Skip to main content
PLOS One logoLink to PLOS One
. 2024 May 14;19(5):e0300916. doi: 10.1371/journal.pone.0300916

Treatment success rate and associated factors among drug susceptible tuberculosis individuals in St. Kizito Hospital, Matany, Napak district, Karamoja region. A retrospective study

Ronald Opito 1, Keneth Kwenya 2, Saadick Mugerwa Ssentongo 2,*, Mark Kizito 3, Susan Alwedo 2, Baker Bakashaba 2, Yunus Miya 2, Lameck Bukenya 2, Eddy Okwir 4, Lilian Angwech Onega 2, Andrew Kazibwe 2, Emmanuel Othieno 5, Fred Kirya 6, Peter Olupot Olupot 7,8
Editor: Hamufare Dumisani Dumisani Mugauri9
PMCID: PMC11093355  PMID: 38743721

Abstract

Background

Tuberculosis (TB) is the leading cause of death among infectious agents globally. An estimated 10 million people are newly diagnosed and 1.5 million die of the disease annually. Uganda is among the 30 high TB-burdenedd countries, with Karamoja having a significant contribution of the disease incidence in the country. Control of the disease in Karamoja is complex because a majority of the at-risk population remain mobile; partly because of the nomadic lifestyle. This study, therefore, aimed at describing the factors associated with drug-susceptible TB treatment success rate (TSR) in the Karamoja region.

Methods

This was a retrospective study on case notes of all individuals diagnosed with and treated for drug-susceptible TB at St. Kizito Hospital Matany, Napak district, Karamoja from 1st Jan 2020 to 31st December 2021. Data were abstracted using a customised data abstraction tool. Data analyses were done using Stata statistical software, version 15.0. Chi-square test was conducted to compare treatment success rates between years 2020 and 2021, while Modified Poisson regression analysis was performed at multivariable level to determine the factors associated with treatment success.

Results

We studied records of 1234 participants whose median age was 31 (IQR: 13–49) years. Children below 15 years of age accounted for 26.2% (n = 323). The overall treatment success rate for the study period was 79.3%(95%CI; 77.0%-81.5%), with a statistically significant variation in 2020 and 2021, 75.4% (422/560) vs 82.4% (557/674) respectively, (P = 0.002). The commonest reported treatment outcome was treatment completion at 52%(n = 647) and death was at 10.4% (n = 129). Older age, undernutrition (Red MUAC), and HIV-positive status were significantly associated with lower treatment success: aPR = 0.87(95%CI; 0.80–0.94), aPR = 0.91 (95%CI; 0.85–0.98) and aPR = 0.88 (95%CI; 0.78–0.98); respectively. Patients who were enrolled in 2021 had a high prevalence of treatment success compared to those enrolled in 2020, aPR = 1.09 (95%CI; 1.03–1.16).

Conclusion

TB TSR in Matany Hospital was suboptimal. Older age, poor nutrition, and being HIV-positive were negative predictors of treatment success. We propose integrating nutrition and HIV care into TB programming to improve treatment success.

Introduction

Globally, tuberculosis (TB) is the leading cause of death among infectious disease. It is estimated that 10 million people fell ill with TB in 2020, albeit only 5.8 million were notified, due to COVID-19 ramifications [1]. In 2020 the global TB treatment success rate (TSR) was 86% and 1.5 million people died of the disease. Notable co-infection was HIV which was an underlying cause of mortality in TB in 14% [1]. The African region contributes 25% of the global TB burden and has a TSR of 79% which is still below the End TB target of 90% [2]. There is significant variation in TSR across sub-Saharan Africa (SSA), with a gradual decline over the years [3, 4]. In uganda, TSR has improved from 72% in 2019 to 78% in 2020, however this is still below 95% as recommended by world health organization (WHO) [5].

Uganda is among the 30 high TB/HIV burden countries [6]. The national TB statitics remain poor. For instance, Uganda’s TB incidence rate of 230-330/100,000, prevalence of 253/100,000 and HIV prevalence among those aged 15–64 of 6.2% are among the worst disease indicators reported [79]. A large proportion, 41% of patients with TB in Uganda have HIV coinfection [79]. Treatment outcome is one of the key indicators of TB program measure of the quality of TB care [8, 10]. A number of factors have been identified to affect TB TSR in many settings, including being male, older patients, previously trated for TB [11, 12], HIV co-onfection [12, 13], and drug stock-outs [14].

The Uganda Ministry of Health national TB and Leprosy program and partners have recommended evidence-based interventions to reduce TB incidence and improve TB treatment outcome [15], but data on its progress remain scanty.

In 2019, the Karamoja region in Northeastern Uganda had one of the highest TB burdens in the country [16]. To date information on factors associated with TB TSR across Karamoja is limited partly because the inhabitants of the region are mainly normadic pastoralists. Within the region, the Ministry of Health and other researchers approximate that only 50% of the TB patients complete treatment successfully [9, 1618]. This is below the national average of 78% in 2020 [5].

Examining factors associated with the low TSR in this region is important for designing tailor-made interventions that may be used to address the barriers to achieving a high treatment success rate. It is very important that people who have TB disease are treated successfully to eliminate pools of infection sources and interrupt disease transmission. Therefore, the orverarching aim of this study was to determine the drug susceptible TB treatment success rate and the associated factors in the northeastern Uganda region of Karamoja.

Materials and methods

Study design

This was a retrospective study which involved quantitative method of data collection and analysis. Using a data abstraction tool we abstracted relevant data from health facility TB treatment register. We included data for individuals notified with drug-susceptible tuberculosis and started on TB treatment in the period 1st January 2020 to 31st December 2021. Records that had treatment outcome were considered. The study data was collected in February 2023.

Study setting

The study was conducted in St. Kizito Hospital Matany, Napak district, southern Karamoja. This is a Private Not-For-Profit (PNFP) hospital under the Catholic Diocese of Moroto (North-Eastern Uganda). The hospital capacity constitutes 226 beds and provides a comprehensive inpatient and outpatient medical services to the people of Karamoja and the neighboring regions. The Hospital is being supported by The AIDS Support Organization (TASO), funded by the U.S President’s Emergency Plan for AIDS Relief (PEPFAR) through Center for Disease Control and Prevention (CDC) health system strengthening grant to implement high quality TB/HIV services. Karamoja region has an estimated population of 1.1million, literacy rate of 11% [19], HIV/AIDS prevalence rate of 3.9% [20], The region is characterized by limited access to health services, inadequate health infrastructure, insufficient quality of care, inadequate human and financial resources for health, and inadequate social protection [19, 21] and these underlying social, health, and demographic determinants need to be adequately addressed to achieve End TB global target. TB diagnosis in this facility is done using laboratory tests such as Gene Xpert, microscopy and urine TB lipoaribomanan (TB LAM) or through clinical assessment. Treatment for drug susceptible TB in this facility is done using standard world health organization (WHO) and national regiments [22, 23], that is, a combination of Rifampicin (R), Isoniazid (H), pyrazinamide (Z) and ethambutol (E) for 2 months and RH for 4 months.

