Medical Student Research DELAY IN DIAGNOSIS OF TUBERCULOSIS IN PATIENTS PRESENTING TO A TERTIARY CARE HOSPITAL IN RURAL CENTRAL INDIA PALLAVI DHANVIJ*, RAJNISH JOSHI**, SP KALANTRI** ABSTRACT Background : Delay in diagnosis of TB and initiation of anti-tubercular treatment (ATT) contributes to more severe disease manifestations in the individual and higher disease transmission in the community. This study was carried out to quantify the delay in diagnosis of TB and the factors which led to pre-provider, provider and in-hospital delays, among seriously ill patients, who required hospitalization because of their symptoms. Methods A cross-sectional study was performed amongst patients with tuberculosis (TB) who were admitted to medicine wards of the hospital. A pilot tested questionnaire was administered to these patients to determine time periods each of them had spent before seeking any healthcare, time spent in the referral chain with various health care providers, and during hospital till the time a definite diagnosis was made and anti-tubercular therapy was initiated. Questions were also asked to determine various factors which could lead to delay in pre-provider, provider, and in-hospital periods. Results A total of 55 patients who were admitted to the medicine wards between 1st March and 30th April 2007 and were initiated on anti-tubercular treatment were included in the study. Pre-provider, provider, and in-hospital delay occurred in 20, 40 and 19 patients respectively. The risk of pre-provider delay was significantly high in smokers (OR 4.1 (1.10-15.31)), risk of provider delay was high in those initiated on antibiotic therapy (OR 4.5 (1.24-16.80)). Conclusion : Being a current smoker was a significant risk factor for pre-provider delay, while antibiotic prescriptions for the delay which occurred between seeking care from the first provider and diagnosis of tuberculosis. Introduction An estimated one-third of the world's population is infected with tuberculosis (TB), and India has the largest number of patients with tuberculosis runs the largest TB control program in the world. The national tuberculosis control program (RNTCP) provides directly observed treatment (DOTS) at no costs to the patients. Despite widespread DOTS coverage at the primary health centers (PHC), the diagnosis of TB is * This author was an intern at the time of this study. Currently Medical Officer KRHTC Anji. ** Department of Medicine, MGIMS Sevagram delayed in many patients, who develop more severe manifestations of the disease and need inpatient care. In a previous study at our hospital 23% of all patients with smear positive pulmonary TB, who required inpatient care, died before completing six months of anti-tuberculosis treatment. 1 This mortality rate is much higher than the national mortality rate of under 5% under RNTCP. 2 Delay in diagnosis of TB and initiation of anti-tubercular treatment (ATT) contributes to more severe disease manifestations in the 56
Pallavi Dhanvij, et al individual and higher disease transmission in the community. This delay occurs at three levels; firstly patients may ignore their symptoms and take longer to approach a health care provider (pre-provider delay). Second, health care providers may fail to diagnose TB, and unsuccessfully treat patients for other competing conditions (provider delay). Lastly, a delay may occur while diagnosis is being established during hospitalization (in-hospital delay). 3 This study was carried out to quantify the delay in diagnosis of TB and the factors which led to pre-provider, provider and in-hospital delays, among seriously ill patients, who required hospitalization because of their symptoms. Methods Setting - Mahatma Gandhi Institute of Medical Sciences, Sevagram is a rural based tertiary care teaching hospital in central India. About 250000 patients visit the hospital out-patient and emergency departments, and 8000 of them are admitted to the medicine wards every year. About 25 to 30 hospitalized patients are diagnosed as having either pulmonary or extra-pulmonary TB every month and are initiated on ATT. Inclusion and exclusion criteria - We prospectively included all consecutive patients who were initiated on ATT after hospitalization in the medicine wards. A daily screen of the nursing drug distribution registers in all medical wards was carried out to obtain a list of all such patients. Patients who were initiated on ATT for their current illness prior to hospitalization, or those admitted with ATT induced complications were excluded. Sources of data - One investigator (PD) interviewed all eligible patients using a standardized and pilot tested questionnaire. The questionnaire had sections on patient demography, their access to health care, socio-economic status, onset of symptoms, chronological sequence and duration of treatment by different healthcare providers. Socio-economic status was determined by scoring seven parameters (Material possessions, house, land, educational, occupational, economic and social profile of the