-
International Journal For Parasitology.... Apr 2021Artemisinin-based combination therapies (ACT) are currently used as a first-line malaria therapy in endemic countries worldwide. This systematic review aims at... (Review)
Review
Artemisinin-based combination therapy (ACT) and drug resistance molecular markers: A systematic review of clinical studies from two malaria endemic regions - India and sub-Saharan Africa.
Artemisinin-based combination therapies (ACT) are currently used as a first-line malaria therapy in endemic countries worldwide. This systematic review aims at presenting the current scenario of drug resistance molecular markers, either selected or involved in treatment failures (TF) during in vivo ACT efficacy studies from sub-Saharan Africa (sSA) and India. Eight electronic databases were comprehensively used to search relevant articles and finally a total of 28 studies were included in the review, 21 from sSA and seven from India. On analysis, Artemether + lumefantrine (AL) and artesunate + sulfadoxine-pyrimethamine (AS + SP) are the main ACT in African and Indian regions with a 28-day efficacy range of 54.3-100% for AL and 63-100% for AS + SP respectively. It was observed that mutations in the Pfcrt (76T), Pfdhfr (51I, 59R, 108N), Pfdhps (437G) and Pfmdr1 (86Y, 184F, 1246Y) genes were involved in TF, which varied with respect to ACTs. Based on studies that have genotyped the Pfk13 gene, the reported TF cases, were mainly linked with mutations in genes associated with resistance to ACT partner drugs; indicating that the protection of the partner drug efficacy is crucial for maintaining the efficacy of ACT. This review reveals that ACT are largely efficacious in India and sSA despite the fact that some clinical efficacy and epidemiological studies have reported some validated mutations (i.e., 476I, 539T and 561H) in circulation in these two regions. Also, the role of PfATPase6 in ART resistance is controversial still, while P. falciparum plasmepsin 2 (Pfpm2) in piperaquine (PPQ) resistance and dihydroartemisinin (DHA) + PPQ failures is well documented in Southeast Asian countries but studied less in sSA. Hence, there is a need for continuous molecular surveillance of Pfk13 mutations for emergence of artemisinin (ART) resistance in these countries.
Topics: Africa South of the Sahara; Antimalarials; Artemisinins; Drug Resistance; Humans; Malaria; Malaria, Falciparum; Plasmodium falciparum
PubMed: 33556786
DOI: 10.1016/j.ijpddr.2020.11.006 -
Journal of Global Antimicrobial... Sep 2021Globally, the incidence and mortality of tuberculosis (TB) are declining; however, low detection of drug-resistant disease threatens to reverse current progress toward... (Meta-Analysis)
Meta-Analysis Review
Prevalence of drug resistance-conferring mutations associated with isoniazid- and rifampicin-resistant Mycobacterium tuberculosis in Ethiopia: a systematic review and meta-analysis.
OBJECTIVES
Globally, the incidence and mortality of tuberculosis (TB) are declining; however, low detection of drug-resistant disease threatens to reverse current progress toward global TB control. Multiple rapid molecular diagnostic tests have recently been developed to detect genetic mutations in Mycobacterium tuberculosis (Mtb) known to confer drug resistance. However, their utility depends on the frequency and distribution of resistance-associated mutations in the pathogen population. This review aimed to assess the prevalence of gene mutations associated with rifampicin (RIF)- and isoniazid (INH)-resistant Mtb in Ethiopia.
METHODS
We searched the literature in PubMed/MEDLINE, Web of Science, Scopus and Cochrane Library. Data analysis was conducted in Stata 11.
RESULTS
Totally, 909 (95.8%) of 949 INH-resistant Mtb isolates had detectable gene mutations: 95.8% in katG315 and 5.9% in the inhA promoter region. Meta-analysis resulted in an estimated pooled prevalence of katGMUT1(S315T1) of 89.2% (95% CI 81.94-96.43%) and a pooled prevalence of inhAMUT1(C15T) of 77.5% (95% CI 57.84-97.13%). Moreover, 769 (90.8%) of 847 RIF-resistant strains had detectable rpoB gene mutations. Meta-analysis resulted in a pooled prevalence of rpoBMUT3(S531L) of 74.2% (95% CI 66.39-82.00%).
CONCLUSION
RIF-resistant Mtb were widespread, particularly those harbouring rpoB(S531L) mutation. Similarly, INH-resistant Mtb with katG(S315T1) and inhA(C15T) mutations were common. Tracking S531L, S315T1 and C15T mutations among RIF- and INH-resistant isolates, respectively, would be diagnostically and epidemiologically valuable. Rapid diagnosis of RIF- and INH-resistant Mtb would expedite modification of TB treatment regimens, and proper timely infection control interventions could reduce the risk of development and transmission of multidrug-resistant TB.
