F1000Research F1000Research 2046-1402 F1000 Research Limited London, UK 10.12688/f1000research.152632.2 Research Article Articles Tuberculosis Case Finding Using Self-Assessment Paradigm Through the E-TIBI Application in HIV Patients

[version 2; peer review: 1 approved with reservations]

 Triyono Erwin Astha Conceptualization Data Curation Formal Analysis Investigation Methodology Supervision Validation Writing – Original Draft Preparation Writing – Review & Editing https://orcid.org/0000-0002-8648-9796 a 1 2 Arini Merita Conceptualization Data Curation Formal Analysis Methodology Supervision Writing – Original Draft Preparation Writing – Review & Editing 2 Tan Feriawan Data Curation Formal Analysis Investigation Project Administration Writing – Original Draft Preparation Writing – Review & Editing https://orcid.org/0000-0003-0799-2199 3 Masyfufah Lilis Data Curation Formal Analysis Methodology Project Administration Writing – Original Draft Preparation Writing – Review & Editing 4 Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia Master of Hospital Administration Study Program, Universitas Muhammadiyah Yogyakarta, Yogyakarta, Special Region of Yogyakarta, Indonesia Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia Medical Record and Health Information, STIKES Yayasan RS Dr. Soetomo, Surabaya, East Java, Indonesia erwintriyono@yahoo.com

No competing interests were disclosed.

 24 2 2025 2024 13 750 17 2 2025 Copyright: © 2025 Triyono EA et al. 2025 This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background

The goal of eliminating tuberculosis has not yet shown a bright spot. Specifically for HIV patients (PLHIV), WHO has made it a special category as a pillar for eliminating tuberculosis. The tuberculosis screening has not yet reached the national target because it is carried out manually by health workers, requiring optimization following technological developments. This study aims to determine the effectiveness of tuberculosis case finding using a self-assessment paradigm in HIV patients.

 Methods

This research was cross-sectional. The data obtained from HIV patients before and after using the E-TIBI application for 3 months each was analyzed using the compare mean independent t-test. Then the Chi-squared test was carried out on the E-TIBI screening characteristic variables.

 Result

In total, there were 921 respondents with 148 (16%) presumptive TB. It was found that there was a significant difference (p<0.05) in the number of presumptive TB cases found in HIV patients before and after using the E-TIBI application. The person with presumptive TB showed 20 of 24 characteristic variables that were statistically significant (p<0.05).

 Conclusion

E-TIBI can increase the tuberculosis case finding in HIV patients so it has the potential to be implemented as a screening tool in the PLHIV community.

 Tuberculosis HIV Case Finding Self-Assessment Digital Health The author(s) declared that no grants were involved in supporting this work. Amendments from Version 1

In this study, the target population of the screening was all HIV patients who came for treatment at the polyclinic of RSUD Dr Soetomo. Cumulative TB-HIV case finding at RSUD Dr Soetomo until December 2022 was 3,147 out of 11,712 HIV patients (27%), while according to the Ministry of Health, the prevalence of TB in HIV patients can reach 49%, meaning that TB case finding is still not optimal. Interventions carried out for PLHIV include socialisation and mentoring involving health workers, cadres and NGOs that shelter PLHIV. Socialisation and mentoring is done especially when PLHIV come to the clinic for treatment and routine medication. We have also revised the infected sentence in the introduction. we have revised and added the multivariable analysis using binary logistic regression test in the table 2. we have added the explanation in the introduction “Meanwhile TB-HIV burden in Indonesia based on the Ministry of Health's report in 2021, the discovery coverage was only 45.7% of the 85% target, while the national TB screening achievement in people living with HIV was 80% of the 100% target, and there are still several provinces with achievements below 50%."

