p u b l i c h e a l t h x x x ( 2 0 1 5 ) 1 e6
Available online at www.sciencedirect.com
Public Health journal homepage: www.elsevier.com/puhe
Original Research
Duration of treatment in pulmonary tuberculosis: are international guidelines on the management of tuberculosis missing something? M. Atif a,*, S.A.S. Sulaiman b, A.A. Shafie c, Z.U. Babar d a
Department of Pharmacy, Islamia University of Bahawalpur, Punjab, Pakistan Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia c Discipline of Social and Administrative Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia d Division of Pharmacy Practice, School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand b
article info
abstract
Article history:
Background: Despite evidence of an association between tuberculosis (TB) treatment outcomes
Received 2 January 2014
and the performance of national tuberculosis programmes (NTP), no study to date has rigor-
Received in revised form
ously documented the duration of treatment among TB patients. As such, this study was
30 December 2014
conducted to report the durations of the intensive and continuation phases of TB treatment and
Accepted 13 April 2015
their predictors among new smear-positive pulmonary tuberculosis (PTB) patients in Malaysia.
Available online xxx
Study design: Descriptive, non-experimental, follow-up cohort study. Methods: This study was conducted at the Chest Clinic of Penang General Hospital between
Keywords:
March 2010 and February 2011. The medical records and TB notification forms of all new
Smear-positive pulmonary tubercu-
smear-positive PTB patients, diagnosed during the study period, were reviewed to obtain
losis
sociodemographic and clinical data. Based on standard guidelines, the normal benchmarks
Duration of tuberculosis treatment
for the durations of the intensive and continuation phases of PTB treatment were taken as
Duration of intensive phase
two and four months, respectively. A patient in whom the clinicians decided to extend the
Duration of continuation phase
intensive phase of treatment by 2 weeks was categorized as a case with a prolonged
Penang
intensive phase. The same criterion applied for the continuation phase. Multiple logistic
Malaysia
regression analysis was performed to find independent factors associated with the duration of TB treatment. Data were analyzed using Predictive Analysis Software Version 19.0. Results: Of the 336 patients included in this study, 261 completed the intensive phase of treatment, and 226 completed the continuation phase of treatment. The mean duration of TB treatment (n ¼ 226) was 8.19 (standard deviation 1.65) months. Half (49.4%, 129/261) of the patients completed the intensive phase of treatment in two months, whereas only 37.6% (85/226) of the patients completed the continuation phase of treatment in four months. On multiple logistic regression analysis, being a smoker, being underweight and having a history of cough for 4 weeks at TB diagnosis were found to be predictive of a prolonged intensive phase of treatment. Diabetes mellitus and the presence of lung cavities at the start of treatment were the only predictors found for a prolonged continuation phase of treatment.
* Corresponding author. Tel.: þ92 622500217. E-mail addresses: [email protected], [email protected] (M. Atif). http://dx.doi.org/10.1016/j.puhe.2015.04.010 0033-3506/© 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Atif M, et al., Duration of treatment in pulmonary tuberculosis: are international guidelines on the management of tuberculosis missing something?, Public Health (2015), http://dx.doi.org/10.1016/j.puhe.2015.04.010
2
p u b l i c h e a l t h x x x ( 2 0 1 5 ) 1 e6
Conclusions: The average durations of the intensive and continuation phases of treatment among PTB patients were longer than the targets recommended by the World Health Organization. As there are no internationally agreed criteria, it was not possible to judge how well the Malaysian NTP performed in terms of managing treatment duration among PTB patients. © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.
Introduction Tuberculosis (TB) is a public health challenge. In 2012, approximately 8.6 million people developed TB. With an estimated 1.3 million deaths every year, TB is the second highest cause of adult mortality from an infectious disease, after human immunodeficiency virus (HIV).1 Malaysia is situated in the Western Pacific region of the World Health Organization (WHO), and is considered to have an intermediate burden of TB.1 According to a recent report, over the past few years, the incidence of TB in Malaysia has been 80e82 cases per 100,000. However, the absolute number of new cases increased from 15,057 in 2000 to 21,851 in 2012.1 These pointers reflect a slowly increasing burden of TB in Malaysia. Provision of standardized treatment regimens, under supervision, is one of the five components of directly observed therapy (DOT). According to the current TB management guidelines, the treatment regimen for new smear-positive pulmonary tuberculosis (PTB) patients should be six months. Standardized TB treatment is divided into two phases: the intensive phase (IP) and the continuation phase (CP). For the IP of treatment, patients are prescribed isoniazid, rifampicin, pyrazinamide and ethambutol for two months, while during the CP of treatment, isoniazid and rifampicin are prescribed for four months. Patients living in isoniazid-resistant areas or diagnosed with isoniazid-resistant TB are prescribed isoniazid, rifampicin and ethambutol for four months during the CP of treatment.2,3 In some situations [e.g. if a TB patient is immunocompromised (e.g. HIV, diabetes mellitus), a smoker and/or exhibits extensive lung involvement (e.g. lung cavities) at the start of the treatment], clinicians may decide to treat patients for a longer duration. In spite of the evidence of an association between TB treatment outcomes and the performance of national tuberculosis programmes (NTP),4e6 no studies to date have rigorously and extensively documented the durations of the IP and CP of treatment among PTB patients. As such, this study was conducted to determine the duration of TB treatment and its predictors among new smear-positive PTB patients.
