Molecular epidemiology of Mycobacterium tuberculosis in adult Filipino TB-HIV co-infected patients

2021 ◽  
Vol 25 (4) ◽  
pp. 285-291
Author(s):  
J. C. M. Malabad ◽  
C. F. Ang ◽  
F. A. R. Palabrica ◽  
M. A. M. Cajucom ◽  
N. G. Gloriani ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Molecular Epidemiology ◽  
Disease Transmission ◽  
Tandem Repeats ◽  
The Philippines ◽  
Variable Number ◽  
People Living With Hiv ◽  
East African ◽  
Living With Hiv

BACKGROUND: TB is the leading cause of death from a single infectious disease, particularly among people living with HIV (PLHIV). Molecular epidemiology provides information on prevalent genotypes of Mycobacterium tuberculosis and disease transmission dynamics, which aid in TB control. Identification of mutations that confer drug resistance is essential for the rapid diagnosis of drug-resistant TB, especially in high TB burden settings, like the Philippines.METHODS: This study aimed to determine mutations in M. tuberculosis drug resistance-conferring genes and circulating genotypes in PLHIV. MIRU-VNTR (mycobacterial interspersed repetitive unit-variable number of tandem repeats) typing using a set of 24-loci and sequencing of drug resistance-conferring genes were performed in 22 M. tuberculosis isolates from TB-HIV co-infected patients.RESULTS: The prevalence of resistance to any drug was 31.8%, 18.2% for isoniazid monoresistance, 4.5% for streptomycin monoresistance and 9.1% for multidrug resistance. The identified mutations in the katG, rpoB, pncA, rpsL and gyrA genes have been reported in the literature; none was found in the inhA and embB genes. All isolates belonged to the EAI2-Manila family and were grouped into four clusters based on their phenotypic drug resistance and mutation profiles.CONCLUSION: The use of 24-loci set may be used as a more discriminatory MIRU-VNTR typing in settings where the East African-Indian lineage is predominant, like the Philippines.

scholarly journals Machine-learning reveals that Mycobacterium tuberculosis genotypes and anatomic disease site impacts drug resistance and disease transmission among patients with proven extra-pulmonary tuberculosis

2020 ◽  
Author(s):  
Doctor Busizwe Sibandze ◽  
Beki Themba Magazi ◽  
Lesibana Anthony Malinga ◽  
Nontuthuko Excellent Maningi ◽  
Bong Akee Shey ◽  
...  
Keyword(s):  
Machine Learning ◽  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Disease Transmission ◽  
East Asian ◽  
Extrapulmonary Tuberculosis ◽  
Machine Learning Algorithms ◽  
East African ◽  
Development Of Resistance ◽  
Asian Lineage

Abstract Background: There is a general dearth of information on extrapulmonary tuberculosis (EPTB). Here, we investigated Mycobacterium tuberculosis (Mtb) drug resistance and transmission patterns in EPTB patients treated in the Tshwane metropolitan area, in South Africa.Methods: Consecutive Mtb culture-positive non-pulmonary samples from unique EPTB patients underwent mycobacterial genotyping and were assigned to phylogenetic lineages and transmission clusters based on spoligotypes. MTBDRplus assay was used to search mutations for isoniazid and rifampin resistance. Machine learning algorithms were used to identify clinically meaningful patterns in data. We computed odds ratio (OR), attributable risk (AR) and corresponding 95% confidence intervals (CI). Results: Of the 70 isolates examined, the largest cluster comprised 25 (36%) Mtb strains that belonged to the East Asian lineage. East Asian lineage was significantly more likely to occur within chains of transmission when compared to the Euro-American and East-African Indian lineages: OR= 10.11 (95% CI: 1.56-116). Lymphadenitis, meningitis and cutaneous TB, were significantly more likely to be associated with drug resistance: OR=12.69 (95% CI: 1.82-141.60) and AR = 0.25 (95% CI: 0.06-0.43) when compared with other EPTB sites, which suggests that poor rifampin penetration might be a contributing factor.Conclusions: The majority of Mtb strains circulating in the Tshwane metropolis belongs to East Asian, Euro-American and East-African Indian lineages. Each of these are likely to be clustered, suggesting on-going EPTB transmission. Since 25% of the drug resistance was attributable to sanctuary EPTB sites notorious for poor rifampin penetration, we hypothesize that poor anti-tuberculosis drug dosing might have a role in the development of resistance.

scholarly journals Can 15-Locus Mycobacterial Interspersed Repetitive Unit-Variable-Number Tandem Repeat Analysis Provide Insight into the Evolution of Mycobacterium tuberculosis?

