PLoS ONEplosplosonePLOS ONE1932-6203Public Library of ScienceSan Francisco, CA USA10.1371/journal.pone.0306076PONE-D-23-42213Research ArticleMedicine and health sciencesMedical conditionsInfectious diseasesBacterial diseasesTuberculosisMedicine and health sciencesMedical conditionsTropical diseasesTuberculosisPeople and placesGeographical locationsAfricaEthiopiaMedicine and health sciencesHealth careHealth care facilitiesMedicine and health sciencesPharmaceuticsDrug therapyMedicine and health sciencesMedical conditionsInfectious diseasesBacterial diseasesTuberculosisMulti-drug-resistant tuberculosisMedicine and health sciencesMedical conditionsTropical diseasesTuberculosisMulti-drug-resistant tuberculosisMedicine and health sciencesMedical conditionsInfectious diseasesBacterial diseasesTuberculosisExtensively drug-resistant tuberculosisMedicine and health sciencesMedical conditionsTropical diseasesTuberculosisExtensively drug-resistant tuberculosisEngineering and technologyTransportationMedicine and health sciencesHealth careSocioeconomic aspects of healthMedicine and health sciencesPublic and occupational healthSocioeconomic aspects of healthDrug-resistant tuberculosis care and treatment outcomes over the last 15 years in Ethiopia: Results from a mixed-method review of trendsDrug-resistant tuberculosis in Ethiopiahttps://orcid.org/0000-0002-6775-4208TesemaE.ConceptualizationData curationFormal analysisInvestigationMethodologyProject administrationSupervisionValidationVisualizationWriting – original draftWriting – review & editing1*BiruM.Data curationFormal analysisMethodologyWriting – review & editing1LetaT.Writing – review & editing2KumsaA.Writing – review & editing2LiaulsegedA.Writing – review & editing2GizatieG.Data curationProject administrationSupervision1BogaleT.Data curationProject administrationSupervision1MillionM.Data curationProject administrationSupervision1DatikoD. G.ConceptualizationFunding acquisitionProject administrationSupervisionWriting – review & editing3GebreyohannesA.ConceptualizationMethodologyWriting – review & editing1MollaY.ConceptualizationMethodologyWriting – review & editing3HiruyN.Data curation3MebngaM.Writing – review & editing4SuarezP. G.Writing – review & editing5DememewZ. G.Data curationFormal analysisWriting – review & editing3JereneD.ConceptualizationFormal analysisMethodologySupervisionValidationVisualizationWriting – review & editing6USAID Eliminate TB Project, KNCV Tuberculosis Foundation, Addis Ababa, EthiopiaMinistry of Health, National TB, Leprosy and other Lung Disease Program, Addis Ababa, EthiopiaUSAID Eliminate TB Project, Management Sciences for Health, Addis Ababa, EthiopiaKNCV Tuberculosis Foundation, Moscow, RussiaManagement Sciences for Health, Arlington, VA, United States of AmericaKNCV Tuberculosis Foundation, The Hague, The NetherlandsDholakiaYatin N.EditorThe Foundation for Medical Research, INDIA
the authors have declared that no competing interests exist.
* E-mail: emawayish.tesema@kncvtbc.org26820242024198e0306076181202411620242024Tesema et alThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background and objectives
Drug resistant tuberculosis (DR-TB) remains a global challenge with about a third of the cases are not detected. With the recent advances in the diagnosis and treatment follow-up of DR-TB, there have been improvements with treatment success rates. However, there is limited evidence on the successful models of care that have consistently registered good outcomes. Our aim was to assess Ethiopia’s experience in scaling up an ambulatory, decentralized model of care while managing multiple regimen transition processes and external shocks.
Methods
This was a cross-sectional, mixed-method study. For the quantitative data, we reviewed routine surveillance data for the period 2009–2022 and collected additional data from publicly available reports. We then analyzed the data descriptively. Qualitative data were collected from program reports, quarterly presentations, minutes of technical working group meetings, and clinical review committee reports and analyzed thematically.
Results
The number of DR-TB treatment initiating centers increased from 1 to 67, and enrollment increased from 88 in 2010 to 741 in 2019, but declined to 518 in 2022. A treatment success rate (TSR) of over 70% was sustained. The decentralized and ambulatory service delivery remained the core service delivery model. The country successfully navigated multiple regimen transitions, including the recently introduced six-month short oral regimen. Several challenges remain, including the lack of strong and sustainable specimen transportation system, lack of established systems for timely tracing and linking of missed DR-TB cases, and data quality issues.
Conclusions
Ethiopia scaled up a decentralized ambulatory model of care, kept up to date with recent developments in treatment regimens, and maintained a high TSR, despite the influence of multiple external challenges. The recent decline in case notification requires a deeper look into the underlying reasons. The feasibility of fully integrating DR-TB treatment and follow up at community level should be explored further.
USAID72066320CA00009DatikoDaniel GemechuThe Global Health Bureau, Office of Health, Infectious Disease, USAID financially supported the study through USAID Eliminate TB Project under the terms of Agreement No. 72066320CA00009. The funding was provided for Management Sciences for Health (MSH) organization for implementing USAID Eliminate TB Project. The authors’ views expressed in this publication do not necessarily reflect the views of USAID or the US Government.Data AvailabilityAll relevant data are within the manuscript and its Supporting Information files.Introduction
Tuberculosis (TB) remained a major public health problem worldwide, affecting over 10 million people each year [1]. About 3–4% of newly diagnosed TB patients have drug resistant forms of TB, and the rate is 18–21% among persons with previous history of treatment [2]. Following the Corona virus disease 2019 (COVID-19) pandemic, the number of people treated for DR-TB in 2020 dropped by 15%, compared to 2019 estimates of half a million cases [3]. Despite a decline in DR-TB patients enrolled in treatment, there has been progressive improvement in treatment outcomes over the years where treatment success rate reached 60% in 2022. However, this translates to 40% unfavorable outcomes calling for better strategies to improve treatment outcomes in high burden settings [2].
The recently recommended all-oral short treatment regimen is one of the major strategies in improving the management of DR-TB, shortening the treatment duration and improving adherence and treatment outcome [4]. However, there are concerns about acquiring resistance with the widespread implementation of regimens containing bedaquiline (BDQ), which require close follow-up of the program and documenting lessons from early adopter countries [5, 6].
