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Abstract
Background One of the major reasons for unsuccessful treatment outcomes among patients with drug-resistant tuberculosis (DR-TB) is the high rate of loss to follow-up (LTFU). However, in Pakistan, no qualitative study has been conducted to explore the perceptions of LTFU patients with regard to DR-TB treatment, the problems they face and the reasons for LTFU in detail.
Methods This was a qualitative study that involved semistructured, indepth, face-to-face interviews of 39 LTFU patients with DR-TB. All interviews were carried out in Pakistan’s national language ‘Urdu’ using an interview guide in two phases: the first phase was from December 2020 to February 2021 among patients with extensively drug-resistant tuberculosis and the second phase from July 2021 to September 2021 among patients with multidrug-resistant tuberculosis.
Results The inductive thematic analysis of audio-recorded interviews generated the following four key themes, which were the major reasons reported by the participants of the current study to have led to LTFU: (1) patient-related factors, such as lack of awareness about the total duration of DR-TB treatment, fatigue from previous multiple failed episodes, lack of belief in treatment efficacy and perception of DR-TB as a non-curable disease; (2) medication-related factors, such as use of injectables, high pill burden, longer duration and adverse events; (3) socioeconomic factors, such as gender discrimination, poor socioeconomic conditions, non-supportive family members, social isolation and unemployment; and (4) service provider-related factors, such as distant treatment centres, non-availability of a qualified person, lack of adequate counselling and poor attitude of healthcare professionals.
Conclusion In the current study, patients’ perceptions about DR-TB treatment, socioeconomic condition, medication and service provider-related factors emerged as barriers to the successful completion of DR-TB treatment. Increasing patients’ awareness about the duration of DR-TB treatment, interacting sessions with successfully treated patients, availability of rapid drug susceptibility testing facilities at treatment centres, decentralising treatment and using the recently recommended all-oral regimen may further decrease the rate of LTFU.
- Tuberculosis
- Infection Control
- Patient Outcome Assessment
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
There are very few published qualitative studies about loss to follow-up (LTFU) among patients with drug-resistant tuberculosis (DR-TB) from all over the world.
WHAT THIS STUDY ADDS
The current study is the first to evaluate the reasons for LTFU among patients with DR-TB in Pakistan and also determined the factors associated with LTFU.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
Applying the findings of this study could help minimise the LTFU of patients undergoing treatment for DR-TB, thereby reducing its prevalence, improving treatment outcomes and minimising the burden on the healthcare system.
Introduction
Drug-resistant tuberculosis (DR-TB) is a form of tuberculosis (TB) that is difficult to treat and is a threat to the successful control and elimination of TB globally. Patients suffering from DR-TB are treated for a prolonged period of time (≥20 months) with a complex, less effective and more toxic regimen of second-line anti-TB drugs of lower or unproven efficacy.1–4 This consequently results in lower rates of treatment success in these patients. The global rates of unsuccessful treatment outcomes among patients with multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB are, respectively, 31% (from a 2018 cohort5) and 61% (from a 2016 cohort6). One of the major reasons for unsuccessful treatment outcomes among patients with DR-TB is the high rate of loss to follow-up (LTFU), which is defined as ‘interruption of TB treatment for at-least two consecutive months for any reason other than medically approved one’.7 In the published literature, the rate of LTFU in patients with MDR-TB and XDR-TB, respectively, ranges from 1.1% to 21%2 4 8–12 and from 5.5% to 37.7%.13–18 As primary transmission is becoming a major route of DR-TB transmission,3 19 20 LTFU of patients with DR-TB, especially prior to sputum culture conversion, is an alarming issue and is a threat to public health.4 In previously published studies, distance from treatment centres, rural residence, patient age, male gender, suffering from extrapulmonary TB, HIV-positive status, number of resistant drugs, lack of sputum culture conversion during the intensive phase of treatment, negative attitude towards treatment, limited social support, dissatisfaction with health services, poor socioeconomic status and occurrence of serious adverse events have been reported as independent risk factors for LTFU in patients with DR-TB.8 9 21–24
Unfortunately, Pakistan harbours a large number of patients with DR-TB. In terms of MDR-TB burden, Pakistan currently ranks fifth globally and first in WHO’s Eastern Mediterranean Region. In Pakistan, the programmatic management of DR-TB (PMDT) was started in 2010, and currently there are 33 functional PMDT units throughout the country. In Pakistan, various quantitative studies have evaluated the management, treatment outcomes, occurrence of adverse events and factors associated with unsuccessful treatment outcomes among patients with DR-TB.2–4 8–10 25–30 These studies have reported the LTFU rate among patients with DR-TB to range from 1.1% to 18.3%2–4 8–10 and identified patient age (>60 years), male gender and rural residence as risk factors for LTFU.3 8 9 However, in Pakistan, no qualitative study has been conducted to explore the perceptions of LTFU patients regarding DR-TB treatment, the problems they face and the reasons for LTFU in detail. Therefore, the current qualitative study was conducted with the aim to explore the perceptions of LTFU patients regarding DR-TB treatment, the problems they face and the reasons for LTFU in detail.
