High mortality during tuberculosis retreatment at a Ghanaian tertiary center: a retrospective cohort study.

INTRODUCTION: High mortality among individuals receiving retreatment for tuberculosis (RT-TB) persists, although reasons for these poor outcomes remain unclear. METHODS: We retrospectively reviewed 394 RT-TB patients diagnosed between January 2010 and June 2016 in Accra, Ghana. RESULTS: Of RT-TB patients, 161 (40.9%) were treated empirically (negative/absent smear, culture or Xpert), of whom 30.4% (49/161) had only extrapulmonary TB signs or symptoms. Mortality during treatment was 19.4%; 15-day mortality was 10.8%. In multivariable proportional hazards regression, living with HIV (aHR=2.69 [95 CI: 1.51, 4.80], p<0.01) and previous loss-to-follow up (aHR=8.27 (95 CI: 1.10, 62.25), p=0.04) were associated with mortality, while drug susceptibility testing (DST, aHR=0.36 (95 CI: 0.13, 1.01), p=0.052) was protective. Isoniazid resistance was observed in 40% (23/58 tested) and rifampin resistance in 19.1% (12/63 tested). CONCLUSION: High rates of extrapulmonary TB and smear/culture negative disease highlight the barriers to achieving DST-driven RT-TB regimens and the need for improved diagnostics. Our finding of poly-drug resistance in rifampin-susceptible cases supports access to comprehensive first line DST. Additionally, interventions to reduce mortality, especially in HIV co-infected RT-TB patients, are urgently needed.

Estimating the incidence of tuberculosis cases reported at a tertiary hospital in Ghana: a time series model approach.

BACKGROUND: The incidence of Tuberculosis (TB) differs among countries and contributes to morbidity and mortality especially in the developing countries. Trends and seasonal changes in the number of patients presenting with TB have been studied worldwide including sub-Saharan Africa. However, these changes are unknown at the Korle-Bu Teaching Hospital (KBTH). The aim of this study was to obtain a time series model to estimate the incidence of TB cases at the chest clinic of the Korle-Bu Teaching hospital. METHODS: A time series analysis using a Box-Jenkins approach propounded as an autoregressive moving average (ARIMA) was conducted on the monthly TB cases reported at the KBTH from 2008 to 2017. Various models were stated and compared and the best was found to be based on the Akaike Information Criterion and Bayesian Information Criterion. RESULTS: There was no evidence of obvious increasing or decreasing trend in the TB data. The log-transformed of the data achieved stationarity with fairly stable variations around the mean of the series. ARIMA (1, 0, 1) or ARMA (1,1) was obtained as the best model. The monthly forecasted values of the best model ranged from 53 to 55 for the year 2018; however, the best model does not always produce the best results with respect to the mean absolute and mean square errors. CONCLUSIONS: Irregular fluctuations were observed in the 10 -year data studied. The model equation to estimate the expected monthly TB cases at KBTH produced an AR coefficient of 0.971 plus an MA coefficient of - 0.826 with a constant value of 4.127. The result is important for developing a hypothesis to explain the dynamics of TB occurrence so as to outline prevention programmes, optimal use of resources and effective service delivery.

A cross-sectional study of tuberculosis drug resistance among previously treated patients in a tertiary hospital in Accra, Ghana: public health implications of standardized regimens.

BACKGROUND: Mycobacterium tuberculosis drug resistance is a major challenge to the use of standardized regimens for tuberculosis (TB) therapy, especially among previously treated patients. We aimed to investigate the frequency and pattern of drug resistance among previously treated patients with smear-positive pulmonary tuberculosis at the Korle-Bu Teaching Hospital Chest Clinic, Accra. METHODS: This was a cross-sectional survey of mycobacterial isolates from previously treated patients referred to the Chest Clinic Laboratory between October 2010 and October 2013. The Bactec MGIT 960 system for mycobactrerial culture and drug sensitivity testing (DST) was used for sputum culture of AFB smear-positive patients with relapse, treatment failure, failure of smear conversion, or default. Descriptive statistics were used to summarize patient characteristics, and frequency and patterns of drug resistance. RESULTS: A total of 112 isolates were studied out of 155 from previously treated patients. Twenty contaminated (12.9%) and 23 non-viable isolates (14.8%) were excluded. Of the 112 studied isolates, 53 (47.3%) were pan-sensitive to all first-line drugs tested Any resistance (mono and poly resistance) to isoniazid was found in 44 isolates (39.3%) and any resistance to streptomycin in 43 (38.4%). Thirty-one (27.7%) were MDR-TB. Eleven (35.5%) out of 31 MDR-TB isolates were pre-XDR. MDR-TB isolates were more likely than non-MDR isolates to have streptomycin and ethambutol resistance. CONCLUSIONS: The main findings of this study were the high prevalence of MDR-TB and streptomycin resistance among previously treated TB patients, as well as a high prevalence of pre-XDR-TB among the MDR-TB patients, which suggest that first-line and second-line DST is essential to aid the design of effective regimens for these groups of patients in Ghana.