 Introduction

The goal of eliminating tuberculosis (TB) by 2030 by WHO has not shown bright spots. This infectious disease is still a major health problem in the world. This disease is caused by Mycobacterium tuberculosis that very easily transmitted through air droplets released by sufferers. The risk of transmission increases many times in individuals with chronic immune problems such as in patients with HIV. 1 , 2 The group of people living with HIV (PLHIV) is specifically categorized by WHO as a pillar for eliminating tuberculosis because of the strong relationship of both. 3

The tuberculosis epidemic has claimed more human lives than any other infectious disease. Globally, a total of 10.6 million people in the world are fell ill with TB in 2021, with an estimated 1.6 million deaths each year and the PLHIV group causes 200,000 deaths. 3 HIV disease is also a global health burden with a total of 70 million sufferers worldwide and 35 million reported dead. Tuberculosis infection in this population can increase the progression of disease to death. 4

Currently, TB-HIV case detection is mostly done manually by taking anamnesis from health workers, TB-HIV cadre approaches, and community. 5 , 6 Manual case finding is still not effective due to limited personnel, lack of training, and lack of health officer motivation. Based on the Ministry of Health's report in 2021, the discovery coverage was only 45.7% of the 85% target, while the national TB screening achievement in people living with HIV was 80% of the 100% target. 7 Meanwhile, the cumulative TB-HIV case finding at RSUD Dr Soetomo until December 2022 was 3,147 out of 11,712 HIV patients (27%), while according to the Ministry of Health, the prevalence of TB in HIV patients can reach 49%, meaning that TB case finding is still not optimal. 8 , 9 Therefore, finding TB-HIV cases requires a more modern system following current developments in digital technology. 10 , 11

The advanced development of digital technology can be utilized to optimize self-assessment-based disease case findings. Through the self-assessment paradigm, people can effectively and efficiently carry out screening independently and proceed to medical examinations if necessary. 12 Therefore, this research aims to determine the effectiveness of tuberculosis case finding using on self-assessment paradigm through the E-TIBI application in HIV patients (PLHIV) at Dr. Soetomo General Hospital, Surabaya so that it can reduce morbidity and mortality in TB-HIV patients.

 Methods

This research method was cross-sectional with the population were all HIV patients undergoing outpatient therapy at Dr. Soetomo General Academic Hospital in Surabaya. Interventions for PLHIV include socialisation and mentoring involving health workers, cadres and NGOs that support PLHIV. Socialisation and mentoring is done especially when PLHIV come to the clinic for treatment and routine medication. The data were collected from the period October – December 2023 for data before (using medical record data filled in by health workers) and January – March 2024 for data after using the E-TIBI application. To assess the effectiveness of pre and post tuberculosis case findings among PLHIV tested using the compare means independent t-test. Then, the characteristic variables were tested using crosstab with a Chi-squared test to look for relationships. Furthermore, the effect of several variables was tested using binary logistic regression test.

E-TIBI application was a website-based application that can be accessed freely at https://dinkes.jatimprov.go.id/assesment-tbc/public/. After accessing the link an informed consent will appear. There were three main section of this screening. First the respondent must fill in the initial identity (determine the screening for her/him or someone else) and second the identity details (age, gender, occupation, and address). Next the screening question section that’s contain 21 questions. After completing and submitting the form a result come out showing whether presumptive TB or Not. On the E-TIBI application, there was also a filling guide and video education.

Presumptive TB were determined according to the following criteria: Main symptom (Cough for more than two weeks) with or without additional symptoms, there were main symptoms or additional symptoms with a contact history, major symptoms or additional symptoms associated with risk factors. The questionnaire in this application was obtained from the Tuberculosis Symptom Screening from the Indonesian Ministry of Health 2022. 13

E-TIBI application was manufactured by utilizing an information technology development standard that involves database connections with Hypertext Preprocessor (PHP) 14 and HTML based programming. The stylesheet language using CSS (Cascading style sheets) with Asynchronous JavaScript and XML (AJAX). Additional tools used was Vue.js, PostgreSQL, VueX, and Vite. The prototype design using Figma and Sketch. The device used in manufacturing this application was a laptop with processor Core i5-7 th gen, 8GB RAM with Windows 10 Operating System, 64-bit, SSD 128GB.