Materials and methods
Study design
This was a qualitative study that involved indepth interviews of LTFU patients with DR-TB.
Study setting and sampling criteria
From 1 May 2010 to 30 June 2019, a total of 559 patients with XDR-TB were registered in 30 PMDT centres all around Pakistan. Among them, 40 patients were declared LTFU. The principal investigator (PI) obtained their contact numbers from the Electronic Nominal Recording Reporting System shared with the National TB Control Program. The PI was able to contact 22 out of these 40 patients with XDR-TB, of whom 14 were judged eligible (at least 18 years old and able to communicate in Urdu, the national language of Pakistan) and were included in the study through convenient sampling technique. To increase the number of study subjects, 49 out of 75 patients with MDR-TB who were lost to follow-up from eight different PMDT units in Pakistan after 2016 were also contacted. Among them, 35 patients were judged eligible for inclusion in the study, but only 25 were included. Interviewing further participants was stopped on the basis of achieving saturation point.
Patient and public involvement
Patients or the public were not involved in the design, or conduct, or reporting or dissemination plans of our research.
Data collection
Interviews were carried out in two phases. In the first phase, 14 patients with XDR-TB were interviewed from December 2020 to February 2021. In the second phase, 25 patients with MDR-TB were interviewed from 25 August 2021 to 10 October 2021 to enhance the number of patients and strengthen perceptions about LTFU from DR-TB treatment. Semistructured, indepth, face-to-face interviews were carried out using an interview guide (online supplemental file 1) prepared based on previous published literature and including all possible factors responsible for patients’ LTFU from DR-TB treatment.9 21–24 31 32 Patients’ interviews were carried out at their homes. All interviews were carried out by the PI himself who was trained in qualitative research and is a PhD scholar. After explaining the nature of the study, oral consent was taken from the participants before the start of the interview. In order to maintain consistency in the interview, open-ended questions based on an interview guide were asked by the PI. Sufficient time was given to the respondents to present their opinions freely. All interviews were carried out in Pakistan’s national language ‘Urdu’ and were audio-recorded unless refused by the participants. All methods used in the current study were in compliance with institutional guidelines and according to the Consolidated criteria for Reporting Qualitative research checklist30 for qualitative study.
Supplemental material
Data analysis
All audio-recorded interviews were analysed using inductive thematic analysis.33 These recordings were listened to several times and were transcribed verbatim to English language. Forward–backward translation method was applied to check for data accuracy. Translations were read and reread many times to get familiarised with the data. Coding was done manually by the PI and the team. Relevant information was labelled, and initial inductive codes were generated. These initial codes were followed to produce focused codes. In focused coding, the relationship between initial coding was explored on the basis of difference, similarity, sequence, frequency, causation and correspondence. Finally, inductive codes were merged by the PI and the team to generate significant categories. By bringing several categories together, subthemes and themes were generated and data were conceptualised. Transcriptions were recursively reviewed, coded and categorised before generating the final themes. Tabulation and quantification (numbering the frequency of each code) were also used to enhance the consistency of findings. Each answer was quantified one per respondent, and greater number of similar statements was considered significant. Ladder of the findings (online supplemental file 2) was done in a descending order based on the calculated frequency to generate the final report.
