ORIGINAL ARTICLE Year : 2022  |  Volume : 11  |  Issue : 4  |  Page : 442-447

Outcomes of latent tuberculosis infection treatment in Istanbul

Abdullah Emre Güner1, Sule Kiziltas2, Aylin Babalik3, Esra Sahin4, Al Sibel4, Mine Safak4, Zeki Kiliçaslan5
1 Department of Public Health, University of Health Sciences, Hamidiye Faculty of Medicine, Istanbul, Turkey
2 Department of Chest Diseases, University of Health Sciences, Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey
3 Department of Chest Diseases, University of Health Sciences, Sureyyapasa Chest Diseases and Thoracic Surgery Teaching and Research Hospital, Istanbul, Turkey
4 Department of Public Health Services, Provincial Directorate of Health, Istanbul, Turkey
5 Department of Chest Diseases, Istanbul University Faculty of Medicine, Istanbul, Turkey

Date of Submission10-Aug-2022Date of Acceptance15-Nov-2022Date of Web Publication10-Dec-2022

Correspondence Address:
Sule Kiziltas
University of Health Sciences, Bursa Yuksek Ihtisas Training and Research Hospital, Mimarsinan Mah. Emniyet Cad. 16310 Yildirim, Bursa
Turkey

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/ijmy.ijmy_196_22

Background and Aim: Increasing the extensity of latent tuberculosis infection (LTBI) treatment which is one of the important parameters of tuberculosis (TB) control and completing the treatment in success are important. The purpose of this study is to evaluate LTBI treatment indications and treatment outcomes of patients who received LTBI treatment in İstanbul between 2016 and 2018. Methods: The treatment outcomes of people who started LTBI treatment registered in TB dispensaries in Istanbul between 2016 and 2018 were analyzed retrospectively according to the variables of the age groups, gender, dispensary subgroups, and prevention treatment indications. Data collected from the health institutions were evaluated. Results: 26.920 patients received LTBI treatment in all Istanbul TB dispensaries between 2016 and 2018. The evaluation of LTBI treatment indications; contact 15.696, Tuberculin skin test (TST) positivity 2224, immunosuppression 8746, TST conversion 58, sequelae lesion 15, and other indications are identified as 181. The groups which diagnosed with TB disease, mortality, transfer, other, and still in treatment are excluded from the analysis of LTBI treatment outcomes. A total of 25.253 patients were analyzed. 65 percent of the patients had completed LTBI treatment. Variables effective for treatment outcomes are analyzed with logistic regression. Treatment discontinuation was statistically significantly lower in 2017 (odds ratio [OR]: 0.906 confidence interval [CI] [95%] [0.849–0.968]) and 2018 (OR: 0.635 CI [95%] [0.594–0.679]) compared to 2016. Treatment lost to follow-up was statistically significantly lower in those receiving LTBI treatment with the indication of tuberculin skin test positivity (OR: 0.541 CI [95%] [0.487–0.600]) and the indication of immunosuppression (OR: 0.284 CI [95%] [0.142–0.569]) compared to those who received LTBI treatment due to contact. When the treatment results are evaluated according to the TB incidence of the region where the dispensaries are located, treatment lost to follow-up was higher in 101–200 per 100,000 incidence group (OR: 1.201 CI [95%] [1.123–1.285]) and incidence of 201–370 per 100,000 (OR: 1.461 CI [95%] [1.358–1.572]). Treatment lost to follow-up was higher in dispensaries on the European side (OR: 1.293 CI [95%] [1.203–1389]) and the 0–35 age group (OR: 1.248 CI [95%] [1.168–1.333]). Conclusion: In conclusion, the treatment completion rate should be improved for an effective LTBI treatment which is one of the important parameters of targeted TB elimination. Particularly people under the age of 35 years and regions with high-TB incidence should receive special care and close follow-up.

