et al.
N Engl J Med. 27 November 2008; Volume 359 (Issue 22); 2398-400.; DOI:10.1056/NEJMc0805644
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 1 February 2014; Volume 18 (Issue 2); 160-167.; DOI:10.5588/ijtld.13.0369
Sanchez-Padilla E, Marquer C, Kalon S, Qayyum S, Hayrapetyan A, et al.
Int J Tuberc Lung Dis. 1 February 2014; Volume 18 (Issue 2); 160-167.; DOI:10.5588/ijtld.13.0369
SETTING
Armenia, a country with a high prevalence of drug-resistant tuberculosis (DR-TB).
OBJECTIVE
To identify factors related to default from DR-TB treatment in Yerevan.
DESIGN
Using a retrospective cohort design, we compared defaulters with patients who were cured, completed or failed treatment. Patients who initiated DR-TB treatment from 2005 to 2011 were included in the study. A qualitative survey was conducted including semi-structured interviews with defaulters and focus group discussions with care providers.
RESULTS
Of 381 patients, 193 had achieved treatment success, 24 had died, 51 had failed treatment and 97 had defaulted. The number of drugs to which the patient was resistant at admission (aRR 1.16, 95%CI 1.05–1.27), the rate of treatment interruption based on patient's decision (aRR 1.03, 95%CI 1.02–1.05), the rate of side effects (aRR 1.18, 95%CI 1.09–1.27), and absence of culture conversion during the intensive phase (aRR 0.47, 95%CI 0.31–0.71) were independently associated with default from treatment. In the qualitative study, poor treatment tolerance, a perception that treatment was inefficient, lack of information, incorrect perception of being cured, working factors and behavioural problems were factors related to treatment default.
CONCLUSION
In addition to economic reasons, poor tolerance of and poor response to treatment were the main factors associated with treatment default.
Armenia, a country with a high prevalence of drug-resistant tuberculosis (DR-TB).
OBJECTIVE
To identify factors related to default from DR-TB treatment in Yerevan.
DESIGN
Using a retrospective cohort design, we compared defaulters with patients who were cured, completed or failed treatment. Patients who initiated DR-TB treatment from 2005 to 2011 were included in the study. A qualitative survey was conducted including semi-structured interviews with defaulters and focus group discussions with care providers.
RESULTS
Of 381 patients, 193 had achieved treatment success, 24 had died, 51 had failed treatment and 97 had defaulted. The number of drugs to which the patient was resistant at admission (aRR 1.16, 95%CI 1.05–1.27), the rate of treatment interruption based on patient's decision (aRR 1.03, 95%CI 1.02–1.05), the rate of side effects (aRR 1.18, 95%CI 1.09–1.27), and absence of culture conversion during the intensive phase (aRR 0.47, 95%CI 0.31–0.71) were independently associated with default from treatment. In the qualitative study, poor treatment tolerance, a perception that treatment was inefficient, lack of information, incorrect perception of being cured, working factors and behavioural problems were factors related to treatment default.
CONCLUSION
In addition to economic reasons, poor tolerance of and poor response to treatment were the main factors associated with treatment default.
Protocol > Research Protocol
van der Heijden J, Stringer B, Gray NSB, Kalon S, Dada M, et al.
1 July 2018
Objectives
This study aims to provide a better understanding of community perceptions toward health and health services in order to inform programme strategies:
• Describe community and local-level perspectives and opinions on health care provision;
• Document gaps, barriers and influences that impact access and acceptance of health care;
• Contribute to best practice and development of health policy for this population
This study aims to provide a better understanding of community perceptions toward health and health services in order to inform programme strategies:
• Describe community and local-level perspectives and opinions on health care provision;
• Document gaps, barriers and influences that impact access and acceptance of health care;
• Contribute to best practice and development of health policy for this population
Journal Article > ResearchFull Text
Lancet Infect Dis. 13 February 2018; Volume 18 (Issue 5); 536-544.; DOI:10.1016/S1473-3099(18)30100-2
Ferlazzo G, Mohr E, Laxmeshwar C, Hewison CCH, Hughes J, et al.
