scholarly journals FIND Tuberculosis Strain Bank: a Resource for Researchers and Developers Working on Tests To Detect Mycobacterium tuberculosis and Related Drug Resistance

2017 ◽  
Vol 55 (4) ◽  
pp. 1066-1073 ◽  
Author(s):  
Belay Tessema ◽  
Pamela Nabeta ◽  
Eloise Valli ◽  
Audrey Albertini ◽  
Jimena Collantes ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Variable Number Tandem Repeat ◽  
Multidrug Resistant ◽  
Variable Number ◽  
Sub Saharan Africa ◽  
Resistance Testing ◽  
Drug Resistant ◽  
Phenotypic Resistance ◽  
Mother And Daughter ◽  
Sub Saharan

ABSTRACT The spread of multidrug-resistant (MDR) tuberculosis (TB) and extensively drug-resistant (XDR) TB hampers global efforts in the fight against tuberculosis. To enhance the development and evaluation of diagnostic tests quickly and efficiently, well-characterized strains and samples from drug-resistant tuberculosis patients are necessary. In this project, the Foundation for Innovative New Diagnostics (FIND) has focused on the collection, characterization, and storage of such well-characterized reference materials and making them available to researchers and developers. The collection is being conducted at multiple centers in Southeast Asia, South America, Eastern Europe, and soon the sub-Saharan Africa regions. Strains are characterized for their phenotypic resistances and MICs to first-line drugs (FLDs) and second-line drugs (SLDs) using the automated MGIT 960 system following validated procedures and WHO criteria. Analysis of resistance-associated mutations is done by whole-genome sequencing (WGS) using the Illumina NextSeq system. Mycobacterial interspersed repetitive-unit–variable-number tandem-repeat analysis and WGS are used to determine strain lineages. All strains are maintained frozen at −80°C ± 10°C as distinct mother and daughter lots. All strains are extensively quality assured. The data presented here represent an analysis of the initial part of the collection. Currently, the bank contains 118 unique strains with extracted genomic DNA and matched sputum, serum, and plasma samples and will be expanded to a minimum of 1,000 unique strains over the next 3 years. Analysis of the current strains by phenotypic resistance testing shows 102 (86.4%), 10 (8.5%), and 6 (5.1%) MDR, XDR, and mono/poly resistant strains, respectively. Two of the strains are resistant to all 11 drugs that were phenotypically tested. WGS mutation analysis revealed FLD resistance-associated mutations in the rpoB , katG , inhA , embB , embA , and pncA genes; SLD resistance in the gyrA , gyrB , rrs , eis , and tlyA genes; and ethionamide resistance in the ethA genes. Most important lineages are represented in the bank, and further collections have been initiated to increase geographic and lineage diversity. The bank provides highly characterized and high-quality strains as a resource for researchers and developers in support of the development and evaluation of new diagnostics and drug resistance detection tools.

scholarly journals Drug-resistant Mycobacterium tuberculosis and its genotypes isolated from an outbreak in western Thailand

2020 ◽  
Author(s):  
Janisara Rudeeaneksin ◽  
Benjawan Phetsuksiri ◽  
Chie Nakajima ◽  
Supranee Bunchoo ◽  
Krairerk Suthum ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Variable Number Tandem Repeat ◽  
Multidrug Resistant ◽  
Variable Number ◽  
Drug Resistant ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Extensively Drug Resistant ◽  
Mdr Tb ◽  
Vntr Analysis

Abstract Background Multidrug-resistant TB (MDR-TB) outbreaks have occurred in the Thamaka district, Kanchanaburi province in Thailand. Methods Seventy-two isolates, which included 7% mono-, 30.6% MDR and extensively drug-resistant TB (XDR-TB), were genotyped by spoligotyping, mycobacterial interspersed repetitive unit-variable-number tandem repeat (MIRU-VNTR) and single nucleotide polymorphism genotyping, and their drug resistance was analysed. Results The spoligotyping results showed that Beijing spoligo-international type (SIT)1 was predominant (n=38; 52.8%) while the remaining were non-Beijing sublineages (n=34). The MIRU-VNTR analysis showed that Beijing isolates, most of which belonged to the modern type (n=37), formed 5 clusters and 13 individual patterns. In katG, only mutation Ser315Thr was identified. In rpoB, Ser531Leu was predominant, except for His526Arg and Leu533Pro, which were found in two isolates. A cluster of 14 Beijing strains contained these common mutations and shared the MIRU-VNTR genotype with isolates in the Thamaka district that had spread previously. Two U SIT523 isolates contained the mutations A1400G in rrs and Asp94Gly in gyrA genes, indicating a spread of XDR-TB. Conclusions Most mutations were associated with drug resistance and the specific MDR Beijing and XDR-TB in U SIT523 isolates remain. This genotyping is a key tool for tracking TB transmission in the Thamaka district of Thailand.