2005 ◽  
Vol 71 (12) ◽  
pp. 8207-8213 ◽  
Author(s):  
Andrea Gibson ◽  
Timothy Brown ◽  
Lucy Baker ◽  
Francis Drobniewski
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Tandem Repeats ◽  
Variable Number Tandem Repeat ◽  
Epidemiological Studies ◽  
Variable Number ◽  
Molecular Techniques ◽  
Nucleotide Polymorphisms ◽  
East African ◽  
Phylogeny And Evolution ◽  
Phylogenetic Lineages

ABSTRACT The phylogeny and evolution of the bacterium Mycobacterium tuberculosis is still poorly understood despite the application of a variety of molecular techniques. We analyzed 469 M. tuberculosis and 49 Mycobacterium bovis isolates to evaluate if the mycobacterial interspersed repetitive units-variable-number tandem repeats (MIRU-VNTR) commonly used for epidemiological studies can define the phylogeny of the M. tuberculosis complex. This population was characterized by previously identified silent single-nucleotide polymorphisms (sSNPs) or by a macroarray based on these sSNPs that was developed in this study. MIRU-VNTR phylogenetic codes capable of differentiating between phylogenetic lineages were identified. Overall, there was 90.9% concordance between the lineages of isolates as defined by the MIRU-VNTR and sSNP analyses. The MIRU-VNTR phylogenetic code was unique to M. bovis and was not observed in any M. tuberculosis isolates. The codes were able to differentiate between different M. tuberculosis strain families such as Beijing, Delhi, and East African-Indian. Discrepant isolates with similar but not identical MIRU-VNTR codes often displayed a stepwise trend suggestive of bidirectional evolution. A lineage-specific panel of MIRU-VNTR can be used to subdivide each lineage for epidemiological purposes. MIRU-VNTR is a valuable tool for phylogenetic studies and could define an evolutionarily uncharacterized population of M. tuberculosis complex organisms.

scholarly journals Prevalence and Molecular Epidemiology of Transmitted Drug Resistance and Genetic Transmission Networks Among Newly Diagnosed People Living With HIV/AIDS in a Minority Area, China

2021 ◽  
Vol 9 ◽  
Author(s):  
Dan Yuan ◽  
Bin Yu ◽  
Yiping Li ◽  
Zixin Wang ◽  
Meijing Liu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Molecular Epidemiology ◽  
Transmitted Drug Resistance ◽  
People Living With Hiv ◽  
Newly Diagnosed ◽  
Transmission Networks ◽  
Genetic Transmission ◽  
Living With Hiv ◽  
Hiv 1 ◽  
Minority Area

Introduction: Transmitted drug resistance (TDR) can compromise antiretroviral therapy (ART) efficacy. We aimed to understand the molecular epidemiology of TDR and its genetic transmission networks among newly diagnosed people living with HIV/AIDS (PLWH).Methods: A total of 1,318 newly diagnosed PLWH, identified in all population-based HIV screening in an HIV-affected county of a minority area of China (i.e., Butuo county), were enrolled between January 1, 2018, and November 31, 2018. HIV-1 pol gene sequences were used for phylogenetic and genotypic drug resistance analyses. The genetic transmission networks were identified.Results: The prevalence of TDR among newly diagnosed PLWH was 8.12% (107/1,318). Patients in the stage of AIDS (adjusted odds ratio, OR: 2.32) and who had a history of sharing a needle ≥5 times (adjusted OR: 3.89) were more likely to have an increased risk of TDR. The prevalence of TDR for non-nucleoside reverse transcriptase inhibitors (NNRTIs) is higher than that of other inhibitors, with a relatively high prevalence of three mutations [V179D/E/DE (4.93%), K103N/KN (3.11%), and E138A/G (1.52%)]. A total of 577 (43.78%) pol sequences were involved in the genetic transmission network, with 171 clusters ranging in size from 2 to 91 pol sequences; 37.38% (40/107) of individuals carrying TDR were involved in the network, and individuals with the same TDR-associated mutations were usually cross-linked.Conclusions: Our data suggest a relatively high level of TDR and many transmission clusters among the newly diagnosed PLWH. Targeted intervention, early identification, and monitoring of resistance are warranted to reduce the TDR and prevent HIV-1 transmission in areas with a high rate of HIV-1.

