Phylogenomic assessment of drug-resistant Mycobacterium tuberculosis strains from Beira, Mozambique.

BACKGROUND: Mozambique is a high-burden tuberculosis (TB) country where TB/HIV co-infection and drug resistant TB (DR-TB) incidence is increasing. Whole genome sequencing (WGS) comprehensively describes the molecular epidemiology of TB, allows prediction of DR-TB phenotypes, lineages strains identification and better understanding of transmission chains. OBJECTIVE: To describe genetic diversity of DR-TB Mycobacterium tuberculosis isolated in Beira, Mozambique. METHODS: Descriptive cross-sectional study with 35 M. tuberculosis isolates, resistant to at least one first-line drug on molecular drug-susceptibility tests (DST). Variant identification, DR prediction and phylogenetic analysis provided by WGS, drug-susceptibility pattern compared to line-probe assay (LPA): Genotype MTBDRTMplus and MTBDRTMsl. FINDINGS: Lineage 4 (L4) was the most prevalent: 25 (71.4%) isolates; 5 (14.3%) L1 and 5 (14.3%) L2. WGS showed 33/35 (94.3%) isolates resistant to at least one drug, two pan-susceptible isolates that were previously diagnosed as DR-TB with genotype MTBDRplus. Concordance between WGS and LPA: 88.6% for isoniazid (INH), 85.7% to rifampicin (RPM), 91.4% for quinolones and 100% to second line injectable drugs. There were three possible TB transmission chains, 10 strains showing recent transmission. CONCLUSION: WGS provided reliable information about the most frequent lineages related to DR-TB in Beira, Mozambique: L4.3 (LAM), L2 (Beijing) and L1 (EAI) and possible recent transmission chain.

Mycobacterium tuberculosis spoligotypes and drug-resistant characterization from Beira compared to genotypes circulating in Mozambique.

INTRODUCTION: Mozambique is one of three countries with high prevalence of tuberculosis (TB), TB/human immunodeficiency virus coinfection, and multidrug-resistant TB. We aimed to describe Mycobacterium tuberculosis spoligotypes circulating among drug resistant (DR) strains from Beira, Mozambique comparing them with genotypes in the country. METHODS: We performed spoligotyping of 79 M. tuberculosis suspected of DR-TB compared all spoligotype patterns published on the international database and PubMed. RESULTS: Both in Beira and Mozambique (n=578), the main clades were Latin-American-Mediterranean, East-African-Indian, Beijing and T, with no extensively DR TB cases. CONCLUSIONS: Beira and Mozambique share the same population genetic structure of M. tuberculosis.

Uncommon testicular localization of Disseminated TB: a case report from Mozambique.

Tuberculosis (TB) of the testicle is a rarely reported and poorly described disease localization. There are no well-defined clinical features suggestive of testicular TB, which makes the diagnosis difficult to establish, especially in low-income settings like Mozambique, where TB is endemic and often associated with HIV-infection; both considered leading causes of death worldwide. We reported the case of a 45-year-old male, HIV positive, naïve to antiretroviral treatment, admitted to the Department of Medicine of the Central Hospital of Beira to investigate chronic enlargement of the testicles.

Mycobacterium tuberculosis spoligotypes and drug-resistant characterization from Beira compared to genotypes circulating in Mozambique

Abstract INTRODUCTION Mozambique is one of three countries with high prevalence of tuberculosis (TB), TB/human immunodeficiency virus coinfection, and multidrug-resistant TB. We aimed to describe Mycobacterium tuberculosis spoligotypes circulating among drug resistant (DR) strains from Beira, Mozambique comparing them with genotypes in the country. METHODS: We performed spoligotyping of 79 M. tuberculosis suspected of DR-TB compared all spoligotype patterns published on the international database and PubMed. RESULTS: Both in Beira and Mozambique (n=578), the main clades were Latin-American-Mediterranean, East-African-Indian, Beijing and T, with no extensively DR TB cases. CONCLUSIONS: Beira and Mozambique share the same population genetic structure of M. tuberculosis.

Accuracy of whole genome sequencing versus phenotypic (MGIT) and commercial molecular tests for detection of drug-resistant Mycobacterium tuberculosis isolated from patients in Brazil and Mozambique.

BACKGROUND: The fast and accurate diagnosis of drug-resistant tuberculosis (DR-TB) is critical to reducing the spread of disease. Although commercial genotypic drug-susceptibility tests (DST) are close to the goal, they are still not able to detect all relevant DR-TB related mutations. Whole genome sequencing (WGS) allows better comprehension of DR-TB with a great discriminatory power. We aimed to evaluate WGS in M. tuberculosis isolates compared with phenotypic and genotypic DST. METHODS: This cross-sectional study evaluated 30 isolates from patients with detected DR-TB in Brazil and Mozambique. They were evaluated with phenotypic (MGIT-SIRE™) and genotypic (Xpert-MTB/RIF™, Genotype-MTBDRplus™, and MTBDRsl™) DST. Isolates with resistance to at least one first- or second-line drug were submitted to WGS and analyzed with TB profiler database. RESULTS: WGS had the best performance among the genotypic DST, compared to the phenotypic test. There was a very good concordance with phenotypic DST for rifampicin and streptomycin (89.6%), isoniazid (96.5%) and ethambutol (82.7%). WGS sensitivity and specificity for detection resistance were respectively 87.5 and 92.3% for rifampicin; 95.6 and 100% for isoniazid; 85.7 and 93.3% for streptomycin while 100 and 77.2% for ethambutol. Two isolates from Mozambique showed a Val170Phe rpoB mutation which was neither detected by Xpert-MTB/RIF nor Genotype-MTBDRplus. CONCLUSION: WGS was able to provide all the relevant information about M. tuberculosis drug susceptibility in a single test and also detected a mutation in rpoB which is not covered by commercial genotypic DST.