scholarly journals Review of multidrug-resistant and extensively drug-resistant TB: global perspectives with a focus on sub-Saharan Africa

2010 ◽  
Vol 15 (9) ◽  
pp. 1052-1066 ◽  
Author(s):  
Giovanni Battista Migliori ◽  
Keertan Dheda ◽  
Rosella Centis ◽  
Peter Mwaba ◽  
Matthew Bates ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Sub Saharan Africa ◽  
Drug Resistant ◽  
Global Perspectives ◽  
Extensively Drug Resistant ◽  
Sub Saharan

scholarly journals 885. HIV-1 Treatment Failure and Extensive Drug Resistance in Perinatally Infected Children Failing First-Line Antiretroviral Therapy in Western Kenya

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S20-S20
Author(s):  
Winstone Nyandiko ◽  
Sabina Holland ◽  
Rachel Vreeman ◽  
Allison DeLong ◽  
Akarsh Manne ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Treatment Failure ◽  
Cd4 Count ◽  
Sub Saharan Africa ◽  
Resistance Testing ◽  
Second Line ◽  
First Line ◽  
Western Kenya ◽  
Extensive Drug Resistance ◽  
Sub Saharan

Abstract Background Understanding drug resistance in perinatally HIV-infected children (PHIC) when viral load (VL) monitoring is limited is critical for life-long antiretroviral use. Resistance data in PHIC in sub-Saharan Africa are limited. Though guidelines recommend PI-based first-line regimens in PHIC, many worldwide remain on NNRTI-based regimens. We examined treatment failure, resistance, and outcomes in Kenyan PHIC on first-line NNRTI-based therapy. Methods PHIC were enrolled in 2010–2013 at the Academic Model Providing Access to Healthcare in Eldoret, Kenya, a large program caring for >160,000 HIV patients; >15,000 PHIC. VL testing, not routinely available then, was done for all, and resistance testing was done in viremic PHIC. Clinical data were derived from medical records. Subtype and resistance interpretation were with Stanford Database tools. Associations between failure (>1,000 copies/mL) or resistance, and demographic, clinical or lab variables were evaluated with Fisher exact and Wilcoxon rank-sum tests. Results Of 482 PHIC enrolled, 52% were female, median age 8.4 years (range 1–15), median CD4% 28 (range 0–53), 79% on zidovudine (AZT)/abacavir (ABC)+lamivudine(3TC)+efavirenz (EFV)/nevirapine (NVP) for median 2.3 years. Treatment failure was seen in 31%, associated with low CD4% and count. Genotypes were available in 124, 47% female, median age 8.3 years (range 2–15), median CD4% 22 (range 0–45), 81% on AZT/ABC+3TC+EFV/NVP for median 2.5 years, median VL 7,515 copies/mL. Subtypes were A 76%, C 3%, D 15%, recombinants 6%. Reverse transcriptase mutations were in 93%; 93%-NNRTIs, median 2/patient, most common Y181C (44%); 89%-NRTIs, median 3/patient, most common M184V (85%); 89%-dual class, median 5/patient. Intermediate-high resistance to potential second-line drugs included 62% etravirine, 66% rilpivirine, and 19% tenofovir. Of 92/124 (74%) PHIC with follow-up data, 27% remained on NNRTI-based first-line (median CD4 count 461), of whom 24% had suppressed VL and 48% died; and 73% switched to PI-based second-line (median CD4 count 591), of whom 72% had suppressed VL and 6% died (P < 0.05 for both). Conclusion PHIC in western Kenya on NNRTI-based first-line regimens had high treatment failure rates and extensive drug resistance with poor clinical outcomes, demanding urgent interventions. Disclosures All Authors: No reported Disclosures.

