Determinants of tuberculosis treatment success among the working population in Malaysia

INTRODUCTION

In Malaysia, the tuberculosis (TB) treatment success rate among the general population is 76%, and it has not yet achieved the target of 85% set by the World Health Organization (WHO). Furthermore, in 2013, the treatment success rate in Malaysia was lower than that of other neighbouring countries such as Indonesia (88%), Thailand (81%) and Singapore (77%). The burden of TB in Malaysia has significant impact on the economy and resources for curbing the TB epidemic, especially in workplaces. Focusing on TB infection in the working population, we note that the impact of TB ranges from treatment and patient costs to loss of working days and productivity. Several studies have demonstrated that other than healthcare centres, mines, plantations, prisons and businesses involving a large number of migrants are among the workplaces with an increased risk of TB infection. Data have also shown that 45%–50% of TB cases in Malaysia occur among workers in the working age population (15–64 years).

Selangor district is one of the most developed states in Malaysia, and it is highly industralised. A previous study showed that the influx of foreign workers, ineffective early case detection and improper implementation of directly observed treatment (DOT) among TB patients are factors that contribute to poor TB control in Selangor. One possible reason for poor TB control may be insufficient TB personnel to implement DOT. This may have resulted in side effects of TB medication being overlooked, a lack of follow-up on patients who missed scheduled DOT, and improper monitoring of TB medication adherence.

The TB control programme in Selangor district consists of four main components: TB treatment and surveillance, Bacillus Calmette–Guérin (BCG) vaccination, investigation and the TB diagnostic lab. All components play a crucial role in ensuring that the national TB control and prevention programme objectives are met. TB surveillance of a patient begins with the notification of a suspected case, and upon confirmation, the case will be fully registered and updated in the MyTB database until the patient completes treatment. Performance meetings will be held quarterly at the district, state and national levels to monitor all TB programme indicators. Selangor district practises ‘modified’ DOT in which medication is given to patients on a weekly basis provided there is a caregiver to observe and ensure compliance with the treatment. It is offered only to patients who are deemed by the treating doctor to be capable of treatment compliance and who have good family or social support. Data from the DOT programme in 2013 showed a slightly higher proportion of DOT TB patients in Selangor district who were supervised by a caregiver (55%) than by a healthcare personnel (45%). In addition, there was no significant difference in TB treatment success recorded based on either type of DOT supervision. Public–public or public–private mixes (PPMs), where patients treated at government health facilities can be monitored by the nearest private health facilities if the patients encounter transportation or timing issues, have been introduced to boost TB treatment compliance.

To date, there have been no baseline references or previously published local studies examining TB treatment success among the working population. Previous studies conducted in Malaysia had focused on the general population and healthcare workers (HCWs), rather than on the entire working population. Hence, knowing the characteristics and determinants of success among workers may provide new inputs to guide various stakeholders and workplaces to undertake specific measures to control TB transmission at the workplace.

METHODS

This research was a cohort study of all TB patients among the working population registered in the state of Selangor, Malaysia, via the national MyTB version 2.1 surveillance database in 2013, with case holding up to 24 months. We included the following four domains of independent variables: 1) sociodemographics; 2) job profiles; 3) TB with comorbidities; and 4) TB disease profile, which includes the method of TB detection, presence of BCG scarring, category of TB cases, sputum smear result, severity of chest radiographic findings, facility of TB diagnosis and initiated TB treatment, and DOT adherence status. Workers who performed predominantly manual labour were classified as blue-collar workers, while workers who performed predominantly ‘brain work’ were classified as white-collar workers.[1] The outcomes of TB treatment were divided into six categories based on WHO recommendations: cure, treatment completion, loss to follow-up, treatment failure, death and transfer out.[2] Treatment success was defined as cases that resulted in cure and had completed a treatment course.[2] All TB patients labelled either cured or completed treatment had completed their TB medication course and were declared to be cured by a medical practitioner.[3] The only difference was that TB patients labelled as having completed treatment were diagnosed with extrapulmonary TB and sputum smear-negative TB throughout the TB treatment.[3] In contrast, TB patients labelled as cured had bacteriological conversion, meaning that the sputum smear result converted from positive to negative at the end of TB treatment.[3] Unsuccessful treatment was defined by all other categories of outcomes: treatment failure, death, transfer out and loss to follow-up. Patients diagnosed with multidrug-resistant TB (MDR-TB), those with a change in diagnosis and those whose outcomes were unknown were excluded from this study.