Ethiopia is among a high TB and TB/HIV burden countries who have registered consistent decline in TB incidence, by an average of 5–10%, from 192 in 2015 to 119 per 100,000 in 2021. However, there was 7% increase to 126/100,000 which was believed to be due to multiple external shocks including conflict, COVID-19 and natural disasters [1]. Despite these challenges, the incidence and mortality rates of TB declined by 31.1% and 34.6%, respectively, compared with the 2015 baseline. As a result, Ethiopia attained the 2020 End TB milestones [7]. The latest drug resistance survey (DRS) report revealed that 1.1% of new and 7.5% of previously treated TB cases were estimated to have MDR-TB in 2019 [8].This is a significant decline from the 2005 DRS rates of 2.7% and 14% among new and previously treated cases, respectively [9]. Based on the updated estimates for DR-TB burden, Ethiopia is no longer among the 30 high MDR/RR-TB burden countries [8].
We previously reported successes and challenges associated with Ethiopia’s scaled-up implementation of the ambulatory model of care [7]. Since then, the country has continued implementing the World Health Organization’s (WHO) updated recommendations, which are based on the best available evidence on model of care and person-centered approaches. Since 2016, there have been various regimen transitions adopted by the country for programmatic implementation. These transitions happened despite multiple challenges, including COVID-19 and widespread conflict with consequent massive internal displacement which could have a negative impact on the overall TB/DR-TB-related program implementation [10, 11].
Our aim was to assess Ethiopia’s experience in scaling up an ambulatory, decentralized model of care with a good treatment success rate (TSR) while managing multiple regimen transition processes and external shocks. The findings will contribute to further refinement of implementation approaches and policy guidance in the country and beyond.
MethodsStudy setting and design
Ethiopia is a low-income country with per capita income of 1028 USD. The country’s population, which is predominantly rural, is estimated to exceed 123 million and the average life expectancy is 65 years. Table 1 summarizes key socio-demographic and health indicators for Ethiopia. The country has a three-tiered pyramidal health system care system with primary health care facilities forming the broad base, secondary health care facilities in the middle, and tertiary care at the apex (see figure as supplemental information). Ethiopia follows a decentralized service delivery model as much as possible with the bulk of the service provided at primary care level. For DR-TB care, the country followed the healthcare tier system in setting up the services. Treatment Initiating Centers (TICs), where patients initiate their treatment and temporarily admitted if needed were initially set up at tertiary level but later much of the TIC role moved to secondary level. Treatment follow-up centers (TFCs) are facilities where patients receive their daily treatment after they are transferred from the TICs. Each TIC has a designated number of TFC within their catchment areas, defined by administrative regions and zones. Detailed description of the roles and responsibilities of TICs and TFCs is provided [7].
10.1371/journal.pone.0306076.t001
Key socio-economic and health indicators.
Value for Ethiopia Characteristic
Estimated population (millions)*
123,379,924
Estimated annual per capita income (US$) *
7510
Life expectancy at birth*
65 years
Infant mortality rate*
34
% of government expenditure on health*
28.3%
% TB patients suffering catastrophic cost [12]
52%
Source*: The World Bank data, 2022
A cross-sectional programmatic data review was done for the period 2009–2022. The assessment followed a mixed study design and used both quantitative and qualitative data collection approaches.
Data sources
Publicly available and national TB program reports were used. Programmatic information from treatment initiation centers (TICs), treatment follow-up centers (TFCs), activity reports, and meeting reports were reviewed to complement the quantitative data. All MDR/RR-TB patients reported in the WHO annual global tuberculosis reports for 2009–2022 were reviewed in this study.
Data collection and procedure
Routine service data were collected from the national Health Management Information System (HMIS) and WHO annual reports for 2009–2022 to document and synthesize the trend of MDR/RR-TB enrollment and treatment success. Data were collected from January 1 to February 28, 2023. It was collected using a tailored case report format from the District Health Information System-2 (DHIS2) and/or standard of care (SOC) tool. The SOC tool is a supervision tool that monitors the implementation of DR-TB service at TICs and TFCs. In addition, national TB program reports and TB and Leprosy (TBL) annual bulletins were reviewed. Trends of MDR/RR-TB enrollment and composite final treatment success of MDR/RR-TB cases were computed.
The quantitative data were supplemented with qualitative programmatic data, including reports, quarterly presentations, minutes of technical working group meetings, and clinical review committee reports.
Data entry and analysis
Quantitative data were entered and analyzed using Excel. Descriptive statistics were computed to get summary results. We conducted a manual thematic analysis of qualitative data. We have synthesized those findings in connection to MDR/RR-TB patient care and services in three thematic areas: Growing demand for MDR/RR-TB service access, MDR/RR-TB Service expansion and data quality, and Resource limitation and lack of locally evidenced solutions. The descriptions of these themes are embedded in the results and discussions.
Ethical consideration
The study carries no more than minimal risk. Hence, permission to use the routinely collected health facility data on tuberculosis services for program implementation was requested from Oromia Health Bureau in Addis Ababa, Ethiopia to proceed and conduct the data analysis. Routinely collected data form health facilities who are implementing TB program services was analyzed for service improvement, provide recommendation, documentation, and possible publication for others to learn the good practice. All potential identifiers were removed from the format to ensure anonymity.
ResultsInception of the MDR-TB program
Ethiopia conducted the first national DRS in 2005 and found a DR-TB rate of 2.3% among new and 17% among previously treated TB cases. This was followed by a Green Lights Committee-approved pilot program to treat MDR/RR-TB patients in 2009 at St. Peter’s Specialized Hospital in Addis Ababa. The program was successful in terms of patient enrollment, good case holding, and improved the treatment outcome, which led to the National TB Program (NTP) scaling up the service and establishing the national Programmatic Management of DR-TB (PMDT) technical working group to support the program.
Hospitalized model of care (2009–2011)
Between 2009 and 2011, the NTP introduced a hospitalized model of DR-TB care in the first two treatment centers during the initial two years of DR-TB care program initiation. In the hospitalized model of care, the facility provides patient care until the patient has culture and smear conversion. During this period, 208 DR-TB patients were enrolled to treatment according to the WHO annual global TB report 2010/11.
