Title of the study:

Investigating the Causes of Delays in Pulmonary TB Diagnosis and

Treatment, and the Resulting Nutritional Changes
Short running title
TB Delays and Nutritional Decline

Abstract

Background: Delays in the diagnosis and treatment of pulmonary tuberculosis (TB) continue
to be a significant public health challenge, contributing to ongoing transmission and
worsened patient outcomes. A critical but under-investigated consequence of these delays is
the deterioration of a patient's nutritional status, which can create a vicious cycle of disease
progression and malnutrition. This study aims to investigate the factors associated with
patient and health system delays in TB care and to quantify the resulting changes in the
nutritional status of affected individuals.

Methods: This cross-sectional study will be conducted among diagnosed adult patients with
drug-sensitive pulmonary TB at a designated TB diagnostic and treatment center. A
structured questionnaire will be administered at the time of medicine collection to collect
socio-demographic information, healthcare-seeking behaviors, and symptom onset data to
determine the duration of patient- and health-system delays. Anthropometric measurements
(weight, height, and Body Mass Index [BMI]) will be taken at diagnosis and again at
treatment initiation to assess nutritional changes. Statistical analyses, including descriptive
statistics will be performed to identify factors independently associated with delays and to
establish the relationship between delay duration and nutritional decline.

Results: The findings of this study will provide a detailed understanding of the primary
drivers of delays in the local context, including behavioral, socio-economic, and systemic
factors. By quantifying the nutritional changes, this research will highlight the clinical impact
of these delays, thereby providing a strong rationale for policy intervention.

Conclusion: This study is expected to provide actionable insights for public health
authorities and healthcare providers to design targeted interventions. By addressing the root
causes of delays and integrating nutritional support, the overall effectiveness of TB control
programs can be significantly improved, leading to a reduction in disease transmission and
better patient outcomes.

Introduction
Pulmonary Tuberculosis (TB) remains a significant global health concern, especially in low-
and middle-income countries. Despite the availability of effective and affordable treatment,
delays within the care continuum—from symptom onset to diagnosis and treatment initiation
—persist as critical barriers that contribute to ongoing transmission and deteriorating patient
health [1,2]. These delays not only increase community transmission but also aggravate
patients’ clinical conditions, notably their nutritional status. Malnutrition, which is both a
cause and consequence of TB, impairs immune function and hampers treatment success,
creating a vicious cycle that complicates disease management [3,4]. Understanding the
multifactorial causes of these delays and their impact on nutritional decline is essential for
designing targeted interventions [5,6].

Aim and Objectives

Aim:
To systematically identify and analyze the factors associated with delays in diagnosis and
treatment initiation of pulmonary TB and to evaluate the associated nutritional changes
during these delays.
Objectives:
1. To determine the duration of patient-related, healthcare system-related, and socio-
economic delays in pulmonary TB diagnosis and treatment [1,5].
2. To identify barriers such as knowledge gaps, healthcare access, stigma, and diagnostic
resource availability that contribute to these delays [2,6].
3. To quantify the nutritional status of patients at diagnosis and at treatment initiation,
using anthropometric measures like BMI [7].
4. To explore the association between delay durations and nutritional deterioration [3,4].
5. To propose evidence-based strategies to reduce delays, improve nutritional support,
and enhance patient outcomes [8,9].

Rationale of the Study

Elucidating the causes of delays is crucial for targeted policy formulation. Prior research
indicates that delays stem from behavioral, systemic, and socio-cultural factors, which often
remain unaddressed by current strategies focusing solely on diagnostics and drug supply
[1,2]. The bidirectional relationship between TB and malnutrition intensifies disease severity
and hampers recovery; undernutrition at treatment initiation is associated with higher
mortality, emphasizing the need for incorporating nutritional interventions from the outset
[3,4,8]. Quantifying nutritional decline during delays underscores the urgency for prompt
diagnosis, with potential implications for reducing transmission and mortality. Addressing
this nexus aligns with the WHO End TB Strategy’s goals of drastically reducing TB
incidence and deaths by 2035 [9].