scholarly journals Machine learning reveals that Mycobacterium tuberculosis genotypes and anatomic disease site impacts drug resistance and disease transmission among patients with proven extra-pulmonary tuberculosis

2020 ◽  
Author(s):  
Doctor Busizwe Sibandze ◽  
Beki Themba Magazi ◽  
Lesibana Anthony Malinga ◽  
Nontuthuko Excellent Maningi ◽  
Bong Akee Shey ◽  
...  
Keyword(s):  
Machine Learning ◽  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Disease Transmission ◽  
East Asian ◽  
Extrapulmonary Tuberculosis ◽  
Machine Learning Algorithms ◽  
East African ◽  
Development Of Resistance ◽  
Asian Lineage

Abstract Background There is a general dearth of information on extrapulmonary tuberculosis (EPTB). We investigated Mycobacterium tuberculosis (Mtb) drug resistance and transmission patterns in EPTB patients treated in the Tshwane metropolitan area, South Africa. Methods Consecutive Mtb culture-positive non-pulmonary samples from unique EPTB patients underwent mycobacterial genotyping and were assigned to phylogenetic lineages and transmission clusters based on spoligotypes. MTBDRplus assay was used to search mutations for isoniazid and rifampin resistance. Machine learning algorithms were used to identify clinically meaningful patterns in data. We computed odds ratio (OR), attributable risk (AR) and corresponding 95% confidence intervals (CI). Results Of the 70 isolates examined, the largest cluster comprised of 25 (36%) Mtb strains that belonged to the East Asian lineage. East Asian lineage was significantly more likely to occur within chains of transmission when compared to the Euro-American and East-African Indian lineages: OR= 10.11 (95% CI: 1.56-116). Lymphadenitis, meningitis and cutaneous TB, were significantly more likely to be associated with drug resistance: OR=12.69 (95% CI: 1.82-141.60) and AR = 0.25 (95% CI: 0.06-0.43) when compared with other EPTB sites, which suggests that poor rifampin penetration might be a contributing factor. Conclusions The majority of Mtb strains circulating in the Tshwane metropolis belongs to East Asian, Euro-American and East-African Indian lineages. Each of these are likely to be clustered, suggesting on-going EPTB transmission. Since 25% of the drug resistance was attributable to sanctuary EPTB sites notorious for poor rifampin penetration, we hypothesize that poor anti-tuberculosis drug dosing might have a role in the development of resistance.

Discrimination of Mycobacterium tuberculosis complex bacteria using novel VNTR-PCR targets

Microbiology ◽  
2002 ◽  
Vol 148 (2) ◽  
pp. 519-528 ◽  
Author(s):  
Robin A Skuce ◽  
Thomas P McCorry ◽  
Julie F McCarroll ◽  
Solvig M. M Roring ◽  
Alistair N Scott ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Molecular Epidemiology ◽  
Tandem Repeats ◽  
Antigenic Variation ◽  
Variable Number ◽  
Strain Typing ◽  
The Novel ◽  
Typing Method ◽  
Intergenic Regions ◽  
Typing Methods

The lack of a convenient high-resolution strain-typing method has hampered the application of molecular epidemiology to the surveillance of bacteria of the Mycobacterium tuberculosis complex, particularly the monitoring of strains of Mycobacterium bovis. With the recent availability of genome sequences for strains of the M. tuberculosis complex, novel PCR-based M. tuberculosis-typing methods have been developed, which target the variable-number tandem repeats (VNTRs) of minisatellite-like mycobacterial interspersed repetitive units (MIRUs), or exact tandem repeats (ETRs). This paper describes the identification of seven VNTR loci in M. tuberculosis H37Rv, the copy number of which varies in other strains of the M. tuberculosis complex. Six of these VNTRs were applied to a panel of 100 different M. bovis isolates, and their discrimination and correlation with spoligotyping and an established set of ETRs were assessed. The number of alleles varied from three to seven at the novel VNTR loci, which differed markedly in their discrimination index. There was positive correlation between spoligotyping, ETR- and VNTR-typing. VNTR-PCR discriminates well between M. bovis strains. Thirty-three allele profiles were identified by the novel VNTRs, 22 for the ETRs and 29 for spoligotyping. When VNTR- and ETR-typing results were combined, a total of 51 different profiles were identified. Digital nomenclature and databasing were intuitive. VNTRs were located both in intergenic regions and annotated ORFs, including PPE (novel glycine-asparigine-rich) proteins, a proposed source of antigenic variation, where VNTRs potentially code repeating amino acid motifs. VNTR-PCR is a valuable tool for strain typing and for the study of the global molecular epidemiology of the M. tuberculosis complex. The novel VNTR targets identified in this study should additionally increase the power of this approach.