Clinic-based ambulatory model of care (2012–2022)
During this period, national policies and guidelines were developed, monitoring and evaluation system established, additional DR-TB treatment facilities renovated, access to drug susceptibility testing (DST) improved, and capacity of health care workers built, all of which further improved DR-TB case finding; enrollment of patients on available, effective treatment; admission capacity of health facilities; and well-coordinated programs. Additional TB culture and DST centers were established in four regions to improve the country’s diagnostic capacity. Health facilities were networked with nearby culture and DST laboratory services. During the same period, 10 additional MDR-TB treatment centers were opened.
This period has brought a major shift in the program design and treatment service delivery model from hospitalized care to a clinic-based ambulatory model of care. In addition, the first-of-its-kind national implementation guide and protocol were prepared for implementation of an ambulatory treatment model at service delivery centers. This supported the rapid decentralization of PMDT services in the local context. The focus gradually shifted to the introduction of rapid molecular diagnostics (X-pert MTB/RIF Assay), introduction of new WHO-endorsed treatment regimens, and expansion of treatment centers to more public hospitals in all regions. The number of TICs increased from 1 in 2009 to 67 in 2022. Between 2014 and 2015 alone, 42 TICs were opened with more than 700 satellite treatment follow-up centers linked to them (Fig 1).
10.1371/journal.pone.0306076.g001
Phased site expansion by calendar period.
It is a map that shows the phase expansion by calendar period (Phase I: 2009–2011; Phase II: 2012–2013; Phase III: 2014–2015; Phase IV: 2016–2022).
The expansion was driven by “growing demand for service access”
The growing demand for managing MDR-TB patients in the country forced the Ministry of Health to come up with a mixed model, with inpatient care for treatment initiation and ambulatory care for treatment follow-up. This approach was found to improve case finding and enrollment and accelerate expansion of DR TB services at the regional level.
The quality of the established approach has been ensured through strong coordination, joint supportive supervision, clinical mentorship, and catchment area meetings. Other activities include involving TICs and TFCs in clinical case consultation in collaboration with specialists and subspecialists to manage difficult and complicated DR-TB cases.
Regimen transition process
From December 2009 to 2016, almost all newly diagnosed MDR/RR-TB patients received a standardized longer regimen with an intensive phase comprising pyrazinamide, capreomycin, levofloxacin, prothionamide (ethionamide), and cycloserine for 8 months (8 Z-Cm6-Lfx–Pto (Eto)–Cs) and a continuation phase for 12 months with all oral drugs but not the injectable capreomycin (12Z-Lfx–Pto (Eto)–Cs). Depending on the patient’s history of using the drugs and isolate susceptibility, patients were put on individualized regimens [12, 13].
In 2016, based on the WHO interim guidance document, patients were started on BDQ and delamanid (DLM) based individualized regimen if they were eligible [14, 15]. Since 2017, Ethiopia has implemented a standardized all-oral BDQ-based long treatment regimen. A shorter treatment regimen with injectables lasting 9 to 12 months was implemented as the standard regimen nationwide from April 2018 to February 2021 for newly enrolled MDR/RR-TB patients in addition to the longer regimen. The shorter regimen comprised four to six months of Km (Am)-Mfx-Pto(Eto)-Cfz-Z-Hhigh-dose-E and five months of Mfx-Cfz-Z-E. Another novel regimen—an all-oral BDQ shorter treatment regimen, which has oral BDQ in place of the injectable—was rolled out in Ethiopia in February 2021 (Fig 2).
10.1371/journal.pone.0306076.g002
Timeline of regimen transition, model of care (2009–2022) with number of patients enrolled and final treatment outcomes (2012–2022).
It shows DR TB treatment transition period: prior to 2016 was injectable based long treatment regimen; 2017 and beyond was regimens with newer drugs; 2018 beyond were short treatment introduction.
Enrollment of patients with TIC expansion and improved treatment success
DR-TB patient enrollment to second-line drugs increased with the expansion of the TICs. Each expansion phase was linked to flagship TB projects that facilitated changes in the models of care. For example, the shift to the ambulatory model of care, supported by the Help Ethiopia Address Low TB Performance (HEAL TB) project, contributed to an increase in patients’ enrollment. (Fig 2). In general, the DR TB case detection has been correlated with the scale up of the GeneXpert machine in the country (Pearson Correlation = 0.82, p-value = 0.002) (Fig 3).
10.1371/journal.pone.0306076.g003
DR TB Enrollment and GeneXpert scale up trend, 2009–2021 (WHO Global reports, 2010–2022).
It shows DR TB Enrollment and GeneXpert scale up trend from 2009–2021.
The national DR-TB treatment coverage rate steadily improved and reached 43% in 2022 (national annual report). The national patient retention to end of treatment with successful treatment outcome (>70%) is one of the highest among high DR-TB burden countries (Fig 2).
As of early 2020, Ethiopia is no longer a high DR-TB burden country. The annual national report of treatment outcomes is more than the average global reports of treatment success for both long and short treatment regimens. (Fig 4).
10.1371/journal.pone.0306076.g004
Treatment success rate trend of MDR/RR-TB cases disaggregated by regimen in Ethiopia<sup>#</sup> 2018−2021 (source: Annual national TB program report).
It shows treatment success rate trend of MDR/RR-TB cases disaggregated by regimen in Ethiopia# 2018−2021. # Outcomes for cohorts of people treated for MDR/RR-TB are reported two year later than the reporting year.
Challenges encountered during program implementation
Several challenges were encountered during the implementation of the project. Security issues in some regions of the country hampered access to services. Addressing the need for the pastoralist community is another challenge due to the nature of the community lifestyle.
“Some health centers were not providing AFB microscopic in pastoralist communities, because of their way of life, and limited access to health facilities”.—HEAL TB Project 2011–2016 final report
Among the strategies to address the pastoralist community was deploying a mobile van in the community. Although vans have been deployed, their utilization was not as expected. More time was needed to adapt to a new way of working.
The existing approach of using postal services as means of sample transportation to GeneXpert sites is not adequate or efficient, and the lack of a strong and sustainable specimen transportation system is a significant challenge; another is the lack of an established system for timely tracing and linking of missed TB/DR-TB cases. Ensuring data quality is an ongoing challenge for the country.
“The evidence shows that, the data collected by the HMIS requires further quality check on regular basis.”
TBL Annual Bulletin No 7, 2021, Ethiopia
Discussion
The review of Ethiopia’s DR-TB program showed significant improvement in treatment access between 2011 and 2021, as defined by the number of TICs expanding from just one at baseline to 67 by the end of the analysis. At the same time, the country successfully managed the transition process of multiple regimens that were optimally implemented throughout the country.