Inclusion and exclusion criteria

All individuals notified as new and relapse drug susceptible TB and started on TB treatment at the study site were eligible for inclusion in the study, while individuals with incomplete data on age, gender, and disease type and with no treatment outcome (not evaluated) and those with multi-drug resistant TB were excluded.

Study variables

Exposures

Demographic characteristics (age, gender), residence (Napak or outside), disease characteristics (disease category, treatment type), disease classification categorized as bacteriologically confirmed (laboratory diagnosis with urine LAM, Gen Xpert or Miscroscopy), clinically diagnosed (based on clinical assessment and chest x-ray diagnosis) and extrapulmonary (a diagnosis of TB outside the lungs) [23], TB Patient type categorized as new or retreatment, HIV status (Positive or negative), point of referral (Facility or community) and Nutritional status measured using mid upper arm circumference (MUAC). The MUAC codes documented in the register were captured and used to classify nutritional status of the study participants, that is, red (severe acute malunitrition), yellow (moderate acute malnutrition), and green (well nourished). The participants whose MUAC were not taken were categorized as unknown nutritional status.

The primary outcome was TB treatment Success defined as treatment completion and/or Cure. The primary outcome was measured as the proportion of drug susceptible TB patients started on treatment who at the end of 12 months was document in the register as completed treatment, and/cured of TB. Unsuccessful treatment outcome included, Death, Lost-to-follow-up or treatment failure.

Definition of Treatment Outcomes

  1. Successful outcome is when a TB patients is cured (negative smear microscopy at the end of treatment and on at least one previous follow-up test) or completed (A TB patient who completed treatment without evidence of failure but with no record to show that sputum smear or culture results in the last month of treatment and on at least one previous occasion were negative, either because tests were not done or because results are unavailable) [24].

  2. Unsuccessful outcome is when treatment resulted in treatment failure (remaining smear-positive after 5 months of treatment), defaulted (patients who interrupted their treatment for two consecutive months or more after registration), died, Lost to follow-up (A TB patient who did not start treatment or who completed more than 1 month of treatment and was interrupted for 2 consecutive months or more) [24].

Data management and analysis

Using a customized data abstraction tool, data was extracted on both the exposure and outcome variables from the health unit TB registers from the time of registration at the TB treatment until treatment outcome was reached. The collected data was entered into an electronic dataset using MS Excel and then exported to Stata version 15.0 where it was cleaned, validated, and analyzed. We summarized the study participant characteristics and TB treatment outcomes using descriptive statistics. We used Chi-square to test the difference in treatment success across the 2-year period. Modified poison regression analysis was conducted to determine factors associated with treatment success rate and reported as prevalence ratios of treatment success. While using modified Poisson regression, the standard errors were estimated using robust method, by applying variance-covariance matrix of the estimators (vce) method. Modified Poisson regression was chosen over logistic regression because, logistic regression overestimates relative risks and prevalence ratios in instances where the binary outcome has a high or moderate incidence/prevalence in the studied population [25]. First, we performed a bivariate analysis by regressing each independent variable to the outcome, and later subjected all variables with biological relevance or confounders and those with a P-value less than 0.1 to a multiple regression. The level of significance was set at 5%.

Ethical approval and consent to participate

Ethical approval and informed consent waiver for the study was sought from TASO Uganda Research and Ethics Committee (REC), approval number TASO-2022-99. Confidentiality was maintained by ensuring that individual patient-level data obtained was de-identified, encrypted, and passworded to ensure access by only an authorized team of investigators. Administrative clearance to collect and utilize medical records of the hospital was sought from the Medical Superintendent- St. Kizito Hospital Matany.

Results

From the table above, the median age of the 1234 participants was 31(IQR: 13–49)years, and 26.2%(n = 323) were children below 15years of age. About a half of the participants, 51.4%(n = 634) were bacteriologically confirmed with TB, while 22.4%(n = 277) were extrapulmonary TB cases. Ten percent (n = 130) of the participants were HIV/TB co-infected (Table 1).

Table 1. Characteristics of study participants.

Variable Population, N = 1234 Proportions (%)
Age/years. median(IQR) 31(13–49)
Body weight/Kg, Median (IQR)  45(24–52)  
Age Category
<15years(Children) 323 26.2
15_49years(Adults) 610 49.4
>49(Elderly) 301 24.4
Sex    
Female 541 43.8
Residence in Napak    
Yes 845 68.5
Disease classification    
Bacteriologically confirmed 634 51.4
Clinically Diagnosed 323 26.2
Extrapulmonary 277 22.4
Nutritional (MUAC)    
Green (Well nourished) 366 29.7
Yellow (Moderate undernourished) 293 23.7
Red (severe undernourished) 322 26.1
Unknown 253 20.5
Treatment Model    
Facility based 1 0.1
Digital Community DOT 4 0.3
Non Digital comm DOT 1229 99.6
Patient Type    
New 1159 93.9
Retreatment 75 6.1
HIV status    
Negative 1104 89.5
Positive 130 10.5
Year of treatment (Cohort)    
year 2020 560 45.4
year 2021 674 54.6

TB treatment outcomes

The treatment outcomes reported were; treatment completion at 52.4% (n = 647), cured at 26.9% (n = 332), death 10.4%(n = 129), Lost to follow up 9.8% (n = 121) and failed at 0.4%(n = 5).

Trends in treatment success

From Fig 1 below, TB TSR improved from 77.9% in Jan-Mar 2020 to 87.7 in Oct-Dec 2021, with improvement more marked in the year 2021. The overall treatment success rate for the 2 years combined was 79.3%(95%CI; 77.0%-81.5%), while treatment success rate for 2020 was 75.4% and 2021 was 82.4% and this difference was sIginificant (P = 0.002).

Fig 1. Trends in TB treatment success rate for 2020 and 2021.

Fig 1

From the Table 2 above, the factors that were negatively associated with treatment success were; Older age, under nutrition/unknown nutritional status (MUAC measurement red or unknown), and HIV positive status, that is.

Table 2. Factors associated with drug susceptibel tuberculosis treatment success rate (TSR) in Matany Hospital.

