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The Potential Impact of Up-Front Drug Sensitivity Testing on India's Epidemic of Multi-Drug Resistant Tuberculosis.

Sachdeva KS, Raizada N, Gupta RS, Nair SA, Denkinger C, Paramasivan CN, Kulsange S, Thakur R, Dewan P, Boehme C, Arinaminpathy N - PLoS ONE (2015)

Bottom Line: The End TB strategy, recently approved by the world health assembly, aims to reduce TB deaths by 95% and new cases by 90% between 2015 and 2035.Synergistic effects were observed with assumptions of simultaneously improving MDR-TB treatment outcomes.Our results illustrate the potential impact of new and emerging technologies that enable widespread, timely DST, and the important effect that universal rapid DST in the public sector can have on the MDR-TB epidemic in India.

View Article: PubMed Central - PubMed

Affiliation: Central TB Division, Government of India, New Delhi, India.

ABSTRACT

Background: In India as elsewhere, multi-drug resistance (MDR) poses a serious challenge in the control of tuberculosis (TB). The End TB strategy, recently approved by the world health assembly, aims to reduce TB deaths by 95% and new cases by 90% between 2015 and 2035. A key pillar of this approach is early diagnosis of tuberculosis, including use of higher-sensitivity diagnostic testing and universal rapid drug susceptibility testing (DST). Despite limitations of current laboratory assays, universal access to rapid DST could become more feasible with the advent of new and emerging technologies. Here we use a mathematical model of TB transmission, calibrated to the TB epidemic in India, to explore the potential impact of a major national scale-up of rapid DST. To inform key parameters in a clinical setting, we take GeneXpert as an example of a technology that could enable such scale-up. We draw from a recent multi-centric demonstration study conducted in India that involved upfront Xpert MTB/RIF testing of all TB suspects.

Results: We find that widespread, public-sector deployment of high-sensitivity diagnostic testing and universal DST appropriately linked with treatment could substantially impact MDR-TB in India. Achieving 75% access over 3 years amongst all cases being diagnosed for TB in the public sector alone could avert over 180,000 cases of MDR-TB (95% CI 44187 - 317077 cases) between 2015 and 2025. Sufficiently wide deployment of Xpert could, moreover, turn an increasing MDR epidemic into a diminishing one. Synergistic effects were observed with assumptions of simultaneously improving MDR-TB treatment outcomes. Our results illustrate the potential impact of new and emerging technologies that enable widespread, timely DST, and the important effect that universal rapid DST in the public sector can have on the MDR-TB epidemic in India.

No MeSH data available.


Related in: MedlinePlus

Schematic illustrating the model structure.Infections are stratified by smear, drug sensitivity, HIV co-infection and history of previous treatment. TB care stages (diagnosis and treatment) are stratified by public and private sectors. ‘FL’ and ‘SL’ denote first- and second-line treatment, respectively. Outgoing dashed lines indicate the loss of patients from the care seeking pathway. These patients reenter the care seeking pathway after a given delay, represented by the incoming dashed line at top right. The red lines indicate the effects of Xpert: that is, to bypass the interval for suspecting and testing for MDR-TB, and to enable wider uptake of upfront drug sensitivity testing. Individuals who are cured are assumed to be non-infectious until death, relapse or reinfection. In the latter two cases, they re-enter the infected, pre-care seeking compartment.
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pone.0131438.g001: Schematic illustrating the model structure.Infections are stratified by smear, drug sensitivity, HIV co-infection and history of previous treatment. TB care stages (diagnosis and treatment) are stratified by public and private sectors. ‘FL’ and ‘SL’ denote first- and second-line treatment, respectively. Outgoing dashed lines indicate the loss of patients from the care seeking pathway. These patients reenter the care seeking pathway after a given delay, represented by the incoming dashed line at top right. The red lines indicate the effects of Xpert: that is, to bypass the interval for suspecting and testing for MDR-TB, and to enable wider uptake of upfront drug sensitivity testing. Individuals who are cured are assumed to be non-infectious until death, relapse or reinfection. In the latter two cases, they re-enter the infected, pre-care seeking compartment.

Mentions: The end TB strategy, approved by world health assembly, aims to end the global TB epidemic and targets to reduce TB deaths by 95% and new cases by 90%, between 2015 and 2035. One of the key pillars of this approach is early diagnosis of tuberculosis, including universal drug susceptibility testing, and systematic screening of high-risk groups [10]. New and emerging technologies could make it feasible to meet such conditions, by lifting the constraints associated with current methods of DST, thereby extending high-quality DST to an increased number of patients. A prominent example of such technology is the Xpert MTB/RIF assay [11] (hereafter referred to as ‘Xpert’), a rapid highly-automated nucleic acid amplification test that can provide a highly-accurate result on M. tuberculosis presence in sputum and rifampicin-resistance status within 2 hours. By decentralizing DST to the district or sub-district level, Xpert may offer the potential for much wider, timelier DST than is feasible with current tools. Moreover, while conventional DST is performed only after TB diagnosis, an assay such as Xpert allows DST to be run concurrently with diagnosis: we refer to this as ‘upfront’ DST. As illustrated in Fig 1, widened access to upfront DST could lead to earlier detection of MDR-TB, particularly amongst smear-negative cases in which it would otherwise be missed. When linked to effective treatment, this improved detection could lead to reduced opportunities for transmission, thus potentially preventing future cases of MDR-TB.