This website-based application has been registered as copyright of the Ministry of Law and Human Rights of the Republic of Indonesia with number EC00202365785.

 Result

The total number of HIV patients (PLHIV) who accessed the E-TIBI application was 921 people with 148 (16%) presumptive tuberculosis. In Table 1 it was found that there was a significant difference (p<0.05) with difference means -43.000 in the number of presumptive TB case findings in HIV patients (PLHIV) before and after using the E-TIBI application. Table 2 shows the characteristics of the E-TIBI screening results, the person with presumptive tuberculosis showed 20 of 24 characteristic variables that were statistically significant (p<0.05).

Differences in the number of presumptive TB case findings in PLHIV.
Screening Result p-Value
Presumptive TB Non-Presumptive TB
Pre E-TIBI 20 6310 0.002
Post E-TIBI 148 773

Difference means: -43.000.

 Characteristics of E-TIBI screening results.
Variable (n=921) Presumptive TB Non-presumptive TB Total p (bivariable analysis)
p (multivariable analysis)
n % n % n %
Age 0.360
0.834
 Adolescent (10-18 y.o) 1 0.1 1 0.1 2 0.2
 Adult (19-59 y.o) 140 15.2 743 80.7 883 95.9
 Elderly (>60 y.o) 7 0.8 29 3.1 36 3.9
Gender 0.720
0.775
 Man 105 11.4 537 58.3 642 69.7
 Woman 43 4.7 236 25.6 279 30.3
Body Mass Index (BMI) 0.005
0.001
 Severely Underweight (<17) 10 1.1 24 2.6 34 3.7
 Underweight (17-18.5) 14 1.5 36 3.9 50 5.4
 Normal (18.5-25) 97 10.5 491 53.3 588 63.8
 Overweight (25-27) 13 1.4 114 12.4 127 13.8
 Obese (>27) 14 1.5 108 11.7 122 13.2
Cough >2 weeks 0.000
0.997
 Yes 21 2.3 0 0.0 21 2.3
 No 127 13.8 773 83.9 900 97.7
Bleeding cough 0.000
0.998
 Yes 6 0.7 0 0.0 6 0.7
 No 142 15.4 773 83.9 915 99.3
Cough <2 weeks 0.000
0.000
 Yes 31 3.4 2 0.2 3.6 33
 No 117 12.7 771 83.7 888 96.4
Weight loss 0.000
0.000
 Yes 46 5.0 1 0.1 47 5.1
 No 102 11.1 772 83.8 874 94.9
Decreased appetite 0.000
0.997
 Yes 25 2.7 0 0.0 25 2.7
 No 123 13.4 773 83.9 896 97.3
Fever 0.000
0.998
 Yes 11 1.2 0 0.0 11 1.2
 No 137 14.9 773 83.9 910 98.8
Fatigue 0.000
0.000
 Yes 76 8.3 2 0.2 78 8.5
 No 72 7.8 772 83.7 843 91.5
Night sweats 0.000
0.997
 Yes 16 1.7 0 0.0 16 1.7
 No 132 14.3 773 83.9 905 98.3
Dyspnea 0.000
0.011
 Yes 21 2.3 1 0.1 22 2.4
 No 127 13.8 772 83.8 899 97.7
Chest pain 0.000
0.997
 Yes 19 2.1 0 0.0 19 2.1
 No 129 14.0 773 83.9 902 97.9
Neck lump 0.000
0.001
 Yes 8 0.9 0 0.0 8 0.9
 No 140 15.2 772 83.8 912 99.0
TB in a family member 0.000
0.998
 Yes 8 0.9 0 0.0 8 0.9
 No 140 15.2 773 83.9 913 99.1
Home Contact 0.000
0.998
 Yes 28 3.0 0 0.0 28 3.0
 No 120 13.0 773 83.9 893 97.0
Room contact 0.000
0.997
 Yes 28 3.0 0 0.0 28 3.0
 No 120 13.0 773 83.9 893 97.0
Diabetes Mellitus 0.020
0.001
 Yes 9 1.0 14 1.5 23 2.5
 No 139 15.1 759 82.4 898 97.5
Malnutrition 0.001
0.007
 Yes 17 1.8 37 4.0 54 5.9
 No 131 14.2 736 79.9 867 94.1
Smoking 0.000
0.000
 Yes 39 4.2 93 10.1 132 14.3
 No 109 11.8 680 73.8 789 85.7
Pregnant 0.490
0.710
 Yes 2 0.2 6 0.7 8 0.9
 No 146 15.9 767 83.3 913 99.1
Elderly > 60 years 0.612
0.556
 Yes 6 0.7 25 2.7 31 3.4
 No 142 15.4 748 81.2 890 96.6
History of complete TBC treatment 0.000
0.000
 Yes 57 6.2 132 14.3 189 20.5
 No 91 9.9 641 69.6 732 79.5
History of incomplete TBC treatment 0.001
0.022
 Yes 6 0.7 6 0.7 12 1.3
 No 142 15.4 767 83.3 909 98.7
Discussion