family) using a validated scale which is specially designed for use in rural India. The total score obtained is converted in five grades (1 to 5 from highest to lowest). The information about ordering of sputum smears, chest-radiographs, and antibiotic prescriptions prior to admission to the hospital was specifically collected and verified by prescription and treatment notes wherever available. The information about the time of admission to the hospital and initiation of ATT was collected from hospital charts, and nursing drug distribution registers respectively. The results of in-hospital investigations were used to classify patients as having pulmonary (parenchymal or pleural) or extra-pulmonary (neural, abdominal, lymph node, bone or joint) tuberculosis. Study definitions - We defined the time interval (in days) from the onset of first symptom to first visit to a health care provider as symptom-provider time. The time interval (in days) from the first visit to a health care provider to the date of admission to the hospital was defined as provider-hospital time. The period from hospital admission to initiation of anti-tubercular treatment was defined as in-hospital time. This later period was determined in hours, and converted to days during the data-analysis for comparability. A health-care provider was defined as an individual who provides pharmacological or non- 57
Delay in diagnosis of tuberculosis in patients presenting to a tertiary care hospital in rural Central India pharmacological treatment to a patient seeking relief in symptoms. The different health-care providers were classified as traditional healers (including but not restricted to religious priests, faith healers etc), paramedical practitioner (village health guides, midwives, nurses, compounders, and non-licensed practitioners), AYUSH practitioner (a graduate of alternate system of medicine : Ayurveda, Yoga, Unani, Sidhha, and Homeopathy), MBBS practitioner(a medical graduate), internist (a specialist in medicine, or chest diseases), or a non-internist practitioner (a specialist in surgery, gynecology, pediatrics). The symptom-provider time of more than 21 days was defined as pre-provider delay. This time period was chosen as under RNTCP, suggestive symptoms of 3 weeks or more should alert patients and providers to seek investigations to diagnose TB. A provider-hospital time of more than 14 days was defined as provider delay. This duration was chosen as non-response to empirical treatment longer than this duration, should alert a practitioner about TB as a possibility. In-hospital time of more than 2 days was defined as in-hospital delay, as we expect that the results of TB specific investigations must be obtained within this period, and specific therapy is initiated. Statistical analysis - The collected data was entered by an investigator (PD) using Epidata software (version 3.0, The Epidata association, Denmark). A second investigator (RJ) cleaned the entered data. We carried out a descriptive analysis of the demographic features, socio-economic grade, presenting symptoms, and access to health care parameters. We determined the mean symptom-provider, provider-hospital and in-hospital times and also used these variables to create outcome measures of pre-provider, provider and in-hospital delay respectively. The contribution of different healthcare providers towards the net provider-hospital time was also determined. We carried out a univariate and multivariable logistic regression to determine the variables which influence pre-provider, provider and in-hospital delay. Our hypothesis was that delay at each of these time-intervals was due to a different set of variables ; hence we tested for different models for them. The model for preprovider delay as an outcome included age, sex, lower socio-economic status, time taken to reach PHC, number of symptoms, and smoking status as the explanatory variables. The additional explanatory variables for provider delay were antibiotic use, obtaining sputum smears, chest radiographs, extra-pulmonary TB, and symptom delay. The model for in-hospital delay as an outcome included age, sex, smoking status, number of symptoms, extra-pulmonary TB, pre-provider and provider delay as explanatory variables. All the explanatory variables were included in the initial logistic model and a backward step wise technique was used in the selection of the final model. For a variable to be removed from the model, the p-value had to be >0.1.The impact of removal of each variable in the model was evaluated using the likelihood ratio test. The fit of the final logistic model was assessed using the Hosmer-Lemeshow goodnessof-fit test.20 The results of the final model are presented as adjusted odds ratios (OR) with 95% confidence intervals (CI). All statistical analyses used Stata (Version 9, Stata Corporation, Texas, USA). Results A total of 55 patients who were admitted to the medicine wards between 1 st March and 58