Variable Overall, N = 1234 Treatment Success, n(%),n = 979 Treatment Failure, n(%), n = 255 cPR(95%CI) aPR(95%CI) P-value
Age Category
<15years(Children) 323 271(83.9) 52(16.1) 1 1  
15_49years(Adults) 610 485(79.5) 125(20.5) 0.95(0.89–1.01) 0.93(0.86–0.99) 0.036
>49(Elderly) 301 223(74.1) 78(25.9) 0.88(0.81–0.96) 0.87(0.80–0.94) 0.001
Sex
Female 541 432(79.9) 109(20.1) 1 1  
Male 693 547(78.9) 146(21.1) 0.99(0.93–1.05) 0.99(0.93–1.04) 0.655
Residence in Napak
No 389 305(78.4) 84(21.6) 1 1  
Yes 845 674(79.8) 171(20.2) 1.02(0.96–1.08) 1.00(0.94–1.06) 0.954
Disease classification
Bacteriologically confirmed 634 512(80.8) 122(19.2) 1 1  
Clinically Diagnosed 323 253(78.3) 70(26.7) 0.97(0.91–1.04) 0.95(0.88–1.03) 0.232
Extrapulmonary 277 214(77.3) 63(22.7) 0.96(0.89–1.03) 0.93(0.87–1.01) 0.075
Nutritional (MUAC)
Green 366 310(84.7) 56(15.3) 1 1  
Yellow 293 243(82.9) 50(17.1) 0.98(0.91–1.05) 0.99(0.92–1.06) 0.709
Red 322 254(78.9) 68(21.1) 0.93(0.87–1.00) 0.91(0.85–0.98) 0.013
Unknown 253 172(68.0) 81(32.0) 0.80(0.73–0.88) 0.80(0.73–0.88) 0.000
Patient Type
New 1159 925(79.8) 234(20.2) 1 1  
Retreatment 75 54(72.0) 21(28.0) 0.90(0.78–1.04) 0.91(0.79–1.04) 0.174
HIV status
Negative 1104 889(80.5) 215(19.5) 1 1  
Positive 130 90(69.2) 40(30.8) 0.86(0.76–0.97) 0.88(0.78–0.98) 0.026
Year of treatmemt (Cohort)
Year 2020 560 422(75.4) 138(24.6) 1 1  
Year 2021 674 557(82.6) 117(17.4) 1.10(1.03–1.16) 1.09(1.03–1.16) 0.003

NB: Bold = significant with P<0.05, cPR = crude prevalence ratio, aPR = adjusted prevalence ratio.MUAC = Mid upper arm circumference All factors were adjusted for each other, Treatment success = cured and/or completed, Treatment failure = died, lost to follow up or failed.

Prevalence of treatment success was lower in adults (15–49 years) compared to children <15years, PR = 0.93(95%CI; 0.86–0.99, P = 0.036). The prevalence was also lower in the elderly patients > 49years compared to children, PR = 0.87(95%CI; 0.80–0.94, P = 0.001). Nutritional status. Those whose MUAC were red, PR = 0.91(95%CI; 0.85–0.98, P = 0.013) and those whose MUAC were unknown(not taken), PR = 0.80(95%CI; 0.73–0.88, P<0.0001) had lower a prevalence of treatment success as compared to clients whose MUAC were normal(green). HIV status. Patients who were HIV/TB coinfected had lower prevalence of treatment success, PR = 0.88(95%CI; 0.78–0.98, P = 0.026) as compared to clients who were HIV negative.

Year of enrollment was a positive predictor of treatment success. Patients who were registered/enrolled in 2021 had high prevalence of treatment success, PR = 1.09(95%CI; 1.03–1.16, P = 0.003).

Discussion

This study was carried out to investigate TB drug-susceptible treatment success rate (DS-TB TSR) and its associated factors among individuals diagnosed and treated for TB between January 2020 through December 2021 in a private not-for-profit hospital in Karamoja, Uganda. The study was unique in that it investigated treatment success in a nomadic community which is highly mobile. In the study, we found that about a half (56%) of the participants completed TB treatment. However, poor TB treatment outcomes (such as lost-to-follow-up, TB relapse and death) were more common among HIV co-infected individuals, older individuals and those with severe malnutrition. The prevalence of TB treatment success was higher in 2021 compared to 2020. Now there is new data indicating that the ramifications of COVID-19 on health and health systems affected the delivery of health care, especially in 2020 [26]. We think that the lower TSR in 2020 were as a result of these effects of COVID-19.

Overall, eight in ten individuals with drug-sensitive TB achieved treatment success which compares well with the national TSR [14], but both are sub-optimal compared to the WHO End TB strategy TSR target of nine in ten [2]. Our findings show a significant improvement from earlier estimates of five in ten treatment success in the region [16], suggesting that there has been improvement in the delivery of TB care services. These acheivements could be as a result of the recent governemnt deliberate efforts to break the transmission cycle for TB through early diagnosis and treatment of both cases and their contacts. Similar to our findings, treatment success rates of 63.9–82.1% [12, 27] were also observed from studies conducted in other rural regions of the country. In SSA sub-optimal TSR is not unique to Uganda alone as a systematic review summarizing TSR among adult bacteriologically confirmed pulmonary tuberculosis patients in the sub continent showed a similar trend [4]. These findings are pointers towards a need for novel, innovative and evidence based interventions designed towards improvement of performance of the national TB program.

In our study, the TSR improved from 75.4% in 2020 to 82.4% in 2021, which is a progressive improvement better than a stagnation or a reversal. Besides the receovery of health services post COVID-19 lockdowns, we also attribute this performance to Continuous Quality Intervention (CQI) projects by The AIDS Support Organization (TASO) and other implementing partners introduced to address the low TSR in the region. Specifically, the TSR retention strategies which entailed introduction and use of an appointment system in the TB Clinic, timely follow up of missed appointments and active cohort monitoring monthly were introduced.

In the current study, older individuals, compared to younger ones, had a lower prevalence of treatment success. This is comparable to what has been reported in other studies such as that by, Izudi et al., who reported that successful treatment of TB was less likely to occur among patients older than 50 years [12]. Similarly, Sebuliba et al found that older individuals (aged 65+ years) had two-fold increased odds of poor TB treatment outcomes, compared to younger individuals, in a Kampala cohort [28]. Older individuals are more likely to have co-morbidities such as hypertension that increase chances of poor TB treatment outcomes [29]. Moreover, older individuals are less likely to have treatment supporter and more likely to suffer from anti-TB drug toxicity such as hepatotoxicity and renal toxicity that also increase the chances of poor treatment outcomes [30, 31]. It is therefore not surprising that patients aged > 49 years had a lower prevalence of treatment success compared to the younger patients. This highlights the need to closely monitor and follow up elderly patients on anti-TB chemotherapy.

Furthermore, we found that HIV positive TB patients had a lower prevalence of TSR than HIV negative individuals. This is similar to findings reported in studies done in other high burden TB countries in Sub-Saharan Africa [32, 33], America [34, 35] and Asia [10, 11]. HIV positive patients had a lower prevalence of treatment success probably due to the drug-drug interactions between anti-TB chemotherapy and the highly active antiretroviral therapy (HAART) and a high pill burden that may affect the adherence to the anti-TB chemotherapy [36, 37]. Non-adherence to anti-TB chemotherapy can in turn lead to a low TSR. Strengthening of HIV and TB treatment and public health programs is thus needed to improve the TSR among patients with HIV.