Lancet Infect Dis. 13 February 2018; Volume 18 (Issue 5); 536-544.; DOI:10.1016/S1473-3099(18)30100-2
BACKGROUND
Bedaquiline and delamanid have been approved for treatment of multidrug-resistant (MDR) tuberculosis in the past 5 years. Because of theoretical safety concerns, patients have been unable to access the two drugs in combination. Médecins Sans Frontières has supported the use of combination bedaquiline and delamanid for people with few treatment options since 2016. We describe early safety and efficacy of regimens containing the bedaquiline and delamanid combination in patients with drug-resistant tuberculosis in Yerevan, Armenia; Mumbai, India; and Khayelitsha, South Africa.
METHODS
We retrospectively analysed a cohort of all patients who received 6-12 months of oral bedaquiline and delamanid in combination (400 mg bedaquiline once per day for 2 weeks, then 200 mg bedaquiline three times per week and 100 mg delamanid twice per day) in MSF-supported projects. We report serious adverse events, QTc corrected using the Fridericia formula (QTcF) interval data, and culture conversion data during the first 6 months of treatment.
FINDINGS
Between Jan 1, 2016, and Aug 31, 2016, 28 patients (median age 32·5 years [IQR 28·5-40·5], 17 men) were included in the analysis. 11 (39%) of 28 patients were HIV-positive. 24 patients (86%) had isolates resistant to fluoroquinolones; 14 patients (50%) had extensively drug-resistant tuberculosis. No patient had an increase of more than 500 ms in their QTcF interval. Four patients (14%) had six instances of QTcF increase of more than 60 ms from baseline but none permanently discontinued the drugs. 16 serious adverse events were reported in seven patients. Of 23 individuals with positive baseline cultures, 17 (74%) converted to negative by month 6 of treatment.
INTERPRETATION
Use of the bedaquiline and delamanid combination appears to reveal no additive or synergistic QTcF-prolonging effects. Access to bedaquiline and delamanid in combination should be expanded for people with few treatment options while awaiting the results of formal clinical trials.
Bedaquiline and delamanid have been approved for treatment of multidrug-resistant (MDR) tuberculosis in the past 5 years. Because of theoretical safety concerns, patients have been unable to access the two drugs in combination. Médecins Sans Frontières has supported the use of combination bedaquiline and delamanid for people with few treatment options since 2016. We describe early safety and efficacy of regimens containing the bedaquiline and delamanid combination in patients with drug-resistant tuberculosis in Yerevan, Armenia; Mumbai, India; and Khayelitsha, South Africa.
METHODS
We retrospectively analysed a cohort of all patients who received 6-12 months of oral bedaquiline and delamanid in combination (400 mg bedaquiline once per day for 2 weeks, then 200 mg bedaquiline three times per week and 100 mg delamanid twice per day) in MSF-supported projects. We report serious adverse events, QTc corrected using the Fridericia formula (QTcF) interval data, and culture conversion data during the first 6 months of treatment.
FINDINGS
Between Jan 1, 2016, and Aug 31, 2016, 28 patients (median age 32·5 years [IQR 28·5-40·5], 17 men) were included in the analysis. 11 (39%) of 28 patients were HIV-positive. 24 patients (86%) had isolates resistant to fluoroquinolones; 14 patients (50%) had extensively drug-resistant tuberculosis. No patient had an increase of more than 500 ms in their QTcF interval. Four patients (14%) had six instances of QTcF increase of more than 60 ms from baseline but none permanently discontinued the drugs. 16 serious adverse events were reported in seven patients. Of 23 individuals with positive baseline cultures, 17 (74%) converted to negative by month 6 of treatment.
INTERPRETATION
Use of the bedaquiline and delamanid combination appears to reveal no additive or synergistic QTcF-prolonging effects. Access to bedaquiline and delamanid in combination should be expanded for people with few treatment options while awaiting the results of formal clinical trials.
Journal Article > ResearchFull Text
PLOS One. 16 June 2020 (Issue 6); DOI:10.1371/journal.pone.0234651.
Chavan VV, Dalal A, Nagaraja SB, Thekkur P, Mansoor H, et al.
PLOS One. 16 June 2020 (Issue 6); DOI:10.1371/journal.pone.0234651.
Background
Imipenem, an intravenous antibiotic is recommended for use in drug resistant tuberculosis (DR-TB) when an effective regimen with combination of other second line drugs is not possible. Though the treatment success rates with carbapenems are promising, the twice daily injection of Imipenem usually requires patients to be hospitalized. The Médecins Sans Frontières independent clinic in Mumbai, India implemented ambulatory and home based management of patients receiving Imipenem through the use of port-a-cath.