Methods
Study Design:
A descriptive, cross-sectional study.
Study Setting:
The study will be conducted at a designated Tuberculosis (TB) treatment center providing
Directly Observed Treatment, Short-course (DOTS) services. The center caters to patients
from both rural and urban areas and maintains detailed patient records, which will be used for
verification of self-reported data.
Study Population:
The study population will consist of adult patients (≥18 years) diagnosed with drug-sensitive
pulmonary tuberculosis and presenting for treatment initiation during the study period
(December 2025 – Feburary 2026).
Sample Size Justification:
Based on outpatient records, approximately 200–220 new cases of drug-sensitive pulmonary
TB are registered at the treatment center every quarter. To ensure feasibility and adequate
representation within the limited timeframe, a sample of 60 patients (~30% of the estimated
new cases in 3 months) will be included. This proportion is considered sufficient for
descriptive analysis of delays and nutritional status, while keeping the study manageable
within the given resources and time. Consecutive sampling of eligible patients will be
followed until the required sample size is reached.
Inclusion and Exclusion Criteria:
 Inclusion Criteria:
o Adult patients (≥18 years) with a confirmed diagnosis of pulmonary TB (drug-
sensitive).
o Patients attending the designated TB treatment center for initiation of anti-TB
treatment.
o Patients who provide informed written consent after explanation of the study
title, objectives, procedures, and benefits.
 Exclusion Criteria:
o Patients with extrapulmonary or drug-resistant TB.
o Patients who are severely ill and unable to respond to the questionnaire.
o Patients not providing consent.
Data Variables, Sources of Data, and Data Collection:
 Data Variables:
o Socio-demographic details: age, gender, education, occupation, income,
family size.
o Clinical history: duration of symptoms, co-morbidities, previous TB
treatment history.
o Health-seeking behavior: first point of contact, number of healthcare visits,
type of provider consulted.
o Delay variables:
 Patient Delay (symptom onset → first health care contact)
 Health System Delay (first health care contact → diagnosis)
 Treatment Initiation Delay (diagnosis → treatment start)
 Total Delay (sum of above).
o Nutritional status: anthropometry (height, weight, BMI). BMI classified as
per WHO standards:
 <16 kg/m²: Severe undernutrition
 16–16.9 kg/m²: Moderate undernutrition
 17–18.5 kg/m²: Mild undernutrition
 ≥18.5 kg/m²: Normal.
 Questionnaire/Tool:
A structured, interviewer-administered, paper-based questionnaire will be used. It will
capture socio-demographic variables, TB knowledge and perceptions, symptom onset
timeline, health-seeking behaviors, reasons for delays, and nutritional assessment.
Patient reports will be validated with available clinic/laboratory records wherever
possible.
Data Analysis and Statistics:
 Data Management and Quality Control:
o Data from questionnaires and clinic records will be coded, entered, and stored
in a secure database.
o Double entry will be done to minimize errors.
o Data will be checked for completeness, missing values, and inconsistencies.
Missing data will be addressed through appropriate statistical methods (e.g.,
imputation or exclusion).
 Descriptive Statistics:
o Continuous variables (e.g., age, BMI, delay durations) → mean, median,
standard deviation, interquartile range.
o Categorical variables (e.g., gender, occupation, reasons for delay) →
frequencies and percentages.
Add information in this section
 Software:
Data will be analyzed using MS Excel 2007 and Epi-Info version 7.2.7.
Timeline of Study (3 months after approval):
 Data collection: 1.5 months
 Data compilation and cleaning: 15 days
 Data analysis and report writing: 1 month

References
1. Storla DG, Yimer S, Bjune GA. A systematic review of delay in the diagnosis and
treatment of tuberculosis. BMC Public Health. 2008;8:15.
2. Sreeramareddy CT, Qin ZZ, Satyanarayana S, et al. Delays in diagnosis and treatment
of pulmonary tuberculosis in India: a systematic review. Int J Tuberc Lung Dis.
2014;18(3):255–66.
3. Cegielski JP, McMurray DN. The relationship between malnutrition and tuberculosis:
evidence from studies in humans and experimental animals. Int J Tuberc Lung Dis.
2004;8(3):286–98.
4. Huang LK, Chen NH, Liu YC, et al. Undernutrition in adults with tuberculosis is
associated with mortality and relapse. J Infect Dev Ctries. 2014;8(9):1180–7.
5. Kamara RF, Odland JO. Cross-sectional study of factors associated with treatment
delay among pulmonary tuberculosis patients in Sudan. BMC Public Health.
2020;20(1):1121.
6. Isaakidis P, Rangan S, Pradhan A, et al. Poor outcomes in slum population with TB:
Reasons and remedies needed. BMC Infect Dis. 2011;11:274.
7. World Health Organization. BMI classification. Geneva: WHO; 2004.
8. Bhargava A, Bhargava M. Tuberculosis deaths are predictable and preventable:
Comprehensive assessment and clinical care is the key. J Clin Tuberc Other
Mycobact Dis. 2020;19:100155.
9. World Health Organization. The End TB Strategy. Geneva: WHO; 2015.
Section 1: Demographics and Socio-Economic Indicators

