Research Article: Extra-pulmonary tuberculosis: A retrospective study of patients in Accra, Ghana

Date Published: January 9, 2019

Publisher: Public Library of Science

Author(s): Sally-Ann Ohene, Mirjam I. Bakker, John Ojo, Ardon Toonstra, Doris Awudi, Paul Klatser, Pere-Joan Cardona.


Information on extrapulmonary TB (EPTB) patients is limited in many African countries including Ghana. The study objective was to describe the epidemiology of EPTB patients diagnosed from different categories of health facilities in Accra, Ghana compared to pulmonary TB (PTB) patients and identify risk factors for mortality among EPTB patients.

We conducted retrospective analyses of demographic and clinical data accessed from medical records of EPTB and PTB patients from different types of health facilities from June 2010 to December 2013. Factors at diagnosis associated with EPTB compared to pulmonary TB (PTB) and factors associated with treatment outcome death among EPTB patients were assessed using logistic regression.

Out of 3,342 new TB patients ≥15 years diagnosed, 728 (21.8%) had EPTB with a male: female ratio of 1.17. The EPTB sites commonly affected were disseminated 32.8%, pleura 21%, spine 13%, and Central Nervous System (CNS) 11%. Treatment success rate for EPTB was 70.1% compared to 84.2% for PTB (p<0.001). In logistic regression, HIV positivity (adjusted Odds Ratio [aOR] 3.19; 95% confidence interval [CI] 2.69–3.79) and female gender (aOR 1.59; 95% CI 1.35–1.88) were found to be significantly associated with EPTB compared with PTB. Older age, being HIV positive (aOR 3.15; 95% CI 1.20–8.25) and having CNS TB (aOR 3.88; 95% CI 1.14–13.23) were associated with mortality among EPTB patients. While more EPTB patients were diagnosed in the tertiary hospital, health facility type was not associated with mortality. EPTB patients in Accra have a worse treatment outcome compared to PTB patients with mortality of EPTB being associated with HIV, older age and CNS TB. Being HIV positive and female gender were found to be significantly associated with EPTB. Increased awareness of these factors may facilitate early case finding and better management outcomes for these patients.

Partial Text

Despite major strides in prevention, diagnosis and treatment, tuberculosis continues to be a major leading cause of death globally [1]. An estimated 1.67 million people died from TB in 2016 [1]. The causative organism Mycobacterium tuberculosis, which is predominantly air-borne, affects the lung causing pulmonary TB. When TB is bacteriologically confirmed or clinically diagnosed in other parts of the body other than the lung such as the abdomen, meninges, genitourinary tract, joints, bones, lymph nodes and skin it is classified as extrapulmonary tuberculosis (EPTB). The prevalence of EPTB among new and relapse TB cases globally in 2016 was 15% [1]. The lowest prevalence (8%) was recorded in the WHO Western Pacific Region while the highest (24%) was recorded in the Eastern Mediterranean. The figure for the African Region was 16% [1].