Objective
We aimed to describe the adverse events and treatment outcomes of ambulatory pre- and XDR-TB patients initiated on imipenem through port-a-cath between January 2015 and June 2018 and to explore the challenges with this regimen as perceived by healthcare providers and patients.
Methods
A convergent mixed methods study with quantitative (longitudinal descriptive study using the routine data) and qualitative (descriptive study) part conducted concurrently. For the quantitative component, all XDR-TB and pre-XDR-TB initiated on imipenem containing regimen during January 2015-June 2018 were included. For qualitative component, interviews were carried out including patients who initiated on imipenem (n = 5) and healthcare providers (n = 7) involved in providing treatment. Treatment outcomes, culture conversion and adverse events during treatment were described. Thematic analysis was carried out for qualitative component.
Results
Of the 70 patients included, the mean age was 28.1 (standard deviation: 11.2) years and 36 (51.4%) were females. Fifty one (72.9%) had XDR-TB. All patients were resistant to fluoroquinilone, levofloxacin. Vomiting was reported by 55 (78.6%) patients and at least one episode of QTC prolongation (more than 500 msec by Fredrecia method) was detected in 25 (35.7%). Port-a-cath block and infection was seen in 11 (15.7%) and 20 (28.6%) patients respectively. Favourable outcomes were seen in 43 (61.4%) patients. Mortality was seen in 22 (31.4%) patients, 2 (2.9%) were lost-to-follow-up and 3 (4.3%) were declared as treatment failure. The overarching theme of the qualitative analysis was: Challenges in delivering Imipenem via port-a-cath device in ambulatory care. Major challenges identified were difficulties in adhering to drug dose timelines, vomiting, restricted mobility due to port-a-cath, paucity of infection control and space constraints at patients’ home for optimal care.
Conclusion
Administration of imipenem was feasible through port-a-cath. Though outcomes with ambulatory based imipenem containing regimens were promising, there were several challenges in providing care. The feasibility of infusion at day care facilities needs to explored to overcome challenges in infusion at patients home.
Imipenem, an intravenous antibiotic is recommended for use in drug resistant tuberculosis (DR-TB) when an effective regimen with combination of other second line drugs is not possible. Though the treatment success rates with carbapenems are promising, the twice daily injection of Imipenem usually requires patients to be hospitalized. The Médecins Sans Frontières independent clinic in Mumbai, India implemented ambulatory and home based management of patients receiving Imipenem through the use of port-a-cath.
Objective
We aimed to describe the adverse events and treatment outcomes of ambulatory pre- and XDR-TB patients initiated on imipenem through port-a-cath between January 2015 and June 2018 and to explore the challenges with this regimen as perceived by healthcare providers and patients.
Methods
A convergent mixed methods study with quantitative (longitudinal descriptive study using the routine data) and qualitative (descriptive study) part conducted concurrently. For the quantitative component, all XDR-TB and pre-XDR-TB initiated on imipenem containing regimen during January 2015-June 2018 were included. For qualitative component, interviews were carried out including patients who initiated on imipenem (n = 5) and healthcare providers (n = 7) involved in providing treatment. Treatment outcomes, culture conversion and adverse events during treatment were described. Thematic analysis was carried out for qualitative component.
Results
Of the 70 patients included, the mean age was 28.1 (standard deviation: 11.2) years and 36 (51.4%) were females. Fifty one (72.9%) had XDR-TB. All patients were resistant to fluoroquinilone, levofloxacin. Vomiting was reported by 55 (78.6%) patients and at least one episode of QTC prolongation (more than 500 msec by Fredrecia method) was detected in 25 (35.7%). Port-a-cath block and infection was seen in 11 (15.7%) and 20 (28.6%) patients respectively. Favourable outcomes were seen in 43 (61.4%) patients. Mortality was seen in 22 (31.4%) patients, 2 (2.9%) were lost-to-follow-up and 3 (4.3%) were declared as treatment failure. The overarching theme of the qualitative analysis was: Challenges in delivering Imipenem via port-a-cath device in ambulatory care. Major challenges identified were difficulties in adhering to drug dose timelines, vomiting, restricted mobility due to port-a-cath, paucity of infection control and space constraints at patients’ home for optimal care.
