Whole-genome sequencing differentiates relapse from re-infection in TB.

BACKGROUND: Distinguishing TB relapse from re-infection is important from a clinical perspective to document transmission patterns. We investigated isolates from patients classified as relapse to understand if these were true relapses or re-infections. We also investigated shifts in drug susceptibility patterns to distinguish acquired drug resistance from re-infection with resistant strains.METHODS: Isolates from pulmonary TB patients from 2009 to 2017 were analysed using whole-genome sequencing (WGS).RESULTS: Of 11 patients reported as relapses, WGS results indicated that 4 were true relapses (single nucleotide polymorphism difference ≤5), 3 were re-infections with new strains, 3 were both relapse and re-infection and 1 was a suspected relapse who was later categorised as treatment failure based on sequencing. Of the 9 patients who went from a fully susceptible to a resistant profile, WGS showed that none had acquired drug resistance; 6 were re-infected with new resistant strains, 1 was probably infected by at least two different genotype strains and 2 were phenotypically misclassified.CONCLUSIONS: WGS was shown to distinguish between relapse and re-infection in an unbiased way. The use of WGS minimises the risk of false classification of treatment failure instead of re-infection. Furthermore, our study showed that strains without major genetic differences can cause re-infection.

Poor treatment outcomes among multidrug-resistant tuberculosis patients in Gomel Region, Republic of Belarus.

SETTINGS: Tuberculosis (TB) health facilities in the Gomel Region, Republic of Belarus-settings with a high burden of multidrug-resistant TB (MDR-TB) and human immunodeficiency virus (HIV) infection. OBJECTIVE: To determine treatment outcomes among MDR-TB patients diagnosed in 2009-2010 and factors associated with unsuccessful outcomes (death, failure and loss to follow-up). DESIGN: Retrospective cohort study involving a review of an electronic patient database maintained under the National Tuberculosis Control Programme. RESULTS: Of 517 patients diagnosed, 78 (15%) did not start treatment. Among 439 patients who started treatment (84% males, median age 45 years, 15% HIV-infected), 291 (66%) had unsuccessful outcomes (35% deaths, 18% treatment failure and 13% lost to follow-up). Multivariate regression analysis showed that patients aged ⩾45 years (aRR 1.2, 95%CI 1.1-1.3), HIV-infected patients and those not receiving antiretroviral therapy (ART) (aRR 1.5, 95%CI 1.4-1.6) and those with a previous history of anti-tuberculosis treatment (aRR 1.2, 95%CI 1.1-1.4) had significantly higher risk of unsuccessful outcomes. CONCLUSION: Treatment outcomes among MDR-TB patients were poor, with high rates of death, failure and loss to follow-up (including pre-treatment loss to follow-up). Urgent measures to increase ART uptake among HIV-infected MDR-TB patients, improved access to second-line anti-tuberculosis drug susceptibility testing and comprehensive patient support measures are required to address this grim situation.

Tuberculosis in health care workers in Belarus.

SETTING: Tuberculosis (TB), including drug-resistant TB, is a serious problem in Belarus. OBJECTIVES: To determine the prevalence of TB among health care workers (HCWs) along with patient characteristics, treatment outcomes and drug resistance patterns between 2008 and 2012. DESIGN: A retrospective national record review. RESULTS: There were 116 HCWs with TB. Case notification rates were higher among HCWs than in the general population (349 vs. 40/100 000 in 2012). Most HCWs with TB were nurses (n = 46, 40%) or nurse assistants (n = 37, 32%), female (n = 100, 86%) and aged 25-44 years (n = 84, 72%). Most common places of work for HCWs with TB were multidrug-resistant (MDR-) and extensively drug-resistant (XDR-TB) wards (n = 23, 20%), general medical (n = 26, 22%) and non-medical (n = 34, 29%) departments. All HCWs had pulmonary TB, 107 (92%) had new TB and 103 (89%) had negative sputum smears. Of the 38 (33%) with culture and drug susceptibility testing (DST), 28 (74%) had MDR-/XDR-TB. In 109 HCWs evaluated for final treatment outcomes, 97 (89%) were successfully treated, and their results were not affected by DST status. CONCLUSION: This study highlights the high prevalence of recorded TB in HCWs in TB health facilities in Belarus: there is a need to better understand and rectify this problem.

High time to use rapid tests to detect multidrug resistance in sputum smear-negative tuberculosis in Belarus.