Data collection, mining and analysis

The Malaysian MyTB version 2.1 database is a mandatory surveillance registry for diagnosed TB patients who started TB treatment regardless of microbiological presentation. Data on all working TB patients between 15 and 64 years of age in Selangor in 2013 were extracted and included in the study. Data extraction and the process of sample selection were based on our inclusion and exclusion criteria [Figure 1]. The listwise deletion method was applied to TB treatment outcomes and job variables to account for the missing data. Regarding sample size calculation, a single proportion formula with a 95% confidence interval (CI) and a 5% absolute precision was applied using a 78.5% prevalence of TB treatment success among the general population from a previous study performed in Malaysia. Thus, the minimum sample required in this study was 338, including a 30% attrition rate. Universal sampling was applied, and the final sample size was 156.

Figure 1.

Flow chart of data extraction and sample size selection. MDR-TB: multidrug-resistant TB, TB: tuberculosis.

The data were analysed using IBM SPSS Statistics version 23.0 (IBM Corp, Armonk, NY, USA). A value of P < 0.05 was considered statistically significant, with α = 0.05 and a power of 90%. Data visualisation and descriptive analysis were performed. Simple and multivariable logistic regression (LR) analyses (the backward LR method) were used to identify determinants of TB treatment success. This study received approval from the Malaysia Ministry of Health Medical Research Ethics Committee (reference number: NMRR-19-224-45927) and the Universiti Teknologi MARA (UiTM) Ethical Board Committee (reference number: 600-IRMI (5/1/6)).

RESULTS

The majority of the patients were blue-collar workers (60.6%), 25–34 years old (32.6%), male (73.8%), educated to a secondary level (58.4%) and of Malay ethnicity (62.6%). One-fifth (21.4%) were non-Malaysian, and the minority (2.4%) were HCWs. Pertaining to TB with comorbidities, less than half (45.7%) of the patients were active smokers, one-sixth (14.5%) had diabetes mellitus and 5.6% were human immunodeficiency virus (HIV) positive. Regarding the TB disease profile, a majority of the patients were diagnosed with pulmonary TB (86.1%), were new TB cases (95.1%), reported the presence of BCG scarring (76.4%), and were diagnosed and had initiated TB treatment at government healthcare facilities (77.4% and 77.6%, respectively). In terms of TB treatment outcomes, a majority (79.9%, n = 1246) of these patients had achieved treatment success, with 48.3% (n = 754) being cured and 31.6% (n = 492) having completed TB treatment. The cure rate for new cases of pulmonary TB was 83.0%. The other one-fifth (20.1%, n = 314) had unsuccessful treatment outcomes. Of these patients, 5.5% (n = 86) died, 5.6% (n = 87) were transferred out, 8.9% (n = 140) were lost to follow-up and 0.1% (n = 1) failed treatment.

Table 1 shows the output of simple and multivariable LR (backward LR) on the determinants of TB treatment success among the working population. Determinants associated with TB treatment success included patients who initiated TB treatment at private healthcare facilities (adjusted odds ratio [AOR] 2.53, 95% CI: 1.07–5.94), those with the presence of BCG scarring (AOR 1.36, 95% CI: 1.12–1.80), those who were new cases of TB compared to previously treated cases (AOR 2.87, 95% CI: 1.16–7.11), those who adhered to the DOT maintenance phase (AOR 150.91, 95% CI: 94.50–240.99) and those who were HCWs (AOR 3.80, 95% CI: 0.64–23.92). This model had excellent predictability and a receiver operating characteristic curve with an area under the curve (AUC) of 93.5% (95% CI: 91.6%–95.4%). The HCW status item was forced into the model even though it was not statistically significant on the multivariate analysis as it improved the model’s AUC from 93.3% (95% CI: 91.4%–95.2%) to 93.5% (95% CI: 91.6%–95.4%).

