National population-based tuberculosis prevalence survey in Ghana, 2013.

BACKGROUND: The prevalence of tuberculosis (TB) disease is one of the three main indicators used to assess the epidemiological burden of TB and the impact change of TB control; the other two are incidence and mortality.OBJECTIVE: To estimate the prevalence of TB disease among adults in Ghana.METHODS: A nationally representative cross-sectional survey was conducted. Participants were screened for TB using interview and chest X-ray (CXR). For those participants with cough ≥2 weeks and/or abnormal CXR, spot and morning sputum specimens were collected and examined by smear microscopy and culture.RESULTS: The study revealed that the prevalence of smear-positive TB among adults (age ≥15 years) was 111 (95%CI 76-145) and that of bacteriologically confirmed TB was 356 (95%CI 288-425) per 100 000 population. Males and older people had a higher prevalence than their counterparts. The majority of TB cases were smear-negative and had an abnormal CXR without reported chronic cough.CONCLUSION: The survey revealed much higher TB disease burden than previously estimated. This implies that the programme needs more effort and resources to find undiagnosed and unreported cases. The higher proportion of smear-negative and asymptomatic TB cases suggests the need to revise the existing screening and diagnostic algorithms.

Detection and characterization of drug-resistant conferring genes in Mycobacterium tuberculosis complex strains: A prospective study in two distant regions of Ghana.

We spoligotyped and screened 1490 clinical Mycobacterium tuberculosis complex strains from Northern and Greater Accra regions of Ghana against INH and RIF using the microplate alamar blue phenotypic assay. Specific drug resistance associated genetic elements of drug resistant strains were analyzed for mutations. A total of 111 (7.5%), 10 (0.7%) and 40 (2.6%) were mono-resistant to INH, RIF, and MDR, respectively. We found the Ghana spoligotype to be associated with drug resistance (INH: 22.1%; p = 0.0000, RIF: 6.2%; p = 0.0103, MDR: 4.6%; p = 0.0240) as compared to the Cameroon spoligotype (INH: 6.7%, RIF: 2.4%, MDR: 1.6%). The propensity for an isolate to harbour katG S315T mutation was higher in M. tuberculosis (75.8%) than Mycobacterium africanum (51.7%) (p = 0.0000) whereas the opposite was true for inhApro mutations; MAF (48.3%) compared to MTBSS (26.7%) (p = 0.0419). We identified possible novel compensatory INH resistance mutations in inhA (G204D) and ahpCpro (-88G/A and -142G/A) and a novel ndh mutation K32R. We detected two possible rpoC mutations (G332R and V483G), which occurred independently with rpoB S450L, respectively. The study provides the first evidence that associate the Ghana spoligotype with DR-TB and calls for further genome analyses for proper classification of this spoligotype and to explore for fitness implications and mechanisms underlying this observation.

The role of technical assistance in expanding access to Xpert(®) MTB/RIF: experience in sub-Saharan Africa.

To improve tuberculosis (TB) diagnosis, many national TB programmes have committed to deploying Xpert(®) MTB/RIF. Implementation of this relatively new technology has suffered from a lack of comprehensive technical assistance, however, including the formulation of policies and plans to address operational issues. While providing technical assistance, we observed numerous operational challenges in the implementation and scale-up of Xpert in five sub-Saharan African countries: low coverage, poor laboratory infrastructure, limited access, poor linkages to treatment, inadequate data on outcomes, problems with specimen transport, diagnostic algorithms that are not aligned with updated World Health Organization recommendations on target patient groups and financing challenges. We recommend better country preparedness and training, laboratory information and quality systems, supply management and referral mechanisms.