Since 2011, WHO has recommended that people living with HIV (PLHIV) undergo routine tuberculosis screening. If 4 cardinal symptoms are found consisting of cough, fever, night sweats and weight loss, PLHIV must undergo a molecular diagnostic examination such as Xpert MTB/RIF/Ultra11. 15 This research is an investigative effort towards a new paradigm to increase TB case finding in key populations. As far as researchers’ best research is concerned, this research is the first to be conducted in Indonesia. In general, this research illustrates the potential benefits of technology as a new approach to finding a person with presumptive TB.

In Indonesia, the tuberculosis case findings still rely on health workers who are assisted by trained cadres in health facilities. The Ministry of Health, through active and passive approaches, is trying to increase the acceleration of case finding. Active case finding is carried out by tracking contact, epidemiological investigations and mass screening of at-risk groups, while passive case finding is by examining patients who come to health facilities. 16 Through E-TIBI a new paradigm is formed by emphasizing public participation as the main actor who initiates the initial examination. It is believed that this public participation can increase the tuberculosis case findings, especially in the PLHIV group. Health facilities will also receive notification and be given the authority to follow up if there is presumptive TB in their working area. Apart from that, E-TIBI is also a medium for information and education about tuberculosis and its management.

In this study, from the screening results, 148 (16%) presumptive TB were found. This result compared with other studies was quite varied. Gersh (2021) found 48 (12.6%) participants with TB symptom, Santos (2020) found 15.4% patients with three symptoms WHO screening, Owiti’s research (2019) found 4160 (0.7%) patients with presumptive symptoms of tuberculosis, Bjerrum (2016) found 12.6-20% tuberculosis suspicion, and Burmen (2016) found 96 (16%) PLHIV patients needed further examination. 17 – 20 The use of E-TIBI shows a significant relationship with the number of presumptive TB in PLHIV patients who undergo TB screening. The number of presumptive TB from the E-TIBI self-assessment results is seven-fold higher when compared to manual screening. This is possible because the use of electronic screening is much simpler and can reduce delay by answering questions that are available on the website application, while manual screening must be carried out at the clinic, this is also found in Woliansky (2024) and Blink (2022) study. 21 , 22

The result found cough, weight loss, decreased appetite, fever, fatigue, night sweats, dyspnea, chest pain, and lumps in the neck were bivariable significant with presumptive tuberculosis meanwhile for the multivariable anaylsis only cough<2 weeks, weight loss, fatigue, dyspnea and neck lump. Based on current research these signs and symptoms are often found in TB patients. 20 In HIV patients (PLHIV) these symptoms become more varied depending on the severity and immunosuppression of the patient. 23

Our study indicated that BMI or body mass index is quite influential in combined TB-HIV infection. Several studies state that patients with a BMI below normal have a three-fold higher risk of being infected with TB than HIV patients compared to those with a normal BMI. 24 Apart from that, a low BMI also has a worse prognosis, increasing the risk of death up to three-fold higher. 25 This is because patients with a BMI below normal are assumed to experience malnutrition which aggravates their immunocompromised condition and leads to death. 26