Supplemental material
Results
Of the 39 patients with DR-TB (14 XDR-TB and 25 MDR-TB) selected for interviews, 21 were male. The mean age of the participants was 35.92±11.17. The average duration of interviews was 27 min (range=19–40 min).
Factors responsible for LTFU
Participants’ indepth interviews identified their perceptions about DR-TB treatment and the various factors that could have contributed to LTFU. The key themes identified during the interviews are presented in table 1, and verbatim quotes from the respondents are described in the following sections.
Factors responsible for patients being lost to follow-up (N=39)
Patient-related factors
Participants were of mixed opinion with regard to treatment continuation and completion. Some of them doubted its efficacy and other considered relief in symptoms as cure. One of the respondents said:
Right after its diagnosis, I was enrolled for the treatment of dangerous form of TB (referring to XDR-TB)… I regularly used pills and injections for four months and did not miss a single pill…. My chest pain and severe cough were subsided and I started to eat food…. Doctor told me that my sputum is now good (referring to sputum culture conversion)… everyone told me that you are getting better and have put on some weight… took the treatment for two more months…. As I was feeling better I decided myself to stop the treatment…. When the treatment has produced better results in six months what is the need to continue it for years?… (P11)
Another patient said:
I was initially taking TB treatment at hospital in my hometown. After four months of treatment the doctor asked my husband to take me to Multan (city)…. Doctors in Multan told me that you are suffering from bad type of TB (referring to MDR-TB) and started treatment… they initially asked me to take injections for a minimum of eight months… but they even did not stop it after 10 months and my condition was not improving…. I thought this treatment is of no use and decided not to continue it further.… (P32)
Patients who took TB treatment in the past were more prone to LTFU, especially in case of XDR-TB treatment (12 patients with XDR-TB had a positive history of treatment for drug-susceptible TB and MDR-TB). Two of the patients expressed their feelings about treatment as follows:
I took my treatment for more than 11 months regularly… but not felt well… why they asked me to continue my treatment up to 24 months (XDR-TB patient)… I am already fed up with the previous TB treatment of more than 20 months (TB and MDR-TB treatment) taken before…. (P06)
It looked like they were asking me to take TB treatment for the rest of my life (XDR-TB patient)…. (P10)
Patients had perceptions and myths about the disease due to lack of awareness about the disease and its treatment. They thought that the disease is not curable with never-ending treatment and will ultimately lead to death. Some of the patients said:
My friend suffered from this disease…. he took regular treatment for 18 months… but… unfortunately… he died…. this disease cannot be cured and its treatment is not effective enough to treat patients and save their life…. (P14)
I had no relief from TB treatment. Even after taking a lot of pills and injections, I was not cured, why should I continue my treatment? It is better to die at home rather than to take these medicines…. (P29)
I took my allopathic treatment for more than 14 months, but not cured… then I stopped it… and go to the Hakeem [sb]… and started treatment there, now I feel better…. (P17)
Medication-related factors
The respondents complained about the duration of treatment (20–60 months), substantial pill burden (15–20 pills per day up to 24 pills) and use of injectables (8–16 months).
