Tuberculosis diagnostic challenges : health care seeking behavior, diagnostic algorithms and drug resistance in Ethiopia

Thesis summary

Tuberculosis (TB) is still an important cause of mortality worldwide. One-third of the world’s population is infected with M. tuberculosis, and many will effectively develop TB disease in their life time, especially patients that belong to the socio-economic lower classes. More than 95% of TB cases and deaths are in developing countries, where TB is closely linked to poverty. Since two decades, HIV and emerging drug-resistant TB pose an additional challenge to control TB.

Ethiopia is one of the 22 TB high-burden countries in the world.  This thesis investigates some elements of challenge in TB diagnosis in Ethiopia. The studies focus on health seeking behavior, epidemiology, diagnostic algorithms and drug resistance.

In our first study we assessed the knowledge about TB, health seeking behavior and stigma towards TB among TB suspects in a rural community in Gilgel Gibe field research area in Southwest Ethiopia.  Our study indicated that there was little knowledge about TB in the Gilgel Gibe field research area. Although 83.0% of the study subjects had ever heard of TB, the majority (50.4%) mentioned that “evil eye” is a cause of TB. Only 33.7% of respondents knew that TB is caused by a microorganism.  Individuals who could read and write, and males were more likely to know that TB is caused by a microorganism. A significant number of study participants had perceived stigma of TB on marital prospects, social and sexual relationships between partners. The health care seeking behavior of our study participants was poor. An appreciable proportion (46.2%) of them did not seek help for their illness. Individuals who were previously treated for TB were more likely to have an appropriate health seeking behavior. The real burden of TB in general and extrapulmonary TB in particular was not well documented in our study area. This is partly because of the difficulties to diagnose TB and the lack of a strong surveillance system. TB lymphadenitis is a common manifestation of extrapulmonary TB. In our second study we determined the prevalence of TB lymphadenitis in TB suspects in a rural community in the Gilgel Gibe field research area in Southwest Ethiopia. Out of 27,597 screened individuals, a total of 87 TB lymphadenitis suspects were identified. The diagnosis of TB lymphadenitis was established when FNA smear microscopy for AFB, culture and/or cytology reported positive. 16 cases were diagnosed with TB lymphadenitis. The prevalence of TB lymphadenitis was thus 58.0 per 100,000 people. All the cases were newly diagnosed during the survey, which reflects the difficulty to diagnose TB lymphadenitis in routine circumstances. Individuals who had a contact history with chronic coughers were more likely to have TB lymphadenitis. Lymph nodes with caseous FNA were more likely to be positive for TB lymphadenitis. From all forms of TB diagnosed at the study setting, TB lymphadenitis accounted for 43.2%. The diagnosis of TB is more complex when the TB suspects are co-infected with HIV. In our third study we evaluated the 2007 WHO recommendation for the diagnosis of smear negative TB in HIV prevalent settings. We evaluated the algorithm in an urban referral hospital in Addis Ababa, Ethiopia. A total of 459 TB suspects were enrolled; 336 (73.2%) were HIV positive. Acid fast bacilli sputum smear microscopy was done for 251 (84.2%) TB suspects; 237 (94.4%) were smear negative. A chest X-ray was performed in 92.8% and a Mycobacterium culture in 63.7%. The median TB diagnostic delay for smear negative cases was 3 days (interquartile range 3-4 days). Of the 75 patients diagnosed with smear negative pulmonary TB, 67 (89. 4%) were diagnosed by chest X-ray, 7 (9.4%) by culture and one (1.3%) by clinical suspicion only. The sensitivity of the algorithm to diagnose smear negative TB in HIV-positive TB suspects was 100%; the specificity 67.4%. Our study indicated that the 2007 WHO algorithm for the diagnosis of smear negative TB is likely to reduce the diagnostic delay and therefore decrease morbidity and mortality of TB in a HIV prevalent settings like Ethiopia. 

Due to inadequate laboratory capacity the diagnosis of drug resistant TB is limited to a few reference centres in Ethiopia.  Our next two studies were related to drug resistance. Correctly diagnosing drug-resistant TB strains is more problematic in resource-limited settings, as there is no or limited infrastructure for drug susceptibility testing (DST) of TB bacilli. The conventional phenotypic DST method for TB takes weeks before declaring the results and initiating proper anti-TB treatment. We reviewed the use of molecular methods and concluded that they offer many advantages for drug-resistant TB case management. First, most of the molecular methods tested so far have shown good specificity and sensitivity for the detection of rifampicine resistance, which is the surrogate predictor of MDR-TB. Second, the implementation of molecular DST for TB can create the capacity for early treatment of MDR-TB cases. Third, the infrastructure that is required to implement molecular DST is less expensive compared to conventional phenotypic methods, and facilities can be shared for various (infectious) diseases. Fourth, tests can be easily centralized. Finally, the safety of technical personnel can be better ensured by using molecular methods than the conventional phenotypic methods.

Next we determined the level of primary drug resistance to first line ant-TB drugs among newly diagnosed patients at the Jimma University specialized hospital. Of the 136 patients enrolled in the study, resistance to at least one drug was identified in 18.4%. The highest prevalence of resistance to any drug was identified against INH (13.2%) followed by STM (8.1%). There was no statistically significant difference in the proportion of any resistance by sex, age, HIV status and history of being imprisoned. The highest mono resistance was observed against INH (7.4%). Mono resistance to streptomycin was associated with HIV infection. MDR-TB was observed in two patients (1.5%).

We conclude that there was little knowledge about TB in the Gilgel Gibe field research area. We observed inappropriate health seeking behavior and stigma towards TB.  The observed prevalence of TB lymphadenitis in Gilgel Gibe is high but similar to the WHO estimates for Ethiopia. The 2007 WHO algorithm for the diagnosis of smear negative TB is likely to reduce the diagnostic delay and therefore decrease morbidity and mortality of TB in a HIV prevalent setting like Ethiopia.  The implementation of molecular DST for TB will lead to the the early diagnosis and treatment of MDR-TB cases. We detected a relatively low prevalence of MDR-TB, yet conditions that can contribute to the development of MDR are common.

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