|Year : 2019 | Volume
| Issue : 2 | Page : 78-84
Comparative study of six-month and eight-month treatment of new smear positive tuberculosis cases at a tertiary health facility in Enugu, South-Eastern Nigeria
Babatunde I Omotowo1, Ijeoma Itanyi2, Edmund O Ndibuagu1, Chuka C Agunwa1, Ikechukwu E Obi1, Arthur C Idoko1, Anne C Ndu1
1 Department of Community Medicine, College of Medicine, University of Nigeria, Enugu, Nigeria
2 Department of Community Medicine and Primary Health Care, College of Medicine, Enugu State University, Enugu, Nigeria
|Date of Web Publication||18-Nov-2019|
Dr. Babatunde I Omotowo
Department of Community Medicine, College of Medicine, University of Nigeria, Ituku-Ozalla, Enugu.
Source of Support: None, Conflict of Interest: None
Introduction: Factors that affect tuberculosis (TB) treatment outcomes are important and should be investigated to achieve the targets of TB control program. Aims and Objectives: The aim of this study was to compare treatment outcomes of new smear positive TB patients treated for six months with those treated for eight months. Materials and Methods: A retrospective study of 600 new smear-positive TB patients was carried out. The data were analyzed using Stata version 22 (SPSS Inc., Chicago, Illinois, USA), and the values of P < 0.05 were considered statistically significant. Binary logistic regression was used to identify factors that influenced treatment outcomes. Results: Overall, a higher proportion of patients (78.6%) who were treated for six months had successful treatment outcomes as compared with those treated for eight months 64.4% (P = < 0.001, OR = 2.03, CI = 1.41–2.91). After adjusting for confounders, sex (P = 0.040, AOR = 0.65, CI = 0.44–0.98), treatment duration (P < 0.001, AOR = 2.27, CI = 1.53–3.39), and pretreatment weight (P = 0.007, AOR = 1.28, CI = 1.07–1.52) independently predicted treatment outcome. Conclusion: The treatment success rate was better among the patients treated for six-month duration than those treated for eight-month duration. The current six-month regimen recommended by WHO should be maintained. Loss to follow-up and TB/HIV coinfection management should be improved.
Keywords: Eight months, Nigeria, six months, smear positive, treatment outcomes, tuberculosis
|How to cite this article:|
Omotowo BI, Itanyi I, Ndibuagu EO, Agunwa CC, Obi IE, Idoko AC, Ndu AC. Comparative study of six-month and eight-month treatment of new smear positive tuberculosis cases at a tertiary health facility in Enugu, South-Eastern Nigeria. Int J Med Health Dev 2019;24:78-84
|How to cite this URL:|
Omotowo BI, Itanyi I, Ndibuagu EO, Agunwa CC, Obi IE, Idoko AC, Ndu AC. Comparative study of six-month and eight-month treatment of new smear positive tuberculosis cases at a tertiary health facility in Enugu, South-Eastern Nigeria. Int J Med Health Dev [serial online] 2019 [cited 2019 Dec 15];24:78-84. Available from: http://www.ijmhdev.com/text.asp?2019/24/2/78/271088
| Introduction|| |
Tuberculosis (TB) is a major global public health problem and one of the most important communicable diseases in the majority of developing countries. Prompt initiation of treatment after diagnosis is essential and the best strategy for prevention is to cure TB patients., The aims of treatment of TB include to cure the patient, prevent death and relapse, reduce transmission of TB to others, and prevent the development and transmission of drug resistance. The discovery of chemotherapy brought improvement in the survival of TB patients by drastic reduction in mortality for majority of patients and increase in the TB cure rate.,, The first standard treatment was for 12 months composed of 2 months for intensive phase with thiacetazone (T), isoniazid (H), and streptomycin (S), and 10 months for continuation phase with thiacetazone (T) and isoniazid (H).