scholarly journals Machine-learning (ML) reveals that Mycobacterium tuberculosis genotypes and anatomic disease site impacts drug resistance and disease transmission among patients with proven extra-pulmonary tuberculosis

2020 ◽  
Author(s):  
Doctor Busizwe Sibandze(Former Corresponding Author) ◽  
Beki Themba Magazi ◽  
Lesibana Anthony Malinga ◽  
Nontuthuko Excellent Maningi ◽  
Bong Akee Shey ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Disease Transmission ◽  
East Asian ◽  
Extrapulmonary Tuberculosis ◽  
East African ◽  
Drug Dosing ◽  
Disease Site ◽  
Asian Lineage ◽  
Phylogenetic Lineages

Abstract Background There is a general dearth of information on extrapulmonary tuberculosis (EPTB). We investigated Mycobacterium tuberculosis (Mtb) drug resistance and transmission patterns in EPTB patients treated in the Tshwane metropolitan, South Africa. Methods Consecutive Mtb culture-positive non-pulmonary samples from unique EPTB patients underwent further mycobacterial genotyping and were assigned to phylogenetic lineages and transmission clusters based on spoligotypes. MTBDR plus assay was used to test for isoniazid and rifampin susceptibility. ML algorithms were used to identify clinically meaningful patterns in data. We computed odds ratio (OR), attributable risk (AR) and corresponding 95% confidence intervals (CI). Results Of the 70 isolates examined, the largest cluster comprised of 25 (36%) Mtb strains that belonged to the East Asian lineage. East Asian lineage was significantly more likely to occur within chains of transmission when compared to the Euro-American and East-African Indian lineages: OR= 10.11 (95% CI: 1.56-116). Lymphadenitis, meningitis and skin TB, were significantly more likely to be associated with drug resistance: OR=12.69 (95% CI: 1.82-141.60) and AR = 0.25 (95% CI: 0.06-0.43) when compared with other EPTB sites, which suggests that poor rifampin penetration might be a contributing factor. Conclusions Majority of Mtb strains circulating in the Tshwane metropolis belongs to East Asian, Euro-American and East-African Indian lineages. Each of these are likely to be clustered, suggesting on-going EPTB transmission. Since 25% of the drug resistance was attributable to sanctuary EPTB sites notorious for poor rifampin penetration, we hypothesize that poor anti-tuberculosis drug dosing might have a role in the resistance.

scholarly journals Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil

2021 ◽  
Vol 22 (10) ◽  
pp. 5304
Author(s):  
Ana Santos-Pereira ◽  
Vera Triunfante ◽  
Pedro M. M. Araújo ◽  
Joana Martins ◽  
Helena Soares ◽  
...  
Keyword(s):  
Drug Resistance ◽  
People Living With Hiv ◽  
Resistance Mutations ◽  
Subtype C ◽  
Viral Loads ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
Low Prevalence ◽  
Living With Hiv ◽  
Hiv 1

The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). Since Brazil presents the largest number of people living with HIV (PLWH) in South America we aimed at understanding the dynamics of DRM in this country. We analyzed a total of 20,226 HIV-1 sequences collected from PLWH undergoing ART between 2008–2017. Results show a mild decline of DRM over the years but an increase of the K65R reverse transcriptase mutation from 2.23% to 12.11%. This increase gradually occurred following alterations in the ART regimens replacing zidovudine (AZT) with tenofovir (TDF). PLWH harboring the K65R had significantly higher viral loads than those without this mutation (p < 0.001). Among the two most prevalent HIV-1 subtypes (B and C) there was a significant (p < 0.001) association of K65R with subtype C (11.26%) when compared with subtype B (9.27%). Nonetheless, evidence for K65R transmission in Brazil was found both for C and B subtypes. Additionally, artificial neural network-based immunoinformatic predictions suggest that K65R could enhance viral recognition by HLA-B27 that has relatively low prevalence in the Brazilian population. Overall, the results suggest that tenofovir-based regimens need to be carefully monitored particularly in settings with subtype C and specific HLA profiles.