Under nutrition is a well-established factor associated with a low TB TSR [38]. Our study also collaborates this finding. Integrating nutritional support into TB treatment programs is thus key in improving TB treatment success rates.

Our study had some limitations, for example, data was collected for a period of 2years, which was not sufficient to demonstrate long term trends in TSR. The use of retrospective data presented some levels of data incompleteness. The treatment outcome was documented in the register only at 12 months after initiation of treatment and not at the point of event. Being a retrospective study, we were unable to obtain some key information which could have influenced our study outcomes. The characteristics such as mobility and accessibility, cultural practices, livelihood priorities, socioeconomic factors and education, were not assessed yet they may impact TB treatment outcomes among pastoralist communities.

Despite these challenges, data were collected from a private-not-for-profit tertiary care facility, and it could be one of the first studies investigating TB TSR in such a setting. This could imply and depict the real practice in many private-not-for-profit tertiary hospitals in Uganda. Also, the sample size was large and thus results could be generalized to other similar settings.

Conclusion

TB Treatment success rate (TSR) in Matany hospital was suboptimal. Older age, poor nutrition and being HIV-positive were negative predictors of treatment success. We propose integrating nutrition and HIV care into TB programming to improve treatment success. Additional research on understanding of TB treatment challenges and enablers among the elderly is important to design tailored interventions for this group. Additional research is needed to determine at what point most clients fail treatment, get lost to follow up or die after initiating TB treatment so as to inform evidence-based guidelines on optimization TSR.

Supporting information

S1 Data

(CSV)

pone.0300916.s001.csv (182.2KB, csv)

Acknowledgments

The authors would like to acknowledge the support rendered by the Medical Superintendent of St.Kisito Hospital-Matany, Dr.Nsubuga JB during the process of data collection for this study. We would also like to acknowledge the contribution of The AIDS Support Organization (TASO) in supporting TB program implementation in Matany Hospital.

List of abbreviations

AIDS

Acquired Immune Deficiency Syndrome

aRR

Adjusted risk ratio

CDC

United States Centers for Disease Control and Prevention

DLG

District Local Government

EPTB

Extrapulmonary Tuberculosis

HC

Health Center

HIV

Human Immuno-deficiency Virus

LAM

Lipoarabinomannan

MoH

Ministry of Health

MUAC

Mid upper arm circumference

PBC

Pulmonary Bacteriologically Confirmed

PCD

Pulmonary Clinically Diagnosed

PEPFAR

President’s Emergency Plan for AIDS Relief

REC

Research Ethics Committee

TB

Tuberculosis

TSR

Treatment Success Rate

Data Availability

All relevant data are within the manuscript and its Supporting Information files.

Funding Statement

This publication was partially (data collection) supported through SUNRIF, Soroti University research and innovation fund, Round1, Award No SUNRIF 2022/22 to Ronald Opito. The views and opinions of the authors expressed herein do not necessarily state or reflect those of the funder. There was no additional external funding received for this study.