Globally in 2017, about 10 million people developed TB. According to the 2018 Global TB Report, Nigeria ranked seventh among the 30 high-TB burden countries, and second in Africa. A total of 104,904 TB cases were notified by Nigeria in 2017, and the WHO estimates of TB burden of 322 per 100,000 population was reported., Nigeria is one of the few countries worldwide where TB control has been slow. The country has not been able to achieve treatment success rate of at least 90% for all new bacteriologically confirmed TB cases.,
The treatment of TB cases should always include an initial intensive phase given for two months, which is effective in eliminating most of the microorganisms and minimizing the influence of those that are resistant to drugs, and the continuation phase given for four to six months which is important to ensure that the patient is permanently cured and does not relapse after completion of treatment.,,
WHO recommended eight-month treatment regime in 1991. The regimen composed of two-month intensive phase therapy with rifampicin (R), isoniazid (H), pyrazinamide (Z), and ethambutol (E) (2RHZE) for adults, whereas children is 2RHZ+E, and six-month continuation phase with ethambutol (E) and isoniazid (H) (6EH) for adults and children.,,, To ensure quality TB treatment and reduce drug resistance, WHO recommended directly observed treatment short course (DOTS) in 1994, and this was adopted by the National Tuberculosis and Leprosy Control Programme (NTBLCP) in Nigeria. The directly observed treatment (DOT) is to ensure TB patients take the right drugs, in the right doses at the right time supervised by a health worker or treatment supporter. DOT should be observed in the intensive phase for both six- and eight-month treatment regimen. DOT should be observed also in the continuation phase of six-month regimen 4RH, whereas the continuation phase of eight-month regimen 6EH is by self-administered therapy daily with monthly DOT at the facility.,,
Globally, in 2010, WHO recommended six-month treatment regimen of 2RHZE + 4RH for treatment of all form of new TB cases. Nigeria started the implementation in 2010, and Enugu state was among the few states that started implementing. Although studies in some countries reported higher successful treatment outcomes with the 6 months regimen,,, to the best of our knowledge no study has validated these findings in Enugu state, Nigeria. We therefore conducted this study to compare the treatment outcomes among new TB patients treated for six and eight months, and to ascertain the determinants.
| Materials and Methods|| |
This study was conducted between July and August 2013 at the chest/DOTS clinic, University of Nigeria Teaching Hospital (UNTH), Enugu, South-East Nigeria. The facility has adopted and implemented the DOTS strategy by use of DOTS providers and treatment supporters for all TB cases during the intensive and continuation phases. All smear positive TB patients during the eight-month treatment received eight months of anti-TB drugs that include two months of 2RHZE in fixed-dose combination followed by 6EH, whereas during the six-month treatment regimen period, TB patients received 2RHZE followed by 4RH.
Study design and data collection
This is a comparative retrospective analytical study of new smear positive TB patients who were treated for six and eight months. A total of 950 folders and treatment cards of patients treated between 2008 and 2012 were retrieved from the TB facility register. New smear positive TB cases within the period who met the eligibility criteria were 600. Among them, 299 received six-month regimen, whereas the remaining 301 were treated for eight months. Extrapulmonary TB cases, relapse, rifampicin resistant cases, childhood TB cases, and other TB cases were excluded from the study. All TB patients in Enugu state were on eight-month treatment regimen before the introduction of six-month treatment regimen in 2010. However, all those who commenced TB treatment before introduction of six months regimen were allowed to complete the treatment.
Standard TB case and treatment outcome definitions
The following TB cases and treatment outcomes were defined according to the National Tuberculosis, Leprosy and Buruli Ulcer Management and Control Guidelines.
New smear positive pulmonary TB. A TB patient who had never taken treatment for TB, or who had taken anti-TB drugs for less than four weeks and had at least one sputum smear positive sample.
Other cases. TB cases who were not new, relapse, treatment after failure, and treatment after loss to follow-up.
Cured. TB patient diagnosed smear or culture positive at the beginning of treatment, who completed treatment, and whose sputum smear culture was negative in the last month of treatment and on at least one previous occasion.