Methods Study setting This study was conducted at the Chest Clinic of Penang General Hospital. In addition to the committed paramedic staff, the Chest Clinic has a minimum of five to six medical officers
and three chest consultants. A fully equipped quality assured TB laboratory, situated adjacent to the Chest Clinic, provides routine TB-specific investigation services to patients and suspected TB cases. The Radiology and Pathology Departments of Penang General Hospital also provide routine investigation services to TB patients. A detailed description of the study setting is available in the authors' other published papers which differ in terms of their objectives and outcomes.7,8
Study design and data collection This descriptive, non-experimental, follow-up cohort study involved all new smear-positive PTB patients who received WHO-recommended standard TB treatment2 at the study site between March 2010 and February 2011. Each patient was followed-up until his/her final treatment outcome was available (i.e. mid December 2011). The medical records and TB notification forms of the patients were reviewed to obtain sociodemographic, clinical and treatment-related data.4,5,8,9 The normal benchmarks for the duration of the IP and CP of treatment are two and four months, respectively.2 A patient in whom the clinicians decided to extend the IP of treatment by two weeks was categorized as a case with a prolonged IP. The same criterion applied for classifying prolonged duration of the CP of treatment. Unfortunately, the current international guidelines on the management of TB2 do not explain the target proportion of new PTB patients in whom the treatment should be completed in a stipulated time period (i.e. two months for the IP of treatment and four months for the CP of treatment).
Statistical analysis Data were analyzed using Predictive Analysis Software Version 19.0. (IBM Corp., Armonk, NY, USA). Simple logistic regression analysis was used to examine possible associations between the dependent variables (i.e. durations of the IP and CP of treatment) and selected sociodemographic and clinical variables. To predict the final independent factors, the variables that were statistically significant on univariate analysis were entered into a multiple logistic regression analysis. Adjusted odd ratio (AOR), 95% confidence interval (CI), beta, standard error and P-value were reported for each predictor. The model fit was assessed using Chi-squared test, degrees of freedom and P-value. Pseudo R2 (Nagelkerke R2) was included to provide information about the percentage of variance explained by the model. P< 0.05 was considered to indicate significance.6,10,11
Please cite this article in press as: Atif M, et al., Duration of treatment in pulmonary tuberculosis: are international guidelines on the management of tuberculosis missing something?, Public Health (2015), http://dx.doi.org/10.1016/j.puhe.2015.04.010
3
p u b l i c h e a l t h x x x ( 2 0 1 5 ) 1 e6
Table 2 e Clinical characteristics of patients.
Results
Variable Three hundred and thirty-six new smear-positive PTB patients were enrolled in the study. The mean age of the patients was 49.1 years [standard deviation (SD) 16.6]. More than 60% of the patients were aged 18e54 years. The Chinese ethnic group constituted the greatest proportion of the patients (53.3%), whilst the Tamils were least represented (9.8%). Table 1 shows the sociodemographic characteristics of the patients. Only 72 patients exhibited five or more TB-related symptoms at the start of their treatment. Approximately, threequarters of the patients had a history of cough for four weeks at TB diagnosis. Table 2 provides a full description of the clinical characteristics of the patients. Of the 336 patients included in this study, 261 completed the IP of treatment, and 226 completed the CP of treatment. Half (49.4%, 129/261) of the patients completed the IP of treatment in two months, whereas only 37.6% (85/226) of patients completed the CP of treatment in four months. The average duration of TB treatment (n ¼ 226) was 8.19 (SD 1.65) months. Only 58 of the 226 patients completed TB treatment in six months (Table 3).