History of contact with TB sufferers is important in TB screening, as this study shows. Household contact research by Karbito (2022) said that spending five hours or more with active TB patients increases the risk of latent TB infection by three-fold higher compared to less than five hours a day. 27 Laghari’s research (2019) states that household contact increases the risk of TB infection by up to fifteen-fold higher. 28

In the result found Diabetes mellitus (DM) was statistically significant with presumptive tuberculosis. The risk of TB in patients with DM increases to three-fold higher. 29 Diabetes mellitus has also been shown to increase the risk of multi-drug-resistant TB. Uncontrolled diabetes mellitus as assessed by high HbA1c and GDP is closely related to TB susceptibility and worsens treatment prognosis. 30 This is also exacerbated by Indonesia being in the top three countries with the highest TB burden in the world and the top 10 countries with DM sufferers in the world. Pathophysiologically, DM itself worsens TB infection through many mechanisms ranging from increasing the risk of infection, increasing the risk of latent TB reactivation, increasing the risk of relapse, and worsening treatment to death. 31 TB infection also often causes temporal hyperglycemia, which is caused by stress, prolonged inflammation, changes in glucose and lipid metabolism, and insulin resistance syndrome. 32

A history of TB treatment or infection is a risk factor that also has an influence, especially in the HIV population, as found in this study. Based on several works of literature, it is stated that the risk of latent TB reactivation becoming active TB in PLHIV is up to twenty-fold higher. 33 Other research states that tuberculosis infections in PLHIV are more likely to be caused by reactivation than by new infections. 34 This is mainly caused by the depletion of CD4 + cells in untreated PLHIV patients. Apart from that, it was also reported that functional disruption of TB-specific T cells, increased regulation of TB receptors on macrophages, manipulation of macrophage bactericidal pathways, deregulation of chemotaxis, and deregulation of macrophage apoptosis by TNF were the reasons why reactivation increased. 35

Smoking is also a risk factor that has a significant relationship with TB-HIV infection. These results are supported by research which states that smoking increases the risk of TB up to three-fold higher and people who have ever smoked up to two-fold higher compared to those who have never smoked in PLHIV. 36 Exposure to cigarette smoke also significantly increases the risk of transmitting TB to family or close contacts. In addition, the prevalence of smoking has doubled in TB patients compared to the general population. 37 Apart from that, smoking also worsens TB symptoms, increases the risk of drug resistance, increases the risk of cardiovascular disease, worsens treatment outcomes and even death. 38

In the future, the research team plans to develop this application not only limited to screening but into a complete TB-HIV management system, through an account application that is used to carry out TB screening in PLHIV, update patient data, namely the results of diagnosis confirmation, drug taking visits and evaluation until completion of treatment. And then this application is also expected to be implemented in all tuberculosis key populations and the wider community.

Strengths and limitation

The tuberculosis case finding using self-assessment through the E-TIBI application is a new paradigm of disease screening conducted in Indonesia. With the help of technological advances through E-TIBI, tuberculosis screening can be done easily and quickly by anyone, anytime and wherever they are. This research has limitations, not all HIV patients (PLHIV) can access the E-TIBI service because some patients do not bring cellphones that have an internet connection and some of them cannot use internet technology.

 Conclusion

E-TIBI has the potential to be a tuberculosis screening tool because the number of TB case findings in HIV patients (PLHIV) before and after using the E-TIBI application was a significant increase (p<0.05). The presumptive tuberculosis showed 20 of 24 characteristic variables that were statistically significant (p<0.05). It is hoped that this application can be implemented widely as a screening tool in the PLHIV community.

Ethical considerations

This research was registered at the Ethical Committee in Health Research Dr. Soetomo General Academic Hospital, Surabaya, Indonesia (0920/KEPK/II/2024 dated February 19, 2024).