Pretreatment HIV-1 drug resistance testing in sub-Saharan Africa

2012 ◽  
Vol 12 (12) ◽  
pp. 911 ◽  
Author(s):  
Lutgarde Lynen ◽  
Katrien Fransen ◽  
Johan Van Griensven ◽  
Robert Colebunders
Keyword(s):  
Drug Resistance ◽  
Sub Saharan Africa ◽  
Resistance Testing ◽  
Drug Resistance Testing ◽  
Sub Saharan ◽  
Hiv 1

Affordable HIV drug-resistance testing for monitoring of antiretroviral therapy in sub-Saharan Africa

2016 ◽  
Vol 16 (11) ◽  
pp. e267-e275 ◽  
Author(s):  
Seth C Inzaule ◽  
Pascale Ondoa ◽  
Trevor Peter ◽  
Peter N Mugyenyi ◽  
Wendy S Stevens ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Sub Saharan Africa ◽  
Resistance Testing ◽  
Hiv Drug Resistance ◽  
Drug Resistance Testing ◽  
Sub Saharan

scholarly journals The Prevalence of Virulence Determinants and Antibiotic Resistance Patterns in Methicillin—Resistant Staphylococcus aureus in a Nursing Home in Poland

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 427
Author(s):  
Martyna Kasela ◽  
Agnieszka Grzegorczyk ◽  
Bożena Nowakowicz-Dębek ◽  
Anna Malm
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Variable Number Tandem Repeat ◽  
Multidrug Resistant ◽  
Variable Number ◽  
Pulse Field ◽  
Virulence Determinants ◽  
Gene Encoding ◽  
Methicillin Resistant ◽  
Pulse Field Gel Electrophoresis

Nursing homes (NH) contribute to the regional spread of methicillin-resistant Staphylococcus aureus (MRSA). Moreover, residents are vulnerable to the colonization and subsequent infection of MRSA etiology. We aimed at investigating the molecular and phenotypic characteristics of 21 MRSA collected from the residents and personnel in an NH (Lublin, Poland) during 2018. All MRSA were screened for 20 genes encoding virulence determinants (sea-see, eta, etb, tst, lukS-F-PV, eno, cna, ebpS, fib, bbp, fnbA, fnbB, icaADBC) and for resistance to 18 antimicrobials. To establish the relatedness and clonal complexes of MRSA in NH we applied multiple-locus variable-number tandem-repeat fingerprinting (MLVF), pulse field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec (SCCmec) typing. We identified four sequence types (ST) among two clonal complexes (CC): ST (CC22) known as EMRSA-15 as well as three novel STs—ST6295 (CC8), ST6293 (CC8) and ST6294. All tested MRSA were negative for sec, eta, etb, lukS-F-PV, bbp and ebpS genes. The most prevalent gene encoding toxin was sed (52.4%; n = 11/21), and adhesins were eno and fnbA (100%). Only 9.5% (n = 2/21) of MRSA were classified as multidrug-resistant. The emergence of novel MRSA with a unique virulence and the presence of epidemic clone EMRSA-15 creates challenges for controlling the spread of MRSA in NH.

scholarly journals Analysis of drug resistance and mutation profiles in Mycobacterium tuberculosis isolates in a surveillance site in Beijing, China

2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098493
Author(s):  
Jie Zhang ◽  
Yixuan Ren ◽  
Liping Pan ◽  
Junli Yi ◽  
Tong Guan ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Drug Testing ◽  
Multidrug Resistant ◽  
High Rate ◽  
Drug Resistant ◽  
Surveillance Site ◽  
Mdr Tb ◽  
Previously Treated Patients ◽  
Beijing China

Objective This study analyzed drug resistance and mutations profiles in Mycobacterium tuberculosis isolates in a surveillance site in Huairou District, Beijing, China. Methods The proportion method was used to assess drug resistance profiles for four first-line and seven second-line anti-tuberculosis (TB) drugs. Molecular line probe assays were used for the rapid detection of resistance to rifampicin (RIF) and isoniazid (INH). Results Among 235 strains of M. tuberculosis, 79 (33.6%) isolates were resistant to one or more drugs. The isolates included 18 monoresistant (7.7%), 19 polyresistant (8.1%), 28 RIF-resistant (11.9%), 24 multidrug-resistant (MDR) (10.2%), 7 pre-extensively drug-resistant (XDR, 3.0%), and 2 XDR strains (0.9%). A higher rate of MDR-TB was detected among previously treated patients than among patients with newly diagnosed TB (34.5% vs. 6.8%). The majority (62.5%) of RIF-resistant isolates exhibited a mutation at S531L in the DNA-dependent RNA polymerase gene. Meanwhile, 62.9% of INH-resistant isolates carried a mutation at S315T1 in the katG gene. Conclusion Our results confirmed the high rate of drug-resistant TB, especially MDR-TB, in Huairou District, Beijing, China. Therefore, detailed drug testing is crucial in the evaluation of MDR-TB treatment.