The model of care transition from mandatory hospital-based treatment of patients to an ambulatory model with limited admission of patients has had a significant impact on improving access to MDR/RR-TB treatment and care services for all patients on waiting lists in different regions of the country and clearing the backlog.
Experiences from other countries have also demonstrated the advantage of service decentralization. In South Africa, services were decentralized up to the community level, enabling site expansion from 17 to 658 sites and increasing the treatment success rate from 40% to 55% [16]. A systematic review showed that treatment success is more likely when treatment is provided through the decentralized model [17]. New global guidelines recommend the use of decentralized and ambulatory models of care for MDR-TB treatment, but the recommendations are based on limited available evidence [18]. Our report from real-life programmatic experience further supports the global recommendations.
The TSR of different patient cohorts observed in this review ranged from 68% to 78%, which is higher than the global average of 60% [2]. Although progress has been observed in this trend over time, it is less than the WHO target set for the end of 2020 of ≥87% TSR [4]. Therefore, this progressive but suboptimal achievement may need further strengthening of programmatic implementation, expedited roll out of WHO recommended shorter and effective treatment regimens, and adoption of new WHO recommended diagnostic tools in the country [19]. Different countries’ treatment outcomes showed significant improvement with implementation of shorter treatment regimens [20, 21]. Data from other countries also suggest good treatment outcomes when intensive adverse event monitoring and management are put in place [22–24].
Ethiopia’s ability to sustain a higher TSR while keeping up with multiple regimen transitions in an environment affected by multiple calamities is a lesson that other settings can learn from. Contributors to this success include strong technical and financial support from partners working on TB prevention and control, a strong NTP that facilitated the efficient use of available resources, rapid adoption of new recommendations and continuous capacity building of health care workers providing TB services [25]. The national technical working group and related technical subgroups worked to ensure that the services delivered were of the best quality possible. In line with WHO latest recommendation, the country updated its national guidelines in consultation with key stakeholders including the national clinical review committee and members of the national technical working group. The revised guidelines provide the latest guidance on patient management using the recommended regimens during different periods under programmatic conditions in Ethiopia.
Several programmatic actions contributed to effective, seamless transition to the new global recommendations. Some of these are decision made to fully adapt the new recommendations at different phases of the program scale-up; training of program managers and clinicians from TICs on the new policy changes; and stock analysis and supply planning.
Despite these successes, several challenges remain. Presumptive DR-TB patients are not routinely screened for DR-TB at all health facilities and are not referred from the community level. The use of DST for patients with extrapulmonary TB and childhood TB is suboptimal. The national treatment coverage rate is far below the national target. Treatment adherence support and tracking mechanisms for lost to follow-up patients are not well developed. Designing and evaluating interventions aimed at these challenges should be priorities for the next phase of the program. Specifically, supporting national data quality audit, and introduction of alternative private specimen transportation could address the data quality and access to X-pert testing, respectively.
The national TB program is also advocating for resource mobilization through developing Multisectoral Accountability Framework policy guide development to allow engagement of different sectors to finance TB services. Domestic resource mobilization is one area where partners and NTP are working together to allocate annual budget for the TB program.
An important limitation of this study is that we relied on secondary data review, and there were difficulties in getting complete information disaggregated by important variables like case detection by sex and treatment outcome by type of regimen. The types of documentation varied from year to year, leading to incompleteness of important variables.
In conclusion, this review showed an expansion and rapid decentralization of PMDT service with progressive improvement in DR-TB case detection, patient enrollment, TSR, and rapid uptake of new WHO recommended regimens. This is a result of strong local leadership combined with partner support. The remaining challenges should be addressed to further enhance the reach and quality of services. In addition, the NTP should consider an integrated DR-TB service with directly observed treatment and further decentralization of PMDT services to the community level.
Supporting information
Diagramatic representation of the Ethiopian health tier system.
Available at file:///C:/Users/ddare/AppData/Local/Temp/MicrosoftEdgeDownloads/b3197175-c020-40b1-b0e3-0910f2ba0499/WHO-HIS-HSR-17.31-eng.pdf.
(JPG)
Minimal data set.
(XLSX)
Our sincere and deepest gratitude goes to the USAID-supported Eliminate TB Project for its comprehensive and uninterrupted support of the TB program in Ethiopia.
We would like to thank all staff from the project and from federal and regional hospitals who were involved in the data collection and compilation.
ReferencesWorld Health Organization |Global tuberculosis report 2023. Geneva, Switzerland: World Health Organization, 2023. Available from: https://www.who.int/tb/publications/global_report/en/. 2022.World Health Organization |Global tuberculosis report 2022.Geneva, Switzerland: World Health Organization, 2022. Available from: https://www.who.int/tb/publications/global_report/en/. 2022.Muhammad DayyabF., et al., Emerging threat of drug-resistant tuberculosis and trends in the era of COVID-19: A descriptive study from northwestern Nigeria.J Clin Tuberc Other Mycobact Dis, 2022. 28: p. 100319. doi: 10.1016/j.jctube.2022.10031935599722Mpobela AgnarsonA., et al., The cost-effectiveness of a bedaquiline-containing short-course regimen for the treatment of multidrug-resistant tuberculosis in South Africa.Expert Rev Anti Infect Ther, 2020. 18(5): p. 475–483. doi: 10.1080/14787210.2020.174210932186925DhedaK., et al., Recent controversies about MDR and XDR-TB: Global implementation of the WHO shorter MDR-TB regimen and bedaquiline for all with MDR-TB?Respirology, 2018. 23(1): p. 36–45. doi: 10.1111/resp.1314328850767TackI., et al., Safety and Effectiveness of an All-Oral, Bedaquiline-Based, Shorter Treatment Regimen for Rifampicin-Resistant Tuberculosis in High Human Immunodeficiency Virus (HIV) Burden Rural South Africa: A Retrospective Cohort Analysis.Clin Infect Dis, 2021. 