After initiating treatment, the pills burden is gradually increased up to 18 pills per day and doctors asked me to use them for two years or maybe more… tell me how one could use 18 pills for such prolonged period of time… it was impossible for me to take such treatment…. (P6)
Oh God, the use of those injections (referring to Second line injectables) was the worst experience of my life, the injections were painful than the disease itself…. No place was spared in my arms and buttock muscles where injections were not administered…. I could not sit properly those days, my mother was used to rub ice on injection site all the night, still I could not sleep properly because of pain…. (P13)
Due to severe pain, I did not want more injections in my treatment…. (P15)
When I used injections… most of the time, immediate inflammation were occurred and I also felt pain in my arms and legs…. (P9)
I took my treatment for more than 16 months…. but hospital staff asked me to continue further for 18 months more, I was tired and did not want to continue my treatment further…. (P5)
Nineteen patients reported adverse events as a major barrier to treatment completion. The most common adverse events were severe body and joint pain, inflammation and redness at the injection site, hearing problems, bitter taste, skin darkening, nausea, vomiting, loss of appetite, sleep disturbance, suicidal thoughts, etc.
After using medicines I was neither able to sleep nor able to move out, I usually had severe body ache seven days a week and thirty days a month thus I discontinued my treatment…. (P38)
When I started my medications… I felt restlessness, vertigo and severe joint pain… I think it was due to my medicines…. I stopped three of them… and felt better… remaining medicines continued but after some time… rashes appeared on my face… then I stopped all my medicines and left the treatment…. (P10)
After getting treatment of this bad form of TB (referring to MDR-TB) for six months or so… I initially started losing interest in daily activities, family and friends… and gradually suicidal thoughts were coming to my mind…. You know once I tried to take my life…. My father took me to a mental doctor (referring to psychiatrist) and he told that it is because of this TB treatment…. I stopped the treatment and felt better…. (P2)
Those medicines were the most bitter medicines I had ever taken in my life…. Every time just after taking the medicine, I felt like my stomach is set on fire…. (P24)
Strong smelled medicines were given to me (ethionamide)… every time I used it I had vomited it out…. (P3)
My chest pain and cough have been improved after treatment initiation…. But After nine months of regular treatment dark spots appeared on my face…. Every time I looked into the mirror I felt ugly…. Initially I stopped looking into the mirror and then stopped taking treatment…. (P39)
After the use of injections, I had noise in my ears, every time I tried to sleep in the night bells were ringing in my ears,…. my listening ability was decreased significantly… stopped the treatment and got my hearing back…. (P35)
Socioeconomic factors
In Pakistan, due to deeply rooted gender discrimination, female patients face enormous problems with regard to seeking healthcare. They are usually not allowed to decide about their health and to go to hospitals without a male member of the family, and this lack of support from a male family member results in discontinuation of TB treatment. One of the female respondents suffering with XDR-TB said:
When I started my treatment, my husband was in Pakistan, he traveled with me for 9 months regularly for my treatment, but after he went to Dubai for earning bread, and was no one my in-laws to accompany me for monthly visiting to treatment center which is at least six hours at a distance of six hours traveling…. (P32)
Patients who do not have joint family system and strong social networking were more prone to LTFU. The most common reasons reported by seven patients were families’ behaviours, unemployment and economic constraints (only men to earn for the whole family).
Some respondents said:
One day, the whole family members have invited in the marriage ceremony of my nephew (my brother son)… but my own brother didn’t allow me to attend the marriage because of my illness…. (P14)
I was not able to move in my circle and communicate freely with my colleagues and family members…. I do not need such treatment that restrict my social mobility…. (P16)
Since… I suffered with this disease… a lot of things… I have missed… like family functions and friends gathering… and even I lost my job because of my illness…. (P19)
In the current study, most of the patients belonged to the economically productive age group. They started the treatment, but after feeling better they left the treatment in order to earn bread and support their families. Six patients in the current study were the sole bread earners for their families. One of them said:
I am the only one to take care of my family, when I started my treatment, I felt better after six…. During this time period, there was no one financially support us, that’s why I quit my treatment to earn bread for my family members…. (P18)
Service provider-related factors
The study participants complained about distant treatment centres, conflict with working hours, healthcare provider behaviours and transportation problems. Four of the participants mentioned about a qualified person not being available in their area to administer the injection on a daily basis for such a prolonged period of time (8–12 months). Two of them said:
I am old age, I wanted to continue my treatment… but no one was available at my home to travel with me for such long distanced treatment site…. (P14)
I have faced a lot of problems with my treatment… when I took my medicines from treatment center and back to my far-flung village, there was no one available in the whole village to administer me injection daily. After going to nearby town on feet which is at a distance of 60 minutes’ walk for five months, I got tired and stopped treatment…. (P08)
The main themes and subthemes of the current qualitative study are presented in table 1.