Table 1.

Bivariate analyses of TB treatment success among the working population registered in Selangor via national MyTB version 2.1 (n=1560).

Variable	n (%)		Crude OR (95% CI)	Adjusted OR (95% CI)
	Successful (n=1246)	Unsuccessful (n=314)
Sociodemographic characteristics
Gender
Male	900 (78.1)	252 (21.9)	1	1
Female	346 (84.8)	62 (15.2)	1.5 (1.15–2.12)†	1.32 (0.61–2.87)
Nationality
Non-Malaysian	221 (66.2)	113 (33.8)	1	1
Malaysian	1025 (83.6)	201 (16.4)	2.61 (1.99–3.42)†	1.02 (0.62–2.57)
Ethnicity (n=1226)
Malay	632 (82.3)	136 (17.7)	1	1
Indian	137 (82.5)	29 (17.5)	1.05 (0.65–1.58)	1.72 (0.71–4.16)
Chinese	205 (90.7)	21 (9.3)	2.10 (1.29–3.42)†	2.19 (0,83–5.744)
Others	51 (77.3)	15 (22.7)	0.73 (0.40–1.34)	0.83 (0.23–2.96)
Level of education
No formal education	102 (65.8)	53 (34.2)	1	1
Primary	65 (67.0)	32 (33.0)	1.06 (0.62–1.80)	0.37 (0.03–3.83)
Secondary	721 (79.1)	190 (20.9)	1.97 (1.36–2.85)†	0.63 (0.15–2.63)
Tertiary	358 (90.2)	39 (9.8)	4.77 (2.99–7.60)†	1.38 (0.31–6.20)
Job profile
Individual monthly income (RM) (n=1210)
≤ 1000	346 (74.9)	116 (25.1)	1	1
1001–2000	450 (83.0)	92 (17.0)	1.64 (1.21–2.23)†	0.62 (0.28–1.41)
≥ 2001	179 (86.9)	27 (13.1)	2.22 (1.41–3.51)†	0.68 (0.20–2.25)
Job collar status
Blue collar	732 (77.4)	214 (22.6)	1	1
White collar	347 (88.5)	45 (11.5)	2.25 (1.60–3.19)†	0.64 (0.27–1.54)
Self-employed	167 (75.2)	55 (24.8)	0.89 (0.63–1.25)	0.39 (0.14–1.08)
Healthcare worker status
No	1211 (79.5)	312 (20.5)	1	1
Yes	35 (94.6)	2 (5.4)	4.51 (1.08–18.85)†	3.80 (0.64–23.92)‡
TB with comorbidities
HIV status (n=1522)
Positive	50 (58.8)	35 (41.2)	1	1
Negative	1164 (81.0)	273 (19.0)	2.99 (1.90–4.69)†	1.65 (0.51–5.31)
TB disease profile
Facility of TB diagnosis
Government health clinic	256 (79.5)	66 (20.5)	1	1
Government hospital	810 (77.8)	231 (22.2)	0.91 (0.67–1.23)	0.86 (0.37–20.14)
Private hospital/clinic	180 (91.4)	17 (8.6)	2.73 (1.55–4.81)†	0.06 (0.02–1.80)
Facility of initiated TB treatment
Government health clinic	257 (79.1)	68 (20.9)	1	1
Government hospital	811 (77.9)	230 (22.1)	0.93 (0.69–1.27)	0.76 (0.45–1.28)
Private hospital/clinic	178 (91.8)	16 (8.2)	2.94 (1.65–5.24)†	2.53 (1.07–5.94)‡
Presence of BCG scarring
No	255 (69.3)	113 (30.7)	1	1
Yes	991 (83.1)	201 (16.9)	2.19 (1.67–2.86)†	1.36 (1.12–1.80)‡
Sputum smear (n=1509)
Positive	777 (78.4)	214 (21.6)	1	1
Negative	431 (83.2)	87 (16.4)	1.36 (1.04–1.80)†	1.03 (0.51–2.10)
Category of TB cases
New case	1196 (80.6)	288 (19.4)	2.16 (1.32–3.53)†	2.87 (1.16–7.11)‡
Previously treated case	50 (65.8)	26 (34.2)	1	1
DOT intensive phase adherence (n=1556)*
No	28 (21.5)	102 (78.5)	1	1
Yes	1218 (85.4)	208 (14.6)	21.33 (13.70–33.23)†	1.26 (0.58–2.71)
DOT maintenance phase adherence (n=1547)*
No	77 (22.0)	273 (78.0)	1	1
Yes	1169 (97.7)	28 (2.3)	148.01 (94.18–233.64)†	150.91 (94.50–240.99)‡
DOT supervisor
Caregiver	698 (81.4)	159 (18.6)	1	-
Healthcare provider	548 (78.0)	155 (22.0)	0.81 (0.63–1.03)	-