73(9): p. e3563–e3571. doi: 10.1093/cid/ciaa189433372989MollaY., et al., The experience of scaling up a decentralized, ambulatory model of care for management of multidrug-resistant tuberculosis in two regions of Ethiopia.J Clin Tuberc Other Mycobact Dis, 2017. 7: p. 28–33. doi: 10.1016/j.jctube.2017.03.00131723698Ministry of Health of Ethiopia. Guidelines for Clinical and Programmatic Management of TB, TB/HIV, DR-TB and Leprosy in Ethiopia, 7th edition, August 2021, Addis Ababa, Ethiopia; https://e-library.moh.gov.et/library/wpcontent/uploads/2022/05/. 2021.Organization, W.H., Global tuberculosis report 2017. World Health Organization. https://apps.who.int/iris/handle/10665/259366. License: CC BY-NC-SA 3.0 IGO. 2017.AgizewT.B., et al., Prospects for tuberculosis elimination in Ethiopia: feasibility, challenges, and opportunities.Pan Afr Med J, 2022. 43: p. 146. doi: 10.11604/pamj.2022.43.146.3555736785687MussieK., et al., Pragmatic Management of Drug-Resistant Tuberculosis: A Qualitative Analysis of Human Resource Constraints in a Resource-Limited Country context—Ethiopia.International Journal of Public Health, 2021. 66.Kebede BiruckA.B., BelayAnteneh, DagnawWubaye, KumsaAndargachew, YilmaAddisalem, et al. GUIDELINES ON PROGRAMMATIC MANAGEMENT OF DRUG RESISTANT TUBERCULOSIS IN ETHIOPIA; DECEMBER 2013.2014.FalzonD., et al., WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update.2011, Eur Respiratory Soc.WHO, Use of bedaquiline in the treatment of multidrug -resistant tuberculosis: World Health Organization; 2013. 2013.Organization, W.H., The use of delamanid in the treatment of multidrug-resistant tuberculosis in children and adolescents: interim policy guidance. 2016.CobelensF.G., et al., Scaling up programmatic management of drug-resistant tuberculosis: a prioritized research agenda. PLoS Med, 2008. 5(7): p. e150. doi: 10.1371/journal.pmed.005015018613746HoJ., et al., Decentralized care for multidrug-resistant tuberculosis: a systematic review and meta-analysis. Bull World Health Organ, 2017. 95(8): p. 584–593. doi: 10.2471/BLT.17.19337528804170OrganizationW.H., WHO consolidated guidelines on tuberculosis. Module 4: treatment-drug-resistant tuberculosis treatment, 2022 update.2022: World Health Organization.MatteelliA., et al., WHO strategies for the programmatic management of drug-resistant tuberculosis. Expert review of respiratory medicine, 2016. 10(9): p. 991–1002. doi: 10.1080/17476348.2016.119927827276361JouegoCG, GilsT, PiubelloA, MbassaV, KuateA, NgonoA, et al. Programmatic management of rifampicin-resistant tuberculosis with standard regimen in Cameroon: a retrospective cohort study.International Journal of Infectious Diseases. 2022Nov1;124:81–8. doi: 10.1016/j.ijid.2022.09.01236108960ToftAL, DahlVN, SifnaA, IgeOM, SchwoebelV, SouleymaneMB, et al. Treatment outcomes for multidrug-and rifampicin-resistant tuberculosis in Central and West Africa: a systematic review and meta-analysis.International Journal of Infectious Diseases. 2022Nov1;124:S107–16. doi: 10.1016/j.ijid.2022.08.01536007688ShinSS, PasechnikovAD, GelmanovaIY, PeremitinGG, StrelisAK, MishustinS, et al. Adverse reactions among patients being treated for MDR-TB in Tomsk, Russia.The International Journal of Tuberculosis and Lung Disease. 2007Dec1;11(12):1314–20. 18034952DelaA.I., et al., Adverse drug reactions and treatment outcome analysis of DOTS-plus therapy of MDR-TB patients at district tuberculosis centre: A four year retrospective study. Lung India, 2017. 34(6): p. 522–526. doi: 10.4103/0970-2113.21756929098997MassudA., et al., Frequency and Management of Adverse Drug Reactions Among Drug-Resistant Tuberculosis Patients: Analysis From a Prospective Study.Front Pharmacol, 2022. 13: p. 883483. doi: 10.3389/fphar.2022.88348335747749NdjekaN., et al., Implementing novel regimens for drug-resistant TB in South Africa: what can the world learn?The International Journal of Tuberculosis and Lung Disease, 2020. 24(10): p. 1073–1080. doi: 10.5588/ijtld.20.01743312694210.1371/journal.pone.0306076.r001Decision Letter 0DholakiaYatin N.Academic Editor2024Yatin N. DholakiaThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Submission Version0
10 Mar 2024
PONE-D-23-42213Drug-resistant tuberculosis care and treatment outcomes over the last 15 years in EthiopiaPLOS ONE
Dear Dr. Tesema,
Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.
Progress of the TB program in Ethiopia as discussed in this article provides a guide to programs in other countries. The guidance can be strengthened by discussing the results in light of the changing scenario over the period of assessment. Further analysis of data is warranted for this. Additionally, specific comments need to be individually addressed satisfactorily.
Please submit your revised manuscript by Apr 24 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.
Please include the following items when submitting your revised manuscript:
A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.
If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.
If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.
We look forward to receiving your revised manuscript.
Kind regards,
Yatin N. Dholakia, MD
Academic Editor
PLOS ONE
Journal Requirements:
1. When submitting your revision, we need you to address these additional requirements.
Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at
https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and
2. Thank you for stating the following in the Acknowledgments Section of your manuscript:
Our sincere and deepest gratitude goes to the USAID-supported Eliminate TB Project for its comprehensive and uninterrupted support of the TB program in Ethiopia, including funding support.
We would like to thank all staff from the project and from federal and regional hospitals who were involved in the data collection and compilation.
We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.
Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:
The author(s) received no specific funding for this work.
Please include your amended statements within your cover letter; we will change the online submission form on your behalf.
3. We note that your Data Availability Statement is currently as follows: All relevant data are within the manuscript and its Supporting Information files.
Please confirm at this time whether or not your submission contains all raw data required to replicate the results of your study. Authors must share the “minimal data set” for their submission. PLOS defines the minimal data set to consist of the data required to replicate all study findings reported in the article, as well as related metadata and methods (https://journals.plos.org/plosone/s/data-availability#loc-minimal-data-set-definition).
For example, authors should submit the following data:
- The values behind the means, standard deviations and other measures reported;
- The values used to build graphs;
- The points extracted from images for analysis.
Authors do not need to submit their entire data set if only a portion of the data was used in the reported study.