Treatment completed. TB patient who completed treatment but without evidence of cure or failure (no record to show that sputum smear or culture results in the last month of treatment and on at least one previous occasion are negative.
Treatment failure. Patient diagnosed smear or culture positive at the beginning of treatment whose sputum smear or culture is positive at month 5 or later during treatment.
Died. TB patients who died for any reason during the course of treatment.
Defaulter/loss to follow-up. A TB patient who had been on treatment for at least four weeks and interrupted treatment for two consecutive months or more.
Successful treatment (good outcome). A treatment that ended up as cure or treatment completed.
Unsuccessful treatment (bad outcome). A treatment that ended up in treatment default/loss to follow-up, treatment failure, or death.
| Data Analysis|| |
The data analysis was performed using Stata software version 11.0. Sociodemographic and clinical characteristics of the patients (age, sex, marital status, occupation, pretreatment weight, human immunodeficiency virus (HIV) status, and history of contact with child less than six years of age) were compared between the two treatment groups using the Pearson’s chi-squared test. Treatment outcomes of the two treatment groups were compared using Z-test for difference in proportions. Binary logistic regression analysis was performed to determine sociodemographic and clinical characteristics of respondents associated with having a good treatment outcome. Variables that reached a statistical significance of ≤0.2 in the bivariable models were included in the multivariable analysis. Strength of association was measured using odds ratio and statistical significance assessed using P values and 95% confidence intervals for odds ratio. For all analyses, the values of P < 0.05 were considered statistically significant.
Does duration of treatment have influence on TB treatment outcomes?
What other factors have influence on TB treatment outcomes?
Do demographic differences have a significant influence on TB treatment outcomes?
What are the major differences in the treatment outcomes among new smear positive pulmonary TB patients who were treated for six-month duration as compared with eight-month duration?
Duration of treatment has influence on TB treatment outcomes.
Demographic differences have influence on TB treatment outcomes.
Duration of treatment has no influence on TB treatment outcomes.
Demographic differences have no influence on TB treatment outcomes.
Ethical approval for this study was obtained from Health Research Ethics Committee of University of Nigeria Teaching Hospital, Enugu, Nigeria. Permission was also obtained from Enugu State TB Control Programme, Heads of the DOTS facility and record department of UNTH.
| Results|| |
A total of 950 records of patients who were treated for TB from January 1, 2008 to December 31, 2012 were reviewed. In total, 350 records were excluded from the analysis because they did not meet the eligibility criteria.
Of the 600 patients who met the eligibility criteria, most were young adults between the age of 21 and 30 years; the majority were men, married, and of the trading profession. Majority of the patients had pretreatment weight of between 41 and 70kg (81.4% in the eight-month group and 83.7% in the six-month group). There were no differences in the sociodemographic characteristics and pretreatment weight of the patients. A higher proportion of patients who were treated for eight months were HIV-negative (75.8%) as compared with those who received six-month treatment (56.9%; P < 0.001) [Table 1].
|Table 1: Comparison of characteristics of patients who received treatment for TB in a DOTS centre in Enugu State from 2008 to 2012|
Click here to view
Differences in treatment outcomes
Treatment outcome was better among patients who received six-month treatment as compared with those who received eight-month treatment as 69.9% and 39.5% were cured in the two groups, respectively (P < 0.001). A higher proportion of patients who received eight-month treatment had treatment failure (2.0%) as compared with patients who received six-month treatment (0.7%). On the contrary, a higher proportion of deaths were reported among the six-month treatment group (4%) as compared with the eight-month treatment group (2.3%). Overall, a higher proportion of patients who were treated for six months had successful treatment outcomes (78.6%) as compared with those who were treated for eight months (64.5%; P < 0.001) [Table 2].
|Table 2: Differences in treatment outcomes of patients who received treatment for TB in a DOTS centre in Enugu State from 2008 to 2012|
Click here to view
Factors associated with successful treatment outcome
After adjusting for age, sex, marital status, pretreatment weight, and HIV status of the patients, the odds of successful treatment outcome were higher in the six-month treatment group as compared with the eight-month treatment group. The odds of successful treatment outcome were lower among male patients as compared with female patients. Also, the odds of successful treatment outcome also increased with the pretreatment weight [Table 3].
