Impact of rapid molecular diagnostic tests on time to treatment initiation and outcomes in patients with multidrug-resistant tuberculosis, Tamil Nadu, India

Nair, Dina; Navneethapandian, Pooranaganga D.; Tripathy, Jaya Prasad; Harries, Anthony; Klinton, Joel Shyam; Watson, Basilea; Sivaramakrishnan, Gomathi; Reddy, Devarajulu; Murali, Lakshmi; Natrajan, Mohan; Swaminathan, Soumya

doi:10.1093/trstmh/trw060

Cited by 22 publications

(20 citation statements)

References 21 publications

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“…Even reductions of several weeks or months are likely to significantly impact community transmission 16 and are likely to improve patient outcomes. 12 , 39 This systematic review and meta-analysis has shown that time to treatment is extremely variable and often lengthy. Overall, the average time to treatment from specimen collection was 2.5 months, with a trend towards reduction in delay in more recent years.…”

Section: Discussionmentioning

confidence: 99%

“…Molecular testing methods result in more rapid laboratory turnaround times, 12 , 68–70 and are therefore likely to reduce time to treatment. This was confirmed in our analysis, with genotypic testing resulting in significantly shorter time to treatment than phenotypic methods; our findings are consistent with the results of a randomized trial 71 and a retrospective cohort study published after our search was concluded.…”

Section: Discussionmentioning

confidence: 99%

“… 4–9 Such delays are likely to increase mortality and loss to follow-up while awaiting treatment, 10 , 11 in addition to potentially poorer treatment outcomes among those who do start treatment. 12 Long delays to treatment are also likely to contribute substantially to transmission in both community and nosocomial settings. 13–15 Given that the majority of RR-TB patients in high-burden settings are likely due to direct transmission, 16 scale-up of diagnosis and rapid initiation of effective treatment are required to improve patient outcomes and reduce ongoing transmission.…”

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confidence: 99%

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Time to treatment for rifampicin-resistant tuberculosis: systematic review and meta-analysis

Boyd

Ford

Padgen

et al. 2017

int j tuberc lung dis

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BACKGROUND:To reduce transmission and improve patient outcomes, rapid diagnosis and treatment of rifampicin-resistant tuberculosis (RR-TB) is required.OBJECTIVE:To conduct a systematic review and meta-analysis assessing time to treatment for RR-TB and variability using diagnostic testing methods and treatment delivery approach.DESIGN:Studies from 2000 to 2015 reporting time to second-line treatment initiation were selected from PubMed and published conference abstracts.RESULTS:From 53 studies, 83 cohorts (13 034 patients) were included. Overall weighted mean time to treatment from specimen collection was 81 days (95%CI 70–91), and was shorter with ambulatory (57 days, 95%CI 40–74) than hospital-based treatment (86 days, 95%CI 71–102). Time to treatment was shorter with genotypic susceptibility testing (38 days, 95%CI 27–49) than phenotypic testing (108 days, 95%CI 98–117). The mean percentage of diagnosed patients initiating treatment was 76% (95%CI 70–83, range 25–100).CONCLUSION:Time to second-line anti-tuberculosis treatment initiation is extremely variable across studies, and often unnecessarily long. Reduced delays are associated with genotypic testing and ambulatory treatment settings. Routine monitoring of the proportion of diagnosed patients initiating treatment and time to treatment are necessary to identify areas for intervention.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Time to treatment for rifampicin-resistant tuberculosis: systematic review and meta-analysis

Boyd

Ford

Padgen

et al. 2017

int j tuberc lung dis

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“…In 2016, a systematic review identified no published evidence linking delay in treatment initiation and MDR-TB outcomes[ 14 ]. Recently, a study from India has reported delayed treatment initiation (>30 days) as a risk factor for unfavourable outcomes [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Patients with MDR-TB on domiciliary care in programmatic settings in Myanmar: Effect of a support package on preventing early deaths