If your submission does not contain these data, please either upload them as Supporting Information files or deposit them to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of recommended repositories, please see https://journals.plos.org/plosone/s/recommended-repositories.
If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. If data are owned by a third party, please indicate how others may request data access.
4. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ
5. Please amend the manuscript submission data (via Edit Submission) to include authors Dr. G. Gizatie, T. Bogale and M. Million.
6. Please upload a new copy of Figures 1, 2, 3 and 4 as the detail is not clear. Please follow the link for more information: https://blogs.plos.org/plos/2019/06/looking-good-tips-for-creating-your-plos-figures-graphics/" https://blogs.plos.org/plos/2019/06/looking-good-tips-for-creating-your-plos-figures-graphics/
7. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.
Additional Editor Comments:
Progress of the TB program in Ethiopia as discussed in this article provides a guide to programs in other countries. The guidance can be strengthened by discussing the results in light of the changing scenario over the period of assessment. Further analysis of data is warranted for this.
[Note: HTML markup is below. Please do not edit.]
Reviewers' comments:
Reviewer's Responses to Questions
Comments to the Author
1. Is the manuscript technically sound, and do the data support the conclusions?
The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.
Reviewer #1: Partly
Reviewer #2: Partly
**********
2. Has the statistical analysis been performed appropriately and rigorously?
Reviewer #1: N/A
Reviewer #2: No
**********
3. Have the authors made all data underlying the findings in their manuscript fully available?
The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.
Reviewer #1: Yes
Reviewer #2: Yes
**********
4. Is the manuscript presented in an intelligible fashion and written in standard English?
PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.
Reviewer #1: Yes
Reviewer #2: Yes
**********
5. Review Comments to the Author
Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)
Reviewer #1: Thank you for the opportunity to review the manuscript Tesema et al. Drug-resistant tuberculosis care and treatment outcomes over the last 15 years in Ethiopia.
This paper is a timely contribution to an important topic. A couple of suggestions to strengthen the paper are noted below:
Overall
I think a very valuable piece of evidence but could be strengthened in a couple of key places to help readers who may be less familiar with the health service context of Ethiopia. Have made a couple of suggested.
Title
• Consider adding the study design to the title of the paper
Abstract
• Would benefit from more structure to the abstract. A couple of sentences on the background to the study would be beneficial.
• Could you say more about how many routine surveillance records was included in this analysis.
Main
• Does this study need permission from an ethics committee? My understanding is that the data are predominantly from published data sources or internal reports. None have been declared, though I commend the authors on seeking permission from one of the provincial health bureaus.
• Please clarify whether the routinely collected data used were patient-level data or aggregated summary data used for program management. Please clarify though which potential identifiers were removed to ensure anonymity – and who’s anonymity. Otherwise hard to assess.
• Pg3 ln 57 – please review this sentence as unclear
• Pg 3 ln 64 – suggest stating the burden of tuberculosis and DR-TB specifically in Ethiopia.
• Pg 4 ln 76 – would be good to know what the denominators are of these percentages.
• Were data used only from Oromia province. How generalisability are these findings to other provinces in Ethiopia?
• Pg 7, ln 131 – what does DRS stand for?
• Would suggest a paragraph summarising the context of DR TB care in Ethiopia, before launcing into the details. As currently names of hospitals are mentioned but may not be clear to the reader how they fit into wider service delivery
• Need more information on the statistical analysis done to produce estimates reported on page 10, ln 207.
• Can you explain a bit more why linked to the introduction of XPert MTB/RIF?
• Would be interesting to see data from Oromia versus other regions of Ethiopia – how are they different or similar?
• Pg 12, ln 235 – why were the utilisation of vans not as expected?
• Pg 12, ln 243 – what is HMIS
• These challenges mentioned focused on pastoralists/ people living in more rural regions – were there any important challenges to mention for the urban areas?
• Pg 13, ln 250 How was treatment access defined and assessed? Could improve this by saying … treatment access defined as XXX and assessed through our analysis of YYY data
• Pg 13 ln 251 – 1 what to 67 what?
• Pg 13 ln 261 – how was treatment success defined here?
• Pg 13, ln 267 what is TSR? Try to explain appreviations in each section of the paper before use and if used only once, rather spell it out
• Think that you could strengthen the paper by adding a paragraph describing Ethiopia’s economic situation ex. GDP per capita, proportion of budget spent on health and proportion of health spending from donor funding. Then discuss key health indicators – first overall then tuberculosis specific. Would then follow this with a descriptive paragraph on how the health system is generally organised and then how tuberculosis care and dr-TB care more generally fits into the health service.
Reviewer #2: The authors deserve appreciation for the commendable work in providing a snapshot of progress of TB programme in Ethiopia, specifically with DR-TB services. High treatment success rate among DR-TB patients would be exemplary for several other countries. However, it would be important to make the article more compact and focused by further analysis of the available data. Overall some major changes are required.
1. As of now the challenges and successes of the programme appear to be based on the assumptions of the authors and not coming out of analysis of the available data. While Table 1 presents the timelines of transition and, corresponding enrollment and treatment success rates, it does not demonstrate any link between them.
2. Other issues with Table 1 are - a) It is not easy to make out the annual enrollment while TSR is provided on annual basis, and b) It is not possible to figure out whether TSR is for the year or earlier cohort. This is specifically important to understand any changes to TSR with introduction of a different regimen.
3. It is also known that new tools, technologies and regimen have a gradual, phased introduction. This aspect is not clearly reflected in the manuscript -specifically proportion of population having access to these new developments.
4. As per the introduction, the aim of the manuscript is "assess Ethiopia’s experience in scaling up an ambulatory, decentralized model of care with a good treatment success rate (TSR) while managing multiple regimen transition processes and external shocks." However, the results do not come out very well answering this question, except some generic statements.
5. There are some challenges mentioned under "Challenges encountered during program implementation". However there is no further discussions on how these were specifically addressed or need to be addressed, such as low utilization of mobile vans, postal services, data quality.
6. Similar to #5 above, under the section "Data entry and analysis, one of the themes is "Resource limitation and lack of locally evidenced solutions". There is not much discussion on this aspect later in the manuscript.
7. Overall, it will also be good to include some specific leadership decisions, effective policy implementation process and planning methodology that led to success of the programme.
8. Minor comment - There is a lot of global information provided at the beginning that may not be relevant to the these of the manuscript. You could consider shortening it
**********
6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.
If you choose “no”, your identity will remain anonymous but your review may still be made public.
Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.
Reviewer #1: No
Reviewer #2: Yes: Vineet Bhatia
**********
[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]
While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.
10.1371/journal.pone.0306076.r002Author response to Decision Letter 0Submission Version1
14 May 2024
24 April 2024
Subject: Point-by-point response to reviewers’ feedback
Dear Editor,
We would like to thank you and the reviewers for the constructive feedback on our manuscript. We addressed the comments point-by-point and made changes to the manuscript. We uploaded both the marked up and clear versions of the manuscript for your review. Our point-by-point responses are in bold to enable easy differentiation them from the reviewer comments. We have also amended the funding related information.
Looking forward to your favourable review,
Yours sincerely,
E.Tesema, primary author
PONE-D-23-42213
Drug-resistant tuberculosis care and treatment outcomes over the last 15 years in Ethiopia
PLOS ONE
Dear Dr. Tesema,
Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.
Progress of the TB program in Ethiopia as discussed in this article provides a guide to programs in other countries. The guidance can be strengthened by discussing the results in light of the changing scenario over the period of assessment. Further analysis of data is warranted for this. Additionally, specific comments need to be individually addressed satisfactorily.
Response: Thank you for the compliment
Please include the following items when submitting your revised manuscript:
• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.
If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.
Thank you for stating the following in the Acknowledgments Section of your manuscript:
Our sincere and deepest gratitude goes to the USAID-supported Eliminate TB Project for its comprehensive and uninterrupted support of the TB program in Ethiopia, including funding support.
We would like to thank all staff from the project and from federal and regional hospitals who were involved in the data collection and compilation.
We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.
Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:
The author(s) received no specific funding for this work.
Please include your amended statements within your cover letter; we will change the online submission form on your behalf.
Response: This is well noted. We have removed the funding related information.
Amended Statement
The Global Health Bureau, Office of Health, Infectious Disease, USAID financially supported the study through USAID Eliminate TB Project under the terms of Agreement No. 72066320CA00009. The authors’ views expressed in this publication do not necessarily reflect the views of USAID or the US Government.
We note that your Data Availability Statement is currently as follows: All relevant data are within the manuscript and its Supporting Information files.
Please confirm at this time whether or not your submission contains all raw data required to replicate the results of your study. Authors must share the “minimal data set” for their submission. PLOS defines the minimal data set to consist of the data required to replicate all study findings reported in the article, as well as related metadata and methods (https://journals.plos.org/plosone/s/data-availability#loc-minimal-data-set-definition).
For example, authors should submit the following data:
- The values behind the means, standard deviations and other measures reported;
- The values used to build graphs;
- The points extracted from images for analysis.
Authors do not need to submit their entire data set if only a portion of the data was used in the reported study.
If your submission does not contain these data, please either upload them as Supporting Information files or deposit them to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of recommended repositories, please see https://journals.plos.org/plosone/s/recommended-repositories.
If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. If data are owned by a third party, please indicate how others may request data access.
Response: We uploaded the minimal data set as supporting information.
PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ
Response: ORCID IDs are updated
Please amend the manuscript submission data (via Edit Submission) to include authors Dr. G. Gizatie, T. Bogale and M. Million.
Response: Manuscript submission data amended and missing authors are included.
Please upload a new copy of Figures 1, 2, 3 and 4 as the detail is not clear. Please follow the link for more information: https://blogs.plos.org/plos/2019/06/looking-good-tips-for-creating-your-plos-figures-graphics/" https://blogs.plos.org/plos/2019/06/looking-good-tips-for-creating-your-plos-figures-graphics/
Response: Clearer copies of figures are uploaded and figure 1 is modified to incorporate the information from Table 1.
Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.
Response: Captions for Supporting Information added at the end of the manuscript
Additional Editor Comments:
Progress of the TB program in Ethiopia as discussed in this article provides a guide to programs in other countries. The guidance can be strengthened by discussing the results in light of the changing scenario over the period of assessment. Further analysis of data is warranted for this.
Response: This is well noted, and we updated the data analysis for the current scenario
Responses to reviewer 1:
Reviewer #1: Thank you for the opportunity to review the manuscript Tesema et al. Drug-resistant tuberculosis care and treatment outcomes over the last 15 years in Ethiopia.
This paper is a timely contribution to an important topic. A couple of suggestions to strengthen the paper are noted below:
Overall
I think a very valuable piece of evidence but could be strengthened in a couple of key places to help readers who may be less familiar with the health service context of Ethiopia. Have made a couple of suggested.
Response: We appreciate the compliments
Title
• Consider adding the study design to the title of the paper
Response: added as suggested
Abstract
• Would benefit from more structure to the abstract. A couple of sentences on the background to the study would be beneficial.
• Could you say more about how many routine surveillance records was included in this analysis.
Response: Comment noted and abstract amended
Main
• Does this study need permission from an ethics committee? My understanding is that the data are predominantly from published data sources or internal reports. None have been declared, though I commend the authors on seeking permission from one of the provincial health bureaus.
• Please clarify whether the routinely collected data used were patient-level data or aggregated summary data used for program management. Please clarify though which potential identifiers were removed to ensure anonymity – and who’s anonymity. Otherwise hard to assess.
Response: We used aggregated summary data used for program management. No patient-level data was collected, nor did we do any interviews with individuals. In principle, no ethics review is needed for this kind of data. However, we wanted to emphasize that the project under which this study was conducted had secured blanket ethical coverage for any potential inclusion of individual-level data based on a generic protocol.
• Pg3 ln 57 – please review this sentence as unclear
Response: Sentence amended
• Pg 3 ln 64 – suggest stating the burden of tuberculosis and DR-TB specifically in Ethiopia.
Response: Ethiopia specific burden added, and the background section substantially updated.
• Pg 4 ln 76 – would be good to know what the denominators are of these percentages.
• Were data used only from Oromia province. How generalisability are these findings to other provinces in Ethiopia?
Response: We provided further details about the denominators and numerators in the results section. Data is for the whole country. Oromia and Amhara are mentioned because this is where we had specific ethical approval for individual-level data analysis which we explained above.
• Pg 7, ln 131 – what does DRS stand for?
Response: DRS stands for Drug Resistance Survey—its full form was available in the background section.
