In this study, we highlighted the high prevalence of smoking among TB patients in Selangor during the period 2013–2017. Almost one-third of the TB patients in this study cohort were active smokers, 27.6% (95% CI: 25.2,28.8), compared to only 22% of active smokers among the adult general population in Malaysia in 2015 (NHMS, 2015). The proportion of TB patient who smoke could be higher if we use only the adult population for this study. Previous studies conducted in Malaysia (16, 27) and other countries, such as Indonesia, Africa, and India (8–10), have reported similar findings, with a higher prevalence of smokers being found among TB patients compared to the general population. This signifies that smoking is one of the main predictors of TB infection. This current study also shows that the proportion of treatment default among TB patients who smoke is higher than that among the overall general TB patients registered in Selangor, with outcomes of 15.1% and 10.3%, respectively. Smoking behaviour among TB patients by itself has a poor prognosis for TB treatment outcomes. TB patients who smoke and who default on TB treatment will experience worse outcomes. Therefore, it is important to examine the factors associated with treatment default among TB patients who smoke to optimize their treatment adherence and assist them in quitting smoking.
Factors associated with treatment default.
Adherence to TB treatment strongly influences the outcome of patients and has an effect on the development of multidrug resistance (MDR-TB)(28). In the current study, the majority of patients who default on TB treatment had sputum samples that were smear positive when they returned for retreatment care, which indicates a high risk of transmission to others(29). Despite full supervision in the form of the directly observed therapy that is currently being delivered in our setting, the outcome was not consistently improved. Sociodemographic factors associated with treatment default among TB patients who smoke were residing in an urban area, having a low education level and a low-income level (median individual income < RM2160), all of which had significant contribution to TB treatment default. This outcome could be possible because smoking is a marker for other social and behavioural factors that make defaulting on treatment more likely(29). A similar finding was also found in a qualitative study performed in urban Morocco, where a low income and a low level of education were barrier resources among TB patients which led to default. The reasons were due to lack of money for transportation, the need to work despite illness, and no one aiding in obtaining medication(30). This shows that socioeconomic support plays important roles in ensuring the continuation of TB treatment. Despite the full subsidization of anti-TB treatment to all TB patients, some out-of-pocket expenditures still exist, especially related transportation costs. An average of RM439.42 out-of-pocket money per patient has been estimated in order to complete a 6-month TB treatment(31). Any intervention that could reduce the cost of TB treatment will help to improve patient compliance with TB treatment.
Other studies from Hong Kong and Morocco have found that male sex and being a nonreligious person have significant associations with smoking habits and defaulting on TB treatment(6, 24). This could account for the large observed differences in the proportion of males and females in this study; however, sex was not included in the final model in this study. The influence of religious belief on the effect of patient adherence to TB treatment could not be quantified, as religious status was not available in the database.
Under the disease profiles domain, patients with a history of previously being treated for TB had an almost threefold risk of default treatment compared to new TB cases. It has been reported that previous experience with TB is a risk factor for defaulting only when there was a previous treatment default(6). This could be related to smoking habits, as studies conducted among TB patients who smoke in Hong Kong have revealed a significant association between retreatment cases among current smokers and TB patients who never smoke(17). The complex psychosocial factors of smoking may explain its association with defaults and non-adherence; however, in this study, we did not address the underlying mechanism. Additional studies from other countries, such as Sudan, Morocco, and Brazil, also found a significant association between retreatment cases and TB treatment default, with ORs ranging from 3.2 to 6.5; this indicates that patients who had been defaulting their treatment will be at higher risk of defaulting on their TB treatment again(30, 32, 33).