Pallavi Dhanvij, et al 30th April 2007 were initiated on anti-tubercular treatment. Most of these patients were young (Mean age 39.3 years, SD 16.8) and 40 (72%) of them were males. Pulmonary tuberculosis was diagnosed in 39 (71%) patients (25 had a positive smears or culture, 14 had pleural effusion) and remaining 16 (29%) patients had extra-pulmonary tuberculosis. The median distance of the place of residence of these patients was 50 kilometers (IQR 30 to 250 km) (Table 1). Table 1: Characteristics of the patients who were initiated on anti-tubercular treatment for the first time at the tertiary care hospital Variable Value* Demography and symptoms Age (in years) 39.3 (16.8) Male sex 40 (72.7) Socioeconomic status grade (Grade 5/5 being lowest) Grade 3 11 (20.0) Grade 4 39 (70.9) Grade 5 05 (9.1) Ever smoker 13 (21.6) Symptoms Fever + cough + breathlessness 22 (40) Fever + Cough 11 (21) Cough + breathlessness 05 (9) Fever + Breathlessness 03 (5.5) Either Fever / Cough / Breathlessness alone 08 (14.5) Neither of these symptoms 06 (10) Access to healthcare Highest health care provider in the settlement where patient resides None 13 (23.6) Traditional healer 8 (32.7) Paramedical or unregistered practitioner 3 (5.4) AYUSH practitioner 7 (12.7) MBBS doctor 14 (25.4) Distance between residence and nearest PHC (in km) 7.4 (5.5) Time taken to travel from residence to nearest PHC (in minutes) 28 (17.4) Patients who had visited PHC prior to admission 11 (21) Number of providers visited prior to admission to hospital 0 5 (9) 1 15 (27.3) 59
Delay in diagnosis of tuberculosis in patients presenting to a tertiary care hospital in rural Central India 2 17 (30.9) 3 15 (27.3) 4 03 (5.5) Number of patients who were treated by each provider Traditional healer 9 (16.3) Paramedical or unregistered medical practitioner 7 (12.7) AYUSH practitioner 15 (27.2) MBBS practitioner 24 (43.6) Non-internal medicine /non-tb chest specialist 24 (43.6) Internal medicine or chest specialist 20 (36.3) Distance between residence and hospital (in km) 139 (164.8) Time taken to travel from residence to hospital (in minutes) 191.4 (181.7) All values indicate mean (SD) unless indicated otherwise * These values indicate number (%) PHC = Primary Health center; km = Kilometers; AYUSH = Ayurveda, Yoga, Unani, Sidhha, and Homeopathy. These practioners predominantly practice Indian system of medicine; MBBS=Bachelor of medicine who predominatly practice western or allopathic system of medicine. The average duration from the onset to symptoms to the initiation of anti-tubercular treatment in these patients was 66.3 days (SD 93.4). The time interval from onset of symptoms and seeking care from the first provider (symptomprovider time) was 40.0 days (SD 82.5). Different Figure : Schematic representation of mean time spent by patients prior to seeking healthcare, while in treatment by different providers, and as an inpatient. 60
Pallavi Dhanvij, et al healthcare providers had treated these patients for 23.7 days (SD 29.7) before they were admitted at MGIMS for further evaluation (providerhospital time). Prior to admission, 5 patients (9%) had a sputum examination and 14 (29%) underwent a chest radiography, and 16 (29%) were received antibiotics. On an average these patients were admitted in the hospital for another 2.5 days (SD 3.4) before initiation of anti-tubercular treatment. (Figure) Pre-provider, provider, and in-hospital delay occurred in 20, 40 and 19 patients respectively. Being a current smoker was a significant risk factor for pre-provider delay. Antibiotic prescriptions and extra-pulmonary TB were significant risk factors for the provider and in-hospital delay respectively. Presence of pre-provider delay protected against in-hospital delay, but increased the risk of provider delay. (Table 2) Table 2 : Univariate and multivariate logistic regression to determine the predictors of delay in initiation of anti-tubercular treatment in patients admitted to a tertiary care hospital Type of delay Variable Univariate analysis OR (95% CI) Multivariate analysis OR (95% CI) Pre-provider delay (n=20) vs No pre-provider delay (n=35) Age (years) 1.0 (0.96-1.02) 1.0 (0.96-1.03) Female sex 0.5 (0.54-2.01) SES grade =4 1.0 (0.25-3.94) Ever smoker 4.0 (1.08-14.08) 4.1 (1.10-15.31) Symptoms (number) 1.2 (0.68-2.13) Travel time to PHC (min) 1.0 (0.96-1.02) Provider delay (n=22) vs No provider delay (n=33) Age (years) 1.0 (0.95-1.02) 1.0 (0.95-1.02) Female sex 0.6 (0.19-2.34) SES grade =4 0.7 (0.19-2.86) Ever smoker 2.1 (0.59-7.40) Symptoms (number) 0.8 (0.46-1.38) Extrapulmonary TB 0.8 (0.26-2.85) Antibiotic prescription 3.7 (1.1-12.69) 4.5 (1.24-16.80) Sputum examination 2.4 (0.37-16.0) Obtaining Chest radiology 2.5 (0.78-8.46) Pre-provider delay 1.9 (0.62-5.87) 2.6 (0.76-8.96) 61