Discussion
In the current study, the indepth interviews evaluated the participants’ perceptions about DR-TB treatment and the various factors that could have contributed to LTFU. Four key themes were identified: (1) patient-related factors, (2) medication-related factors, (3) socioeconomic factors and (4) service provider-related factors.
Patients’ misconceptions about symptom remission as cure during the initial months of DR-TB treatment, lack of awareness about the total duration of DR-TB treatment, fatigue from previous multiple failed episodes, lack of belief in treatment efficacy and perceptions about DR-TB as a non-curable disease were some of the patient-related factors responsible for LTFU. Similar findings have been reported by studies carried out elsewhere.23 31 34–37 After being put on drug susceptibility testing (DST)-based effective anti-TB regimen, patients with DR-TB usually get substantial symptom remission during the early course of treatment, leading to misperceptions about treatment success and therefore discontinuing the treatment. Furthermore, patients’ lack of awareness about the total duration of treatment, confusing and comparing it with the treatment duration in drug-susceptible TB, is another potential cause of LTFU. As providing correct information about the disease and drugs is as important as providing correct therapy,38 39 it is necessary to counsel and make patients and their treatment supporters aware about the duration of DR-TB treatment. This could be achieved by arranging intermittent awareness programmes at PMDT units. Furthermore, the lack of belief regarding treatment efficacy could be countered by patient counselling and arranging interacting sessions with those who have been successfully treated.34 Another important factor referred to as reason for premature discontinuation of treatment was fatigue from previously failed TB treatment episodes and prolonged duration of DR-TB treatment.23 33–35 Majority of these patients have been previously treated with Category-I anti-TB regimen and upon treatment failure were then put on Cat-II regimen rather than testing them for drug susceptibility and initiating treatment for DR-TB. This consequently had resulted in a substantial delay in diagnosing DR-TB and putting them on optimal regimen, prolonged treatment and disbelief in achieving successful TB treatment outcome. If rapid DST facility is made available at TB treatment centres all over the country and Cat-I failures are tested for drug resistance rather than empirically putting the patients on ineffective Category-II regimen, delay in initiating optimal DR-TB treatment regimen could be avoided and fatigue and patient distrust on achieving successful TB outcomes could be reduced.35
Deeply rooted gender discrimination, poor socioeconomic conditions, non-supportive family members particularly in-laws, stigma, social isolation and unemployment were some of the socioeconomic factors that led to LTFU among the participants of the current study. Similar causes of LTFU have been previously reported by studies conducted elsewhere.23 34 38 40–43 Majority of the male participants of the current study belonged to economically productive age group and were bread earners for their families. After starting treatment and feeling better, they left the treatment prematurely to earn bread and support their families. In previous studies, patients’ economic stability had been reported as an important factor for treatment adherence and completion.23 34 38 40 43 44 In poor communities, due to social taboos, female patients face enormous problems with regard to seeking healthcare. They are usually not allowed to decide about their health and to visit hospitals without a male member of the family. The lack of male support to take female patients to PMDT sites and non-supportive in-laws were cited as reasons for LTFU.41 42
In the current study, lengthy treatment, high pill burden, use of injectables and adverse events were the frequently reported medication-related barriers to completing DR-TB treatment. Use of injectables was cited as the most difficult part of treatment and caused physical and emotional distress in the study participants. Seventeen of the interviewed patients said that they had requested the doctors to stop injectables. Similar factors for LTFU have been previously reported by studies conducted elsewhere.34 35 Although the updated DR-TB guidelines have recommended all-oral regimens,45 injectables continue to be part of the DR-TB treatment in many countries due to poor supply of newer medicines and issues in the implementation of all-oral regimen.34