Table 1 e Sociodemographic characteristics of patients. Characteristics Sex Male Female Age 45 (years); mean 49.11 (SD 16.58) Yes No Ethnicity Malay Chinese Tamil Foreigners Marital status Single Married Widowed/divorced Illiterate Yes No Drug abuser Yes No Smoking status Smoker Non-smoker Alcoholica Yes No Employment status Employed Unemployed Monthly income (MYR) 1000 >1000 MYR, Malaysian Ringgit; SD, standard deviation. a DSM-IV diagnostic criteria.
Patients n (%)
Form of TB Sþ PTB Sþ PTB and EPTB Body mass index Underweight (4 months
129 (49.43) 132 (50.57) 85 (37.61) 141 (62.39)
a
In 75 patients, treatment was not completed as they defaulted, died or transferred. b Percentages calculated on the basis of 261 patients who completed the intensive phase of treatment. c In 75 patients, treatment was not started as the patients defaulted, died or transferred during the intensive phase of treatment. d In 35 patients, treatment was not completed as they defaulted, died or transferred during the continuation phase of treatment. e Percentages calculated on the basis of 226 patients who completed the continuation phase of treatment.
Similarly, a German study reported that the duration of treatment for PTB patients was nine months.10 In the present study, the duration of the IP of treatment was >two months in 50.6% of patients, and 62.4% of patients were unable to complete the CP of treatment in four months. As such, the majority of patients did not finish their TB treatment in the time period recommended by WHO.2 In addition to placing an additional financial burden on the NTP, this may have compromised the mental and physical health of the patients. Smoking is known to have an adverse effect on the cellmediated immune response, and patients may be prone to more progressive and severe disease.14,15 However, it has been shown that below normal body mass index (BMI), which is an important indicator of malnutrition,16 may compromise the immune system. A weaker immune system could delay the recovery process in infectious diseases.17 In the present study, the higher probability of a prolonged IP of treatment among smokers and patients with lower BMI supports these arguments. A history of cough for four weeks at the time of TB diagnosis was another significant predictor of prolonged IP of treatment. Chronic cough at the time of TB diagnosis indicates patient-related delay in seeking appropriated health care.
Table 4 e Predictors of longer duration of the intensive phase of treatment: multiple logistic regression analysis. Independent variables Alcoholic Smoker Underweight (BMI
Available online at www.sciencedirect.com
Public Health journal homepage: www.elsevier.com/puhe
Original Research
Duration of treatment in pulmonary tuberculosis: are international guidelines on the management of tuberculosis missing something? M. Atif a,*, S.A.S. Sulaiman b, A.A. Shafie c, Z.U. Babar d a
Department of Pharmacy, Islamia University of Bahawalpur, Punjab, Pakistan Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia c Discipline of Social and Administrative Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia d Division of Pharmacy Practice, School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand b
article info
abstract
Article history:
Background: Despite evidence of an association between tuberculosis (TB) treatment outcomes
Received 2 January 2014
and the performance of national tuberculosis programmes (NTP), no study to date has rigor-
Received in revised form
ously documented the duration of treatment among TB patients. As such, this study was
30 December 2014
conducted to report the durations of the intensive and continuation phases of TB treatment and
Accepted 13 April 2015
their predictors among new smear-positive pulmonary tuberculosis (PTB) patients in Malaysia.
Available online xxx
Study design: Descriptive, non-experimental, follow-up cohort study. Methods: This study was conducted at the Chest Clinic of Penang General Hospital between
Keywords:
March 2010 and February 2011. The medical records and TB notification forms of all new
Smear-positive pulmonary tubercu-
smear-positive PTB patients, diagnosed during the study period, were reviewed to obtain
losis
sociodemographic and clinical data. Based on standard guidelines, the normal benchmarks
Duration of tuberculosis treatment
for the durations of the intensive and continuation phases of PTB treatment were taken as
Duration of intensive phase
two and four months, respectively. A patient in whom the clinicians decided to extend the
Duration of continuation phase
intensive phase of treatment by 2 weeks was categorized as a case with a prolonged
Penang
intensive phase. The same criterion applied for the continuation phase. Multiple logistic
Malaysia
regression analysis was performed to find independent factors associated with the duration of TB treatment. Data were analyzed using Predictive Analysis Software Version 19.0. Results: Of the 336 patients included in this study, 261 completed the intensive phase of treatment, and 226 completed the continuation phase of treatment. The mean duration of TB treatment (n ¼ 226) was 8.19 (standard deviation 1.65) months. Half (49.4%, 129/261) of the patients completed the intensive phase of treatment in two months, whereas only 37.6% (85/226) of the patients completed the continuation phase of treatment in four months. On multiple logistic regression analysis, being a smoker, being underweight and having a history of cough for 4 weeks at TB diagnosis were found to be predictive of a prolonged intensive phase of treatment. Diabetes mellitus and the presence of lung cavities at the start of treatment were the only predictors found for a prolonged continuation phase of treatment.