De nombreux programmes nationaux tuberculose (TB) se sont engagés à déployer le Xpert® MTB/RIF afin d'améliorer le diagnostic de la TB. La mise en oeuvre de cette technique relativement nouvelle a cependant souffert d'un manque d'assistance technique d'ensemble, notamment la formulation de politiques et de plans destinés à prendre en compte les problèmes opérationnels. Lorsque nous avons fourni cette assistance technique, nous avons observé de nombreux défis opérationnels dans la mise en oeuvre et l'expansion du Xpert dans cinq pays d'Afrique sub-saharienne : une faible couverture, une infrastructure de laboratoire limitée, un accès limité, des liens médiocres avec la prise en charge thérapeutique, des données insuffisantes sur les résultats, des problèmes de transport des échantillons, des algorithmes de diagnostic qui ne sont pas en accord avec les dernières recommandations de l'Organisation Mondiale de la Santé relatives aux groupes cibles de patients et des défis financiers. Nous recommandons une meilleure préparation et formation des pays, une information des laboratoires et des systèmes de contrôle de qualité, une gestion des stocks et des mécanismes de référence.

Con el propósito de mejorar el diagnóstico de la tuberculosis, muchos programas nacionales han decidido generalizar la práctica de la prueba Xpert® MTB/RIF. Sin embargo, la introducción de esta técnica relativamente nueva se ha dificultado debido a una falta de asistencia técnica integral, que comprenda la formulación de normas y de planes que aborden los aspectos operativos. Durante la experiencia de prestación de asistencia técnica, se observaron múltiples dificultades operativas en la ejecución y en la ampliación de escala de la técnica Xpert en cinco países de África subsahariana, a saber: la baja cobertura, la insuficiencia de las infraestructuras de laboratorio, el acceso limitado, la escasa vinculación con el tratamiento, la deficiencia de los datos sobre los desenlaces, los problemas relacionados con el transporte de las muestras, los algoritmos diagnósticos que no corresponden a las recomendaciones actualizadas de la Organización Mundial de la Salud en materia de grupos destinatarios de pacientes y las dificultades de financiamiento. Se recomienda procurar una mejor preparación y una mayor capacitación en el país, perfeccionar los sistemas de información y control de calidad de los laboratorios y poner en práctica procedimientos de gestión de los suministros y mecanismos de remisión.

TIME Impact - a new user-friendly tuberculosis (TB) model to inform TB policy decisions.

Tuberculosis (TB) is the leading cause of death from infectious disease worldwide, predominantly affecting low- and middle-income countries (LMICs), where resources are limited. As such, countries need to be able to choose the most efficient interventions for their respective setting. Mathematical models can be valuable tools to inform rational policy decisions and improve resource allocation, but are often unavailable or inaccessible for LMICs, particularly in TB. We developed TIME Impact, a user-friendly TB model that enables local capacity building and strengthens country-specific policy discussions to inform support funding applications at the (sub-)national level (e.g. Ministry of Finance) or to international donors (e.g. the Global Fund to Fight AIDS, Tuberculosis and Malaria).TIME Impact is an epidemiological transmission model nested in TIME, a set of TB modelling tools available for free download within the widely-used Spectrum software. The TIME Impact model reflects key aspects of the natural history of TB, with additional structure for HIV/ART, drug resistance, treatment history and age. TIME Impact enables national TB programmes (NTPs) and other TB policymakers to better understand their own TB epidemic, plan their response, apply for funding and evaluate the implementation of the response.The explicit aim of TIME Impact's user-friendly interface is to enable training of local and international TB experts towards independent use. During application of TIME Impact, close involvement of the NTPs and other local partners also builds critical understanding of the modelling methods, assumptions and limitations inherent to modelling. This is essential to generate broad country-level ownership of the modelling data inputs and results. In turn, it stimulates discussions and a review of the current evidence and assumptions, strengthening the decision-making process in general.TIME Impact has been effectively applied in a variety of settings. In South Africa, it informed the first South African HIV and TB Investment Cases and successfully leveraged additional resources from the National Treasury at a time of austerity. In Ghana, a long-term TIME model-centred interaction with the NTP provided new insights into the local epidemiology and guided resource allocation decisions to improve impact.

Free tuberculosis diagnosis and treatment are not enough: patient cost evidence from three continents.