Wai¹,

Shewade²,

Kyaw³

et al. 2017

PLoS ONE

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BackgroundThe community-based MDR-TB care (CBMDR-TBC) project was implemented in 2015 by The Union in collaboration with national TB programme (NTP) in 33 townships of upper Myanmar to improve treatment outcomes among patients with MDR-TB registered under NTP. They received community-based support through the project staff, in addition to the routine domiciliary care provided by NTP staff. Each project township had a project nurse exclusively for MDR-TB and a community volunteer who provided evening directly observed therapy (in addition to morning directly observed therapy by NTP).ObjectivesTo determine the effect of CBMDR-TBC project on death and unfavourable outcomes during the intensive phase of MDR-TB treatment.MethodsIn this cohort study involving record review, all patients diagnosed with MDR-TB between January 2015 and June 2016 in project townships and initiated on treatment till 31 Dec 2016 were included. CBMDR-TBC status was categorized as “receiving support” if project initiation in patient’s township was before treatment initiation, “receiving partial support” if project initiation was after treatment initiation, and “not receiving support” if project initiation was after intensive phase treatment outcome declaration. Time to event analysis (censored on 10 April 2017) and cox regression was done.ResultsOf 261 patients initiated on treatment, death and unfavourable outcomes were accounted for 13% and 21% among “receiving support (n = 163)”, 3% and 24% among “receiving partial support (n = 75)” and 13% and 26% among “not receiving support (n = 23)” respectively. After adjusting for other potential confounders, the association between CBMDR-TBC and unfavourable outcomes was not statistically significant. However, when compared to “not receiving support”, those “receiving support” and “receiving partial support” had 20% [aHR (0.95 CI: 0.8 (0.2–3.1)] and 90% lower hazard [aHR (0.95 CI: 0.1 (0.02–0.9)] of death, respectively. This was intriguing. Implementation of CBMDR-TBC coincided with implementation of decentralized MDR-TB centers at district level. Hence, patients that would have generally not accessed MDR-TB treatment before decentralization also started receiving treatment and were also included under CBMDR-TBC “received support” group. These patients could possibly be expected to sicker at treatment initiation than patients in other CBMDR-TBC groups. This could be the possible reason for nullifying the effect of CBMDR-TBC in “receiving support” group and therefore similar survival was found when compared to “not receiving support”.ConclusionCBMDR-TBC may prevent early deaths and has a scope for expansion to other townships of Myanmar and implications for NTPs globally. However, future studies should consider including data on extent of sickness at treatment initiation and patient level support received under CBMDR-TBC.

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“…In 2016, a systematic review identified no published evidence linking delay in treatment initiation to MDR-TB outcomes [ 5 ]. Recently, a study from India has reported delayed treatment initiation (>30 days) as a risk factor for unfavorable outcomes [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Community-based MDR-TB care project improves treatment initiation in patients diagnosed with MDR-TB in Myanmar

Wai¹,

Shewade²,

Kyaw³

et al. 2018

PLoS ONE

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BackgroundThe Union in collaboration with national TB programme (NTP) started the community-based MDR-TB care (CBMDR-TBC) project in 33 townships of upper Myanmar to improve treatment initiation and treatment adherence. Patients with MDR-TB diagnosed/registered under NTP received support through the project staff, in addition to the routine domiciliary care provided by NTP staff. Each township had a project nurse exclusively for MDR-TB and 30 USD per month (max. for 4 months) were provided to the patient as a pre-treatment support.ObjectivesTo assess whether CBMDR-TBC project’s support improved treatment initiation.MethodsIn this cohort study (involving record review) of all diagnosed MDR-TB between January 2015 and June 2016 in project townships, CBMDR-TBC status was categorized as “receiving support” if date of project initiation in patient’s township was before the date of diagnosis and “not receiving support”, if otherwise. Cox proportional hazards regression (censored on 31 Dec 2016) was done to identify predictors of treatment initiation.ResultsOf 456 patients, 57% initiated treatment: 64% and 56% among patients “receiving support (n = 208)” and “not receiving support (n = 228)” respectively (CBMDR-TBC status was not known in 20 (4%) patients due to missing diagnosis dates). Among those initiated on treatment (n = 261), median (IQR) time to initiate treatment was 38 (20, 76) days: 31 (18, 50) among patients “receiving support” and 50 (26,101) among patients “not receiving support”. After adjusting other potential confounders (age, sex, region, HIV, past history of TB treatment), patients “receiving support” had 80% higher chance of initiating treatment [aHR (0.95 CI): 1.8 (1.3, 2.3)] when compared to patients “not receiving support”. In addition, age 15–54 years, previous history of TB and being HIV negative were independent predictors of treatment initiation.ConclusionReceiving support under CBMDR-TBC project improved treatment initiation: it not only improved the proportion initiated but also reduced time to treatment initiation. We also recommend improved tracking of all diagnosed patients as early as possible.

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Impact of rapid molecular diagnostic tests on time to treatment initiation and outcomes in patients with multidrug-resistant tuberculosis, Tamil Nadu, India

Abstract: Rapid molecular diagnostic tests shortened the time to initiate treatment which was associated with reduced unfavourable outcomes in MDR-TB patients. This supports the policy to scale up these tests in India.

Cited by 22 publications

References 21 publications

Time to treatment for rifampicin-resistant tuberculosis: systematic review and meta-analysis

Time to treatment for rifampicin-resistant tuberculosis: systematic review and meta-analysis

Patients with MDR-TB on domiciliary care in programmatic settings in Myanmar: Effect of a support package on preventing early deaths

Community-based MDR-TB care project improves treatment initiation in patients diagnosed with MDR-TB in Myanmar

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