* Corresponding author. Tel.: þ92 622500217. E-mail addresses: [email protected], [email protected] (M. Atif). http://dx.doi.org/10.1016/j.puhe.2015.04.010 0033-3506/© 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Atif M, et al., Duration of treatment in pulmonary tuberculosis: are international guidelines on the management of tuberculosis missing something?, Public Health (2015), http://dx.doi.org/10.1016/j.puhe.2015.04.010
2
p u b l i c h e a l t h x x x ( 2 0 1 5 ) 1 e6
Conclusions: The average durations of the intensive and continuation phases of treatment among PTB patients were longer than the targets recommended by the World Health Organization. As there are no internationally agreed criteria, it was not possible to judge how well the Malaysian NTP performed in terms of managing treatment duration among PTB patients. © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.
Introduction Tuberculosis (TB) is a public health challenge. In 2012, approximately 8.6 million people developed TB. With an estimated 1.3 million deaths every year, TB is the second highest cause of adult mortality from an infectious disease, after human immunodeficiency virus (HIV).1 Malaysia is situated in the Western Pacific region of the World Health Organization (WHO), and is considered to have an intermediate burden of TB.1 According to a recent report, over the past few years, the incidence of TB in Malaysia has been 80e82 cases per 100,000. However, the absolute number of new cases increased from 15,057 in 2000 to 21,851 in 2012.1 These pointers reflect a slowly increasing burden of TB in Malaysia. Provision of standardized treatment regimens, under supervision, is one of the five components of directly observed therapy (DOT). According to the current TB management guidelines, the treatment regimen for new smear-positive pulmonary tuberculosis (PTB) patients should be six months. Standardized TB treatment is divided into two phases: the intensive phase (IP) and the continuation phase (CP). For the IP of treatment, patients are prescribed isoniazid, rifampicin, pyrazinamide and ethambutol for two months, while during the CP of treatment, isoniazid and rifampicin are prescribed for four months. Patients living in isoniazid-resistant areas or diagnosed with isoniazid-resistant TB are prescribed isoniazid, rifampicin and ethambutol for four months during the CP of treatment.2,3 In some situations [e.g. if a TB patient is immunocompromised (e.g. HIV, diabetes mellitus), a smoker and/or exhibits extensive lung involvement (e.g. lung cavities) at the start of the treatment], clinicians may decide to treat patients for a longer duration. In spite of the evidence of an association between TB treatment outcomes and the performance of national tuberculosis programmes (NTP),4e6 no studies to date have rigorously and extensively documented the durations of the IP and CP of treatment among PTB patients. As such, this study was conducted to determine the duration of TB treatment and its predictors among new smear-positive PTB patients.
Methods Study setting This study was conducted at the Chest Clinic of Penang General Hospital. In addition to the committed paramedic staff, the Chest Clinic has a minimum of five to six medical officers
and three chest consultants. A fully equipped quality assured TB laboratory, situated adjacent to the Chest Clinic, provides routine TB-specific investigation services to patients and suspected TB cases. The Radiology and Pathology Departments of Penang General Hospital also provide routine investigation services to TB patients. A detailed description of the study setting is available in the authors' other published papers which differ in terms of their objectives and outcomes.7,8
Study design and data collection This descriptive, non-experimental, follow-up cohort study involved all new smear-positive PTB patients who received WHO-recommended standard TB treatment2 at the study site between March 2010 and February 2011. Each patient was followed-up until his/her final treatment outcome was available (i.e. mid December 2011). The medical records and TB notification forms of the patients were reviewed to obtain sociodemographic, clinical and treatment-related data.4,5,8,9 The normal benchmarks for the duration of the IP and CP of treatment are two and four months, respectively.2 A patient in whom the clinicians decided to extend the IP of treatment by two weeks was categorized as a case with a prolonged IP. The same criterion applied for classifying prolonged duration of the CP of treatment. Unfortunately, the current international guidelines on the management of TB2 do not explain the target proportion of new PTB patients in whom the treatment should be completed in a stipulated time period (i.e. two months for the IP of treatment and four months for the CP of treatment).