Throughout the course of treatment, majority of the study participants encountered various adverse events, including but not limited to hearing loss, tinnitus, depression, unpleasant taste, nausea, vomiting, dark spots on the face and body, joint pain, inflammation and pain at the injection site. The occurrence of these adverse events emerged as a significant obstacle leading to early termination of the treatment. This aligns with findings from other studies conducted among patients with DR-TB experiencing LTFU.34 46 The management of these adverse events often involves prescribing ancillary medications, thereby increasing pill burden and contributing to patient non-adherence. To address the challenge of LTFU due to adverse events, solutions such as the active involvement of pharmacists in clinical practice, patient counselling, reassurance efforts,46–49 availability of newer and safer medications, early detection, effective management of adverse events and administration of updated shorter all-oral regimens for eligible patients with DR-TB have been proposed.41 48
In this study, some of the service provider-related factors that were mentioned as factors responsible for patients’ LTFU including the non-availability of qualified persons in their vicinity to administer the injection on a daily basis for a prolonged time of 8–12 months. Distant treatment centres, where participants travelled for more than 6 hours to reach it, and transportation problems were also reported as major reasons for not completing the treatment. Prolonged use of painful injectables due to contamination of sputum culture samples, poor attitude of healthcare professionals, lack of adequate counselling with regard to the disease and medication, long waiting hours, etc, were some other service provider-related factors that patients mentioned as hurdles to a successful completion of treatment. These findings were in compliance with studies conducted elsewhere.34 38 40 41
Limitations
There are several limitations associated with this study. Although not ideal, some patients did not talk freely at the start of the interview, but gradually improved their conversation. Another limitation is the omission of perspectives from key stakeholders in the caregiving process. The study did not include insights from caregivers, healthcare professionals and those who provide support to patients during their treatment. This exclusion limits the comprehensiveness of the study as these individuals play crucial roles in the care ecosystem. By not incorporating their viewpoints, the study misses valuable information regarding the challenges and perspectives faced by those directly involved in the patients’ care journey. In summary, the limitations mentioned highlight challenges related to initial patient communication and the absence of perspectives from important stakeholders in the caregiving process. These limitations could impact the study’s ability to provide a holistic understanding of the experiences and challenges faced by both patients and those involved in their care.
Conclusions
In the current study, various factors related to patients, perceptions about DR-TB treatment, socioeconomic conditions, medications and service providers have emerged as barriers to the successful completion of DR-TB treatment. To mitigate LTFU, it is crucial to educate patients about the minimum duration of DR-TB treatment and the risks associated with LTFU. Patients should understand that the alleviation of symptoms early in the course of DR-TB treatment does not equate to a cure. Building trust in DR-TB treatment can be facilitated through interactive sessions with individuals who have successfully completed the treatment. Additionally, widespread availability of rapid DST facilities at TB treatment centres throughout the country can significantly reduce delays in diagnosing DR-TB and ensure timely initiation of optimal treatment regimens. Furthermore, commencing DR-TB treatment with the recently recommended all-oral regimen, decentralising treatment services and video-observed treatment have the potential to further decrease the rate of LTFU and enhance overall treatment outcomes.
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
Ethics statements
Patient consent for publication
Ethics approval
This study involves human participants and was approved by the Research and Ethics Committee of the Faculty of Pharmacy and Health Sciences, University of Balochistan Quetta (ref: DRF04/12/2019) and NTP Islamabad. Participants gave informed consent to participate in the study before taking part.
Acknowledgments
The authors are thankful to NTP Islamabad for their full support.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Contributors MA and MU conceptualised and designed the study. MA collected the data. MA, MU, OA and MAS analysed the data and helped in the revisions. MA wrote the manuscript. All authors critically reviewed the manuscript. MA supervised the study. MA is the author acting as guarantor.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.