Risk factors for mortality among inpatients with smear positive pulmonary tuberculosis

Objective: To evaluate risk factors having significant effect on mortality of smear positive Pulmonary Tuberculosis (PTB) inpatients Methods: A descriptive cross-sectional study was conducted at Ojha Institute of Chest Diseases, Dow University Hospital Ojha Campus, Karachi. One hundred and seventy (170) inpatients of smear positive PTB confirmed by Acid Fast Bacilli (AFB) smear, aged between 13-80 years were enrolled by using consecutive sampling technique while patients with drug resistant Tuberculosis (TB) and extra pulmonary TB were excluded from the study. Selected patients were interviewed for collecting demographic data and risk factor data by using a standard questionnaire. Results: Out of 170 PTB inpatients, mortality was observed in 23 (13.5%) patients among which male patients were 12 (52.2%), and female were 11 (47.8%). Mortality was significantly associated with increasing age (p=0.003), socioeconomic status (p=0.019), anemia (p=0.03), Chronic Liver Disease (CLD) (p=0.005), Diabetes Mellitus (DM) (p=0.001), Human Immunodeficiency Virus (HIV) (p=0.007), Hypertension (HTN) (p=0.006), recurrent TB (p=0.001), and smoking (p=0.001). Conclusion: Increasing age, poverty, smoking history, and presence of comorbidities like DM, CLD, HIV, hypertension, and anemia are associated with higher mortality in smear positive PTB cases.


INTRODUCTION
Tuberculosis (TB) is among the oldest infectious epidemic diseases, developed due to airborne bacterium i.e. Mycobacterium tuberculosis. 1 It is multi-system infectious disease that mostly affect the lungs, commonly known as Pulmonary Tuberculosis (PTB). Tuberculosis affects the different body systems including respiratory, gastrointestinal, lymphoreticular, musculoskeletal, reproductive, and central nervous system. 2 It is among the world's major health related problems, affecting the one third population latently. 3 World Health Organization (WHO) reports ten million new TB cases in 2017 including 5.8 million men, 3.2 million women, and one million children. 4 Pakistan is ranked among leading eight countries in which 66.6% of new cases of PTB were reported. 4 Human Immunodeficiency Virus (HIV) is a leading risk

Original Article
Risk factors for mortality among inpatients with smear positive pulmonary tuberculosis factor reported by WHO, that causes 11% of newly diagnosed PTB. 5 Pulmonary Tuberculosis patients frequently present with cough with or without sputum, fever, weight loss, night sweats, breathlessness, and chest pain. Sputum smear test is the most commonly used diagnostic method for PTB patients. 6 Smear positive PTB patients are considered as most infectious ones because these are capable of spreading infection to 15 non-PTB people per year. Smear test is a corner stone in early diagnosis of PTB in patients and to initiate the treatment with anti-tuberculosis therapy (ATT). 7 Despite the fact, PTB is early diagnosed and treated but still the leading cause of mortality. WHO reports the 1.3 million and 0.3 million deaths throughout the world in 2017 due to HIV negative TB and HIV positive TB respectively. 4 PTB mortality rate varies in different regions of world, developing countries with high mortality rate whereas developed countries with low mortality rate. 8 However, PTB is directly associated with different risk factors that increases the mortality such as delay in diagnosis of PTB, poor compliance with ATT, lack of proper health facilities and ignorance of patients towards health in developing countries, homelessness, increasing age, HIV infection, anemia, DM, CLD, HTN, recurrent TB, and smoking. These several risk factors increase the chances of development of drug resistance that leads towards therapy failure, recurrence of PTB, and ultimately deaths of patients. [9][10][11][12][13][14] The research objective of this study was evaluation of risk factors associated with mortality of smear positive PTB patients treated at Ojha institute of chest diseases.

