During July-September 2018, a total of 74 eligible patients were interviewed among 128 patients registered and put on treatment at the study site (Figure 1). The mean (SD) age of participants was 32.4 (+13.6) years. Of the 74 patients, 44 (59.5%) were male; 46 (62.2%) were educated up to secondary school; 54 (73%) belonged to below poverty line; 60 (81.1%) were residing in urban area; and 64 (86.5%) had tuberculosis in the past. The socio-demographic, behavioral and clinical characteristics of the participants are given in table 1. A total of 22 (29.7%) patients were tobacco users (either smokeless or smoking) and 24 (32.4%) reported presence of at least one comorbidity.
All 74 patients experienced at least one adverse event during the first three months of treatment and a total of 207 events were reported. The incidence rate of AEs (per 100 person days) during the study period was 3.11 (4.6, 2.7 and 2.02 for the first, second and third month from initiation of treatment respectively). System wise AEs have been described in figure 1. AEs related to gastro-intestinal, ophthalmic and otolaryngology were the the most commonly experienced AEs, occurring among 59 (28.3%), 32 (15.4%) and 25 (11.9%) of the participants, respectively. The most common symptoms under each systems have been described in the supplementary table B. The pattern and month wise distribution of AEs is depicted in figure 2. Proportion of AEs as per month of occurrence and organ system involved among patients is depicted in figure 3.
Of the 207 AEs experienced by patients, treatment was sought for 124 (61.7%) AEs (Figure 1). Patients were categorized as ‘having sought treatment’ if they reported more than 50% of their experienced AEs, ‘not having sought treatment’ if they reported less than 50% of their experienced AEs. None of the patient characteristics were significantly associated with the patient not seeking treatment (Table 2).
To further explore the factors associated with low treatment seeking or reporting of AEs and to identify challenges from patient’s and health care provider’s perspective, exploratory qualitative interview was carried out with patients and health care providers.
The perceptions regarding adverse events in DR-TB treatment and treatment seeking behaviour for AE management from patients and health care provider perspective were coded under 12 codes organised into four categories. These four categories were grouped into two broad themes a) Health system related challenges and b) Patient-related challenges and listed in table 3.
The qualitative findings from the health system and programmatic point of view were explored using manual content analysis to segregate them as per issues related to the providers, health care facility and the program. The health care workers and providers showed an acceptance to presence of AEs during the treatment; which translated to neglecting and/or acknowledgment of their occurrence. Some of the providers also mentioned that since the patients were loss to follow up (often); they find one or the other reason to adhere less to prescribed medication. Stigma, discrimination was thus inherent among the providers. (Table 3).
“There is no other treatment regimen available free of cost, patients have to complete course or have to die with TB.” (Male, DOTS provider, Urban)
“They are defaulters, they always complain more and adhere less to prescribed medicines” (Male DOTS provider, Urban)
Poor treatment capacity, lack of coordination between the DR TB Centre and the hospital for prompt treatment of AEs and management of the patients; as well as lack of Standard operating procedures (SOPs), guidelines and training for the reporting/ treatment and addressing of AEs were evident health care related and programmatic challenges.
“With multiple referrals in government hospitals, patient have to come back without being attended many times due to high load of patients. It would be better to have special OPD for them” (Male, program manager, Urban)
“We could not decide based on symptoms and history alone whether it is really AE or complication of MDR TB.”(Female PHC-MO Rural)
The qualitative data suggested lack of awareness among patients regarding importance of management of AE and most common AE . It suggested serious gap in pre-treatment counselling. There were many misconceptions among the patients related to treatment and based on their experience of AE management with previous treatment regimen, they avoided contacting health care provider. This misconception regarding AE management could have been countered with active support from health care providers but as described above; the awareness and attitude towards managing AE was found to be unsatisfactory among health care providers too, which leads AE unattended. It was observed that patients chose to stop medications for a few days to get relief from AEs.
“Doctor had advised me on the first day of treatment that, being defaulter of TB treatment, I have to bear all side effects of higher dose anti-TB drugs”. (Female patient, Rural)
“Side effects are sign of effectiveness of drug which is killing power of Bacteria.”(Male patient Rural)
“….….. now I stop taking drugs for few days whenever I do not feel good” (Male patient, Urban)
Taking medications by missing work due to disease or daily treatment was superimposed with having to take treatment for AE or pay for its management. This led to loss of wages; or fear of additional medications; which may have reduced AE reporting among patients.
“I asked for help regarding skin rashes and ANM referred me to district hospital which is far and time consuming, I cannot afford to lose my day” (Male patient, Urban)
These patient related challenges were supported by findings with interview of HCP, as mentioned above, wherein, stigmatizing attitude were quite evident from frontline worker to professionals. Misconceptions regarding DR-TB treatment were also present in HCP. (Table 3)