Initiation, scale-up and outcomes of the Cambodian National MDR-TB programme 2006–2016: hospital and community-based treatment through an NGO–NTP partnership

Sam, S; Shapiro, Adrienne E.; Thim, Sok; Khann, S; So, Rassi; Khem, S.; Chhun, Sokhem; Noun, Sarith; Koy, Bonamy; Sayouen, Prum Chhom; Sin, Chun Im; Bunsieth, Heng; Mao, Tan Eang; Goldfeld, Anne E.

doi:10.1136/bmjresp-2017-000256

Cited by 11 publications

(10 citation statements)

References 14 publications

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“…38 Another study reported four XDR-TB cases (0.7%) and only one pre-XDR-TB case (0.1%) confirmed by DST among MDR-TB patients between 2006 and 2016, but only the patients who did not respond to the treatment regimen were tested for SLD resistance. 13 The present study reports the first description of SLD drug resistance in M.tb in Cambodia using a combination of molecular screening for mutations in the gyrA/B gene conferring FQ resistance and the rrs-F2 gene conferring SLID resistance followed by pDST confirmation. Overall, only 25 of the 37 M.tb isolates harboring mutations in the gyrA/B and/or rrs-F2 genes were resistant to FQ or SLID by pDST.…”

Section: Discussionmentioning

confidence: 85%

“…This retrospective cross-sectional study included FLDresistant M.tb isolates taken from the collection of clinical isolates obtained via a platform established for routine screening of MDR-TB among high-risk groups by the National Tuberculosis Program (NTP). 13 Since 2012, people at risk of developing MDR-TB were screened using Xpert MTB/RIF, followed by culture and phenotypic drug susceptibility testing (pDST) for FLD. All confirmed RIF resistant (RR) or MDR-TB cases received a 24-month standardized regimen in two phases: an 8-month intensive phase and a 16-month continuation phase.…”

Section: Mtb Strain Collection and Ntp Routine For Mdr-tb Screeningmentioning

confidence: 99%

“…11 Prior to 2017, streptomycin (STM) was also included in the first-line TB treatment for retreated patients (WHO category II regimen) in many countries where conventional or molecular DST was not routinely available. 12,13 However, due to its resistance and toxicity, STM is now a reserved second-line injectable agent and used as a substitute for amikacin in the MDR-TB regimen. Some FLD such as INH, EMB and PZA also play an important role in the chemotherapy of drug-resistant TB.…”

Section: Introductionmentioning

confidence: 99%

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Resistance to Second-Line Anti-TB Drugs in Cambodia: A Phenotypic and Genetic Study

Cheng¹,

Hide²,

Pheng³

et al. 2021

IDR

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Background: Due to the emergence of Mycobacterium tuberculosis (M.tb) clinical isolates resistant to most potent first-line drugs (FLD), second-line drugs (SLD) are being prescribed more frequently. We explore the genetic characteristics and molecular mechanisms of M.tb isolates phenotypically resistant to SLD, including pre-extensively drug-resistant (pre-XDR) and extensively drug-resistant (XDR) isolates. Methods: Drug-resistant (DR) M.tb isolates collected from 2012 to 2017 were tested using sequencing and phenotypic drug susceptibility testing. Genotypes were determined to explore their links with SLD resistance patterns. Results: Of the 272 DR M.tb isolates, 6 non-multidrug resistant (non-MDR) isolates were fluoroquinolones (FQ)-resistant, 3 were XDR and 16 were pre-XDR (14 resistant to FQ and 2 to second-line injectable drugs). The most frequent mutations in FQ-resistant and secondline injectable drugs resistant isolates were gyrA D94G (15/23) and rrs a1401g (3/5), respectively. Seventy-five percent of pre-XDR isolates and 100% of XDR isolates harbored mutations conferring resistance to pyrazinamide. All XDR isolates belonged to the Beijing genotype, of which one, named XDR+, was resistant to all drugs tested. One cluster including pre-XDR and XDR isolates was observed. Conclusion: This is the first description of SLD resistance in Cambodia. The data suggest that the proportion of XDR and pre-XDR isolates remains low but is on the rise compared to previous reports. The characterization of the XDR+ isolate in a patient who refused treatment underlines the risk of transmission in the population. In addition, genotypic results show, as expected, that the Beijing family is the main involved in pre-XDR and XDR isolates and that the spread of the Beijing pre-XDR strain is capable of evolving into XDR strain. This study strongly indicates the need for rapid interventions in terms of diagnostic and treatment to prevent the spread of the pre-XDR and XDR strains and the emergence of more resistant ones.

