Delays and risk factors in the management of patients with active pulmonary tuberculosis: national cohort study

This study is the first to investigate the possible types and causes of delay and the time from symptom onset to treatment initiation in South Korea using a large sample from the KTBC database. We found significant epidemiological evidence supporting the effective control of PTB.

First, the median length of time to presentation was 16.0 days; this result could be disappointing because the WHO and the national active case finding program recommend screening for PTB for people who have had a cough for two weeks or more. However, two-thirds of patients went to hospital within 40 days of symptom onset, while half of patients went to hospital within 16 days. This result shows that although the diagnosis was not too late in the majority of patients with PTB, the excessive delay in some patients had a significant impact on the average duration of the delay. After adjusting for potential confounders, the longer time to presentation was affected by heavy alcohol consumption and underlying conditions, such as neuropsychiatric diseases. This finding suggests that future active case-finding programs will need to focus on vulnerable patients with neuropsychiatric conditions, those who are heavy alcoholics, and those who are unlikely to notice or seek help for their symptoms.

It is very important to identify the risk factors that contribute to delayed presentation, as they will serve as targets for active screening programs. However, the presentation delay and its associated risk factors vary greatly depending on the situation in each country. Very different results have been reported in previous studies. In high-income countries, older age and language barriers were frequently associated with prolonged delays in one country, but were considered independent factors in other countries.8,11,12. In contrast, low (uninsured) income, low education, smoking, old age, and female sex were frequently associated with long delays in two countries, while male sex was more associated with long delays In other countries. On the other hand, in our analysis of KTBC 2019, it did not show differences between male and female sex in terms not of presentation delay but also of health care and overall delay. In addition, previous studies have reported lack of knowledge regarding tuberculosis, human immunodeficiency virus (HIV) infection, and immunosuppressive therapy as risk factors for prolonged delays in low- and middle-income countries.10,15,16,19,25,26. Thus, risk factors vary from country to country depending on cultural characteristics, socioeconomic status and health system. Thus, the delays cannot be attributed to a single cause; therefore, the problems must be considered from several angles and their connection must be determined in order to solve them.

Second, the median time to care was only 5.0 days. This result is similar to that of the presentation delay. A few determined the general trend. After adjusting for potential confounders, longer time to care was affected by malignancy, autoimmune disease, and low bacterial load manifesting as AFB-negative and TBPCR-negative smear status. According to previous studies, the risk factors for care delay are also diverse, similar to presentation delay, but more concise. They can be broadly divided into two categories, primarily related to health care resources and diagnostics associated with the system, such as referral to TB specialists and limited laboratory testing8,11,15,16,18,22. In the present study, healthcare delay was also similar to that found in previous studies, which reported that healthcare delays are related to underlying host conditions and disease characteristics, such as old age, cause of immunosuppression and low microbiological load.7,12,22,27.

The risk factors for care delay identified in our study were not significantly different from those previously reported, whereas those for presentation delay vary considerably from those reported in previous studies. The characteristics of TB patients have changed, especially in high-income countries, including South Korea, as society ages. Tuberculosis patients expected to have another medical illness before an aging society. In these changing epidemiological conditions, careful attention and understanding of the risk factors for delayed care will improve TB control without delaying diagnosis.28. To improve time to care according to our data, cases of malignancy and autoimmune disease as comorbidities should be targeted and carefully assessed for the possibility of tuberculosis infection. Tuberculosis has no unique clinical feature and can occur in any site of the human body, then it could be easily misdiagnosed as another disease and ultimately lead to delayed diagnosis29.30. In another important area of ​​treatment delay, early forms of PTB with a low bacterial load must also be diagnosed in time. In our data, the AFB smear-negative group has less cavitation and bilateral disease on their chest x-ray. Additionally, they have fewer symptoms, including cough/phlegm, generalized weakness, and loss of body weight, with the exception of chest pain. These features are still a barrier that makes early diagnosis of PTB difficult despite advances in medical diagnostic technology. This could be a time-limited step because it is difficult to take into account several factors such as the incidence of tuberculosis in the community, individual characteristics, medical resources, referral system and suspicion. health care providers clinic. However, this measure must be carried out to eliminate or at least control the tuberculosis infection.

This study has several limitations. First, this study was conducted in South Korea, a high-income country with an aging population, intermediate TB burden, and low HIV prevalence. Thus, this limitation could overestimate or underestimate our results. Second, this study was conducted using a questionnaire, which included questions about the date of onset of symptoms. This means that recall bias may have influenced the time to presentation on the patient side. Additionally, on the side of the researchers, confirmation bias (the tendency to favor PTB-related symptoms and overlook non-specific PTB symptoms) may have influenced the time to presentation when we assessed the duration of reported symptoms. by patients during interviews after diagnosis of PTB.

Third, the study results were based on TP cases in hospitals participating in the PPM. In South Korea, more than 70% of all TB patients were diagnosed and treated at PPM hospitals. Most PPM hospitals are university-affiliated hospitals. Thus, patients with serious and complicated diseases were overrepresented in our study. This feature could overestimate our results and lead to selection bias.

Fourth, as just mentioned, this study was conducted in high-income countries and using data from PPM participating hospitals consisting of advanced medical institutions based on the National Tuberculosis Elimination Project of South Korea. Under these clinical conditions, we could not study the role of the Xpert test, a rapid and automated real-time PCR, in the early diagnosis of PTB, since it had already been widely used since 2014 in South Korea and, also in almost the hospitals in this study. Thus, we could not collect Xpert results different from other TBPCR results. This factor may have influenced the time to treatment. However, we believe that rapid TBPCR has helped improve early diagnosis of TB compared to before its introduction, although national data is lacking.31.32.

Fifth, the timing of presentation delay may differ between passive screening and active screening scenarios, since its definition is the time from symptom onset to hospital visit for symptom evaluation and between the onset of symptoms and hospitalization. screening visit. Thus, the time to presentation of active screening may be shorter than that of passive screening. However, we hypothesized that the presentation delay would only occur in symptomatic patients, since South Korea has a national health insurance system and it allows all services to operate. citizens, regardless of economic problems. Koreans are more likely to visit medical facilities than those in other Organization for Economic Co-operation and Development countries, indicating easy access to medical services. We assumed that symptomatic patients would have visited a hospital. However, in the real world, some patients may not have visited a medical facility for individual reasons despite having symptoms. For these reasons, the KTBC has decided to investigate the reasons for hospital visits to understand the diagnostic situations in detail, starting from March 2022, through a meeting with the K-CDA.

In conclusion, we measured presentation times and treatment times (median: 16 days and 5 days respectively). After assessing risk factors, we found that different factors were more associated with time to presentation than time to care. This may be due to the different delay type clinical situations. Our results suggest that active case-finding programs should focus on patients with heavy alcohol use or neuropsychiatric conditions to reduce community transmission of tuberculosis. In addition, healthcare providers should pay more attention to patients with malignancy or autoimmune disease and those with a high index of suspicion for PTB to diagnose the disease early.