METHODS
A descriptive cross-sectional study was conducted at Ojha institute of Chest Disease, Dow University Hospital Ojha Campus Karachi. One hundred and seventy (170) inpatients of smear positive PTB patients, receiving ATT category I were selected in first four months of study and each patient was followed during intensive phase of treatment i.e., two months. Study period was from 1 st October 2018 to 31 st March 2019. PTB patients having age between 13-80 years were enrolled by using consecutive sampling technique and patients with drug resistant TB (on Gene Xpert) and extrapulmonary TB were excluded from the study. Research approval was obtained from Institutional Review Board (IRB) of Dow University of Health Sciences, Karachi. Selected patients were interviewed for collecting demographic data and associated risk factors like; anemia, CLD, DM, HIV, HTN, and history of smoking and PTB by using a standard questionnaire.
Socioeconomic status of patients was categorized into different classes on the basis of per month income in Pakistani Rupees (PKR), such as lower class (<20000 PKR), middle class (20000-50000 PKR), and upper class (> 50000 PKR). Different risk factors were confirmed by using standard protocol, such as blood pressure of each PTB patient was measured for confirmation of hypertension. Specific laboratory tests were performed for confirming associated risk factors such as Complete Blood Count (CBC) for anemia, Fasting and Random blood sugar (RBS) for diabetes mellitus, HIV screening, ultrasound abdomen and Liver Function Test (LFT) for chronic liver disease. All collected data was interpreted with SPSS version 22, by applying chi-square test and using < 0.05 as significant p-value.

DISCUSSION
Pulmonary tuberculosis (PTB) is among the major health related problems in developing or lowincome countries. Despite extensive development in medical field, and improvements in health-related facilities PTB is still among the life-threatening diseases in poor countries. 15 Direct involvement of different risk factors for this dilemma are the distinct reason of increasing infection susceptibility, and PTB progression. 15,16 These factors also play vital role in prediction of mortality in PTB patients, such as increasing age, poor health care facilities due to poverty, low income, anemia, CLD, DM, HIV, HTN, recurrent TB, and smoking. 17,18 WHO reports that morbidity and mortality of TB is continuously increasing throughout the world, and TB is leading cause of mortality among infectious diseases. 4,5 Current study have two important findings first one is the increased mortality rate in PTB patients, and second one is the significant relation of different risk factors with PTB.
First important finding of current study was the higher rate of mortality in PTB patients i.e., 13.5%, whereas most of the other studies reported the lower mortality prevalence than current study such as Asgedom SW et al., 11.3%, 17 Shahrezaei M et al., 1.6%, 18 and Rodrigo T et al., 3.5%. 19 Another study by Takarinda KC et al. reported the higher prevalence of mortality 22.0% in TB patients. 20 In current study mortality rate was high due to several reasons such as illiteracy, poverty, and presence of comorbidities.
Second important finding is the direct and significant relation of different risk factors with mortality in PTB patients. Mortality shows significant relation with increasing age, poverty, anemia, CLD, DM, HIV, HTN, recurrent TB, and smoking. Similar to our result different studies show the significance of various risk factors and mortality. 18 18 Another study by Alavi-Naini R et al. reports the anemia, smoking, DM, HIV, drug abuse, hepatitis, and recurrent TB as a predictor for PTB mortality. 22 In low income countries, poverty is the most common cause of increasing malnutrition and diseases such as TB. Malnutrition directly affects the Smear positive pulmonary tuberculosis  cell mediated immunity i.e., the principal defense against TB resulting in rapid progression of TB in malnourished as well as in immunocompromised patients such as in HIV. 23 Increasing age is another important factor that increases the comorbidities and makes the situation worse for appropriate management of TB, ultimately mortality rate increases. PTB patients suffering from DM are at a higher risk of developing TB with increased progression and mortality. TB is most commonly known as disease of poverty because of its direct association with other risk factors that increases the emergence and progression of TB. Current study also reports the higher prevalence of illiteracy, lower socioeconomic status, and presence of comorbid conditions, which are not only directly, associated with progression of PTB but also increase the chances of failure of therapy resulting in death of patients. [23][24][25]