Early results of systematic drug susceptibility testing in pulmonary tuberculosis retreatment cases in Cameroon

German Development Cooperation (GIZ), P,O, Box 7814, Yaounde, Cameroon.
BMC Research Notes 03/2012; 5(1):160. DOI: 10.1186/1756-0500-5-160
Source: PubMed


The number of pulmonary tuberculosis (PTB) patients reported with resistance to first-line anti-tuberculosis drugs after a standardized retreatment regimen in Cameroon is increasing. Hence, the National Tuberculosis Control Program (NTP) implemented, in one of the ten Regions of the country, a pilot programme aimed at performing routine drug susceptibility testing (DST) for previously treated PTB cases. The objectives of the programme were to evaluate the feasibility of monitoring drug resistance among retreatment cases under programme conditions and to measure the presence and magnitude of anti-TB drug resistance in order to inform NTP policies.
This retrospective cohort study was conducted in the Littoral Region of Cameroon in 2009. It included all sputum smear positive (SM+) PTB cases registered for retreatment. TB cases were identified and classified according to World Health Organization (WHO) recommendations for national TB programs. Bacterial susceptibility testing to first-line anti-TB drugs was performed using standard culture methods. In 2009, 5,668 TB cases were reported in the Littoral Region, of which 438 (7.7%) were SM + PTB retreatment cases. DST results were available for 216 (49.4%) patients. Twenty six patients (12%) harbored multi-drug resistant (MDR) strains. Positive treatment outcome rates were particularly low in retreatment patients with MDR-TB (46.2%; 95% CI: 27.1-66.3). Thirteen MDR-TB patients were treated using a standardized MDR treatment regimen. Delivery of laboratory results took on average 17 (12-26) weeks.
WHO-recommended routine DST in retreatment patients seems feasible in Cameroon. However, coverage needs to be improved through better management. Moreover, diagnostic delay should be shortened by introducing more rapid diagnostic tools. The high risk of MDR in standard regimen failure cases virtually rules out the standard retreatment regimen for such patients without prior DST.