scholarly journals The Search for a Schistosomiasis Vaccine: Australia’s Contribution

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 872
Author(s):  
Donald P. McManus
Keyword(s):  
Public Health ◽  
Drug Resistance ◽  
Sub Saharan Africa ◽  
Effective Vaccine ◽  
Neglected Tropical Disease ◽  
Vaccine Research ◽  
Health Measures ◽  
Leading Role ◽  
Invaluable Tool ◽  
Sub Saharan

Schistosomiasis, a neglected tropical disease caused by parasitic flatworms of the genus Schistosoma, results in considerable human morbidity in sub-Saharan Africa, in particular, but also parts of the Middle East, South America, and Southeast Asia. The anti-schistosome drug praziquantel is efficacious and safe against the adult parasites of all Schistosoma species infecting humans; however, it does not prevent reinfection and the development of drug resistance is a constant concern. The need to develop an effective vaccine is of great importance if the health of many in the developing world is to be improved. Indeed, vaccination, in combination with other public health measures, can provide an invaluable tool to achieve lasting control, leading to schistosomiasis elimination. Australia has played a leading role in schistosomiasis vaccine research over many years and this review presents an overview of some of the significant contributions made by Australian scientists in this important area.

Global threat from drug resistant HIV in sub-Saharan Africa

BMJ ◽  
2012 ◽  
Vol 344 (jun18 1) ◽  
pp. e4159-e4159 ◽  
Author(s):  
R. L. Hamers ◽  
C. Kityo ◽  
J. M. A. Lange ◽  
T. F. R. d. Wit ◽  
P. Mugyenyi
Keyword(s):  
Sub Saharan Africa ◽  
Drug Resistant ◽  
Sub Saharan ◽  
Global Threat

scholarly journals Addressing Pediatric HIV Pretreatment Drug Resistance and Virologic Failure in Sub-Saharan Africa: A Cost-Effectiveness Analysis of Diagnostic-Based Strategies in Children ≥3 Years Old

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 567
Author(s):  
Mutita Siriruchatanon ◽  
Shan Liu ◽  
James G. Carlucci ◽  
Eva A. Enns ◽  
Horacio A. Duarte
Keyword(s):  
Drug Resistance ◽  
Cost Effectiveness ◽  
Virologic Failure ◽  
Pediatric Hiv ◽  
Sub Saharan Africa ◽  
Financial Investment ◽  
Switching Strategy ◽  
Wide Range ◽  
Sub Saharan ◽  
Living With Hiv

Improvement of antiretroviral therapy (ART) regimen switching practices and implementation of pretreatment drug resistance (PDR) testing are two potential approaches to improve health outcomes for children living with HIV. We developed a microsimulation model of disease progression and treatment focused on children with perinatally acquired HIV in sub-Saharan Africa who initiate ART at 3 years of age. We evaluated the cost-effectiveness of diagnostic-based strategies (improved switching and PDR testing), over a 10-year time horizon, in settings without and with pediatric dolutegravir (DTG) availability as first-line ART. The improved switching strategy increases the probability of switching to second-line ART when virologic failure is diagnosed through viral load testing. The PDR testing strategy involves a one-time PDR test prior to ART initiation to guide choice of initial regimen. When DTG is not available, PDR testing is dominated by the improved switching strategy, which has an incremental cost-effectiveness ratio (ICER) of USD 579/life-year gained (LY), relative to the status quo. If DTG is available, improved switching has a similar ICER (USD 591/LY) relative to the DTGstatus quo. Even when substantial financial investment is needed to achieve improved regimen switching practices, the improved switching strategy still has the potential to be cost-effective in a wide range of sub-Saharan African countries. Our analysis highlights the importance of strengthening existing laboratory monitoring systems to improve the health of children living with HIV.

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