|Table 3: Factors associated with successful treatment outcomes among patients who received TB treatment in a DOTS centre in Enugu State from 2008 to 2012|
Click here to view
| Discussion|| |
We compared treatment outcomes among new smear positive pulmonary TB patients treated for six-month and eight-month duration. The sociodemographic characteristics of the two groups were similar. The findings in our study showed that successful treatment outcomes were better among those treated for six-month duration as compared with those treated for eight months.
Our study found statistically significant lower cure rate among patients treated for eight months as compared with those treated for six months. Also, overall, a higher proportion of patients treated for six months had successful treatment as compared with those treated for eight months. This result is similar to the findings in the studies conducted in Ethiopia and Nigeria where they reported higher odds of unsuccessful treatment outcomes among patients treated for eight months as compared with six-month treatment duration.,, The higher successful treatment outcomes reported in the six-month regimen in this study could be because of drug combinations where rifampicin was included throughout the duration of the treatment as compared with eight-month regimen that rifampicin was included only in the intensive phase for two months possibly because of the efficacy of the drug. The findings also confirmed that the best therapeutic regimen is the one in which a combination of the two main drugs, isoniazid and rifampicin, is given daily for six months.
In our study, higher proportion of patients who took treatment for eight-month duration defaulted as compared with those who took treatment for six months. This is similar to some studies that reported significantly higher defaulter rates in regimens that used rifampicin for only two months in eight-month regimens as compared with regimens that used rifampicin for six months.,,, The lower defaulter rates in six-month regimens could be attributed to the introduction of directly observed therapy used throughout the duration of treatment, whereas it is observed only in the intensive phase of two months, and monthly DOT during collection of drugs in eight-month treatment regimen. The treatment failure in this study was not significantly higher in patients who received treatment for eight months as compared with those who received treatment for six months. This result is similar to findings in some studies.,, DOT used for different durations in the six- and eight-month treatment regimens could be responsible for differences observed in the treatment failure rates in this study.
Surprisingly, despite the higher proportion of HIV coinfection among TB patients who received eight-month regimen as compared with six-month regimen, the death rate was higher during treatment for six months as compared with eight months. This is similar to the study conducted in Lagos where death rate was higher in patients managed during six-month treatment regimen, but is contrary to findings in some other studies conducted in Brazil and Tanzania.,, We could not explain reasons for the differences in the death rates in our study as compared with some other studies despite high HIV coinfection rate.
This study showed about two times higher odds of successful treatment outcomes among patients treated for six-month duration as compared with those who were treated for 8-months treatment. This is similar to findings in some other studies that reported higher odds of unsuccessful outcomes among those who were treated for eight-month duration., This could be related to the explanation given for longer duration of the use of rifampicin in the management of patients for six months and also DOT used throughout the duration of the treatment regimens as compared with eight-month treatment regimens. WHO recommended direct observation of all doses of rifampicin to prevent rifampicin resistance, which is associated with much worse treatment outcomes.
We found that sex, pretreatment weight of patients, and duration of treatment independently predicted the treatment outcomes. The study found that odds for successful treatment outcomes becomes (10%) lower as per 10-year increase in age. This is similar to other studies that reported older patients were more likely to have unsuccessful treatment outcomes than those who are younger.,, This could be attributed to the higher risk of comorbid infections among older age patients who eventually lead to poor treatment outcomes. The odds of successful treatment outcomes were 35% lower among men as compared with women. Occupation of the patients could be responsible for the differences as more men engaged in work such as trading and farming that make adherence to treatment poor.
The study found out that the married TB patients are more likely to have successful treatment outcomes as compared with those single/widowed/divorced/separated. The support from the spouses of married patients could be responsible for the better treatment outcomes among the married. In this study, the odds for successful treatment outcomes becomes 1.2 times higher per 10kg increase in pretreatment weight of TB patients. This could be as a result of the dosage of rifampicin involved in the treatment, which increases with pretreatment weight, and the reduction in the chances of comorbid conditions as pretreatment weight increases among TB patients.