Keywords: Latent tuberculosis infection treatment, latent tuberculosis infection, mycobacterium tuberculosis

How to cite this article:
Güner AE, Kiziltas S, Babalik A, Sahin E, Sibel A, Safak M, Kiliçaslan Z. Outcomes of latent tuberculosis infection treatment in Istanbul. Int J Mycobacteriol 2022;11:442-7
How to cite this URL:
Güner AE, Kiziltas S, Babalik A, Sahin E, Sibel A, Safak M, Kiliçaslan Z. Outcomes of latent tuberculosis infection treatment in Istanbul. Int J Mycobacteriol [serial online] 2022 [cited 2022 Dec 12];11:442-7. Available from: https://www.ijmyco.org/text.asp?2022/11/4/442/363172   Introduction 

Tuberculosis (TB) still maintains its importance as the deadliest infectious disease in the world. TB is a major cause of human deaths worldwide and the leading cause of death due to an infectious disease after COVID-19.[1] Globally, an estimated 9.9 million people fell ill with TB in 2020. There were 1.3 million TB deaths among HIV-negative people and an additional 214.000 deaths among HIV-positive people.[1] The WHO's End TB Strategy includes targets of a 95% reduction in TB deaths and a 90% reduction in TB incidence by 2035.[2]

Increasing the extensity of latent tuberculosis infection (LTBI) treatment which is one of the important parameters of TB control and completing the treatment in success is important. High rate of LTBI treatment completion rate will decrease the progression of TB infection to TB illness and will contribute to the management of a successful TB control program. Patients should be trained, supported, tracked, and received controls by dispensary staff to provide adaptation to treatment and complete it with success.[3],[4]

The primary purpose of this study is to evaluate LTBI treatment indications and treatment results of patients who received LTBI treatment in İstanbul between 2016 and 2018.

Methods

A total of 26,920 patients who are recorded at TB dispensary in İstanbul during 2016, 2017, and 2018 are included in the retrospective cohort study. Data collected from the health institutions were evaluated.

The ages of patients who received protection treatment were grouped as 0–5 ages, 6–15 ages, 16–35 ages, 36–65 ages, and 66 ages and above.

LTBI treatment indications are grouped as; contact with TB patients, tuberculin skin test (TST), immunosuppression, TST conversion, fibrotic sequelae lesion, and other (The bacille Calmette-Guérin (BCG) adverse effects it is, in contact with animals, positive Quantiferon, and intravesical BCG therapy).

Dispensaries are divided into subgroups according to regions and TB incidence of the region where the dispensaries are located. Dispensaries are grouped as European or Asian side by their region and grouped as 19–100, 101–200 and 201 and above per 100,000 population incidence rate per annual TB incidence of dispensary.

Treatment results of patients receiving protection treatment are grouped as; treatment completion, loss to follow-up, mortality, transfer or still in treatment, being a TB patient, and others (LTBI treatment was stopped). The groups of which treatment result is other are anti-tumor necrosis factor users and patients whose treatment was discontinued by the doctor due to reasons such as elevated liver enzymes or patients who had a stopped treatment as they are multidrug-resistance TB contact.

A total of 1667 patients with mortality (n = 61), transfer (n = 378) or still in treatment (n = 7), diagnosed with TB (n = 133), and others (n = 1088) are excluded from the study. Treatment outcomes (treatment completion and loss to follow-up) of a total of 25,253 participants were analyzed (analyzed by age groups, gender, dispensary subgroups, and prophylactic indications variables).

LTBI treatment indications and protective medicine dose and exposure time are defined according to the Ministry of Health TB diagnosis and treatment guide. The following regimen is recommended for the treatment of LTBI: 6 or 9 months of daily isoniazid (5 mg/kg for adults; 10 mg/kg for children).[3]

Statistical analysis

Categorical variables were summarized using proportions. The Chi-square test was used. Logistic regression, clustered analyses yielding odds ratios (ORs), 95% confidence interval (CI), and P values (SPSS) were reported to describe the association between variables (years, preventive treatment indications, dispensary groups according to TB incidence rate and specific region, and demographic characteristics of persons receiving treatment for LTBI) and treatment outcomes.

Data collection

Twelve Istanbul TB association dispensaries and 16 Ministry of Health dispensaries are located in Istanbul. Dispensary data are collected regularly both in electronic environment (National TB System – UTS) and as written documental.

Ethical approval for the study was obtained from the institutional review board of health science University Süreyyapaşa Chest Disease and Thoracic Surgery Education and Research Hospital in accordance with the Helsinki recommendations (approval no 116.2017.204).

