The effect of malnutrition and diabetes on outcomes for drug-resistant and drug sensitive patients starting anti-tuberculosis treatment

Adverse TB treatment outcome at end of study defined as death, loss to follow-up, default (two or more consecutive months of interrupted treatment) or treatment failure.

1. Adverse treatment outcome in the secondary outcome also includes relapse/ recurrent active TB diagnosed clinically or bacteriologically confirmed within 2 years of completing treatment.
2. Catastrophic household expenditure assessed by measuring total patient costs (direct medical costs, direct on-medical costs, indirect costs and coping strategies) using an adapted version of the WHO costing tool, with data collected at the start of treatment, end of intensive treatment phase, mid continuation phase and end of treatment
3. Reduced lung function assessed using the St Georges Respiratory Questionnaire and FEV1 measured by spirometry at the start of treatment, end of intensive treatment phase, mid continuation phase and end of treatment
4. Development/evolution of hyperglycaemia and diabetes. For participants with newly diagnosed diabetes during TB treatment, we will assess the proportion who remain diabetic during post-treatment follow-up. Conversely, we will assess the proportion who were non-diabetic during TB treatment who become diabetic during post-treatment follow-up (HbA1c >=6.5% or diagnosed externally and placed on treatment)

Exposures outcomes:
1. Diabetes – primary exposure will be diabetes present at any one time point during treatment (HbA1c >= 6.5% or on recognized drug treatment for diabetes), secondary will be HbA1C >= 7% at 2 or more time points or on recognized drug treatment for diabetes. Exploratory analysis will assess the effect of degree of hyperglycaemia during treatment on TB treatment outcomes
2. Malnutrition - primary exposure will be moderate/severe malnutrition at the start of treatment defined as BMI< 17kg/m². Secondary analyses will explore the effect of changes in nutritional status during treatment using repeated measures analysis. Risk of recurrent TB will be explored by BMI status (moderate/severe malnutrition) at the end of TB treatment as the primary analysis

Co-factors outcomes:
Measured during treatment:
1. Demographic factors; age, sex, DOTS center, education level, social service category, occupation, cigarette smoking, alcohol and etc
2. Clinical management; TB diagnosis, symptom history, treatment regimen, treatment history, co-morbidities, chest x-ray, drug related adverse events
3. Nutrition status; height (cm), weight (kg) using SECA digital scale, handgrip strength using Jamar Hand Dynamometer, mid-upper arm circumference and waist/hip circumferences (cm) using SECA measuring tape, weight loss, appetite and body composition by bio-impedance analysis
4. Clinical investigations: blood pressure (mmHg) using Tanita, and haemoglobin using Hemocue 301+, random plasma glucose and HbA1c. Oral glucose tolerance test is conducted for participants whose HbA1c is 5.7 - 6.5%. HIV rapid diagnostic test is conducted if consent is given
5. Household food security is adapted from U.S. Household Food Security Survey Module (US HFSSM)
6. Quality of life is measured using the WHO Quality of Life BREF survey
7. Risk factors related to adherence; depression using Hospital Anxiety Depression Scale (HADS), Social & family support by using Multidimensional scale of perceived social support (MSPSS), stigma using Berger scale of stigma, self-esteem using Rosenberg Self-esteem Scale (RSES) and TB treatment adherence last 7 days
Measured at end of treatment and post-treatment
1. Chest x-ray
2. Anthropometry, household food security, quality of life and the risk factors related to adherence as described in during treatment.
3. Clinical investigations: blood pressure, and haemoglobin, random plasma glucose and HbA1c.
4. Active TB screening is adapted from WHO symptom screening
5. Lung health; lung spirometry using ndd EasyOne, 6-minute walk test, modified Medical Research Council Dyspnea score, St George Respiratory Questionnaire
6. Functional impairment on work/school, social life and family life using Sheehan Disability scale
7. Health-related behaviors; smoking, alcohol and substance abuse
8. Symptom history and health seeking behavior