Drug-resistant tuberculosis in Central Mozambique: the role of a rapid genotypic susceptibility testing.

BACKGROUND: Genotypic molecular testing may be very helpful for tuberculosis (TB) drug-resistance surveillance and for treatment guidance in low resource settings. METHODS: Descriptive analysis of M. tuberculosis isolates from Beira Central Hospital, Mozambique, during 2014-2015. Genotype MTBDRplus and MTBDRsl were used and patient medical records reviewed. To explore genotypic susceptibility profile of Mycobacterium tuberculosis, to first and second line drugs (SLD) in Beira Mozambique. RESULTS: Of 155 isolates, 16.1 % (25) were multidrug resistant (MDR), 8.4 % (13) isoniazid-monoresistant and 1.3 % (2) rifampicin-monoresistant. Among MDR-TB, 22.2 % showed primary and 77.8 % represented acquired resistance. The majority of patients with drug resistance had a history of previous TB treatment. Among 125 isolates tested for ethambutol and SLD, 7.2 % (9) were resistant to ethambutol, 4.8 % (6) to fluoroquinolones and 0.8 % (1) to ethambutol and fluoroquinolones. Resistance to injectable SLD was not detected. CONCLUSIONS: As far as we know this is the first report of a genotypic testing used to provide information about SLD resistance in Mozambique, where phenotypic susceptibility testing is usually unavailable. Extensively drug resistant TB was not detected in this isolates from Beira Mozambique.

Drug-resistant tuberculosis in Central Mozambique: the role of a rapid genotypic susceptibility testing

Background: Genotypic molecular testing may be very helpful for tuberculosis (TB) drug-resistance surveillance and for treatment guidance in low resource settings. Methods: Descriptive analysis of M. tuberculosis isolates from Beira Central Hospital, Mozambique, during 2014-2015. Genotype MTBDRplus and MTBDRsl were used and patient medical records reviewed. To explore genotypic susceptibility profile of Mycobacterium tuberculosis, to first and second line drugs (SLD) in Beira Mozambique. Results: Of 155 isolates, 16.1 % (25) were multidrug resistant (MDR), 8.4 % (13) isoniazid-monoresistant and 1.3 % (2) rifampicin-monoresistant. Among MDR-TB, 22.2 % showed primary and 77.8 % represented acquired resistance. The majority of patients with drug resistance had a history of previous TB treatment. Among 125 isolates tested for ethambutol and SLD, 7.2 % (9) were resistant to ethambutol, 4.8 % (6) to fluoroquinolones and 0.8 % (1) to ethambutol and fluoroquinolones. Resistance to injectable SLD was not detected. Conclusions: As far as we know this is the first report of a genotypic testing used to provide information about SLD resistance in Mozambique, where phenotypic susceptibility testing is usually unavailable. Extensively drug resistant TB was not detected in this isolates from Beira Mozambique

Perfil de sensibilidade dos isolados de Mycobacterium tuberculosis de pacientes com tuberculose e coinfectados TB/HIV na cidade da Beira, Sofala, Moçambique / Susceptibility profile of isolates of Mycobacterium tuberculosis from patients with tuberculosis and co-­­infection TB/HIV in city of Beira, Sofala, Mozambique

A tuberculose (TB) é uma doença infecciosa que ameaça a humanidade há séculos. Recentemente grandes avanços foram conseguidos no combate à tuberculose, entretanto a resistência bacilar e a coinfecção pelo Vírus de Imunodeficiência Humana (HIV) persistem como os principais desafios dos programas de combate à tuberculose globalmente e também em Moçambique.O objetivo deste trabalho foi estimar a prevalência e caracterizar o perfil genotípico da resistência do bacilo da tuberculose às drogas de primeira e segunda linha do tratamento da TB. Foi realizado um estudo descritivo com 155 isolados correspondentes ao mesmo número de pacientes,obtidos no Hospital Central da Beira-­Moçambique em 2014 e 2015.

Tuberculosis (TB) is an infectious disease that has threatened humanity for centuries. Recently large advances have been made in the fight against tuberculosis, however bacillary resistance and coinfection by Human Immunodeficiency Virus (HIV) persist as the main challenges of programs to combat tuberculosis globally and also in Mozambique. The objective of this work was to estimate the prevalence and to characterize the genotypic profile of the resistance of the tuberculosis bacillus to the first and second line drugs of TB treatment. A descriptive study was carried out with 155 corresponding to the same number of patients, obtained at the Central Hospital of Beira-Mozambique in 2014 and 2015. Tuberculosis (TB) is an infectious disease that has threatened humanity for centuries. Recently large advances have been made in the fight against tuberculosis, however bacillary resistance and coinfection by Human Immunodeficiency Virus (HIV) persist as the main challenges of programs to combat tuberculosis globally and also in Mozambique. The objective of this work was to estimate the prevalence and to characterize the genotypic profile of the resistance of the tuberculosis bacillus to the first and second line drugs of TB treatment. A descriptive study was carried out with 155 concessions corresponding to the same number of patients, obtained at the Central Hospital of Beira-Mozambique in 2014 and 2015.