References

  • 1.World Health Orgnaization. Global tuberculosis report. 2021.
  • 2.World Health Organization. The End TB strategy. 2015.
  • 3.Ukwaja KN, Oshi SN, Alobu I, Oshi DC. Profile and determinants of unsuccessful tuberculosis outcome in rural Nigeria: Implications for tuberculosis control. World J Methodol. 2016. Mar;6(1):118. doi: 10.5662/wjm.v6.i1.118 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Izudi J, Semakula D, Sennono R, Tamwesigire IK, Bajunirwe F. Treatment success rate among adult pulmonary tuberculosis patients in sub-Saharan Africa: A systematic review and meta-analysis. BMJ Open. 2019. Sep;9(9). doi: 10.1136/bmjopen-2019-029400 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Ministry of Health. Uganda National TB and Leprosy Program: July 2019-June 2020 report. 2020.
  • 6.World Health Orgnaization. Global tuberculosis report 2022. Geneva. 2022.
  • 7.Karamagi E, Sensalire S, Muhire M, Kisamba H, Byabagambi J, Rahimzai M, et al. Improving TB case notification in northern Uganda: evidence of a quality improvement-guided active case finding intervention. 2018;2:1–12. doi: 10.1186/s12913-018-3786-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Ministry of Health U. National tuberculosis amd Leprosy control program. Revised National Strategic Plan 2015 / 16–2019 / 20. 2017.
  • 9.Ministry of Health U. The Uganda National Tuberculosis Prevalence Survey, 2014–2015 Survey Report 1. Report. 2015;2014–5. [Google Scholar]
  • 10.Atif M, Sulaiman SAS, Shafie AA, Ali I, Asif M, Babar ZUD. Treatment outcome of new smear positive pulmonary tuberculosis patients in Penang, Malaysia. BMC Infect Dis. 2014. Mar;14(1). doi: 10.1186/1471-2334-14-399 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Jackson C., Stagg H. R., Doshi A., Pan D., Sinha A., Batra R., et al. Tuberculosis treatment outcomes among disadvantaged patients in India. Int Union Against Tuberc Lung Dis. 2017;I(2):134–40. doi: 10.5588/pha.16.0107 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Izudi J, Tamwesigire IK, Bajunirwe F. Treatment success and mortality among adults with tuberculosis in rural eastern Uganda: A retrospective cohort study. BMC Public Health. 2020;20(1):1–10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Ukwaja KN, Oshi SN, Alobu I, Oshi DC. Profile and determinants of unsuccessful tuberculosis outcome in rural Nigeria: Implications for tuberculosis control. World J Methodol. 2016;6(1):118–25. doi: 10.5662/wjm.v6.i1.118 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Musaazi J., Kiragga A. N., Castelnuovo B., Kambugu A., Bradley AMR J. Tuberculosis treatment success among rural and urban Ugandans living with HIV: a retrospective study. Int Union Against Tuberc Lung Dis. 2017;I(2):100–9. doi: 10.5588/pha.16.0115 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Minidstry of Health. National strategic plan for tuberculosis and leprosy control 2020/21–2024/25. 2020.
  • 16.USAID PACT. USAID Program for Accelerated Control of TB in Karamoja, 2020–2025. 2021.
  • 17.Nidoi J, Muttamba W, Walusimbi S, Imoko JF, Lochoro P, Ictho J, et al. Impact of socio-economic factors on Tuberculosis treatment outcomes in north-eastern Uganda: a mixed methods study. BMC Public Health. 2021. Dec;21(1). doi: 10.1186/s12889-021-12056-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Simbwa BN, Katamba A, Katana EB, Laker EAO, Nabatanzi S, Sendaula E, et al. The burden of drug resistant tuberculosis in a predominantly nomadic population in Uganda: a mixed methods study. BMC Infect Dis. 2021. Dec;21(1). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Uganda Bureau of Statistics(UBOS) and ICF. Uganda Demographic and Health Survey 2016. Kampala, Uganda and Rockville, Maryland, USA. 2016.
  • 20.Bank W. The World Bank Annual Report 2006. 2006 Sep.
  • 21.United Nations Office for the Coordination of Humanitarian Affairs. FOCUS ON KARAMOJA: SPECIAL REPORT N°2 URGENT HUMANITARIAN NEEDS FROM AUGUST TO OCTOBER 2008. 2008.
  • 22.World Health Orgnaization. Guidelines for treatment of drug-susceptible tuberculosis and patient care. 2017.
  • 23.Ministry of Health Uganda. Uganda National Tuberculosis and Leprosy Control Program. Manual for management and control of tuberculosis and leprosy. 2017.
  • 24.World Health Organization (WHO). WHO Consolidated Guidelines on Tuberculosis Treatment. Who. 2020. 99 p. [PubMed]
  • 25.Gnardellis C, Notara V, Papadakaki M, Gialamas V, Chliaoutakis J. Overestimation of Relative Risk and Prevalence Ratio: Misuse of Logistic Modeling. 2022;1–10. doi: 10.3390/diagnostics12112851 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Andia-Biraro I, Baluku JB, Olum R, Bongomin F, Kyazze AP, Ninsiima S, et al. Effect of COVID-19 pandemic on inpatient service utilization and patient outcomes in Uganda. Sci Rep [Internet]. 2023;13(1):1–10. Available from: doi: 10.1038/s41598-023-36877-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Baluku JB, Nanyonjo R, Ayo J, Obwalatum JE, Nakaweesi J, Senyimba C, et al. Trends of notification rates and treatment outcomes of tuberculosis cases with and without HIV co-infection in eight rural districts of Uganda (2015–2019). BMC Public Health. 2022. Dec;22(1):651. doi: 10.1186/s12889-022-13111-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Sebuliba N, Id K, Kimuli D, Dejene S, Nanziri C, Birabwa E, et al. Response to anti-tuberculosis treatment by people over age 60 in Kampala, Uganda. 2018;1–10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Seegert AB, Patsche CB, Sifna A, Gomes VF, Wejse C, Storgaard M, et al. Hypertension is associated with increased mortality in patients with tuberculosis in Guinea-Bissau. Int J Infect Dis [Internet]. 2021;109:123–8. Available from: doi: 10.1016/j.ijid.2021.06.062 [DOI] [PubMed] [Google Scholar]
  • 30.Hase I, Gardner K, Hitomi T, Kimiko H, David S, Saito T, et al. Pulmonary Tuberculosis in Older Adults: Increased Mortality Related to Tuberculosis Within Two Months of Treatment Initiation. Drugs Aging [Internet]. 2021;38(9):807–15. Available from: doi: 10.1007/s40266-021-00880-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Byng-maddick R, Noursadeghi M. Does tuberculosis threaten our ageing populations? BMC Infect Dis [Internet]. 2016;1–5. Available from: doi: 10.1186/s12879-016-1451-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Adane K, Spigt M, Dinant G. Tuberculosis treatment outcome and predictors in northern Ethiopian prisons: a five-year retrospective analysis. 2018;1–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Torres NMC, Rodríguez JJQ, Andrade PSP, Arriaga MB, Netto EM. Factors predictive of the success of tuberculosis treatment: A systematic review with meta-analysis. PLoS One. 2019;14(12):1–24. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Lackey B, Seas C, Van Der Stuyft P, Otero L. Patient characteristics associated with tuberculosis treatment default: A cohort study in a high-incidence area of Lima, Peru. PLoS One. 2015;10(6):1–11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Ana Maria Viegas SS de M1, João Paulo Haddad M, das Graças Ceccato W da SC. Association of outcomes with comprehension, adherence and behavioral characteristics of tuberculosis patients using fixed-dose combination therapy in Contagem, Minas Gerais, Brazil Ana. Rev Inst Med Trop Sao Paulo. 2017;11(2):48–56. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Gebremariam MK, Bjune GA, Frich JC. Barriers and facilitators of adherence to TB treatment in patients on concomitant TB and HIV treatment: A qualitative study. BMC Public Health. 2010;10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Gugssa Boru C, Shimels T, Bilal AI. Factors contributing to non-adherence with treatment among TB patients in Sodo Woreda, Gurage Zone, Southern Ethiopia: A qualitative study. J Infect Public Health [Internet]. 2017;10(5):527–33. Available from: doi: 10.1016/j.jiph.2016.11.018 [DOI] [PubMed] [Google Scholar]
  • 38.Padmapriyadarsini C, Shobana M, Lakshmi M, Beena T, Swaminathan S. Undernutrition & tuberculosis in India: Situation analysis & the way forward. Indian J Med Res 144,. 2016;(July):11–20. [DOI] [PMC free article] [PubMed] [Google Scholar]

Decision Letter 0

Hamufare Dumisani Dumisani Mugauri

24 Jan 2024

PONE-D-23-35125Tuberculosis treatment success rate, associated factors and outcomes in St.Kizito Hospital, Matany, Napak district, Karamoja region. A retrospective study.PLOS ONE

Dear Dr. MUGERWA SSENTONGO,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Mar 09 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Hamufare Dumisani Dumisani Mugauri, Ph.D. Public Health

Academic Editor

PLOS ONE

Journal Requirements:

1. When submitting your revision, we need you to address these additional requirements.

Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at 

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and 

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Did you know that depositing data in a repository is associated with up to a 25% citation advantage (https://doi.org/10.1371/journal.pone.0230416)? If you’ve not already done so, consider depositing your raw data in a repository to ensure your work is read, appreciated and cited by the largest possible audience. You’ll also earn an Accessible Data icon on your published paper if you deposit your data in any participating repository (https://plos.org/open-science/open-data/#accessible-data).

3. Thank you for stating in your Funding Statement: 

This publication was partially (data collection) supported through SUNRIF, Soroti University research and innovation fund, Round1, Award No SUNRIF 2022/22 to Ronald Opito. The views and opinions of the authors expressed herein do not necessarily state or reflect those of the funder.

Please provide an amended statement that declares all the funding or sources of support (whether external or internal to your organization) received during this study, as detailed online in our guide for authors at http://journals.plos.org/plosone/s/submit-now.  Please also include the statement “There was no additional external funding received for this study.” in your updated Funding Statement. 

Please include your amended Funding Statement within your cover letter. We will change the online submission form on your behalf.

4. Please amend the manuscript submission data (via Edit Submission) to include author Dr. Ronald Opito.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thanks for submitting the manuscript to PLOS one

Interesting data about the clinical outcomes in TB patients in Napak District, Southern Karamoja, However I have several concerns and comments below.

Title: I suggest author to be clearly about what is the outcome, author should state for example associated factors and treatment success. and this study includes only the TB drug susceptible so author should state the population clearly in the Title.

- Journal: Please check again for the journal Format and should follow journal format.

-Language: Please check and proof the English Language again throughout the whole manuscript.

