Treatment outcome of tuberculosis patients at Gondar University Teaching Hospital, Northwest Ethiopia. A five - year retrospective study

Tuberculosis (TB) is the leading cause of death from a curable infectious disease [1]. According to the 2007 report of World Health Organization (WHO), one-third of the world's population is estimated to be infected with tubercle bacilli and hence at risk of developing active disease, in 2005, the annual incidence of TB, expressed as the number of new TB cases, was globally about 8.8 million people (7.4 million of these were in Asia and sub-Saharan Africa), and the annual number of deaths due to TB was 1.6 million, including 195,000 patients infected with HIV [2].

Important challenges for TB control are human immunodeficiency virus (HIV) co-infection and drug resistance [3, 4]. HIV co-infection is the strongest known risk factor for progression of latent TB infection to TB disease [5]. Although HIV co-infection has been shown not to affect the failure rate of TB treatment, high mortality has been reported among HIV-infected TB patients in sub-Saharan Africa [6].

According to the 2008 report of WHO, Ethiopia ranks seventh among the world's 22 countries with a high tuberculosis burden [7]. The Ethiopian Federal Ministry of Health (FMOH) hospital statistics data has shown that tuberculosis is the leading cause of morbidity, the third cause of hospital admission (after deliveries and malaria), and the second cause of death in Ethiopia, after malaria [8]. Based on the 2007 WHO estimates, in Ethiopia, the incidence of TB of all forms and smear positive TB stand at 341 and 152 per 100,000 population, respectively. The prevalence and mortality of tuberculosis of all forms is estimated to be 546 and 73 per 100,000 population respectively [2].

In Ethiopia a standardized TB prevention and control programme, incorporating Directly Observed Treatment, Short Course (DOTS), was started in 1992 as a pilot in Arsi and Bale zone, Oromia Region. The DOTS strategy has been subsequently scaled up in the country and implemented at national level. DOTS as a strategy was introduced to the tuberculosis control programme at Gondar University Teaching Hospital in 2000. Currently the DOTS geographic coverage reaches 90%, whereas the health facility coverage is 75% [8]. Like other developing countries, in Ethiopia, culture and drug susceptibility testing for M. tuberculosis are not performed routinely; even for patients suspected of harboring drug-resistant strains.

DOTS during at least the first 2 months of treatment, in which patients take drugs directly under the observation of health care providers, has been recommended by international tuberculosis authorities[9, 10], and has been shown to be effective in achieving a high successful treatment rate, from 86% to 96.5% [11]. The utility of DOTS has also been demonstrated in developed countries. Jasmer et al reported that DOTS was significantly associated with a higher treatment success rate than self-administered therapy (97.8% vs. 88.6%, p < 0.002) and a lower tuberculosis-related mortality rate (0% vs. 5.5%, p = 0.002) [12]. DOTS also leads to significant reductions in the frequency of primary drug resistance, acquired drug resistance and relapse [13].

Correct treatment of tuberculosis aims at curing the patient, interrupting transmission of tuberculosis to other persons and preventing bacilli from becoming drug resistant. These aims are not achieved in many regions of the world even when anti tuberculosis drugs are available [14]. The main reasons are death of the patients during treatment, default before the scheduled end of treatment or resistance to the drugs prescribed. Patient non-adherence to treatment is interpreted as a failure of the health care system to cope with the natural tendency of humans to quit treatment as soon as they feel subjectively better, or better without treatment if adverse drug events supervene [12].

Treatment outcome results serve as a proxy of the quality of TB treatment provided by a health care system. Recommendations on how to evaluate treatment outcomes using standardized categories have been issued by the World Health Organization (WHO) in conjunction with the European Region of the International Union Against Tuberculosis and Lung Disease (IUATLD) [15]. These categories were defined to assess the risk of future relapse and drug resistance. Ideally, treatment outcome in all patients should be routinely monitored by the epidemiological surveillance system. This would make it possible to recognize and amend system failures before the incidence and proportion of resistant isolates rise. However, treatment outcome of tuberculosis patients has not been assessed yet in northwest Ethiopia. Therefore, this study is aimed to assess treatment outcomes of pulmonary tuberculosis and extrapulmonary tuberculosis cases at Gondar University Teaching Hospital, Northwest Ethiopia.

According to the WHO 2005 report on global tuberculosis control [16], the treatment success rates under the DOTS programs among 22 high-burden countries (HBCs) varied from 60% in Uganda to 93% in China, with an average of 83%. Moreover, the study conducted by B Shargie et al., in Southern Ethiopia has shown that the treatment success rate of all tuberculosis cases was 49% [17]. Our study found that the treatment outcome of tuberculosis patients treated under DOTS program at Gondar University Teaching Hospital was unsatisfactory. The treatment success rate of all tuberculosis cases was 29.5%. The low treatment success rate observed in this study might be due to high transferred out rate (42%), default rate (18.3%) and death rate (10.1%), but the high treatment default rate and death rate deserve special attention.