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Section: Discussionmentioning

confidence: 85%

Section: Mtb Strain Collection and Ntp Routine For Mdr-tb Screeningmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Resistance to Second-Line Anti-TB Drugs in Cambodia: A Phenotypic and Genetic Study

Cheng¹,

Hide²,

Pheng³

et al. 2021

IDR

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“…Previous studies in China have shown that urban migrants have higher TB rates, more drug resistance, and poorer treatment outcomes than urban residents [32, 33]. Several decentralized models of care for MDR-TB have been introduced to improve the linkage between diagnosis and treatment initiation especially for patients from rural areas [34, 35]. MDR-TB patients treated under community-based care involving healthcare workers and treatment supporters at sub-district or village level achieved equally high treatment success as those with hospital-based initiation [36].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Xpert MTB-RIF guided diagnosis and treatment of rifampicin-resistant tuberculosis in Indonesia: A retrospective cohort study

et al. 2019

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Background Rifampicin-resistant tuberculosis (RR-TB) is largely underdetected in Indonesia. Xpert MTB/RIF (Xpert) has recently been introduced, prioritizing patients at risk of RR-TB, followed by phenotypic drug-susceptibility (DST) if rifampicin resistance is detected. Objective This study investigated Xpert-based management of presumptive RR-TB cases under routine practice in West Java, Indonesia. Methods We examined all records of patients tested with Xpert in the referral hospital for West Java in 2015–2016. We measured loss across a limited cascade of care, time to Xpert diagnosis and the commencement of initial second-line treatment, and identified factors associated with diagnostic and treatment delay. Additionally, we analyzed the appropriateness of treatment according to DST results. Results Of 3415 patients with presumptive RR-TB, 3215 (94%) were tested by Xpert, of whom 339 (10.5%) were diagnosed as RR-TB. 288 (85%) of 339 RR-TB patients started initial second-line TB treatment, with 48 (14%) patients being lost between diagnosis and pre-treatment assessment. Second-line treatment was commenced at a median of 41 days (IQR 29–70) after RR-TB diagnosis. Delays in both diagnosis and treatment initiation were observed in 104 (52%) of 201 RR-TB patients with identifiable referral date. Rural residence was associated with delay to diagnosis (adjusted OR 2.7; 95%CI 1.5–5.2) and treatment initiation (adjusted OR 2.0; 1.2–3.4). Of 162 patients with available DST result, 107 (66%) had multidrug-resistant tuberculosis (MDR-TB) and 32 (20%) had either pre-extensively drug resistant (pre-XDR) or extensively drug resistant tuberculosis (XDR-TB). We estimated that with the current algorithm 41% of pre-XDR or XDR-TB patients are diagnosed, and 33% of them started on an appropriate treatment regimen. Conclusions Many patients with Xpert-diagnosed RR-TB either do not start MDR-TB treatment or encountered diagnostic and treatment delays under programmatic conditions in Indonesia, and most pre-XDR and XDR-TB cases remain undiagnosed. Further expansion and ongoing quality improvement of RR-TB services are urgently needed.

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“…Since 2009, treatment success and completion rates have declined steadily. Rising rates of drug-resistant TB also indicate that poor adherence may be a concern [ 30 ].…”

Section: Methodsmentioning

confidence: 99%

Perceptions and Acceptability of Digital Interventions Among Tuberculosis Patients in Cambodia: Qualitative Study of Video-Based Directly Observed Therapy

Rabinovich¹,

Molton²,

Ooi³

et al. 2020

J Med Internet Res

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Background Despite the development of effective drugs for treatment, tuberculosis remains one of the leading causes of death from an infectious disease worldwide. One of the greatest challenges to tuberculosis control is patient adherence to treatment. Recent research has shown that video-based directly observed therapy is a feasible and effective approach to supporting treatment adherence in high-income settings. However, few studies have explored the potential for such a solution in a low- or middle-income country setting. Globally, these countries’ rapidly rising rate of mobile penetration suggests that the potential for translation of these results may be high. Objective We sought to examine patient perceptions related to the use of mobile health, and specifically video-based directly observed therapy, in a previously unstudied patient demographic: patients with tuberculosis in a low-income country setting (Cambodia). Methods We conducted a cross-sectional qualitative study in urban and periurban areas in Cambodia, consisting of 6 focus groups with tuberculosis patients who were receiving treatment (standard directly observed therapy) through a nongovernmental organization. Results Familiarity with mobile technology and apps was widespread in this population, and overall willingness to consider a mobile app for video-based directly observed therapy was high. However, we identified potential challenges. First, patients very much valued their frequent in-person interactions with their health care provider, which may be reduced with the video-based directly observed therapy intervention. Second, there may be technical issues to address, including how to make the app suitable for illiterate participants. Conclusions While video-based directly observed therapy is a promising technology, even in country settings where mobile penetration is reportedly almost universal, it should be introduced with caution. However, the results were generally promising and yielded important insights that not only will be translated into the further adaptation of key features of video-based directly observed therapy for tuberculosis patients in Cambodia, but also can inform the future design and successful implementation of video-based directly observed therapy interventions in low- and middle-income settings more generally.

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Initiation, scale-up and outcomes of the Cambodian National MDR-TB programme 2006–2016: hospital and community-based treatment through an NGO–NTP partnership

Cited by 11 publications

References 14 publications

Resistance to Second-Line Anti-TB Drugs in Cambodia: A Phenotypic and Genetic Study

Resistance to Second-Line Anti-TB Drugs in Cambodia: A Phenotypic and Genetic Study

Evaluation of Xpert MTB-RIF guided diagnosis and treatment of rifampicin-resistant tuberculosis in Indonesia: A retrospective cohort study

Perceptions and Acceptability of Digital Interventions Among Tuberculosis Patients in Cambodia: Qualitative Study of Video-Based Directly Observed Therapy

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