Topics: Drug Resistance; Ethiopia; Humans; Isoniazid; Microbial Sensitivity Tests; Mutation; Mycobacterium tuberculosis; Prevalence; Rifampin; Tuberculosis, Multidrug-Resistant
PubMed: 34214698
DOI: 10.1016/j.jgar.2021.06.009 -
Malaria Journal Apr 2017Parasite resistance to anti-malarials represents a great obstacle for malaria elimination. The majority of studies have investigated the association between... (Review)
Review
Assessment of copy number variation in genes related to drug resistance in Plasmodium vivax and Plasmodium falciparum isolates from the Brazilian Amazon and a systematic review of the literature.
BACKGROUND
Parasite resistance to anti-malarials represents a great obstacle for malaria elimination. The majority of studies have investigated the association between single-nucleotide polymorphisms (SNPs) and drug resistance; however, it is becoming clear that the copy number variation (CNV) is also associated with this parasite phenotype. To provide a baseline for molecular surveillance of anti-malarial drug resistance in the Brazilian Amazon, the present study characterized the genetic profile of both markers in the most common genes associated with drug resistance in Plasmodium falciparum and Plasmodium vivax isolates. Additionally, these data were compared to data published elsewhere applying a systematic review of the literature published over a 20-year time period.
METHODS
The genomic DNA of 67 patients infected by P. falciparum and P. vivax from three Brazilian States was obtained between 2002 and 2012. CNV in P. falciparum multidrug resistance gene-1 (pfmdr1), GTP cyclohydrolase 1 (pfgch1) and P. vivax multidrug resistance gene-1 (pvmdr1) were assessed by real-time PCR assays. SNPs in the pfmdr1 and pfcrt genes were assessed by PCR-RFLP. A literature search for studies that analysed CNP in the same genes of P. falciparum and P. vivax was conducted between May 2014 and March 2017 across four databases.
RESULTS
All analysed samples of P. falciparum carried only one copy of pfmdr1 or pfgch1. Although the pfcrt K76T polymorphism, a determinant of CQ resistance, was present in all samples genotyped, the pfmdr1 N86Y was absent. For P. vivax isolates, an amplification rate of 20% was found for the pvmdr1 gene. The results of the study are in agreement with the low amplification rates for pfmdr1 gene evidenced in the Americas and Africa, while higher rates have been described in Southeast Asia. For P. vivax, very low rates of amplification for pvmdr1 have been described worldwide, with exceptions in French Guiana, Cambodia, Thailand and Brazil.
CONCLUSIONS
The present study was the first to evaluate gch1 CNV in P. falciparum isolates from Brazil, showing an absence of amplification of this gene more than 20 years after the withdrawal of the Brazilian antifolates therapeutic scheme. Furthermore, the rate of pvmdr1 amplification was significantly higher than that previously reported for isolates circulating in Northern Brazil.
Topics: Adult; Brazil; Drug Resistance; Female; Gene Dosage; Gene Frequency; Humans; Male; Middle Aged; Plasmodium falciparum; Plasmodium vivax; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Protozoan Proteins; Real-Time Polymerase Chain Reaction
PubMed: 28420389
DOI: 10.1186/s12936-017-1806-z -
Journal of Applied Microbiology Jan 2022The emergence of polymyxin resistance, due to transferable mcr genes, threatens public and animal health as there are limited therapeutic options. As polymyxin is one of... (Review)
Review
The emergence of polymyxin resistance, due to transferable mcr genes, threatens public and animal health as there are limited therapeutic options. As polymyxin is one of the last-line antibiotics, there is a need to contain the spread of its resistance to conserve its efficacy. Herein, we describe current and emerging polymyxin resistance diagnostics to inform faster clinical diagnostic choices. A literature search in diverse databases for studies published between 2016 and 2020 was performed. English articles evaluating colistin resistance methods/diagnostics were included. Screening resulted in the inclusion of 93 journal articles. Current colistin resistance diagnostics are either phenotypic or molecular. Broth microdilution is currently the only gold standard for determining colistin MICs (minimum inhibitory concentration). Phenotypic methods comprise of agar-based methods such as CHROMagar™ Col-APSE, SuperPolymyxin, ChromID Colistin R, LBJMR and LB medium; manual MIC-determiners viz., UMIC, MICRONAUT MIC-Strip and ComASP Colistin; automated antimicrobial susceptibility testing systems such as BD Phoenix, MICRONAUT-S, MicroScan, Sensititre and Vitek 2; MCR-detectors such as lateral flow immunoassay (LFI) and chelator-based assays including EDTA- and DPA-based tests, that is, combined disk test, modified colistin broth-disk elution (CBDE), Colispot, and Colistin MAC test as well as biochemical colorimetric tests, that is, Rapid Polymyxin NP test and Rapid ResaPolymyxin NP test. Molecular methods only characterize mobile colistin resistance; they include PCR, LAMP and whole-genome sequencing. Due to the faster turnaround time (≤3 h), improved sensitivity (84%-100%) and specificity (93.3%-100%) of the Rapid ResaPolymyxin NP test and Fastinov , we recommend this test for initial screening of colistin-resistant isolates. This can be followed by CBDE with EDTA or the LFI as they both have 100% sensitivity and a specificity of ≥94.3% for the rapid screening of mcr genes. However, molecular assays such as LAMP and PCR may be considered in well-equipped clinical laboratories.