*Adherence to DOT defined as achievement of at least 80% of the scheduled treatment for both intensive and maintenance phases. ^†Significant factor in simple logistic regression analysis. ^‡Significant determinant included in the final model (multivariable logistic regression analysis). BCG: Bacillus Calmette-Guérin, CI: confidence interval, DOT: directly observed treatment, HIV: human immunodeficiency virus, OR: odds ratio, RM: ringgit, TB: tuberculosis

DISCUSSION

In the present study, we used the old TB treatment outcome guidelines and focused only on treatment success for drug-susceptible TB patients. We are aware of WHO’s new TB treatment outcome guidelines in 2021, in which the treatment outcomes will be standardised for all TB patients and all treatment regimens, regardless of the drug resistance status, type of TB drugs used or duration of TB treatment.

This study shows that four out of five (79.9%) registered TB patients among the working population in Selangor achieved treatment success. The treatment success rate in this population was slightly higher than that in the general Malaysian population (76%).[4] Our findings showed that TB patients who adhered to the DOT maintenance phase, initiated TB treatment at private healthcare facilities, were new TB patients, previously received BCG vaccination and were HCWs were significantly associated with TB treatment success. TB patients who adhered to DOT had 151-fold higher odds of successful treatment than non-adherent patients. This finding is similar to that from a study conducted in Singapore, in which DOT patients were more likely to achieve treatment success.[5]

Patients who initiated TB treatment at private healthcare facilities were found to have 2.5-fold higher odds of achieving treatment success than those who initiated TB treatment in government healthcare clinics. A previous study also reported that private healthcare facilities showed slightly better performance in treating TB than government healthcare facilities.[6] It was found that the ability to provide good TB diagnostic and treatment services at private healthcare facilities was one of the underlying reasons for this outcome. However, it was not the main issue faced by Malaysian healthcare facilities. Both private and or public healthcare facilities are equally equipped with good sputum collection or microbiology services and chest X-ray services. Perhaps private facilities have a lower doctor–patient ratio, which allowed closer monitoring and more follow-up visits than public healthcare facilities. Also, patients who were treated at private healthcare facilities may have presented with less-severe disease forms, which could heighten the possibility of treatment success. However, a more detailed study needs to be conducted to obtain clear, definitive results regarding the health-seeking behaviour of TB patients, which plays a vital role in adherence to and completion of TB treatment. Furthermore, we found that the prevalence of TB patients among the working population who were diagnosed and initiated TB treatment at private facilities was higher than that in the general population (12.4% and 5.0%, respectively).[7] This preference for treatment at private healthcare facilities among the working population may be due to the provision of health insurance coverage by their companies.