SETTING: The National Tuberculosis Programs of Ghana, Viet Nam and the Dominican Republic. OBJECTIVE: To assess the direct and indirect costs of tuberculosis (TB) diagnosis and treatment for patients and households. DESIGN: Each country translated and adapted a structured questionnaire, the Tool to Estimate Patients' Costs. A random sample of new adult patients treated for at least 1 month was interviewed in all three countries. RESULTS: Across the countries, 27-70% of patients stopped working and experienced reduced income, 5-37% sold property and 17-47% borrowed money due to TB. Hospitalisation costs (US$42-118) and additional food items formed the largest part of direct costs during treatment. Average total patient costs (US$538-1268) were equivalent to approximately 1 year of individual income. CONCLUSION: We observed similar patterns and challenges of TB-related costs for patients across the three countries. We advocate for global, united action for TB patients to be included under social protection schemes and for national TB programmes to improve equitable access to care.

High initial default in patients with smear-positive pulmonary tuberculosis at a regional hospital in Accra, Ghana.

Sputum smear-positive TB patients, diagnosed in the laboratory, who never start anti-TB treatment are classified as 'initial defaulters'. In Ridge Hospital, Accra, Ghana, there were 84 laboratory confirmed TB cases in 2009, of whom 32 (38%) were initial defaulters. Cure and default rates based on this cohort were 54% and 43% respectively, compared with rates of 87% and 8% when using the cohort based on 52 patients registered for treatment. This study highlights the problem of initial defaulters, and shows that programme performance may be poor when patients in laboratory registers are used as the cohort to evaluate treatment outcomes.

Diagnosis of tuberculosis in ghana: the role of laboratory training.

OBJECTIVES: The laboratory is considered the cornerstone of tuberculosis (TB) control programme. International review of Ghana's programme in the late nineties identified the laboratory services as the weakest component. Sputum smear microscopy (SSM) being the main method of diagnosing pulmonary TB in Ghana, the training objectives were to: (i) strengthen the knowledge and skills of laboratory personnel on SSM (ii) impart necessary techniques in biosafety and (iii) introduce a Quality Assurance (QA) system in order to strengthen SSM services. METHODS: Personnel were selected for training during a nationwide situation analysis of SSM centres in 2000/2001. Four training sessions on SSM/QA were held between 2001/2004. RESULTS: A total of 80 personnel were trained: 10 regional TB coordinators and 70 laboratory personnel. The participants upon return to their respective regions also organized training within their districts. This approach resulted in another 100 district TB coordinators and 200 laboratory personnel being trained. Improvement in smear preparation, staining and reading ability of the participants were observed during the post-test and subsequent visit to their respective laboratories. The training has led to strengthening of TB laboratory services in the country and has contributed to increase in case detection from 10,745 in 2000 to 11,827 in 2004 and 14,022 in 2008. It was observed during the post-training follow-up and quarterly supervision visits that morale of the personnel was high. CONCLUSION: Continuous training and re-training of laboratory personnel on SSM and QA at regular intervals do play an important role for effective and efficient TB control programme.

Culture and sensitivity of mycobacterial isolates from cases of pulmonary tuberculosis classified as treatment failures in a teaching hospital.

BACKGROUND: The level of drug resistance in mycobacterial isolates from previously treated cases in Ghana is not known although drug resistant tuberculosis threatens efforts to control the disease. OBJECTIVE: To identify and determine the susceptibility of mycobacterial isolates from tuberculosis cases with clinical treatment failure. METHODS: This prospective survey was undertaken at the Chest Clinic of Korle Bu Teaching Hospital in Accra, Ghana. The participants were twenty-eight cases referred to the hospital with clinical treatment failure. Two sputum specimens from each case were stained by Ziehl-Neelsen method, cultured, identified and sensitivity tests performed by the proportion method. RESULTS: Eighteen isolates of mycobacteria were identified from 28 failed treatment cases. Five were atypical mycobacteria. Approximately fifty percent (13/28) of cases had Mycobacterium tuberculosis, 5(18%) had atypical mycobacteria, 7(25%) had pure fungal growth and 3(11% 8) had no growth. Fifteen isolates were resistant to two or more drugs, of which 6 were resistant to all four drugs tested. CONCLUSION: Continuous drug resistance monitoring must be instituted as part of the tuberculosis control programme.