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Available from: Jean-Louis Abena Foe, Jun 13, 2014
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    • "Another survey of WHO in 2010 showed that the estimated MDR-TB among the notified re-treatment cases (n = 7,795) was 2,200 (28%) [5]. So the Global Plan to STOP TB (2006–2015) proposed that by 2015 all countries should carry out DST for all re-treatment tuberculosis patients [6]. In order to control the MDR-TB,it was important for re-treatment PTB patients to develop a rapid, reliable and high-throughput drug susceptibility testing to obtain first- and second-line anti-tuberculosis drugs susceptibility result simultaneously, as it was essential to decrease patient morbidity and mortality as well as treatment-associated costs. "
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    ABSTRACT: Multidrug-resistant tuberculosis (MDR-TB) is a major public health problem. Early diagnosis of MDR-TB patients is essential for minimizing the risk of Mycobacterium tuberculosis (MTB) transmission. The conventional drug susceptibility testing (DST) methods for detection of drug-resistant M.tuberculosis are laborious and cannot provide the rapid detection for clinical practice. The aim of this study was to develop a pyrosequencing approach for the simultaneous detection of resistance to rifampin (RIF), isoniazid (INH), ethambutol (EMB), streptomycin (SM), ofloxacin (OFL) and amikacin (AMK) in M. tuberculosis clinical isolates and sputum samples from re-treatment pulmonary tuberculosis ( PTB) patients. We identified the optimum conditions for detection mutation of rpoB, katG, rpsl, embB, gyrA and rrs gene by pyrosequencing. Then this approach was applied to detect 205 clinical isolates and 24 sputum samples of M. tuberculosis from re-treatment PTB patients. The mutations of rpoB and gyrA gene were detected by pyrosequencig with the SQA mode, and the mutations of katG, rpsl, embB, gyrA and rrs gene were detected by pyrosequencing with SNP mode. Compared with the Bactec MGIT 960 mycobacterial detection system, the accuracy of pyrosequencing for the detection of RIF, INH, EMB, SM, AMK and OFL resistance in clinical isolates was 95.0%, 79.2%, 70.3%, 84.5%, 96.5% and 91.1%, respectively. In sputum samples the accuracy was 83.3%, 83.3%, 60.9%, 83.3%, 87.5% and 91.7%, respectively. The newly established pyrosequencing assay is a rapid and high-throughput method for the detection of resistance to RIF, INH, SM, EMB, OFL and AMK in M.tuberculosis. Pyrosequencing can be used as a practical molecular diagnostic tool for screening and predicting the resistance of re-treatment pulmonary tuberculosis patients.
    Full-text · Article · Apr 2014 · BMC Infectious Diseases
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    • "In some cases, physicians probably did not change to second-line treatment because of the clinical condition of the patient; only 16% of patients overall had smear-positive test results at month 5 (data not shown). Persistence of smear-negative test results among identified MDR TB cases has been cited as a reason for not changing to a standardized MDR TB treatment regimen; other reasons have included patient loss to follow-up, patient death, and patient refusal to change treatment (14). A study evaluating the influence of the microscopic observation drug susceptibility (MODS) assay, which allows for determination of drug susceptibility directly from sputum in just 7–10 days, on the clinical management of TB patients also reported that even when indicated, appropriate treatment regimen changes were not always made (15). "
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    ABSTRACT: In 2004, routine use of culture and drug-susceptibility testing (DST) was implemented for persons in 5 Thailand provinces with a diagnosis of tuberculosis (TB). To determine if DST results were being used to guide treatment, we conducted a retrospective chart review for patients with rifampin-resistant or multidrug-resistant (MDR) TB during 2004-2008. A total of 208 patients were identified. Median time from clinical sample collection to physician review of DST results was 114 days. Only 5.8% of patients with MDR TB were empirically prescribed an appropriate regimen; an additional 31.3% received an appropriate regimen after DST results were reviewed. Most patients with rifampin -resistant or MDR TB had successful treatment outcomes. Patients with HIV co-infection and patients who were unmarried or had received category II treatment before DST results were reviewed had less successful outcomes. Overall, review of available DST results was delayed, and results were rarely used to improve treatment.
    Full-text · Article · Mar 2014 · Emerging Infectious Diseases
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    • "Les résultats de la lutte antituberculeuse dépendent du contexte, des politiques de santé qui sont mises en oeuvre et e ´galement de l'interaction entre le programme de lutte contre la tuberculose et le système de santé en général [10]. Au Cameroun, la lutte antituberculeuse a traversé des changements au cours des trois dernières décennies, mais la plupart des e ´tudes sur l'interface entre le Programme national de lutte contre la tuberculose (PNLT) et les systèmes de santé ont concerné des aspects tels que l'accès aux soins [11] [12] [13], le financement des soins [14], ou le pronostic des patients [14] [15] [16] [17] [18]. A ` notre connaissance, aucune e ´tude n'a mis en perspective l'e ´volution des politiques de santé, l'interaction entre le PNLT et les services de santé généraux et les indicateurs de prise en charge de la tuberculose. "
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    ABSTRACT: Background In sub-Saharan Africa, tuberculosis remains endemic despite reforms of health systems and the tuberculosis control organization carried out in the last decades.Methods We conducted a retrospective study of tuberculosis control in Cameroon from the period 2009 back to 1980. Data were collected from documents and activity reports of tuberculosis control, and interviews with managers of the National tuberculosis control program.FindingsThe history of tuberculosis control in Cameroon from 2009 back to 1980 can be divided into three main periods. The first period, from 1980 to 1994, corresponded to the implementation of the ‘primary health care’ policy. At that time, tuberculosis case management was delivered free of charge, but centralized in specialized services with a gradual and mild increase in new cases detected. The second period, from 1995 to 2000, was characterized by the implementation of the ‘primary health care reorientation’ policy that decentralized tuberculosis care to all health facilities, but introduced cost recovery – which came along with a dramatic drop in the number of tuberculosis cases detected. The National tuberculosis control program, established in 1996, entrusted health facilities – especially hospitals – with the responsibility of tuberculosis diagnosis and treatment, and referred to them as tuberculosis diagnosis and treatment centers. During the third period, from 2001 to 2009, owing to major support from global health initiatives, the number of tuberculosis diagnosis and treatment centers was increased (reaching 216 centers in 2009), with a significant increase of new cases detected that peaked in 2006, from where the situation started declining till 2009.ConclusionTuberculosis control indicators have never been optimal in Cameroon, despite the generally positive trend from 1980 to 2009. The strategy of tuberculosis diagnosis and treatment centers, which are essentially nested within hospitals, seems to have reached its intrinsic limitations. Better performance in tuberculosis control will henceforth require greater decentralization of tuberculosis detection and treatment to health centers. This careful decentralization will improve access for tuberculosis patients and lead to a comprehensive use of hospital technical expertise for tuberculosis care.RésuméPosition du problèmeEn Afrique sub-saharienne, la tuberculose reste endémique en dépit des réformes des systèmes de santé et de l’organisation de la lutte antituberculeuse entreprises ces dernières décennies.MéthodesNous avons procédé à une étude rétrospective de la lutte antituberculeuse au Cameroun dans la période 1980–2009. Les données ont été collectées à partir des documents et des rapports d’activités sur le contrôle de la tuberculose, et d’entretiens avec des responsables du Programme national de lutte contre la tuberculose.RésultatsL’histoire de la lutte antituberculeuse au Cameroun dans la période 1980–2009 peut se décliner en trois grandes périodes. La première va de 1980 à 1994 et correspond à la mise en œuvre de la politique ‘des soins de santé primaires’. Les soins antituberculeux étaient gratuits, mais centralisés au niveau de services spécialisés. La détection des nouveaux cas a augmenté de façon progressive mais modeste. Dans la deuxième période de 1995 à 2000, la politique de ‘réorientation des soins de santé primaires’ a introduit le recouvrement des coûts et a décentralisé la prise en charge de la tuberculose à toutes les formations sanitaires. En revanche, le Programme national de lutte contre la tuberculose, créé en 1996, a désigné les formations sanitaires – centres de diagnostic et de traitement –, autorisées à offrir les soins antituberculeux. Dans la troisième période, de 2001 à 2009, d’importants appuis venant des initiatives globales de santé ont permis d’augmenter le nombre de centres de diagnostic et de traitement (216 centres en 2009) et d’améliorer significativement la détection de nouveaux cas, qui a malheureusement stagné après 2006.Conclusion Les indicateurs de prise en charge de la tuberculose au Cameroun n’ont jamais été optimaux entre 1980 et 2009 malgré leur évolution globalement positive. La stratégie des centres de diagnostic et de traitement, nichés essentiellement dans les hôpitaux, semble avoir atteint ses limites intrinsèques. Une meilleure performance de la lutte antituberculeuse nécessitera une décentralisation de la prise en charge vers les centres de santé. Cette décentralisation minutieuse améliorerait l’accès des patients tuberculeux aux soins et une meilleure utilisation de l’expertise technique de l’hôpital pour la prise en charge de la tuberculose.
    Full-text · Article · Apr 2013 · Revue d Épidémiologie et de Santé Publique
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