- All abbreviations should state the full name first.

Introduction

- Line 54: I don't quite understand "single infectious agent" please use other word.

- Please add more previous study about factors associated with treatment success or failure and tell more about your study gap of knowledge why author would like to conduct this study. Are there any differences about the factors between your population VS others

Methods

- What is customized proforma, may be used other word.

-Study setting. Because we have more than one method for TB diagnosis and also TB laboratories. Author have to state how your institutes register patients with TB, what is your criteria for TB diagnosis and LAB (PCR, AFB or others)

Inclusion: Why author includes only TB drug susceptible patients?

Definition: To make reader understand more, Authors have to give the definition >> New and relapse drug susceptible TB by the standard and reliable guideline. Author have to give the definition for all the treatment outcomes and which guideline author used for the reference.

Statistical analysis: This study is retrospective study. I would like to ask author why author use poison rather than logistic regression for factors associated with treatment outcome.

Result.

Table 1 should add more data: Body weight, underlying disease. For sex and residence can show only female or yes.

For table 1 please add the definition of disease classification in the method session.

For table 1 add more data about the TB drug regimens and duration of anti-TB drug treatment

For table 1 add more data about patients' compliance, % Hospitalization, IPD or OPD patients.

Table2: add the full name for all the abbreviation at the footnote under the table ex. cPR,aPR

For Table 2 I suggest author the show only one outcome (Treatment success or failure).

Discussion

I don't quite understand the phase ".......... in a nomadic community which is highly mobile". please clarify

" In the study, we found that a majority of the participants complete TB treatment" In my opinion, 56% of patients are not the majority.

Please discuss the prevalence in your study VS others

Please check the references, some paraphrase didn't state the Ref. ex. This is comparable to what has been in other studies (Ref.???).

-Please clarify more why Hypertension and endocrine abnormalities associated with poor outcome ?

-Please clarify more why Drug interaction related to HIV positive and low prevalence of treatment failure

- What is your strength and limitation

- I suggest author to add the discussion more about the system between the year 2020 and 2021. Are there any different systems between these 2 years because this study's result showed the different treatment outcome.

Reference

Check all the format of the references

Hope these comments might help authors for better manuscript.

Reviewer #2: The authors report a retrospective study on the Tuberculosis treatment success rate, associated factors and outcomes in St.Kizito Hospital, Matany, Napak district, Karamoja region. I have several concerns that should be addressed

General

The authors need to proofread their manuscript to correct all grammatical errors in the manuscript. I have identified several problems with grammar/spelling/punctuation. For example, the word “repported” in line 44 is misspelt, while writing 1st January 2020 in the Study Design paragraph, the “st” should be Superscripted, to mention a few.

Introduction

The authors started using the term DR-NCDs without first explaining the meaning of it. I know this has been explained in the abstract, but it is recommended that when you start writing the main text, all the initials are explained again. The authors should make sure all the abbreviations are explained before starting to use them.

Results

Generally, the authors should not use abbreviations in the titles of the tables. The rule is also for a table to be able to stand alone and be understandable, so it is recommended that all abbreviations used in the table should be explained below the table, as footnotes.

In Table 1, Nutritional (MUAC) is classified as Green, Yellow, and Red without clarifying what the colours represent.

I also suggest that the results for Table 2 should be re-written because the way the paragraph is written now is confusing. My suggestion is that the authors could first mention all the factors and then start explaining them one by one.

Discussion

While reporting the limitation of the study, the authors should have mentioned the inability to obtain data which might have influenced their results. The characteristics that may impact TB treatment outcomes among pastoralist communities include Mobility and Accessibility, Cultural Practices, Livelihood Priorities, Socioeconomic Factors, Education Levels etc.

Reviewer #3: 1. Inclusion and exclusion: I am afraid that excluding those with missing age, gender and disease type would introduce bias in the estimates. The authors need to assess if complete case analysis did not produce biased results. By doing multiple imputation and then compare results (complete case vs imputed data) to check if there is consistence in the findings would help.

2. Inclusion and exclusion: Since those not evaluated were also initiated on treatment, I think they should be part of the denominator. Excluding them especially if they are many can lead to overestimation of the treatment success rate. Can the authors estimate the treatment success rate with the "not evaluated" included?

3. Inclusion and exclusion: Please clarify why the multi-drug resistant TB patients were excluded.

4. Under methods and materials, the authors mention to have used a customized proforma to abstract data. A reference to this proforma at its first mention would be helpful.

5. Study variables: A clear definition of the primary outcome should be given. I suppose this was a proportion. If yes, please define the primary outcome mentioning the numerator and the denominator.

6. Under data management and analysis, the authors mention to have used a modified poison regression to estimate prevalence ratios. Did the authors fit the model with robust standard errors? Since Poison regression if used for binary outcome, it can estimate confidence interval for the prevalence that exceeds a 1, and consequently this affects estimates for the prevalence ratio. Please check that robust standard errors were used and mention this in the analysis methods.

7. It's not clear how a multivariable Poison regression model was built. What factors were considered in the multivariable model and how did the authors arrive at a final fit. Also, how did they decide which factors to include in the model? All these details are needed to make things clear and for reproducibility reasons.

8. Under results in Table 2, it seems like all variables in the data were included in the multivariable analysis and no model building was considered. Would the results be different if only variables with say a p-value at bivariable analysis less than 0.1 were included? Did the authors check for multicollinearity? What about overdispersion, noting that Poisson model assumes equality of variance and mean, which assumption if it does not hold, the model can give misleading results. A negative binomial would be helpful.

9. In reference to my point 1, would the results in Table 2 remain the same if missing data were considered (instead of excluding them)?

10. Below table 2, statements like "Nutrition status", "HIV status" and others look like hanging statements. Please revise the paragraph as you list the significant factors.

11. Please add line numbers to the manuscript as this will make the review process easier.

12. Somewhere you are missing full stops. For example, a full stop is missing before the statement that begins "We used chis-square to test ..."

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Attachment

Submitted filename: Review comments.docx

pone.0300916.s002.docx (12.7KB, docx)
PLoS One. 2024 May 14;19(5):e0300916. doi: 10.1371/journal.pone.0300916.r002

Author response to Decision Letter 0


20 Feb 2024

The Editor

PlosOne Journal

Dear Professor, Hamufare Dumisani Dumisani Mugauri,

REF: RESPONSE TO THE ACADEMIC EDITOR AND REVIEWERS TO THE ARTICLE:

Title: “Tuberculosis treatment success rates, associated factors and outcomes in St.Kizito Hospital, Napak district, Karamoja region, A retrospective study”

I on behalf of the authors would like to express our sincere gratuity for the positive consideration you have given this article and for the positive feedback so far given by the academic editor and reviewers.

Please find highlighted in red our responses to reviewers and academic editor’s comments.

Reviewer #1: Thanks for submitting the manuscript to PLOS one

Interesting data about the clinical outcomes in TB patients in Napak District, Southern Karamoja, However I have several concerns and comments below.