Delay in diagnosis of tuberculosis in patients presenting to a tertiary care hospital in rural Central India In-hospital delay (n=19) vs No in-hospital delay (n=36) Age (years) 1.0 (0.97-1.03) 1.0 (0.96-1.03) Female sex 1.4 (0.40-4.72) Ever smoker 0.5 (0.11-2.04) Symptoms (number) 0.8 (0.46-1.40) Extrapulmonary TB 5.5 (1.58-19.52) 4.6 (1.2-17.17) Pre-provider delay 0.2 (0.05-0.84) 0.3 (0.06-1.13) Provider delay 0.4 (0.11-1.34) PHC = Primary Health center; SES = Socio-economic status; TB= Tuberculosis. Pre-provider delay was defined as duration of symptoms of 21 days or more prior to seeking any medical care. Provider delay was defined as duration of treatment of 14 days or more without initiation of anti-tubercular treatment. Hospital delay was defined as duration of hospital stay of 2 days or more, prior to initiation of anti-tubercular treatment. Discussion The current study found that being a smoker is a significant factor causing pre-provider delay while receiving an antibiotic prescription caused at the level of health care provider. Having extra-pulmonary tuberculosis caused a delay in diagnosis after admission to the hospital. Smoking has been found to cause a delay in diagnosis of TB in previous studies as well. A previous study from Uganda3 found that individuals with TB who smoked, perceived their symptoms to be caused by smoking, and not due to TB. Smokers often have cough as a part of chronic bronchitis. Hence smokers perceive these symptoms to be of usual occurrence, and present late to a health care provider for diagnosis and treatment. On the other hand antibiotic treatments mask clinical features due to tuberculosis. Patients who receive antibiotics may be more patient, and wait longer for improvement in their symptoms as compared to those who do not. Previous studies from Ethiopia and Uganda have found antibiotic prescriptions as well as other informal treatments to delay presentation of tuberculosis. 3,4 Extrapulmonary tuberculosis is more difficult to diagnose, has many potential differential diagnoses, and often require intensive investigations before a diagnosis can be reached. Presence of extrapulmonary tuberculosis hence had highest potential for delay even after admission to the hospital. A recently published systematic review of delay in diagnosis of tuberculosis has found coexistence of chronic cough due to another lung disease (such as smokers cough), rural access, presence of a low level health care facilities before presentation to a tuberculosis care facility, HIV positivity, substance abuse, low awareness of TB, incomprehensible beliefs, self treatment and stigma as potential cause. Our study did not investigate all such potential causes, but rather looked at access to health care, socio-demographic factors, and disease characteristics. We did not find distance of health care facility as a predictor for delay. This is likely due to the fact that under 62
Pallavi Dhanvij, et al National Rural Health Mission primary care facilities present at fairly approachable distances. Our patients did not spend too much time getting themselves treated from traditional healers either. Higher the professional qualification of the provider greater was the delay. This calls for a serious appraisal of the referral chain through which the patient passes through before reaching a tertiary care hospital at MGIMS. Strength of our study was the detailed questionnaire and detailed interviewing of each case admitted to the hospital during the study period. Major limitation was small sample size and a short duration of the study. The results of the study can be generalized to include only those patients who become seriously ill so as to seek inpatient care. Patients who got treated on an outpatient basis were not included in this study. Pre-provider delay can be decreased by health educating the community about TB and importance of early sputum AFB as people now focus on blood investigation after having fever or other complains. This can be done by improving health education sessions at the village level by community health wokers such as ASHA since she is the new village level DOTS provider. Providers delay can be decreased by periodic reeducation of heath providers, including private primary care physicians. Such programs should emphasize the importance of sputum microscopy, and following RNTCP algorithm with due diligence. References : 1. Pai M, Joshi R, Bandopadhaya M, Narang P, Dogra S, Taksande B, Kalantri S. Sensitivity of whole blood gama interferon assay among patients with pulmonary tuberculosis and variations in T-cell responses during anti-tuberculosis treatment. Infection 2007; 35 (2): 98. 2. Dhingra VK, Aggarwal N, Chandra C, Vashist RP. Tuberculoais mortality and trends in Delhi after implementation of RNTCP. Indian J Tuberc 2009; 56: 77-81. 3. Kiwuwa MS, Charles K and Harriet MK. Patient and health service delay in pulmonary tuberculosis patients attending a referral hospital : across sectional study. BMC Public Health 2005; 5: 122. 4. Mesfin MM, Newell JN, Walley JD, Gessessew A, Madeley RJ. Delayed consultation among pulmonary tuberculosis patients: A cross-sectional study of 10 DOTS districts in Ethiopia. BMC Public Health 2009; 9: 53. 5. Storla DG, Yimer S, Bjune GA. A systematic review of delay in diagnosis and treatment of tuberculosis. BMC Public Health 2008; 8:15. 63