The emerging threat of pre-extensively drug-resistant tuberculosis in West Africa: preparing for large-scale tuberculosis research and drug resistance surveillance.

BACKGROUND: Drug-resistant tuberculosis (TB) is a global public health problem. Adequate management requires baseline drug-resistance prevalence data. In West Africa, due to a poor laboratory infrastructure and inadequate capacity, such data are scarce. Therefore, the true extent of drug-resistant TB was hitherto undetermined. In 2008, a new research network, the West African Network of Excellence for Tuberculosis, AIDS and Malaria (WANETAM), was founded, comprising nine study sites from eight West African countries (Burkina Faso, The Gambia, Ghana, Guinea-Bissau, Mali, Nigeria, Senegal and Togo). The goal was to establish Good Clinical Laboratory Practice (GCLP) principles and build capacity in standardised smear microscopy and mycobacterial culture across partnering laboratories to generate the first comprehensive West African drug-resistance data. METHODS: Following GCLP and laboratory training sessions, TB isolates were collected at sentinel referral sites between 2009-2013 and tested for first- and second-line drug resistance. RESULTS: From the analysis of 974 isolates, an unexpectedly high prevalence of multi-drug-resistant (MDR) strains was found in new (6 %) and retreatment patients (35 %) across all sentinel sites, with the highest prevalence amongst retreatment patients in Bamako, Mali (59 %) and the two Nigerian sites in Ibadan and Lagos (39 % and 66 %). In Lagos, MDR is already spreading actively amongst 32 % of new patients. Pre-extensively drug-resistant (pre-XDR) isolates are present in all sites, with Ghana showing the highest proportion (35 % of MDR). In Ghana and Togo, pre-XDR isolates are circulating amongst new patients. CONCLUSIONS: West African drug-resistance prevalence poses a previously underestimated, yet serious public health threat, and our estimates obtained differ significantly from previous World Health Organisation (WHO) estimates. Therefore, our data are reshaping current concepts and are essential in informing WHO and public health strategists to implement urgently needed surveillance and control interventions in West Africa.

Factors associated with mortality and default among patients with tuberculosis attending a teaching hospital clinic in Accra, Ghana.

Tuberculosis (TB) remains a major cause of mortality despite availability of effective chemotherapy. This study was performed to identify contributing factors for poor outcome during anti-tuberculosis treatment at a teaching hospital chest clinic. Medical records of registered patients treated for TB between 1 January and 31 December, 2009 were reviewed and abstracted for demographic, clinical and outcome data. Risk factors for mortality during therapy were assessed using bivariate and multivariate logistics approaches. Of 599 patients, 355 (58.9%) completed therapy and/or were cured, 192 (32.1%) died, and 39 (6.5%) defaulted. In multivariate analysis, independent risk factors for mortality included pulmonary cases for which sputum smear status was unknown (odds ratio [OR] 13.7; 95% confidence interval [CI] 6.0, 31.4), HIV coinfection (OR, 3.6; 95% CI 2.4, 5.4), disseminated TB (OR, 2.2; 95% CI 1.0, 4.9), TB meningitis (OR, 2.8; 95% CI 1.5, 5.3), not having a treatment supporter (OR, 2.0; 95% CI 1.3, 3.1), and low body weight (OR, 11.0; 95% CI 3.1, 38.6). Not having a treatment supporter (OR, 3.2; 95% CI 1.6, 6.6) and HIV coinfection (OR, 2.4; 95% CI 1.2, 5.2) were also independently associated with treatment default. Our findings suggest that enhanced measures to reduce mortality and default in TB patients with HIV coinfection, disseminated or meningeal disease and those who have no treatment supporters may help improve treatment outcomes in Ghana.