Consent: In this study, before the participant undergo screening, written informed consent will appear in the website application and if participants agree, they must click “willing” before they can carry out screening.

 Data availability Underlying data

Figshare: Tuberculosis Case Finding Using Self-Assessment Paradigm Through the E-TIBI Application in HIV Patients_Raw Data E-TIBI. https://doi.org/10.6084/m9.figshare.25953712.v2 39

This project contains the following underlying data:

Raw Data Spss E-TIBI.xlsx (Anonymised answers to questionnaire, correct answer +1 incorrect answer 0)

Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)

 Extended data

Figshare: Tuberculosis Case Finding Using Self-Assessment Paradigm Through the E-TIBI Application in HIV Patients_Screening form, https://doi.org/10.6084/m9.figshare.26082367.v3 40

This project contains the following extended data:

Screening form.docx (Blank Indonesian version of questionnaire.

Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).

 Reporting guidelines

Figshare: Tuberculosis Case Finding Using Self-Assessment Paradigm Through the E-TIBI Application in HIV Patients_STROBE.docx, https://doi.org/10.6084/m9.figshare.25991857.v2 41

Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)

 Acknowledgments

The researchers would like to thank the East Java Provincial Health Office, Indonesia and the Department of Internal Medicine, Dr. Soetomo General Academic Hospital Surabaya, Indonesia.

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Public Health Action. 2017 Mar 21;7(1):39–45. 28775942 10.5588/pha.16.0045 PMC5526492 Triyono EA : Tuberculosis Case Finding Using Self-Assessment Paradigm Through the E-TIBI Application in HIV Patients_Raw Data E-TIBI.[Dataset]. figshare. 2024. 10.6084/m9.figshare.25953712.v2 Triyono EA : Tuberculosis Case Finding Using Self-Assessment Paradigm Through the E-TIBI Application in HIV Patients_Screening form. [Journal contribution]. figshare. 2024. 10.6084/m9.figshare.26082367.v3 Triyono EA : Tuberculosis Case Finding Using Self-Assessment Paradigm Through the E-TIBI Application in HIV Patients_STROBE.docx. [Preprint]. figshare. 2024. 10.6084/m9.figshare.25991857.v2 10.5256/f1000research.167418.r301074 Reviewer response for version 1 Satyanarayana Srinath 1 Referee Centre for Operational Research, International Union against Tuberculosis and Lung Disease (The Union), New Delhi, India

Competing interests: No competing interests were disclosed.

 7 8 2024 Copyright: © 2024 Satyanarayana S 2024 This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. recommendation approve-with-reservations

Majorly, the target population (the denominator) for the screening services is unclear.

How many PLHIV were there, how many of them were informed about the new E-TIBI, what was the uptake, what were the mechanisms that were adopted by the researchers for educating the PLHIV about the new method of screening? Need more details about how the intervention was rolled. In addition, there is hardly any gap between pre-and post-periods. Without these details it is not possible to assess the data and the appropriateness of the results in table 1.

Table 2 presents data on bi-variable analysis. Recommend the researchers to conduct a multivariable analysis to find out the independent variables that are associated with the outcome of interest.

 Other issues:

In the introduction, it is mentioned that globally 10.6 million people are infected with this. This is incorrect. An estimated ~10.6 million develop the disease every year and disease is not the same as infection.

In the introduction, no details are provided about TB and HIV disease burden of Indonesia and the levels of TB-HIV co-disease burden.

Overall, the contents of the manuscript need to be significantly enhanced to get a clear understanding of what was done and to get a better sense of the results.

Is the work clearly and accurately presented and does it cite the current literature?

Partly

If applicable, is the statistical analysis and its interpretation appropriate?

No

Are all the source data underlying the results available to ensure full reproducibility?

Partly

Is the study design appropriate and is the work technically sound?

Partly

Are the conclusions drawn adequately supported by the results?

Partly

Are sufficient details of methods and analysis provided to allow replication by others?

Partly

Reviewer Expertise:

All aspects related to TB service delivery.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.