The study was a retrospective secondary data analyses making use of the database of TB patients diagnosed from June 2010 to December 2013 during a TB case finding initiative implemented in 11 health facilities in Accra, the capital of Ghana. The details of the TB finding initiative were described elsewhere [22]. Accra, with a population of 1.7 million in the 2010 census, recorded HIV prevalence of 2.1% among antenatal clinic attendees over the period of 2010 to 2013 [23,24]. The facilities from which the study participants were derived included outpatient departments (OPD), HIV clinics and diabetes clinics in polyclinics, general hospitals, a regional hospital and a teaching hospital. The participants from the teaching hospital were from the HIV clinic only and did not include patients from the OPD or other clinics. These facilities accounted for 70% of TB cases in Accra at the time. From the TB case finding initiative database which consisted of 3,704 records, the participants for this study were selected using the following inclusion criteria: patients 15 years and older newly diagnosed with smear positive pulmonary TB, smear negative pulmonary TB or extra-pulmonary TB. The exclusion criteria were patients less than 15 years and those previously treated for TB. The classification of PTB and EPTB by the National Tuberculosis Control Program (NTP) in Ghana falls in line with WHO guidelines [25]. With the exception of cerebro-spinal fluid (CSF) samples, which were usually quite small in volume, EPTB samples for microscopy and culture were taken through a decontamination process to get rid of other bacteria using a 4% sodium hydroxide (NaOh) and N-acetyl L-cysteine (NALC) preparation. [26] An equal volume of NaOH-NALC solution was added to the sample for a quarter of an hour followed by neutralization with phosphate buffer solution pH 6.8. The preparation was then subjected to centrifugation for concentration of the specimen and to wash off the sodium hydroxide reagent. The decontaminated concentrated sample was then inoculated for culture and smear preparation. At the time of the case finding initiative, sputum smear samples for examination under light or light emitting diode (LED) microscopy were processed using Ziehl Nielsen staining method. Sputum smear positive PTB was defined as a patient with acid fast bacilli in at least one sample of sputum. A patient was considered to have sputum smear negative PTB if he or she had two sputum smears negative for mycobacteria on microscopy, but Chest X-ray showed evidence consistent with active tuberculosis. EPTB was classified as per organs or systems affected exclusive of the lungs, such as lymphatic comprising of TB in lymph nodes, pleura, spine, TB in bones and joints other than the spine, central nervous systems CNS (TB meningitis, brain), abdominal and other such as genito-urinary tract. EPTB diagnosis was based on having one culture-positive specimen using fine needle aspiration biopsy or organ fluid samples such as ascetic or pleural fluid depending on the suspected site involved, or histological evidence or strong clinical confirmation of active EPTB for which the clinician makes the decision to treat with a full course of TB drugs. Culture methods available included solid culture using Lowenstein-Jensen media and liquid culture by means of Bactec Mycobacteria Growth Indicator Tube (MGIT960, BD, Sparks, USA). These diagnostic methods were available at the teaching hospital laboratory which also performed culture on samples that were delivered from other lower level facilities. In the event that a patient has EPTB in several organs, the patient is classified according to the site that is most severely affected. In NTP registration, patients diagnosed with both PTB and EPTB were registered as pulmonary TB. It is therefore not possible to distinguish which patients had both types of TB. At the time of the case-finding initiative, the same standardized first line TB drugs were used to treat new cases of EPTB and PTB for the duration of 6 months [25]. Classification of treatment outcomes were cure, treatment completed, default, died, transfer out and treatment failure as per WHO guidelines. The combination of those recorded as having been cured and completed treatment were designated as having a favorable treatment outcome. Data of study participants obtained from their medical records included age, gender, HIV status, type of TB, site of the EPTB, facility of diagnosis, year of diagnosis and treatment outcome.

Out of 3,704 TB patients recorded in the TB case finding initiative database, 219 children less than 15 years and 143 patients who were not new TB cases were excluded from the analysis. The study participants consisted of 3,342 new TB patients who were aged 15 years and above. The overall male female ratio was 1.68. A total of 1,443 (42.9%) of these TB patients, were from the polyclinics; 775 (23.2%) were from the general hospital; 775 (23.2%) were from the HIV clinic of the teaching hospital and 359 patients (10.7%) were from the regional hospital. There were 728 patients (21.8%) who had extra-pulmonary TB while 2,614 patients had pulmonary TB. Out of the 728 EPTB patients, 400 (55%) were diagnosed from the HIV clinic of the teaching hospital. Almost half (48.5%) of the 2,614 pulmonary TB patients, were diagnosed in the general hospitals.

This study elaborates on EPTB diagnosed among patients attending different types of facilities and HIV clinics in Accra over a period of three and a half years and compares demographic and clinical characteristics of these patients with those having pulmonary TB. One fifth of the newly diagnosed tuberculosis had EPTB. The most common form of EPTB was disseminated TB followed by pleural TB. A favorable treatment outcome was observed for seven out of ten EPTB patients with documented treatment outcome. Being HIV positive and female gender were found to be significantly associated with EPTB compared with PTB while older age, being HIV positive and having CNS TB was associated with mortality among EPTB patients.

This study in summary showed female gender and HIV co-infection as risk factors for EPTB, and HIV and CNS TB as risk factors for death among EPTB patients. Increased awareness of these factors, provision of and training in country-adapted diagnostic algorithms and making more sensitive diagnostic tools accessible may contribute to earlier case finding and diagnosis of EPTB patients especially at lower level health facilities for initiation of treatment and possibly better management outcomes [41,47].