  Results 

A total of 26,920 patients received LTBI treatment in all Istanbul TB dispensaries between 2016 and 2018. [Table 1] demonstrates LTBI treatment indications and treatment results. Per evaluation of LTBI treatment indications; Contact TB 15.696, TDT positivity 2224, immunosuppression 8746, TDT conversion 58, sequelae lesion 15, and other indications are identified as 181. Treatment results of patients who received LTBI treatment are evaluated. Treatment completion rate 60.2% (n = 16204), loss to follow-up 33.6% (n = 9049), TB disease 0.5% (n = 133), mortality 0.2% (n = 61), transfer 1.4% (n = 378), other 4.0% (n = 1088), and still in treatment is identified as 0.0% (n = 7). The groups which diagnosed with TB disease, mortality, transfer, other, and still in treatment are excluded from the analysis of LTBI treatment results. The number of patients excluded was 1667 (TB disease diagnosed: 133, mortality: 61, transfer: 378, other: 1088, and in treatment: 7). A total of 25,253 patients were analyzed. Variables affecting the result of treatment (treatment completion and loss to follow-up were analyzed with the Chi-square test). The Chi-square analysis of factors affecting treatment results is shown in [Table 1]. 64. 2% of 25,253 patients who received LTBI treatment completed treatment, whereas 35. 8% of the patients' quitted the treatment.

Table 1: Chi-square analysis of variables affecting latent tuberculosis infection treatment outcomes

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Treatment completion is detected as 59.6% in 2016, 62.0% in 2017, and 70.2% in 2018. Year (P = 0.000) is identified as statistically significant. Treatment completion on and under the age of 35 years is 60.2% and at above 36 is identified as 72.2%. Age groups are identified as statistically significant (P = 0.000). When the indications for LTBI treatment were evaluated, treatment completion was found to be TB contact at 56%, TST positivity at 72%, immunosuppression at 76.7%, TST conversion at 82.1%, sequelae at 69.2%, and other at 70.8%. Treatment outcomes according to LTBI treatment indications are identified as statistically significant (P = 0.000). The treatment completion rate is 69.2% at dispensaries with 19–100 incidences per 100,000 population, 65.8% at dispensaries with 101–200 incidences per 100,000 population, and identified as 56.9% at dispensaries with 201–370 incidences per 100,000 population while evaluating treatment results according to TB incidence of dispensaries' regions. Treatment outcomes according to TB incidence of dispensaries' regions are identified as statistically significant (P = 0.000). Treatment completion rates in the European side dispensaries are detected as 61.3%, whereas it is detected as 71.8% in the Anatolian side while evaluating the location of TB dispensaries in the European and Anatolian sides. Evaluations in the European and Asian sides are identified as statistically significant (P = 0.000). The treatment completion rate for men is identified as 64.3%, whereas it is identified as 64.0% for women. The gender variable was not statistically significant in the treatment outcomes (P = 0.333).

Variables effective for treatment outcomes are analyzed with logistic regression [Table 2]. Treatment loss to follow-up was statistically significantly lower in 2017 (OR: 0.906 CI [95%] [0.849–0.968]) and 2018 (OR: 0.635 CI [95%] [0.594–0.679]) compared to 2016.

Table 2: Logistic regression analysis of variables affecting latent tuberculosis infection treatment outcomes

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Treatment lost to follow-up was statistically significantly lower in those receiving LTBI treatment with the indication of TST positivity (OR: 0.541 CI [95%] [0.487–0.600]) and the indication of immunosuppression (OR: 0.284 CI [95%] [0.142–0.569]) compared to those who received LTBI treatment due to TB contact.

When the treatment results are evaluated according to the TB incidence of the region where the dispensaries are located, treatment lost to follow-up was higher in 101–200 per 100,000 incidence group (OR: 1.201 CI [95%] [1.123–1.285]) and incidence of 201–370 per 100,000 (OR: 1.461 CI [95%] [1.358–1.572]).

Loss to follow-up rate in European side dispensaries is identified statistically significantly high in comparison to dispensaries in the European side (OR: 1.293 CI [95%] [1.203–1389]). In age groups, 0–35 age group (OR: 1.248 CI [95%] [1.168–1.333]), loss to follow-up rate at 35 age group and above is identified as statistically significantly high.