The Potential Impact of Up-Front Drug Sensitivity Testing on India's Epidemic of Multi-Drug Resistant Tuberculosis.

Sachdeva KS, Raizada N, Gupta RS, Nair SA, Denkinger C, Paramasivan CN, Kulsange S, Thakur R, Dewan P, Boehme C, Arinaminpathy N - PLoS ONE (2015)

Schematic illustrating the model structure.Infections are stratified by smear, drug sensitivity, HIV co-infection and history of previous treatment. TB care stages (diagnosis and treatment) are stratified by public and private sectors. ‘FL’ and ‘SL’ denote first- and second-line treatment, respectively. Outgoing dashed lines indicate the loss of patients from the care seeking pathway. These patients reenter the care seeking pathway after a given delay, represented by the incoming dashed line at top right. The red lines indicate the effects of Xpert: that is, to bypass the interval for suspecting and testing for MDR-TB, and to enable wider uptake of upfront drug sensitivity testing. Individuals who are cured are assumed to be non-infectious until death, relapse or reinfection. In the latter two cases, they re-enter the infected, pre-care seeking compartment.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488842&req=5

pone.0131438.g001: Schematic illustrating the model structure.Infections are stratified by smear, drug sensitivity, HIV co-infection and history of previous treatment. TB care stages (diagnosis and treatment) are stratified by public and private sectors. ‘FL’ and ‘SL’ denote first- and second-line treatment, respectively. Outgoing dashed lines indicate the loss of patients from the care seeking pathway. These patients reenter the care seeking pathway after a given delay, represented by the incoming dashed line at top right. The red lines indicate the effects of Xpert: that is, to bypass the interval for suspecting and testing for MDR-TB, and to enable wider uptake of upfront drug sensitivity testing. Individuals who are cured are assumed to be non-infectious until death, relapse or reinfection. In the latter two cases, they re-enter the infected, pre-care seeking compartment.
Mentions: The end TB strategy, approved by world health assembly, aims to end the global TB epidemic and targets to reduce TB deaths by 95% and new cases by 90%, between 2015 and 2035. One of the key pillars of this approach is early diagnosis of tuberculosis, including universal drug susceptibility testing, and systematic screening of high-risk groups [10]. New and emerging technologies could make it feasible to meet such conditions, by lifting the constraints associated with current methods of DST, thereby extending high-quality DST to an increased number of patients. A prominent example of such technology is the Xpert MTB/RIF assay [11] (hereafter referred to as ‘Xpert’), a rapid highly-automated nucleic acid amplification test that can provide a highly-accurate result on M. tuberculosis presence in sputum and rifampicin-resistance status within 2 hours. By decentralizing DST to the district or sub-district level, Xpert may offer the potential for much wider, timelier DST than is feasible with current tools. Moreover, while conventional DST is performed only after TB diagnosis, an assay such as Xpert allows DST to be run concurrently with diagnosis: we refer to this as ‘upfront’ DST. As illustrated in Fig 1, widened access to upfront DST could lead to earlier detection of MDR-TB, particularly amongst smear-negative cases in which it would otherwise be missed. When linked to effective treatment, this improved detection could lead to reduced opportunities for transmission, thus potentially preventing future cases of MDR-TB.

Bottom Line: The End TB strategy, recently approved by the world health assembly, aims to reduce TB deaths by 95% and new cases by 90% between 2015 and 2035.Synergistic effects were observed with assumptions of simultaneously improving MDR-TB treatment outcomes.Our results illustrate the potential impact of new and emerging technologies that enable widespread, timely DST, and the important effect that universal rapid DST in the public sector can have on the MDR-TB epidemic in India.

View Article: PubMed Central - PubMed

Affiliation: Central TB Division, Government of India, New Delhi, India.

ABSTRACT

Background: In India as elsewhere, multi-drug resistance (MDR) poses a serious challenge in the control of tuberculosis (TB). The End TB strategy, recently approved by the world health assembly, aims to reduce TB deaths by 95% and new cases by 90% between 2015 and 2035. A key pillar of this approach is early diagnosis of tuberculosis, including use of higher-sensitivity diagnostic testing and universal rapid drug susceptibility testing (DST). Despite limitations of current laboratory assays, universal access to rapid DST could become more feasible with the advent of new and emerging technologies. Here we use a mathematical model of TB transmission, calibrated to the TB epidemic in India, to explore the potential impact of a major national scale-up of rapid DST. To inform key parameters in a clinical setting, we take GeneXpert as an example of a technology that could enable such scale-up. We draw from a recent multi-centric demonstration study conducted in India that involved upfront Xpert MTB/RIF testing of all TB suspects.

Results: We find that widespread, public-sector deployment of high-sensitivity diagnostic testing and universal DST appropriately linked with treatment could substantially impact MDR-TB in India. Achieving 75% access over 3 years amongst all cases being diagnosed for TB in the public sector alone could avert over 180,000 cases of MDR-TB (95% CI 44187 - 317077 cases) between 2015 and 2025. Sufficiently wide deployment of Xpert could, moreover, turn an increasing MDR epidemic into a diminishing one. Synergistic effects were observed with assumptions of simultaneously improving MDR-TB treatment outcomes. Our results illustrate the potential impact of new and emerging technologies that enable widespread, timely DST, and the important effect that universal rapid DST in the public sector can have on the MDR-TB epidemic in India.

No MeSH data available.


Related in: MedlinePlus