Topics: Animals; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Laboratories, Clinical; Microbial Sensitivity Tests; Polymyxins
PubMed: 34152057
DOI: 10.1111/jam.15184 -
Parasitology Research Oct 2022A plethora of studies analyse the molecular markers of drug resistance and hence help in guiding the evidence-based malaria treatment policies in India. For reporting... (Review)
Review
A plethora of studies analyse the molecular markers of drug resistance and hence help in guiding the evidence-based malaria treatment policies in India. For reporting mutations, a number of techniques including DNA sequencing, restriction-fragment length polymorphism and mutation-specific polymerase chain reaction have been employed across numerous studies, including variations in the methodology used. However, there is no sufficient data from India comparing these methods as well as report the prevalence of polymorphisms in SP drug resistance molecular markers independently using such methods. Therefore, all data from Indian studies available for molecular marker studies of Plasmodium falciparum drug resistance to sulphadoxine-pyrimethamine was gathered, and a systematic review was performed. This systematic review identifies the molecular methods in use in India and compares each method for detecting sulphadoxine-pyrimethamine drug resistance marker. To delay the spread of drug-resistant parasite strains, a simplified and standardized molecular method is much needed which can be obtained by analysing the performance of each method in use and answering the necessity of newer methodological approaches.
Topics: Antimalarials; Drug Combinations; Drug Resistance; Humans; India; Malaria, Falciparum; Plasmodium falciparum; Pyrimethamine; Sulfadoxine
PubMed: 35980472
DOI: 10.1007/s00436-022-07623-3 -
AIDS Reviews 2011Antiretroviral therapy is being rapidly scaled-up in Western Pacific region countries. Prevention and assessment of HIV drug resistance is an essential component of... (Review)
Review
Antiretroviral therapy is being rapidly scaled-up in Western Pacific region countries. Prevention and assessment of HIV drug resistance is an essential component of successful global antiretroviral therapy scale-up. We performed a systematic review of public health surveys and HIV drug resistance studies conducted in the low- and middle-income countries in the Western Pacific region. A total of 38 publications assessing HIV drug resistance were reviewed. Studies assessing transmitted drug resistance in recently infected individuals or drug resistance among individuals starting antiretroviral therapy found low rates of HIV drug resistance. Assessments of HIV drug resistance emerging in populations receiving antiretroviral therapy demonstrated variable rates of drug resistance, but suggest an urgent need to support antiretroviral therapy adherence and retention in care, ensure the use of quality assured drugs, and guarantee continuous drug supplies. Additionally, programmatic assessment informed by routine standardized surveillance of transmitted and acquired HIV drug resistance is essential to optimize antiretroviral therapy delivery in the Western Pacific region.
Topics: Anti-HIV Agents; Developing Countries; Drug Resistance, Viral; HIV Infections; HIV-1; Humans; Public Health
PubMed: 21975357
DOI: No ID Found -
PloS One 2023Antimicrobial resistance (AMR) is a silent pandemic that has claimed millions of lives, and resulted in long-term disabilities, limited treatment options, and high... (Meta-Analysis)
Meta-Analysis
A systematic review and meta-analysis of antimicrobial resistance knowledge, attitudes, and practices: Current evidence to build a strong national antimicrobial drug resistance narrative in Ethiopia.
Antimicrobial resistance (AMR) is a silent pandemic that has claimed millions of lives, and resulted in long-term disabilities, limited treatment options, and high economic costs associated with the healthcare burden. Given the rising prevalence of AMR, which is expected to pose a challenge to current empirical antibiotic treatment strategies, we sought to summarize the available data on knowledge, attitudes, and practices regarding AMR in Ethiopia. Articles were searched in international electronic databases. Microsoft Excel spreadsheet and STATA software version 16 were used for data extraction and analysis, respectively. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 checklist was followed. The methodological quality of the studies included was assessed by the Joana Briggs Institute critical appraisal checklists. The random-effect meta-analysis model was used to estimate Der Simonian-Laird's pooled effect. Statistical heterogeneity of the meta-analysis was checked through Higgins and Thompson's I2 statistics and Cochran's Q test. Publication bias was investigated by funnel plots, and the regression-based test of Egger for small study effects with a P value < 0.05 was considered to indicate potential reporting bias. In addition, sensitivity and subgroup meta-analyses were performed. Fourteen studies with a total of 4476 participants met the inclusion criteria. Overall, the pooled prevalence of good AMR knowledge was 51.53% [(95% confidence interval (CI): 37.85, 65.21), I2 = 99.0%, P <0.001]. The pooled prevalence of favorable attitudes and good practices were 63.43% [(95% CI: 42.66, 84.20), I2 = 99.6, P <0.001], and 48.85% [(95% CI: 38.68, 59.01), I2 = 93.1, P <0.001] respectively. In conclusion, there is a significant knowledge and practice gap on AMR among the general public, patients, and livestock producers. As a result, we call for greater educational interventions to raise awareness and build a strong national AMR narrative.