Title: I suggest author to be clearly about what is the outcome, author should state for example associated factors and treatment success. and this study includes only the TB drug susceptible so author should state the population clearly in the Title.

Response: The title has been modified as per the recommendation to, “Treatment success rate and associated factors among drug susceptible tuberculosis individuals in St.Kizito Hospital, Matany, Napak district, Karamoja region. A retrospective study.”

- Journal: Please check again for the journal Format and should follow journal format.

Response: This has been checked and the manuscript edited in line with the journal format.

-Language: Please check and proof the English Language again throughout the whole manuscript.

Response: This has been checked and proofreading done.

- All abbreviations should state the full name first.

Response: All abbreviations have been explained at their first mention.

Introduction

- Line 54: I don't quite understand "single infectious agent" please use other word.

Response. This has been modified as indicated in line 59.

- Please add more previous study about factors associated with treatment success or failure and tell more about your study gap of knowledge why author would like to conduct this study. Are there any differences about the factors between your population VS others

Response. This has been addressed in the introduction, lines 74-76.

Methods

- What is customized proforma, may be used other word.

Response: We have changed to data abstraction tool.

-Study setting. Because we have more than one method for TB diagnosis and TB laboratories. Authors have to state how your institutes register patients with TB, what is your criteria for TB diagnosis and LAB (PCR, AFB or others)

Response. This has been added, line 112-117.

Inclusion: Why author includes only TB drug susceptible patients?

In Uganda (and more specifically Matany Hospital), Multi drug-resistant TB (MDR-TB) patients receive extra support such as food, and transport among others. These enablers have a high potential of biasing the outcome which will eventually give good treatment success rates. We deliberately left out MDR-TB patients to allow us to eliminate this potential bias.

Definition: To make reader understand more, Authors have to give the definition >> New and relapse drug susceptible TB by the standard and reliable guideline. Author have to give the definition for all the treatment outcomes and which guideline author used for the reference.

Response: This has been well defined, lines 154-166.

Statistical analysis: This study is retrospective study. I would like to ask author why author use poison rather than logistic regression for factors associated with treatment outcome.

Response: We applied modified Poisson with robust error estimations (rather than just poisson) because logistic regression overestimates relative risks/prevalence ratios more so if the binary outcome is high or moderate, more than 10% (Gnardelis C et al 2022; Misuse of logistic modelling).

Result.

Table 1 should add more data: Body weight, underlying disease. For sex and residence can show only female or yes.

Response. Body weight has been added to table1. Other underlying diseases other than HIV are not routinely captured on the TB register. The sex and residence presentations have been adjusted as advised.

For table 1 please add the definition of disease classification in the method session.

Response: This has been added, lines 125-128.

For table 1 add more data about the TB drug regimens and duration of anti-TB drug treatment

Response: Treatment for drug susceptible TB in this facility is done using standard national regiments, that is, for a combination of Rifampicin (R), Isoniazid (H), pyrazinamide (Z) and ethambutol (E) for 2 months and RH for 4 months.

So we felt it was unnecessary to add since it does not vary from patient to patient. We have however added this information on the methods section, lines 114-117.

For table 1 add more data about patients' compliance, % Hospitalization, IPD or OPD patients.

Response: We collected data from the TB register which does not specify whether the clients were admitted however most of the clients are managed as OPD and the adherence is not routinely documented in the TB treatment register.

Table2: add the full name for all the abbreviation at the footnote under the table ex. cPR, aPR.

Response. This has been added at the footnote.

For Table 2 I suggest author the show only one outcome (Treatment success or failure).

Response: We appreciate the suggestion to show only one outcome (treatment success for our case). However, we feel it causes no harm to have both outcomes shown, for purposes of clarity.

Discussion

I don't quite understand the phase ".......... in a nomadic community which is highly mobile". please clarify

Response. The study population come from a pastoralist community, and they are quite mobile as they move from one place to another in search of pasture and water for their animals. The settlement arrangements are temporary. This influences treatment outcomes, more so on the lost to follow up.

" In the study, we found that a majority of the participants complete TB treatment" In my opinion, 56% of patients are not the majority.

Response. We acknowledge this recommendation and agree with the reviewer. We have changed the statement.

Please discuss the prevalence in your study VS others

Please check the references, some paraphrase didn't state the Ref. ex. This is comparable to what has been in other studies (Ref.???).

Response: This has been discussed, the references have been inserted.

-Please clarify more why Hypertension and endocrine abnormalities associated with poor outcome?

Response: A reference on the interactions between hypertension and TB TSR has been included. Line 273.

-Please clarify more why Drug interaction related to HIV positive and low prevalence of treatment failure

Response: “HIV positive patients had a lower prevalence of treatment success probably due to the drug-drug interactions between anti-TB chemotherapy and the highly active antiretroviral therapy (HAART) and a high pill burden that may affect the adherence to the anti-TB chemotherapy.” This is what we have indicated in our discussion section, which is well referenced. HIV positivity is associated with low prevalence of treatment success, and not the other way round.

- What is your strength and limitation

Response: The strengths and limitations of the study have been presented as part of the discussions, lines 293-306.

- I suggest author to add the discussion more about the system between the year 2020 and 2021. Are there any different systems between these 2 years because this study's result showed the different treatment outcome.

Response: The systems were not different as per say, however, there were programmatic interventions done by The AIDS Support Organization (TASO) geared towards improving TB treatment outcomes in Karamoja region. These interventions included quality improvement projects at facility and community levels. These have been discussed in the discussion sections, lines 228-265.

Reference

Check all the format of the references.

Response: This has been checked and corrected.

Hope these comments might help authors for better manuscript.

Reviewer #2: The authors report a retrospective study on the Tuberculosis treatment success rate, associated factors and outcomes in St.Kizito Hospital, Matany, Napak district, Karamoja region. I have several concerns that should be addressed

General

The authors need to proofread their manuscript to correct all grammatical errors in the manuscript. I have identified several problems with grammar/spelling/punctuation. For example, the word “repported” in line 44 is misspelt, while writing 1st January 2020 in the Study Design paragraph, the “st” should be Superscripted, to mention a few.

Response: The manuscript has been proofread and the grammatical errors corrected.

Introduction

The authors started using the term DR-NCDs without first explaining the meaning of it. I know this has been explained in the abstract, but it is recommended that when you start writing the main text, all the initials are explained again. The authors should make sure all the abbreviations are explained before starting to use them.

Response: All abbreviations have been explained and written in full at first mention.

Results

Generally, the authors should not use abbreviations in the titles of the tables. The rule is also for a table to be able to stand alone and be understandable, so it is recommended that all abbreviations used in the table should be explained below the table, as footnotes.

Response. The recommendation has been taken into consideration and all abbreviations used in the tables explained below as footnotes. The title abbreviations have been explained equally in their first mention.