This study also demonstrated that death rate of tuberculosis patients was significantly decreased across the years from13.9% in (September 2003 - August 2004) to 3.4% in (September 2006 - August 2007) (p < 0.001). This might be due to increasing efforts to encourage tuberculosis patients for HIV screening and initiating anti retroviral therapy for TB/HIV co - infected patients at this hospital. Patient registration documents we reviewed lack information about the HIV status of our study subjects. However, a previous study conducted by Kassu et al showed that high proportions (52.1%) of TB patients were co-infected with HIV at Gondar University Hospital [18].

As shown in table 3, we analyzed the death rate across the age groups of tuberculosis patients and as the age increase the death rate of patients was steadily increased from 4.6% in the age group of 0 - 14 years to 15.8% in the age group of 55 - 64 years. This is in agreement with the finding of a study conducted by Lee et al [19]. High age has been previously reported to be a risk factor for death, partly due to increasing comorbidities as well as the general physiological deterioration with age [20–22], because of which close monitoring of treatment in older patients is necessary.

The default rate in this study (18.3%) was higher than the average 6.2% among the 22 HBCs [16] and 10% among the rural households in northwest Ethiopia [23]. On top of that default rate of tuberculosis patients was significantly (p < 0.001) increased across the years from 97(9.2%) in (September 2003 - August 2004) to 228(42.9%) in (September 2007 - May 2008) (Table 2). According to studies conducted in central India [24] and in Malawi [25] patients who completed treatment had a better understanding of the duration of TB treatment than patients who interrupted treatment. In other settings, counseling [26], better supervision [27, 28], home visits and motivation [29, 30] and health education [31] have been used successfully as interventions to reduce default rate of tuberculosis patients. The complementary results obtained from the quantitative and qualitative components of the study conducted in northwest Ethiopia also indicate that the TB club approach has a significant impact in improving patients' compliance to anti-TB treatment and in building positive attitudes and practice in the community regarding TB [32]. Thus, the finding of this study indicating the necessity of strengthening defaulter tracing and interventions to reduce default rate of tuberculosis patients in the study area.

The treatment failure rate varied from 0.1% in Zimbabwe to 9.1% in the Russian Federation, with an average of 1.5% in HBCs [16]. The treatment failure rate in this study was 0.2%, which is lower than the average failure rate of the HBCs. This might be due to lower prevalence of multi drug resistant strains of M. tuberculosis at the study area.

In our study the number of smear negative pulmonary tuberculosis cases (53.9% -56.5%) remained highest compared to smear positive and extrapulmonary tuberculosis cases over the years. Similarly, registration in DOTS (directly observed therapy, short course) programme areas in Addis Ababa, Ethiopia has shown a continuous increase in the proportion of smear-negative pulmonary TB from 36.3% in 1992 to 66.3% in 1999 (G. Fishay, TB co-ordinator, National Tuberculosis and Leprosy Control Programme, personal communication, 1999). The large number of smear negative pulmonary tuberculosis cases might be due to high proportion of TB - HIV co-infection at the study area, as shown by a previous study [18]. HIV-infected patients are twice as likely to have sputum smear-negative, culture-positive pulmonary TB (PTB) [33–35]. This results from their compromised immune response causing less cavity formation [36].

The main limitations of our study were selection bias and lack of information about the HIV status of the study subjects. Nevertheless, our study reveals that TB is still a major public health problem in Gondar University Teaching Hospital. The results of the present study also indicate a need for a coordinated tuberculosis control program which should include active case surveillance, effective care and treatment and quality laboratory diagnosis services. Therefore, physicians should be encouraged to assess HIV risk factors in patients who present with TB and to offer HIV testing to all TB patients, to document the HIV status of TB patients at TB clinic and to monitor treatment responses. Furthermore, efforts should be made to improve the quality of the laboratory diagnosis services.

The treatment success rate of pulmonary and extrapulmonary tuberculosis patients treated at Gondar University Teaching Hospital in northwest Ethiopia was unsatisfactorily low (29.5%). A high proportion of patients died (10.1%) or defaulted (18.3%), which is a serious public health concern that needs to be addressed urgently. To improve treatment outcome of tuberculosis patients we recommend enhanced supervision and monitoring, improved counseling during the intensive and continuation phases of treatment, home visits and motivation of patients (defaulter tracing) and health education to reduce treatment interruption.