1. What is your age?

a) 18–29 years
b) 30–44 years
c) 45–59 years
d) 60 years or older
2. What is your highest level of education?
a) No formal education
b) Primary school completed
c) Secondary school completed
d) College or university degree
3. What is your current occupation?
a) Unemployed or homemaker
b) Unskilled laborer (e.g., farm worker, daily wage earner)
c) Skilled worker (e.g., tradesman, clerk)
d) Professional (e.g., teacher, engineer)
4. How many people are in your immediate household?
a) 1–2
b) 3–5
c) 6–8
d) More than 8
5. What is the approximate distance from your home to this health facility?
a) Less than 1 km
b) 1–5 km
c) 6–10 km
d) More than 10 km

Section 2: Symptom Timeline and Healthcare-Seeking Behaviors

6. When did your symptoms first begin?

a) Less than 2 weeks ago
 b) 2 weeks to 1 month ago
c) 1–3 months ago
d) More than 3 months ago
7. What was your first symptom?
a) Cough
b) Fever
c) Weight loss
d) Night sweats
8. Where did you first go for treatment when you became sick?
a) A local pharmacy
b) A private clinic
c) A government hospital or health center
d) A traditional healer or spiritual leader
9. What was your main reason for choosing your first point of care?
a) It was the cheapest option
b) It was the closest option
c) It was recommended by family/friends
d) I trusted this type of provider
10. How many different providers did you visit before you were finally diagnosed with TB?
a) 1
b) 2
c) 3
d) 4 or more
11. What was the main reason you visited multiple providers?
a) The first provider's treatment was not working
b) I could not afford treatment at the first provider
c) I was not given a proper diagnosis
d) The first provider was too far away
12. How long did you wait from the onset of your first symptom to your first visit to any healthcare
provider?
a) Less than 1 week
b) 1–4 weeks
c) 1–3 months
d) More than 3 months
13. How long did it take from your first visit to a healthcare provider until you received a TB
diagnosis?
a) Less than 1 week
 b) 1–4 weeks
c) 1–3 months
d) More than 3 months
14. How long did it take you to start treatment after you were given a TB diagnosis?
a) Immediately (same day)
b) Within 1 week
c) 1–4 weeks
d) More than 4 weeks
15. What was the main reason for the delay in starting your treatment?
a) Financial problems
b) Waiting for a drug supply to be available
c) Fear of side effects
d) Deciding whether to accept the diagnosis

Section 3: Knowledge and Perceptions about TB

16. What causes TB?

a) Evil spirits or a curse
b) Malnutrition
c) A germ or bacteria
d) I don't know
17. Can TB be spread from person to person?
a) Yes
b) No
c) I don't know
18. What are the common symptoms of TB? (Select all that apply)
a) Persistent cough
b) Fever
c) Weight loss
 d) All of the above
19. Is TB a curable disease?
a) Yes
b) No
c) Only sometimes
d) I don't know
20. Where can you get free TB diagnosis and treatment?
a) In the private sector
b) At government health centers
c) Only in hospitals
d) It is never free
21. Do you believe that people with TB face discrimination from their community?
a) Yes
b) No
c) I'm not sure
22. What do you think is the best way to prevent the spread of TB?
a) Isolating TB patients
b) Taking all TB medications as prescribed
c) Improving sanitation
d) Eating healthy food
23. Would you have sought treatment sooner if you knew the symptoms of TB better?
a) Yes
b) No
24. What do you believe is the most important part of TB treatment?
a) Eating nutritious food
b) Taking the full course of medication
c) Resting a lot
d) Taking vitamins
25. Do you believe your weight loss is related to your TB symptoms?
a) Yes, definitely
b) Maybe, but I'm not sure
c) No, it is not related

Section 4: Patient-Reported Nutritional Status

26. Have you noticed any change in your weight since your symptoms began?
a) I have gained a lot of weight
b) My weight is the same
c) I have lost some weight
d) I have lost a lot of weight
27. On a scale of 1 to 5, how would you rate your appetite since your illness began? (1 = no appetite,
5 = very good appetite)
a) 1
b) 2
c) 3
d) 4
e) 5
28. Have you been advised by any health professional about what to eat since your illness started?
a) Yes
b) No
29. Before you got sick, did you consider yourself to be:
a) Underweight
b) Normal weight
c) Overweight
d) Obese
30. Do you believe your current nutritional status is:
a) Severely undernourished (WHO BMI <16 kg/m²)
b) Moderately undernourished (WHO BMI 16–16.9 kg/m²)
c) Mildly undernourished (WHO BMI 17–18.5 kg/m²)
d) Normal or overweight