scholarly journals Barriers to timely disclosure of HIV serostatus: A qualitative study at care and treatment centers in Dar es Salaam, Tanzania

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256537
Author(s):  
Neelam Ismail ◽  
Nancy Matillya ◽  
Riaz Ratansi ◽  
Columba Mbekenga
Keyword(s):  
Social Status ◽  
Disease Transmission ◽  
Qualitative Content Analysis ◽  
Dar Es Salaam ◽  
Hiv Care ◽  
People Living With Hiv ◽  
Negative Consequences ◽  
Hiv Serostatus ◽  
Care And Treatment ◽  
Living With Hiv

Introduction Disclosure of Human Immunodeficiency Virus (HIV) status is important to prevent the spread of HIV and maintain the health of people living with HIV, their spouses, and the community. Despite the benefits of disclosure, many people living with HIV delay disclosing their status to those close to them thereby increasing the risk for disease transmission. This study aimed to determine the barriers to timely disclosure of HIV serostatus for people living with HIV in Dar es Salaam, Tanzania, and identify what motivated disclosure. Methods A qualitative descriptive study using in-depth individual interviews was conducted with10 participants attending HIV care and treatment centers in Dar es Salaam. The participants were people living with HIV who had delayed disclosing their serostatus for more than one month after diagnosis. Data was analyzed using qualitative content analysis. Results Three categories emerged from the analysis: Barriers hindering timely disclosure, motivation for disclosure of serostatus, and consequences of delayed disclosure. Barriers to timely disclosure included denial of one’s status, the fear of stigmatization, fear of being separated or divorced, the need to protect loved ones, and lack of adequate knowledge about the disease. Reasons that motivated disclosure included gaining social support, preventing disease transmission and wanting to be at peace. Conclusion Timely disclosure is hindered by stigma because HIV is negatively perceived by the public. People living with HIV prefer not to disclose to avoid the negative consequences of disclosure, especially because of fear of being discriminated against and losing their social status, which plays a major role in social status in Tanzania. Trust and adequate counseling from health care workers helps prompt disclosure.

scholarly journals Characterization of Mutations Conferring Extensive Drug Resistance to Mycobacterium tuberculosis Isolates in Pakistan

2011 ◽  
Vol 55 (12) ◽  
pp. 5654-5659 ◽  
Author(s):  
Asho Ali ◽  
Rumina Hasan ◽  
Kauser Jabeen ◽  
Nusrat Jabeen ◽  
Ejaz Qadeer ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Hot Spot ◽  
East African ◽  
Content Type ◽  
Diagnostic Assays ◽  
Asian Strain ◽  
Central Asian ◽  
Extensive Drug Resistance ◽  
Detection Of Mutations

ABSTRACTThe increasing incidence of extensively drug-resistant (XDR)Mycobacterium tuberculosisin high-tuberculosis-burden countries further highlights the need for improved rapid diagnostic assays. An increasing incidence of XDRM. tuberculosisstrains in Pakistan has been reported, but drug resistance-associated mutations in these strains have not been evaluated previously. We sequenced the “hot-spot” regions ofrpoB,katG,inhA,ahpC,gyrA,gyrB, andrrsgenes in 50 XDRM. tuberculosisstrains. It was observed that 2% of rifampin, 6% of isoniazid, 24% of fluoroquinolone, and 32% of aminoglycoside/capreomycin resistance in XDRM. tuberculosisstrains would be undetected if only these common hot-spot regions were tested. The frequencies of resistance-conferring mutations were found to be comparable among all XDRM. tuberculosisstrain families present, including the Central Asian Strain, Beijing, and East African Indian genogroups and the Unique isolates. Additional genetic loci need to be tested for detection of mutations conferring fluoroquinolone, aminoglycoside, and capreomycin resistance in order to improve molecular diagnosis of regional XDRM. tuberculosisstrains.

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