Conclusion
Administration of imipenem was feasible through port-a-cath. Though outcomes with ambulatory based imipenem containing regimens were promising, there were several challenges in providing care. The feasibility of infusion at day care facilities needs to explored to overcome challenges in infusion at patients home.
Journal Article > ResearchFull Text
PLOS One. 10 March 2021; Volume 16 (Issue 3); DOI:10.1371/journal.pone.0248408
Das M, Mathur T, Ravi S, Meneguim A, Iyer AS, et al.
PLOS One. 10 March 2021; Volume 16 (Issue 3); DOI:10.1371/journal.pone.0248408
Background: Childhood multidrug-resistant TB (MDR-TB) still affects around 25000 children every year across the globe. Though the treatment success rates for drug-resistant TB (DR-TB) in children are better than adults, children and adolescents face unique hurdles during DR-TB (MDR-TB, Pre-XDR TB and XDR-TB) treatment. This study aimed to understand the patients, guardians and healthcare providers' perspectives about DR-TB treatment journey of patients and caregivers.
Methods: This is a qualitative study involving in depth-interviews of purposively selected adolescents (n = 6), patients guardians (for children and adolescents, n = 5) and health care providers (n = 8) of Médecins Sans Frontières (MSF) clinic, Mumbai, India. In-depth face to face interviews were conducted in English or Hindi language using interview guides during September-November 2019. The interviews were audio-recorded after consent. Thematic network analysis was used to summarize textual data. ATLAS.ti (version 7) was used for analysis.
Result: The age of adolescent patients ranged from 15-19 years and four were female. Five guardians (of three child and two adolescent patients) and eight healthcare providers (including clinicians- 2, DOT providers-2, counselors-2 and programme managers-2) were interviewed. The overarching theme of the analysis was: Challenging DR-TB treatment journey which consisted of four sub-themes: 1) physical-trauma, 2) emotional-trauma, 3) unavailable social-support and 4) non-adapted healthcare services. Difficulties in compounding of drugs were noted for children while adolescents shared experiences around disruption in social life due to disease and treatment. Most of the patients and caregivers experienced treatment fatigue and burnout during the DR-TB treatment. Participants during interviews gave recommendations to improve care.
Discussion: The TB programmes must consider the patient and family as one unit when designing the package of care for paediatric DR-TB. Child and adolescent friendly services (paediatric-formulations, age-specific counselling tools and regular interaction with patients and caregivers) will help minimizing burnout in patients and caregivers.
Methods: This is a qualitative study involving in depth-interviews of purposively selected adolescents (n = 6), patients guardians (for children and adolescents, n = 5) and health care providers (n = 8) of Médecins Sans Frontières (MSF) clinic, Mumbai, India. In-depth face to face interviews were conducted in English or Hindi language using interview guides during September-November 2019. The interviews were audio-recorded after consent. Thematic network analysis was used to summarize textual data. ATLAS.ti (version 7) was used for analysis.
Result: The age of adolescent patients ranged from 15-19 years and four were female. Five guardians (of three child and two adolescent patients) and eight healthcare providers (including clinicians- 2, DOT providers-2, counselors-2 and programme managers-2) were interviewed. The overarching theme of the analysis was: Challenging DR-TB treatment journey which consisted of four sub-themes: 1) physical-trauma, 2) emotional-trauma, 3) unavailable social-support and 4) non-adapted healthcare services. Difficulties in compounding of drugs were noted for children while adolescents shared experiences around disruption in social life due to disease and treatment. Most of the patients and caregivers experienced treatment fatigue and burnout during the DR-TB treatment. Participants during interviews gave recommendations to improve care.
Discussion: The TB programmes must consider the patient and family as one unit when designing the package of care for paediatric DR-TB. Child and adolescent friendly services (paediatric-formulations, age-specific counselling tools and regular interaction with patients and caregivers) will help minimizing burnout in patients and caregivers.
Journal Article > ResearchFull Text
PLOS One. 21 November 2019; Volume 14 (Issue 11); DOI:10.1371/journal.pone.0225631
Gill N, Van Den Berg R, Wut Yee Kyaw K, Laxmeshwar C, Das M, et al.