Mycobacterial species causing pulmonary tuberculosis at the korle bu teaching hospital, accra, ghana.

SUMMARY OBJECTIVE: Characterize mycobacterial species causing pulmonary tuberculosis (PTB) at the Korle-Bu Teaching Hospital in Ghana. DESIGN: Sputum smear positive samples, two (2) from 70 patients diagnosed as having tuberculosis, after they had consented, were collected from the Korle-Bu Teaching Hospital Chest Clinic between January and July 2003. SETTING: Korle-Bu Teaching Hospital Chest Clinic, Accra. RESULTS: Sixty-four mycobacterial isolates were obtained and confirmed as members of Mycobacterium tuberculosis complex by colonial morphology and conventional biochemical assays. Forty-seven (73%) were M. tuberculosis, the human strain, 2 (3%) M. bovis, the bovine strain, 13 (20%) M. africanum I (West Africa type), and 2 (3%) M. africanum II (East Africa type). CONCLUSION: The results indicate that, there are various strains causing PTB at the Korle-Bu Teaching Hospital and of great concern is M. bovis, which mostly causes extra-PTB in humans but found to cause PTB in this study. This calls for the need to conduct a nationwide survey using both conventional and molecular techniques to characterize various mycobacterial species causing TB in Ghana. This will result in better understanding of the various strains circulating in the country and inform individual TB treatment regimen especially the inclusion or exclusion of pyrazinamide.

Situation analysis of TB microscopy centres in Ghana.

SETTING: Public health laboratories in Ghana performing tuberculosis (TB) microscopy. OBJECTIVE: To assess the situation of the laboratories in terms of staff strength, technical skills, documentation, biosafety practices, equipment, supplies and disposal systems. DESIGN: Methods used for data collection were interviews using a structured questionnaire, informal observation of laboratory registers, disposal systems and safety measures for sputum handling. RESULTS: Of 114 laboratories visited between 2000 and 2001, 102 (89.5%) were performing TB microscopy. Of the staff working in the laboratories, 9% were medical technologists, 24% laboratory technicians, 37% laboratory assistants and 30% orderlies. Average false-negative and -positive rates were respectively 13% and 14%. Although most of the centres (85.3%) were using the recommended TB laboratory register for recording, in most cases they were not filled in accurately or completely. The majority of the available microscopes had mechanical or optical faults. Availability of other materials for smear preparation and staining ranged from 44% to 82%. The main methods employed for disposal of laboratory waste were burning and burying, but conditions were poor in most of the facilities visited. CONCLUSION: Training of laboratory personnel in TB microscopy and establishment of a quality assurance system are needed in Ghana.

Improving the laboratory diagnosis of TB in Ghana: the impact of a quality assurance system.

SETTING: Greater Accra region, Ghana. OBJECTIVE: To establish a pilot quality assurance (QA) system in sputum smear microscopy and to evaluate its impact. DESIGN: Quarterly supporting visits were paid to participating laboratories between 2000 and 2002. Fifteen examined slides were selected randomly from each laboratory during the visits and blindly re-assessed. Feedback was given promptly to the various laboratories. Training and stakeholder workshops were organised whenever necessary. RESULTS: General improvements in smear preparation and staining as well as the reading ability of the laboratory personnel included in the study were observed. The average marks for specimen quality, staining ability, smear cleanness, thickness, size and evenness increased from 64%, 79%, 69%, 46%, 67% and 60% in the last quarter of 2000 to 81%, 90%, 86%, 79%, 80% and 74%, respectively, 24 months after the establishment of the QA system. Within the same period, the rate of false-positives and -negatives decreased from respectively 14.8% and 20.5% to 0%, and agreements in positivity grade increased from 74% to 95%. The performance of the participating laboratories in keeping the laboratory registers up to date also improved. CONCLUSION: The QA system needs to be extended to the rest of the country.