Statistical analysis Data were analyzed using Predictive Analysis Software Version 19.0. (IBM Corp., Armonk, NY, USA). Simple logistic regression analysis was used to examine possible associations between the dependent variables (i.e. durations of the IP and CP of treatment) and selected sociodemographic and clinical variables. To predict the final independent factors, the variables that were statistically significant on univariate analysis were entered into a multiple logistic regression analysis. Adjusted odd ratio (AOR), 95% confidence interval (CI), beta, standard error and P-value were reported for each predictor. The model fit was assessed using Chi-squared test, degrees of freedom and P-value. Pseudo R2 (Nagelkerke R2) was included to provide information about the percentage of variance explained by the model. P< 0.05 was considered to indicate significance.6,10,11
Please cite this article in press as: Atif M, et al., Duration of treatment in pulmonary tuberculosis: are international guidelines on the management of tuberculosis missing something?, Public Health (2015), http://dx.doi.org/10.1016/j.puhe.2015.04.010
3
p u b l i c h e a l t h x x x ( 2 0 1 5 ) 1 e6
Table 2 e Clinical characteristics of patients.
Results
Variable Three hundred and thirty-six new smear-positive PTB patients were enrolled in the study. The mean age of the patients was 49.1 years [standard deviation (SD) 16.6]. More than 60% of the patients were aged 18e54 years. The Chinese ethnic group constituted the greatest proportion of the patients (53.3%), whilst the Tamils were least represented (9.8%). Table 1 shows the sociodemographic characteristics of the patients. Only 72 patients exhibited five or more TB-related symptoms at the start of their treatment. Approximately, threequarters of the patients had a history of cough for four weeks at TB diagnosis. Table 2 provides a full description of the clinical characteristics of the patients. Of the 336 patients included in this study, 261 completed the IP of treatment, and 226 completed the CP of treatment. Half (49.4%, 129/261) of the patients completed the IP of treatment in two months, whereas only 37.6% (85/226) of patients completed the CP of treatment in four months. The average duration of TB treatment (n ¼ 226) was 8.19 (SD 1.65) months. Only 58 of the 226 patients completed TB treatment in six months (Table 3).
Table 1 e Sociodemographic characteristics of patients. Characteristics Sex Male Female Age 45 (years); mean 49.11 (SD 16.58) Yes No Ethnicity Malay Chinese Tamil Foreigners Marital status Single Married Widowed/divorced Illiterate Yes No Drug abuser Yes No Smoking status Smoker Non-smoker Alcoholica Yes No Employment status Employed Unemployed Monthly income (MYR) 1000 >1000 MYR, Malaysian Ringgit; SD, standard deviation. a DSM-IV diagnostic criteria.
Patients n (%)
Form of TB Sþ PTB Sþ PTB and EPTB Body mass index Underweight (4 months
129 (49.43) 132 (50.57) 85 (37.61) 141 (62.39)
a
In 75 patients, treatment was not completed as they defaulted, died or transferred. b Percentages calculated on the basis of 261 patients who completed the intensive phase of treatment. c In 75 patients, treatment was not started as the patients defaulted, died or transferred during the intensive phase of treatment. d In 35 patients, treatment was not completed as they defaulted, died or transferred during the continuation phase of treatment. e Percentages calculated on the basis of 226 patients who completed the continuation phase of treatment.
Similarly, a German study reported that the duration of treatment for PTB patients was nine months.10 In the present study, the duration of the IP of treatment was >two months in 50.6% of patients, and 62.4% of patients were unable to complete the CP of treatment in four months. As such, the majority of patients did not finish their TB treatment in the time period recommended by WHO.2 In addition to placing an additional financial burden on the NTP, this may have compromised the mental and physical health of the patients. Smoking is known to have an adverse effect on the cellmediated immune response, and patients may be prone to more progressive and severe disease.14,15 However, it has been shown that below normal body mass index (BMI), which is an important indicator of malnutrition,16 may compromise the immune system. A weaker immune system could delay the recovery process in infectious diseases.17 In the present study, the higher probability of a prolonged IP of treatment among smokers and patients with lower BMI supports these arguments. A history of cough for four weeks at the time of TB diagnosis was another significant predictor of prolonged IP of treatment. Chronic cough at the time of TB diagnosis indicates patient-related delay in seeking appropriated health care.
Table 4 e Predictors of longer duration of the intensive phase of treatment: multiple logistic regression analysis. Independent variables Alcoholic Smoker Underweight (BMI
