Health system delay in pulmonary tuberculosis treatment in a country with an intermediate burden of tuberculosis: a cross-sectional study

Prompt diagnosis and early treatment of tuberculosis (TB) constitute the most effective intervention in controlling and reducing the transmission of Mycobacterium tuberculosis. It is generally assumed that a delay in the diagnosis and treatment of TB increases the severity of the disease and the risk of death and leads to newly infected persons who can become reservoirs of new tuberculosis cases at a future point in time [1]. The timely and accurate diagnosis and treatment of TB are therefore essential. TB diagnosis can be delayed when patients postpone seeking care after the onset of symptoms or when more time is required for health providers to diagnose and treat patients. Since the same variable can move in opposite directions, being a risk factor for one delay and a protective factor for another, it is important to consider the two types of delay separately [2, 3]. Health system delays show the level of TB knowledge and the efficiency of a country’s National Tuberculosis Control Programme (NTP). Thus, the importance and significance of this particular issue is important for the evaluation and planning of interventions through a particular NTP [1, 4], drafted in line with the sixth component of the Stop TB Strategy [5].

A number of studies have addressed the issue of health system delay in the treatment of tuberculosis, though mostly in high- or low-incidence countries [2, 3]. This problem, however, is found to be important in both developed and developing countries. Still, there is no consensus on the acceptable duration of delay. Our understanding of the extent and causative factors of health system delay in medium incidence countries is quite limited. In settings where TB is not frequent, it is usually difficult to achieve a high degree of suspicion and to perform immediate diagnostic procedures for tuberculosis. One of these settings is Croatia, with a TB incidence rate of 19 / 100 000 in 2009 and showing a decreasing trend [6, 7].

The potential loss of time in the diagnosis and treatment of TB patients, resulting from health system delays, has never been explored in this country.

A study investigating both types of delay was conducted on the same participants. The results of patient delay have already been published [8]. Identifying the duration and the factors related to the health system delay was the objective of this part of the study.

A total of 300 subjects were potentially eligible for this study. Among them, 41 patients had no clearly defined symptom onset or no symptoms before the diagnosis, 5 were identified during contact tracing, and 11 patients had a previous history of TB treatment. A total of 243 subjects were found to be eligible, two of whom refused to participate. A total of 241 participants were interviewed, 134 (56%) males and 107 (44%) females. The median health system delay was 15 days while the 75^th percentile was 42 days (the 5^th and 95^th percentile being 1 and 105 days respectively).

Within 10 days of their first visit to a health care facility, 99 (40.9%) cases were diagnosed, 29 (12%) within 11-20 days, 42 (17.4%) in the fourth week, while 71 (29.3%) remained undiagnosed for more than 30 days after the initial health care visit.

The present study is one of the few studies of tuberculosis delay performed in countries with an intermediate burden of TB and the first one exploring health system delays in Croatia. We found that the median health system delay was 15 days. Numerous studies conducted elsewhere report longer delays [2, 12, 16–22], although a few studies show shorter delays [13, 23–25].

Among demographic factors, only the female gender was found to be significantly associated with both a long and extreme delay. This finding was also reported in other countries [18, 22, 26–28], usually without proper explanation. In some of these countries (Uganda, Bangladesh) [22, 26], cultural factors which might not have been relevant for Croatian females were likely to be involved. In our study, TB was clearly suspected and investigated more readily among men, although women did not seek care any later than men, as had previously been thought [8]. Therefore, this interesting finding warrants further investigation. Although it cannot be explained why women experienced delay in being treated, it is clear that women with symptoms suggestive of TB should receive more attention after seeking care.

The symptoms most frequently reported by patients were a cough, fatigue and weight loss. Unexpectedly, median delays were the same or similar both in the case of having one of the symptoms or having none. In addition, the presence of other symptoms was significantly associated with a long delay. Symptoms, either usual or not, are obviously not thought to be alarming and/or TB-related.

One of the challenges of diagnosing TB in primary care is to distinguish the symptoms of TB from those of other common respiratory diseases especially common in settings where community-acquired pneumonia and other lung diseases are more frequent than TB [29]. However, physicians have to be aware that a certain number of patients seeking medical assistance with symptoms of respiratory tract infections may have TB. It has been estimated that, on average, each general practitioner/family practice physician in Croatia has one TB patient every two years [30]. Under these circumstances, it is easy to neglect many important issues in TB management and control, resulting from a lack of experience and expertise which had previously been found to be associated with health system delays [31]. There was also a significant association between the sputum-smear status and health system delay among patients with negative smears who had double the median, as recently reported [27, 32, 33]. Smear-negative TB was obviously more difficult to diagnose and may have required an assessment of the response to antibiotic treatment, as well as chest radiography. These findings also indicate the urgent need for a more robust diagnostic test for diagnosing smear-negative cases in a timely manner.

The findings of this study need to be interpreted in the light of certain limitations. There may be a recall bias with reference to the symptoms and the timeliness of the health providers consulted. However, the participants were included prospectively and interviewed within one month after the TB diagnosis was made. Moreover, interviewers had received special training in two-day courses for proper data collection and control through as many sources as possible. This approach is believed to have minimised the bias. Another limitation of this study was the lack of data on the first point of contact with health professionals consulted for TB symptoms. However, the Croatian health care system is geared towards general practitioners/family practice physicians providing health care irrespective of socioeconomic class. If necessary, patients are referred to a specialist and TB drugs are available on prescription, and only on prescription. The few exceptions to this rule (emergency care, private doctor visit) are not likely to have significantly influenced our results.

The strength of this study lies in the fact that it was purpose designed. Secondly, this study covered almost 50% of all Croatian TB cases during the preceding year and more than 50% of the overall Croatian population in randomly selected counties. The dual TB notification system (physician and laboratory notification) had been successfully implemented since 1998 and so it can confidently be assumed that all confirmed cases were included in this study. Moreover, a larger sample size or more participating counties might have caused an under- or overestimation of delay.

Despite free health care being universally available in Croatia and notwithstanding the ready availability of health services, it is of great concern that almost 20% of the patients under study remained undiagnosed in the fourth week after the initial health care visit, while one month later, a high proportion of the participants (29.3%) were still a source of infection within the community. Our findings appear to indicate some groups of TB patients having experienced a health system delay mainly due to a lack of suspicion. Although the health system delay in this study was found to be shorter than in many other countries, we believe that it could have been even shorter or avoided altogether had appropriate TB investigation been conducted earlier.

All authors have been deeply involved in TB control in Croatia from different standpoints. AJS, BB, KK, LJBI, JV, GPC and SMD are regional TB managers, AS is a national TB manager. IG is an experienced pulmonologist and RM is an experienced epidemiologist with a strong scientific background. AJS is continuously conducting and publishing studies on different aspects of TB control.