PLOS One. 21 November 2019; Volume 14 (Issue 11); DOI:10.1371/journal.pone.0225631
BACKGROUND:
HIV programs are increasingly confronted with failing antiretroviral therapy (ART), including second-line regimens. WHO has provided guidelines on switching to third-line ART. In a Médecins Sans Frontières clinic in Mumbai, India, receiving referred presumptive second-line ART failure cases, an evidence-based protocol consisting of viral load (VL) testing, enhanced adherence counselling (EAC) and genotype for switching was implemented.
OBJECTIVE:
To document the outcome and genotype of presumptive second-line ART failure cases switched to third-line or maintained on second-line ART.
DESIGN:
Retrospective cohort study of patients referred between January 2011 and September 2017.
RESULTS:
The cases (n = 120) were complex with median 9.2 years of ART exposure, poor adherence at baseline, and exposure to multiple ART regimens other than recommended by WHO. Out of 90 evaluated cases, 39(43%) were maintained on second-line ART. Forty-nine (54%) were ever switched to third-line ART. Twelve months virological suppression was 72% in the second-line and 93% in the third-line ART cohort, while retention in care was 80% and 94% respectively. Genotyping showed 62% resistance for PIs, and 52% triple class resistance to NRTIs, NNRTIs and PIs. Resistance was noted for the new class of integrase inhibitors, and for different drugs without any documented previous exposure to the same drug.
CONCLUSION:
Adopting WHO guidelines on switching ART regimens and provision of EAC can prevent unnecessary switching/exposure to third-line ART regimens. Genotyping is urgently required in national HIV programs, which currently use only the exposure history of patients for switching to third-line ART regimens.
HIV programs are increasingly confronted with failing antiretroviral therapy (ART), including second-line regimens. WHO has provided guidelines on switching to third-line ART. In a Médecins Sans Frontières clinic in Mumbai, India, receiving referred presumptive second-line ART failure cases, an evidence-based protocol consisting of viral load (VL) testing, enhanced adherence counselling (EAC) and genotype for switching was implemented.
OBJECTIVE:
To document the outcome and genotype of presumptive second-line ART failure cases switched to third-line or maintained on second-line ART.
DESIGN:
Retrospective cohort study of patients referred between January 2011 and September 2017.
RESULTS:
The cases (n = 120) were complex with median 9.2 years of ART exposure, poor adherence at baseline, and exposure to multiple ART regimens other than recommended by WHO. Out of 90 evaluated cases, 39(43%) were maintained on second-line ART. Forty-nine (54%) were ever switched to third-line ART. Twelve months virological suppression was 72% in the second-line and 93% in the third-line ART cohort, while retention in care was 80% and 94% respectively. Genotyping showed 62% resistance for PIs, and 52% triple class resistance to NRTIs, NNRTIs and PIs. Resistance was noted for the new class of integrase inhibitors, and for different drugs without any documented previous exposure to the same drug.
CONCLUSION:
Adopting WHO guidelines on switching ART regimens and provision of EAC can prevent unnecessary switching/exposure to third-line ART regimens. Genotyping is urgently required in national HIV programs, which currently use only the exposure history of patients for switching to third-line ART regimens.
Journal Article > ResearchAbstract
Nat Genet. 19 January 2015; Volume 47 (Issue 3); DOI:10.1038/ng.3195
Merker M, Blin C, Mona S, Duforet-Frebourg N, Lecher S, et al.
Nat Genet. 19 January 2015; Volume 47 (Issue 3); DOI:10.1038/ng.3195
Mycobacterium tuberculosis strains of the Beijing lineage are globally distributed and are associated with the massive spread of multidrug-resistant (MDR) tuberculosis in Eurasia. Here we reconstructed the biogeographical structure and evolutionary history of this lineage by genetic analysis of 4,987 isolates from 99 countries and whole-genome sequencing of 110 representative isolates. We show that this lineage initially originated in the Far East, from where it radiated worldwide in several waves. We detected successive increases in population size for this pathogen over the last 200 years, practically coinciding with the Industrial Revolution, the First World War and HIV epidemics. Two MDR clones of this lineage started to spread throughout central Asia and Russia concomitantly with the collapse of the public health system in the former Soviet Union. Mutations identified in genes putatively under positive selection and associated with virulence might have favored the expansion of the most successful branches of the lineage.