In our study, patients who were newly diagnosed with TB were 2.9 times more likely to achieve TB treatment success than patients who were previously treated. This finding is in agreement with a study performed in Thailand that reported an odds ratio of 2.26 (95% CI: 1.21–5.52) for TB treatment success in new TB cases compared to previously treated cases.[8] Regarding job profiles, we found that HCWs had a higher percentage of treatment success than non-HCWs. Non-HCWs also had a higher likelihood of defaulting treatment or transferring out, similar to findings from an African study.[9] HCWs also had higher DOT compliance rates (89%) than non-HCWs (77%). This could be attributed to a better understanding of TB among HCWs. Other factors that may contribute to treatment completion among HCWs include close monitoring by their supervisors and ‘peer pressure’ to comply to their treatment due to healthcare colleagues’ knowledge of their TB diagnosis. Although the initial model showed that job categories were not a significant factor, the final model proved that this variable remains an important determinant of successful TB treatment.

Patients who had received BCG vaccination were also found to be associated with better TB treatment outcomes. This finding is in agreement with the findings of another study.[10] Interestingly, not smoking and not having a diagnosis of diabetes mellitus were not predictors of TB treatment success, which contradicts previous findings in other studies.[11,12]

Identifying all the significant determinants of TB treatment success among the working population will enable us to provide inputs for stakeholders to enhance the current TB control programmes for workplaces. Nonetheless, to ensure success, there is a need for strong collaborations at various levels. For example, at the ministerial level, the number of doctors in public health facilities should be increased to provide close monitoring of TB patients. The introduction of a PPM programme by the Malaysia Ministry of Health in 2018 was one of the initiatives to augment early TB case detection and improve patient monitoring throughout TB treatment. Furthermore, there should be guidelines and policies on pre-employment screening for workers in workplaces that have a high risk of TB transmission such as the mines, construction sites and plantations. Special recognition by the ministry should be given to companies that support the DOT programme; for example, by giving time off to workers to attend the sessions. Workers with suspected poor TB treatment outcomes, such as relapse cases, should be closely monitored through proper implementation of a DOT programme at the organisational level. Employers play a vital role in ensuring that workers undergoing TB treatment comply with DOT. For example, employers need to appoint and train a supervisor, selected from among the working staff, to ensure close monitoring of TB patients during working hours. The supervisor must ensure that patients are adhering to TB medications, remind workers to attend the TB follow-up sessions and provide moral support to complete TB treatment. Employers may implement financial enabler schemes to foster patient adherence to DOT; for example, providing grocery vouchers for each clinic visit. A local non-governmental organisation in Singapore implemented this scheme, and it was proven to be effective in improving the country’s TB treatment completion rate.[13] Employers may also need to develop excellent partnerships with private and government healthcare facilities to manage TB patients more efficiently. They can take responsibility to provide insurance coverage and to properly monitor workers with TB in the workplace to increase the success rate. Implementation of the above recommendations at workplaces could be a good opportunity to enhance TB control activities.

One of the limitations encountered in this study was that the data were collected from the TB registry and focused only on workers with TB in one state; thus, the results and findings may not represent the working population with TB in Malaysia. Nonetheless, this study had several strengths. First, it involved a large sample size and represented Selangor. Secondly, this study was the first to investigate the successful treatment of TB in a working population using a large national database. We recommend that similar future studies be conducted in other Malaysian states and in developing countries with a high TB burden among their working population.

In conclusion, the treatment success rate of TB patients in the working population in Selangor was lower than the expected target of 85%. Significant determinants of TB treatment success include patient compliance with the DOT maintenance phase, the initiation of TB treatment at private healthcare facilities, diagnosis of new cases of TB, previous receipt of BCG vaccination and employment as an HCW. A comprehensive TB control programme in the workplace might minimise the risk of workplace TB transmission and improve the treatment success rate in the future.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

The study was funded by the Malaysian Thoracic Society (Research Grant: MTS Research Grant 2018/2019).