In Table 1, Nutritional (MUAC) is classified as Green, Yellow, and Red without clarifying what the colours represent.

Response. The meaning of each color has been explained under methodology, lines 131-134.

I also suggest that the results for Table 2 should be re-written because the way the paragraph is written now is confusing. My suggestion is that the authors could first mention all the factors and then start explaining them one by one.

Response. This suggestion is noted and adopted for clarity.

Discussion

While reporting the limitation of the study, the authors should have mentioned the inability to obtain data which might have influenced their results. The characteristics that may impact TB treatment outcomes among pastoralist communities include Mobility and Accessibility, Cultural Practices, Livelihood Priorities, Socioeconomic Factors, Education Levels etc.

Response. This recommendation is much appreciated and has been included as part of the study limitations, lines 297-301.

Reviewer #3: 1. Inclusion and exclusion: I am afraid that excluding those with missing age, gender and disease type would introduce bias in the estimates. The authors need to assess if complete case analysis did not produce biased results. By doing multiple imputation and then compare results (complete case vs imputed data) to check if there is consistence in the findings would help.

Response: The total number of excluded data was 35 (of which 10 were not evaluated and 25 had missing values). We think this proportion, being less than 5% is small compared to the overall and may not have had significant effect on the outcome. The effect if any is countered by the large sample size we used.

2. Inclusion and exclusion: Since those not evaluated were also initiated on treatment, I think they should be part of the denominator. Excluding them especially if they are many can lead to overestimation of the treatment success rate. Can the authors estimate the treatment success rate with the "not evaluated" included?

Response: We found only 10 participants were not evaluated. We think this number is too small to affect the overall outcome, especially that our sample size was quite large, and as such we decided to exclude them from the analysis.

3. Inclusion and exclusion: Please clarify why the multi-drug resistant TB patients were excluded.

In Uganda Multi drug-resistant TB patients receive extra support such as food, and transport among others. These enablers have a high potential of biasing the outcome which will eventually give good treatment success rates.

4. Under methods and materials, the authors mention to have used a customized proforma to abstract data. A reference to this proforma at its first mention would be helpful.

Response. The customized proforma was data abstraction tool designed based on the durg susceptible TB treatment register. The name has been changed to data abstraction tool as suggested by reviewer1. Lines 87

5. Study variables: A clear definition of the primary outcome should be given. I suppose this was a proportion. If yes, please define the primary outcome mentioning the numerator and the denominator.

Response: The primary outcome is well defined, lines 154-166.

6. Under data management and analysis, the authors mention to have used a modified poison regression to estimate prevalence ratios. Did the authors fit the model with robust standard errors? Since Poison regression if used for binary outcome, it can estimate confidence interval for the prevalence that exceeds a 1, and consequently this affects estimates for the prevalence ratio. Please check that robust standard errors were used and mention this in the analysis methods.

Response. Yes, we used robust standard errors to fit the model. This has now been fully explained under the data analysis section, lines 177-185.

7. It's not clear how a multivariable Poison regression model was built. What factors were considered in the multivariable model and how did the authors arrive at a final fit. Also, how did they decide which factors to include in the model? All these details are needed to make things clear and for reproducibility reasons.

Response. The details of how the models were built is now well explained under the data analysis section, lines 182-185.

8. Under results in Table 2, it seems like all variables in the data were included in the multivariable analysis and no model building was considered. Would the results be different if only variables with say a p-value at bivariable analysis less than 0.1 were included? Did the authors check for multicollinearity? What about overdispersion, noting that Poisson model assumes equality of variance and mean, which assumption if it does not hold, the model can give misleading results. A negative binomial would be helpful.

Response: Multicollinearity and over-dispersion were checked and that’s how body weight and treatment models were dropped off from the final model. All the other variables included either had biological relevance, confounders or had a P-Value less than 0.1 at bivariate level.

9. In reference to my point 1, would the results in Table 2 remain the same if missing data were considered (instead of excluding them)?

Response: The total number of excluded data was 35 (of which 10 were not evaluated and 25 had missing values). We think this proportion, being less than 5% is small compared to the overall and may not have had significant effect on the outcome. The effect if any is countered by the large sample size we used.

10. Below table 2, statements like "Nutrition status", "HIV status" and others look like hanging statements. Please revise the paragraph as you list the significant factors.

Response. Revisions have been made as recommended.

11. Please add line numbers to the manuscript as this will make the review process easier.

Response: The line numbers have been added.

12. Somewhere you are missing full stops. For example, a full stop is missing before the statement that begins "We used chis-square to test ..."

Response: The revision has been made.

Dr.Ssentongo Saadick

Corresponding Author

Attachment

Submitted filename: Response to reviews TSR manucript.docx

pone.0300916.s003.docx (26KB, docx)

Decision Letter 1

Hamufare Dumisani Dumisani Mugauri

7 Mar 2024

Treatment success rate and associated factors among drug susceptible tuberculosis individuals in St.Kizito Hospital, Matany, Napak district, Karamoja region. A retrospective study.

PONE-D-23-35125R1

Dear Dr. Sentongo,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter, and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up to date by logging into Editorial Manager at http://www.editorialmanager.com/pone/ and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Hamufare Dumisani Dumisani Mugauri, Ph.D. Public Health

Academic Editor

PLOS ONE

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: No

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The authors have addressed all of the comments which I raised previously. I have no further comments

Reviewer #3: All my comments were addressed. There are however a few typos, which I suggest to authors to pay keen attention or consider sending their paper to an English reviewer. Examples below;

1. In Line 164, "A TB" patient should be "a TB patient"

2. Line 185, "P-value" should be "p-value"

3. Line 208, "susceptibel" should be "susceptible"

4. Line 129, "Patient" should be "patient", "Positive" should be "positive"

5. Line 137, "was document" should be "was documented"

6. etc...

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Reviewer #3: No

**********

Acceptance letter

Hamufare Dumisani Dumisani Mugauri

12 Mar 2024

PONE-D-23-35125R1

PLOS ONE

Dear Dr. Ssentongo,

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team.

At this stage, our production department will prepare your paper for publication. This includes ensuring the following:

* All references, tables, and figures are properly cited

* All relevant supporting information is included in the manuscript submission,

* There are no issues that prevent the paper from being properly typeset

If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps.

Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

If we can help with anything else, please email us at customercare@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Mr Hamufare Dumisani Dumisani Mugauri

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Data

    (CSV)

    pone.0300916.s001.csv (182.2KB, csv)
    Attachment

    Submitted filename: Review comments.docx

    pone.0300916.s002.docx (12.7KB, docx)
    Attachment

    Submitted filename: Response to reviews TSR manucript.docx

    pone.0300916.s003.docx (26KB, docx)

    Data Availability Statement

    All relevant data are within the manuscript and its Supporting Information files.


    Articles from PLOS ONE are provided here courtesy of PLOS

    RESOURCES