This study reported that the odds for successful treatment outcomes decreased by 36% among HIV coinfected TB patients as compared with those who were HIV negatives. The findings are consistent with other studies that reported that HIV positive TB patients are more likely to have unsuccessful treatment outcomes as compared with those negatives.,,, It is also similar to a study conducted in Ethiopia that reported TB/HIV coinfected patients were more likely to die, with adjusted hazard rate of 1.6 as compared with HIV negative TB patients. HIV influence on TB treatment could be responsible for the poor treatment outcomes. Many studies reported better outcomes among patients who had TB/HIV collaborative services such as co-trimoxazole preventive therapy (CPT) and antiretroviral therapy (ART). Also, our study reported lower odds of successful treatment outcomes among unknown HIV status TB patients. This is similar to the findings in another study conducted in Ethiopia. This could be that many of the unknown HIV cases were actually HIV positives, and so the outcomes will be unsuccessful.
| Conclusion|| |
The treatment success rate was higher among new pulmonary TB patients treated for six-month duration as compared with those treated for eight months. Sex, pretreatment weight, and duration of treatment are determinants of treatment outcomes. There is need for improved defaulter/loss to follow-up management and comprehensive management of TB/HIV coinfection to be able to meet WHO tub erculosis control targets.
Strengths and limitations of this study
This is the first study that compared treatment outcomes of six-month and eight-month treatment of new smear positive pulmonary TB cases in a tertiary health facility in Enugu state, South-east Nigeria
The participants selected from the hospital records for the study were new smear positive pulmonary TB cases who met the eligibility criteria.
This is a retrospective study of patients’ records prone to bias, and incomplete or wrong documentation, so the authors carefully selected those who met the eligibility criteria with complete and correct documentation.
Sputum microscopy results of some patients could not be found in the folders, so authors relied on the final outcomes documented for the patients.
The patients without management outcomes did not meet the eligibility criteria.
Data availability statement
The data will be available from the corresponding author on demand.
We would like to thank the staff of DOTS clinic, University of Nigeria Teaching Hospital, Enugu, Nigeria for their support. A word of thanks also goes to the Enugu State Tuberculosis, Leprosy and Buruli ulcer Control Programme Officer for the permission for this study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
World Health Organization. Global Tuberculosis Report. Geneva, Switzerland: World Health Organization; 2015.
World Health Organization. Global Tuberculosis Report. Geneva, Switzerland: World Health Organization; 2018.
World Health Organization. Guidelines for Treatment of Drug-susceptible Tuberculosis and Patient Care. Geneva, Switzerland: World Health Organization; 2017.
Federal Ministry of Health. National Tuberculosis and Leprosy Control Programme. National Tuberculosis, Leprosy and Buruli Ulcer Management and Control Guidelines. Abuja; Nigeria, 6th Edition. 2015.
Hill AB. Suspended judgment. Memories of the British streptomycin trial in tuberculosis. The first randomized clinical trial. Control Clin Trials 1990;11:77-9.
World Health Organization. Treatment of Tuberculosis: Guidelines for National Programmes. Geneva, Switzerland: World Health Organization; 2003.
Asres A, Jerene D, Deressa W. Tuberculosis treatment outcomes of six and eight month treatment regimens in districts of southwestern Ethiopia: A comparative cross-sectional study. BMC Infect Dis 2016;16:653-61.
International Union Against Tuberculosis and Lung Disease. Management of Tuberculosis: A Guide to the Essentials of Good Practice. Paris; France, 6th edition. 2010.
Daniel OJ, Alausa OK. Treatment outcome of TB/HIV positive and TB/HIV negative patients on directly observed treatment, short course (DOTS) in Sagamu, Nigeria. Niger J Med 2006;15:222-6.