This study also found that TB patients who smoke and who were detected through active screening methods had a double-risk AOR of 2.047 (95% CI 1.206–3.473) for defaulted treatment compared to those who were detected through passive detection methods. This finding could be the result of the implementation of the national guideline for systematic screening for TB high-risk groups, such as TB/HIV comorbidities, inmate prisoners, diabetes patients, elderly individuals and patients in methadone replacement therapy since 2015, where the majority of these high-risk groups were significantly associated with unfavourable TB treatment outcomes (NSPTB 2016–2020). This action was intended to improve TB detection rates and to provide early TB treatment to them. Most detected TB comorbidities, for example, TBHIV and TBDM, are known to be predictors of poor TB treatment outcomes in many studies. Studies from Brazil, Kenya and Peru have found that HIV-infected patients are at higher risk of defaulted treatment than are HIV-negative patients(23, 34, 35). The outcomes are similar for diabetes mellitus (DM); clinical evidence has found DM to be a significant risk factor for poor TB treatment outcomes, including treatment default. The literature has suggested that DM is significantly associated with the development of adverse drug reactions and delayed sputum conversion at the end of 2 months of treatment(36), which explains the high default rates among TB/DM patients in certain countries, including Kuwait and Brazil(37). In this study, TB patients who smoked and had HIV were significant in the univariable analysis but were not found to have an independent relationship to treatment default in the multiple logistic regression analysis. While TB/DM patients had no association with treatment default. The lower rates of treatment default among TB patients with comorbidities may be due to their better treatment compliance, as these patients are frequently followed up with for anti-retroviral treatment in HIV patients and chronic diabetes mellitus management(11). The increased TB detection rate and earlier TB treatment among DM patients have been improved under the National Diabetes Programme (NSPTB 2016–2020). TB/HIV collaborative activities between the National TB Control Programme and the National HIV/AIDS Control Programme have also contributed to the better surveillance, management, and treatment outcome of this group (NSPTB 2016–2020).
TB patients who smoked who received TB treatment of less than 6 months in duration had a seven times higher risk of defaulting on treatment, AOR 7.653 (95% CI 5.742–9.918) compared to those receiving treatment for 6 months or more. This result is parallel with the finding from Peru and Estonia, where the majority of patients default on treatment after the completion of the intensive phase(35) with a median duration of 124.5 days(38). In Malaysia, national TB treatment strongly recommends using patient-centred case management and utilizes the DOTS strategy when treating people with TB. DOTS supervisors could be healthcare workers, family members, NGOs, and community volunteers. Statistics have found that more patients are lost to follow-up when supervised by NGOs and volunteers than when supervised by family members and healthcare workers. The literature from other studies has showed that patients who do not adhere to their treatment and default on treatment are largely unsupervised or supervised outside the chest clinic. In Hong Kong, patient supervision by community nurses, family members and NGOs is often incomplete after a short period of time, which accounts for almost 50% of their TB patients(6). It is crucial to ensure that the selection of DOT supervisors is appropriate depending on the patients’ risk of default treatment, as the determinant with the highest strength of the predictability to default treatment was patients who were not on DOTS during the continuation phase of TB treatment, with a more than twenty-fold increased risk (AOR 27.961; 95% CI 21.098–37.058). The percentage of patients on DOTS decreased from 87.7% during the intensive phase to 72.6% in the continuation phase. Many patients who do not receive DOTS will usually stop taking their medications after 2 months because they feel better or are less symptomatic(39). Other common significant factors associated with non-adherence to DOTS are poor knowledge towards TB and its treatment, the cost of transportation for DOTS at every visit and the distance of the DOTS centre from individual’s home(40).
Addressing smoking issues among TB patients requires a strategic plan on its own. A study performed among TB patients who smoke in Penang showed a poor score of tobacco use knowledge and its health consequences in general among newly diagnosed patients(27). Most patients report that they are not informed about the impact of continued smoking on TB outcomes and have only received general health information and not TB-specific information(41). Evidence on the effects of smoking cessation on TB treatment outcomes, especially on treatment default, is limited. It is also not well known whether quitting smoking during TB treatment would have an immediate impact and produce similar outcomes as those of individuals who have never smoked. However, a study performed by Wang and Shen in Hong Kong found that TB patients without smoking cessation are twice as likely to default on TB treatment than are those who achieve cessation (OR 2.03; 95% CI 0.99–4.18). This outcome is similar to a local study performed in Malaysia, which found that TB patients who receive tobacco cessation intervention during DOTS have a lower rate of treatment default than TB patients in the usual care group(42). Additionally, the literature has shown that smoking-related immunological abnormalities in TB are reversible within six weeks of smoking cessation(43). Therefore, initiating tobacco cessation intervention during DOTS will benefit TB patients in terms of their treatment outcome and improve their adherence to TB treatment. A prospective cohort in Hong Kong also found that 49.6% of smokers who quit will remain nonsmoking 5 years after the cessation intervention while receiving TB treatment(44). This finding supports the long-term effect of the TB smoking cessation intervention delivered by TB chest clinics in reducing smoking prevalence among TB patients who smoke.