  Discussion 

In our study, 64.2% of the total 25,253 patients who received latent TB infection treatment are identified as completing the treatment, whereas 35.8% are identified as quitted the treatment. In previous studies, LTBE treatment completion rates were identified between 34% and 68%.[5],[6],[7],[8],[9],[10],[11] In our study, increase is identified in treatment completion rates by years (in 2016 – 59.6%, in 2017 – 62.0%, and in 2018 – 70.2%). Treatment discontinuation was statistically significantly lower in 2017 (OR: 0.906 CI [95%] [0.849–0.968]) and 2018 (OR: 0.635 CI [95%] [0.594–0.679]) compared to 2016.

In previous studies with different selected groups, adherence to LTBE treatment was identified as higher. In the study of White et al., treatment with directly observed preventive therapy) is (70.3%) identified higher than self-administered therapy (47.9%). Although women's adherence to treatment was found to be higher in many studies, the gender variable was not found to be statistically significant in treatment outcomes in our study.[12],[13],[14] In our study, the treatment completion rate at age of 35 years and below was identified as 60.2%, whereas the treatment completion rate at age of 36 years and above is identified as72.2%. In the literatures, the treatment completion rate of old people is identified as similar to our study (74.5%).[15],[16] In our study, loss to follow-up rates were found to be statistically higher in the 0–35 age group (OR: 1.248 CI [95%] [1.168–1333]) compared to the 35 and older age group. While there are studies that found low adherence to treatment in groups similar to our study,[7],[17],[18] there are also studies showing that treatment compliance is higher in the younger age groups (e.g., under 18 years of age).[14],[19],[20],[21]

Treatment completion rates per LTBI treatment indications; TB contact: 56%, TST positivity: 72%, immunosuppression: 76.7%, TST conversion: 82.1%, sequala: 69.2%, and other is identified as 70.8%. Treatment discontinuation was statistically significantly lower in those receiving LTBI treatment due to TST positivity (OR: 0.541 CI (95%) (0.487–0.600) and immune suppression (OR: 0.284 CI (95) (0.487–0.600). In many studies, adherence to treatment is identified as low due to reasons such as disbelief in treatment for not having the disease, long period of treatment, disbelief in INH credibility, and side effects.[22],[23],[24] Reichler et al. and Machado et al. found the rates of completion of treatment in TB contacts as low as in our study (in order 51% and 53.5%).[25],[26]

According to the WHO, in Europe Zone, our country is situated among countries with low incidences.[27] Estimated incidence of TB is 15 per 100,000 population in 2020.[28] Istanbul which is the biggest city of Turkey carries an utmost important as it has 29.48% of total TB patients.[29] In Turkey's fight against TB 2019 report, it was determined that while the total incidence rate was 14.1 per 100,000 in Turkey, it was 22.9 per 100,000 in Istanbul.[30] Istanbul consists of districts which have demographically, social economically, and culturally different and are located in Asia and Europe regions. In the evaluation of treatment completion according to TB incidence per region of dispensaries, treatment completion at dispensaries with 19–100 incidence in 100,000 is 69.2%, treatment completion at dispensaries with 101–200 incidence in 100,000 is 65.8%, and treatment completion at dispensaries with 201–370 incidence in 100,000 is 56.9%. When the treatment results are evaluated according to the TB incidence of the region, where the dispensaries are located, treatment lost to follow-up was higher in 101–200 per 100,000 incidence group (OR: 1.201 CI (95%) (1.123–1.285), and incidence of 201–370 per 100,000 (OR: 1.461 CI [95%] [1.358–1.572]).

Treatment completion rates in dispensaries at the European side are 61.3%, whereas it is identified as 71.8% in dispensaries at the Asian side. In comparison to dispensaries at the Asian side, treatment abandonment is identified as statistically higher (OR: 1.293 CI [95%] [1.203–1389]). In districts where immigration is higher and social economic level is low, TB incidence is higher and adaptation to LTBI treatment is lower. Sufficiency of medical staff, patient training, and supporting patients for adaptation per region's social economic and cultural situation is very important at dispensaries where the number of patients is very high.

The retrospective method is one of the barriers in our study. In addition, factors such as immigrants, drug addicts, educational status of individuals, psychosocial factors, and subgroups of immunosuppression could not be analyzed.

  Conclusion 

In conclusion, treatment completion rate and adherence should be improved for an effective LTBI treatment which is one of the important parameters of targeted TB elimination. Particularly people under the age of 35 years and regions with high TB incidence should receive special care and close follow-up.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 

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  [Table 1], [Table 2]