• Would suggest a paragraph summarizing the context of DR TB care in Ethiopia, before launching into the details. As currently names of hospitals are mentioned but may not be clear to the reader how they fit into wider service delivery
Response: This comment is well noted and we added a paragraph under the setting: Ethiopia is a low-income country. The country’s population, which is predominantly rural, is estimated to exceed 123 million and the average life expectancy is 65 years. Table 1 summarizes key socio-demographic and health indicators for Ethiopia. The country has a three-tiered pyramidal health system care system with primary health care facilities forming the broad base, secondary health care facilities in the middle, and tertiary care at the apex (See Figure as supplemental information). Ethiopia follows a decentralized service delivery model as much as possible with the bulk of the service provided at primary care level. For DR-TB care, the country followed the healthcare tier system in setting up the services. Treatment Initiating Centers (TICs), where patients initiate their treatment and temporarily admitted if needed were initially set up at tertiary level but later much of the TIC role moved to secondary level. Treatment follow-up centers (TFCs) are facilities where patients receive their daily treatment after they are transferred from the TICs. Each TIC has a designated number of TFC within their catchment areas, defined by administrative regions and zones. Detailed description of the roles and responsibilities of TICs and TFCs is provided in reference 7.
• Need more information on the statistical analysis done to produce estimates reported on page 10, ln 207.
Response: We thank the reviewer for this observation. After through discussion among authors, we decided to remove the correlation analysis because of potentials for huge compounding.
• Can you explain a bit more why linked to the introduction of XPert MTB/RIF?
Response: The introduction of Xpert MTB/RIF was linked to more Rifampicin resistant cases. Prior to the Xpert introduction, DR-TB diagnosis was done through culture and DST, which takes 6-8 weeks, when available.
• Would be interesting to see data from Oromia versus other regions of Ethiopia – how are they different or similar?
Response: Our goal was to show trends in national data. We do not expect any unique trends in Oromia. Oromia was mentioned in connection with the ethics review and approval as explained earlier.
• Pg 12, ln 235 – why were the utilisation of vans not as expected?
Response: This appeared to be linked to lack of experience with the use of vans. We added a sentence about this.
• Pg 12, ln 243 – what is HMIS
Response: HMIS stands for Health Management Information System. This was explained under Data collection and procedures.
• These challenges mentioned focused on pastoralists/ people living in more rural regions – were there any important challenges to mention for the urban areas?
Response: We did not identify challenges worth reporting.
• Pg 13, ln 250 How was treatment access defined and assessed? Could improve this by saying … treatment access defined as XXX and assessed through our analysis of YYY data
Response: This was defined by the number of TICs which increased nearly 70-fold. The text is slightly amended.
• Pg 13 ln 251 – 1 what to 67 what?
Response: TICs, this is in the sentence itself, but we made minor modifications to make it clearer.
• Pg 13 ln 261 – how was treatment success defined here?
Response: Treatment success is defined according to the national/global guidelines, i.e, treatment completed plus cured divided by total cohort evaluated.
• Pg 13, ln 267 what is TSR? Try to explain appreviations in each section of the paper before use and if used only once, rather spell it out
Response: TSR stands for treatment success rate. All abbreviations were spelled out in the preceding sections.
• Think that you could strengthen the paper by adding a paragraph describing Ethiopia’s economic situation ex. GDP per capita, proportion of budget spent on health and proportion of health spending from donor funding. Then discuss key health indicators – first overall then tuberculosis specific. Would then follow this with a descriptive paragraph on how the health system is generally organised and then how tuberculosis care and dr-TB care more generally fits into the health service.
Response: This comment is well noted and we made substantial improvement to the flow of the background information as well as description of the study setting. A new table summarizing the socio-economic and health indicators is added and we included supplemental figure describing the Ethiopian healthcare system.
Reviewer #2: The authors deserve appreciation for the commendable work in providing a snapshot of progress of TB programme in Ethiopia, specifically with DR-TB services. High treatment success rate among DR-TB patients would be exemplary for several other countries. However, it would be important to make the article more compact and focused by further analysis of the available data. Overall some major changes are required.
Response: We appreciate the reviewer’s constructive feedback and made changes as suggested.
1. As of now the challenges and successes of the programme appear to be based on the assumptions of the authors and not coming out of analysis of the available data. While Table 1 presents the timelines of transition and, corresponding enrollment and treatment success rates, it does not demonstrate any link between them.
Response: The challenges and successes are based on qualitative dat
Submitted filename: Response to Reviewers.docx
10.1371/journal.pone.0306076.r003Decision Letter 1DholakiaYatin N.Academic Editor2024Yatin N. DholakiaThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Submission Version1
11 Jun 2024
Drug-resistant tuberculosis care and treatment outcomes over the last 15 years in Ethiopia: results from a mixed-method review of trends
PONE-D-23-42213R1
Dear Dr. Emawayish Tesema
We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.
Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.
An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org.
If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.
Kind regards,
Yatin N. Dholakia, MD
Academic Editor
PLOS ONE
Additional Editor Comments (optional):
Progress of the TB program in Ethiopia as discussed in this article provides a guide to programs in other countries.
Reviewers' comments:
Reviewer's Responses to Questions
Comments to the Author
1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.
Reviewer #2: All comments have been addressed
**********
2. Is the manuscript technically sound, and do the data support the conclusions?
The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.
Reviewer #2: Yes
**********
3. Has the statistical analysis been performed appropriately and rigorously?
Reviewer #2: Yes
**********
4. Have the authors made all data underlying the findings in their manuscript fully available?
The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.
Reviewer #2: Yes
**********
5. Is the manuscript presented in an intelligible fashion and written in standard English?
PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.
Reviewer #2: Yes
**********
6. Review Comments to the Author
Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)
Reviewer #2: (No Response)
**********
7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.
If you choose “no”, your identity will remain anonymous but your review may still be made public.
Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.
Reviewer #2: Yes: Vineet Bhatia
**********
10.1371/journal.pone.0306076.r004Acceptance letterDholakiaYatin N.Academic Editor2024Yatin N. DholakiaThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
27 Jun 2024
PONE-D-23-42213R1
PLOS ONE
Dear Dr. Tesema,
I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team.
At this stage, our production department will prepare your paper for publication. This includes ensuring the following:
* All references, tables, and figures are properly cited
* All relevant supporting information is included in the manuscript submission,
* There are no issues that prevent the paper from being properly typeset
If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps.
Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.
If we can help with anything else, please email us at customercare@plos.org.
Thank you for submitting your work to PLOS ONE and supporting open access.