SETTING: Belarus (Eastern Europe) is facing an epidemic of multidrug-resistant tuberculosis (MDR-TB). In 2012, rapid molecular diagnostics were prioritised for sputum smear-positive pulmonary tuberculosis (PTB) patients to diagnose MDR-TB, while pulmonary sputum smear-negative pulmonary TB (SN-PTB) patients were investigated using conventional methods, often delaying the diagnosis of MDR-TB by 2-4 months. OBJECTIVE: To determine the proportion of MDR-TB among SN-PTB patients registered in 2012 and associated clinical and demographic factors. DESIGN: Retrospective cohort study using countrywide data from the national electronic TB register. RESULTS: Of the 5377 TB cases registered, 2960 (55%) were SN-PTB. Of the latter, 1639 (55%) were culture-positive, of whom 768 (47%) had MDR-TB: 33% (363/1084) were new and 73% (405/555) previously treated patients. Previous history of treatment, age, region, urban residence, human immunodeficiency virus (HIV) status and being a pensioner were independently associated with MDR-TB. CONCLUSION: About half of culture-positive SN-PTB patients have MDR-TB and this rises to over 7/10 for retreatment cases. A national policy decision to extend rapid molecular diagnostics universally to all PTB patients, including SN-PTB, seems justified. Steps need to be taken to ensure implementation of this urgent priority, given the patient and public health implications of delayed diagnosis.

Contexte : Le Belarus (Europe de l'Est) est confronté à une épidémie de tuberculose multirésistante (TB-MDR). En 2012, les patients atteints de tuberculose pulmonaire (TBP) à frottis positif ont bénéficié en priorité de diagnostics moléculaires pour confirmer une TB-MDR, tandis que les patients atteints de TBP à frottis négatif (SN-PTB) ont bénéficié de méthodes conventionnelles qui retardaient souvent le diagnostic de TB-MDR de 2 à 4 mois.Objectif : Déterminer la proportion de TB-MDR parmi les patients SN-PTB enregistrés en 2012, ainsi que les facteurs cliniques et démographiques associés.Schéma : Etude de cohorte rétrospective basée sur des données émanant de tout le pays grâce au registre électronique national de la TB.Résultats : Sur 5377 cas de TB enregistrés, 2960 (55%) étaient des SN-PTB. Parmi ces derniers, 1639 (55%) avaient une culture positive, dont 768 (47%) avaient une TB-MDR : 33% (363/1084) nouveaux cas et 73% (405/555) patients déjà traités préalablement. La notion de traitement antérieur, l'âge, la région, la résidence en milieu urbain, le statut à l'égard du virus de l'immunodéficience humaine et le fait d'être retraité étaient indépendamment associés à la TB-MDR.Conclusion : Près de la moitié des patients SN-PTB à culture positive ont une TB-MDR, et dans les cas de retraitement, on arrive à plus de sept patients sur dix. La décision politique nationale d'extension des diagnostics moléculaires rapides à tous les patients TBP, y compris les patients SN-PTB, semble donc justifiée. Il est nécessaire de prendre des mesures afin d'assurer la mise en œuvre de cette priorité urgente, en raison des implications d'un diagnostic retardé à la fois pour les patients et en termes de santé publique.

Marco de referencia: El país de Bielorrusia, en Europa oriental, afronta una epidemia de tuberculosis multidrogorresistente (TB-MDR). En el 2012, se privilegió la práctica de las pruebas moleculares rápidas con el fin de diagnosticar la TB-MDR en los pacientes con TB pulmonar (TBP) y baciloscopia positiva y los casos con baciloscopia negativa (SN-PTB) se investigaron mediante los métodos clásicos, lo cual solía retardar de dos a cuatro meses el diagnóstico de la TB-MDR.Objetivo: Determinar en los pacientes SN-PTB registrados en el 2012, la proporción de casos TB-MDR y examinar los factores clínicos y demográficos que se asociaban con este diagnóstico.Método: Un estudio retrospectivo de cohortes a partir de los datos del Registro Nacional Informatizado de Tuberculosis.Resultados: De los 5377 casos de TB registrados, 2960 correspondían a SN-PTB (55%). De estos pacientes, 1639 presentaron un cultivo positivo (55%) y en 768 casos se diagnosticó TB-MDR (47%). De los pacientes con diagnóstico de TB-MDR, el 33% correspondió a casos nuevos (363/1084) y el 73% consistió en pacientes previamente tratados (405/555). Los factores que se asociaron de manera independiente con el diagnóstico de TB-MDR fueron el antecedente de tratamiento antituberculoso, la edad, el domicilio en zona urbana, la situación frente al virus de la inmunodeficiencia humana y el hecho de ser jubilado.Conclusión: Cerca de la mitad de los pacientes con SN-PTB presentó TB-MDR. Esta proporción llegó a ser siete de cada 10 de los casos en retratamiento. Con base en estos resultados, está justificada una decisión política a escala nacional de ampliación del uso de las pruebas rápidas de diagnóstico molecular de manera universal a todos los pacientes con TBP, incluidos los pacientes con SN-PTB. Es necesario tomar medidas encaminadas a fomentar la ejecución de esta prioridad urgente, dadas las repercusiones que un diagnóstico tardío impone a los pacientes y al sistema de salud pública.