World Health Organization. Guidelines for Tuberculosis Treatment in Adult and Children in National Tuberculosis Programmes. Geneva, Switzerland: World Health Organization; 1991.
Federal Ministry of Health. National Tuberculosis and Leprosy Control Programme. Abuja; Nigeria, 5th Edition. 2010.
World Health Organization. WHO Tuberculosis Control Programme: Framework for Effective Tuberculosis. Geneva, Switzerland: World Health Organization; 1994.
World Health Organization. Treatment of Tuberculosis: Guidelines. Geneva, Switzerland: World Health Organization; 2010.
Nunn AJ, Jindani A, Enarson DA; Study A investigators. Results at 30 months of a randomised trial of two 8-month regimens for the treatment of tuberculosis. Int J Tuberc Lung Dis 2011;15:741-5.
Wolde K, Lema E, Roscigno G, Abdi A. Fixed dose combination short course chemotherapy in the treatment of pulmonary tuberculosis. Ethiop Med J 1992;30:63-8.
Jindani A, Nunn AJ, Enarson DA. Two 8-month regimens of chemotherapy for treatment of newly diagnosed pulmonary tuberculosis: International multicentre randomised trial. Lancet 2004;364:1244-51.
Ukwaja KN, Oshi SN, Alobu I, Oshi DC. Six- vs. eight-month anti-tuberculosis regimen for pulmonary tuberculosis under programme conditions. Int J Tuberc Lung Dis 2015;19:295-301, i–vii.
Mail DC, Benedetti A, Paydar A, Marin I, Roce S, Pai M, et al
. Effect of duration and intermittency of rifampicin on tuberculosis treatment outcomes: A systemic review and meta-analysis. PLoS Med 2009;6:146-54.
Daniel OJ, Adejumo OA, Abdulrazzaq H, Gidado M, Onazi O, Akang G. Eight months vs six months anti-TB regimen in the treatment of newly diagnosed pulmonary tuberculosis patients in Nigeria. Br J Med Med Res 2015;8:836-41.
Albuquerque MF, Leitão CC, Campelo AR, de Souza WV, Salustiano A. [Prognostic factors for pulmonary tuberculosis outcome in Recife, Pernambuco, Brazil]. Rev Panam Salud Publica 2001;9:368-74.
Tanzania-British Medical Research Council. Congtrolled trial of two 6-month regimen of chemotherapy in the treatment of pulmonary tuberculosis. Am Respir Dis 1985;131:727-31.
East and Central African-British Medical Research Council. Controlled clinical trial of 4 short course regimens of chemotherapy (three 6 month and one 8 month) for pulmonary tuberculosis: Final report. Tubercle 1986;67:5-15.
Berhe G, Enquselassie F, Aseffa A. Treatment outcome of smear-positive pulmonary tuberculosis patients in Tigray region, northern Ethiopia. BMC Public Health 2012;12:537.
Muñoz-Sellart M, Cuevas LE, Tumato M, Merid Y, Yassin MA. Factors associated with poor tuberculosis treatment outcome in the southern region of Ethiopia. Int J Tuberc Lung Dis 2010;14:973-9.
Tessema B, Muche A, Bekele A, Reissig D, Emmrich F, Sack U. Treatment outcome of tuberculosis patients at Gondar University Teaching Hospital, northwest Ethiopia. A five-year retrospective study. BMC Public Health 2009;9:371.
Maher D, Harries A, Getahun H. Tuberculosis and HIV interaction in sub-Saharan Africa: impact on patients and programmes; implications for policies. Trop Med Int Health 2005;10:734-42.
Shaweno D, Worku A. Tuberculosis treatment survival of HIV positive TB patients on directly observed treatment short-course in southern Ethiopia: A retrospective cohort study. BMC Res Notes 2012;5:682-9.
Uyei J, Coetzee D, Macinko J, Guttmacher S. Integrated delivery of HIV and tuberculosis services in sub-Saharan Africa: A systematic review. Lancet Infect Dis 2011;11:855-67.
[Table 1], [Table 2], [Table 3]