Topics: Humans; Anti-Bacterial Agents; Ethiopia; Health Knowledge, Attitudes, Practice; Drug Resistance, Bacterial; Prevalence
PubMed: 37294747
DOI: 10.1371/journal.pone.0287042 -
AIDS Reviews 2020The continuous rising of HIV drug resistance in low- and middle-income countries and its impact on treatment failure is a growing threat for the HIV treatment response....
The continuous rising of HIV drug resistance in low- and middle-income countries and its impact on treatment failure is a growing threat for the HIV treatment response. This review aimed to document pre-antiretroviral therapy (ART) CD4 counts, emerging drug resistance, and treatment failure in HIV-infected individuals initiating ART. We performed an online search in PubMed, Embase, Web of Science, African Index Medicus, Cochrane library, and The National Institute for Health Clinical Trials Registry of relevant articles published from January 1996 to June 2019. Of 1755 original studies retrieved, 28 were retained for final analysis. Treatment failure varied between 5% (95% confidence interval [CI]: 2.7-7.4) and 72% (95% CI: 55-89.6), while resistance varied between 1% (95% CI: 0.47-1.5) and 48% (95% CI: 28.4-67.6). Participants with a pre-ART CD4 count below 200 cell/μl and low adherence showed higher percentages of resistance and failure, while those with CD4 count above 200 showed lower resistance and failure regardless adherence levels. Most frequent resistance mutations included the M184I/V for the nucleoside reverse-transcriptase inhibitors (NRTIs), K103N, and Y181 for the non-NRTIs (NNRTIs), and L90M for the Protease inhibitors. Pre-ART CD4 count and adherence to treatment could play a key role in reducing drug resistance and treatment failure. The increased access to ART in resources limited settings should be accompanied by regular CD4 count testing, drug resistance monitoring, and continuous promotion of adherence. In addition, the rising of resistance mutations associated with NRTIs and NNRTIs, suggest that alternative ART regimens should be considered. (AIDS Rev. 2020;22:
-0). Topics: Anti-HIV Agents; CD4 Lymphocyte Count; Drug Resistance, Viral; HIV Infections; Humans; Risk Factors; Treatment Failure
PubMed: 32655148
DOI: 10.24875/AIDSRev.20000012 -
Microbial Drug Resistance (Larchmont,... Jun 2018This study critically reviewed the published literature and performed a meta-analysis to determine the overall burden of antibiotic-resistant bacteria in food animals in... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This study critically reviewed the published literature and performed a meta-analysis to determine the overall burden of antibiotic-resistant bacteria in food animals in Africa.
METHODS
English and French published articles indexed in EBSCOhost, PubMed, Web of Science, and African Journals Online were retrieved, with searches being conducted up to August, 2015. Data were pooled and meta-analysis performed using a random-effects model, and the results are described as event rates.
RESULTS
According to the predefined inclusion and exclusion criteria, 17 articles out of the 852 retrieved were eligible for the qualitative and quantitative analysis. The studies included were mainly conducted in Nigeria, with Escherichia coli, Salmonella spp., and Campylobacter spp. being the main bacteria. The pooled estimates showed high level of antibiotic resistance (ABR) (86%; p < 0.001) and multidrug resistance (73%; p = 0.003).
CONCLUSION
Our results suggest that ABR is substantively prevalent and poses a serious threat for food safety and security in Africa. These findings shed light on areas for future research concerning antibiotic-resistant and multidrug-resistant bacteria in food animals as etiological agents of infectious diseases in humans. They further yielded some interesting findings on the burden of ABR that could be useful in developing measures to contain this threat in the farm-to-plate continuum in Africa.
Topics: Africa; Animals; Anti-Bacterial Agents; Bacteria; Drug Resistance, Bacterial; Humans
PubMed: 29683779
DOI: 10.1089/mdr.2017.0383 -
The Science of the Total Environment Jul 2021Antibiotics and antibiotic resistance genes (ARGs) are prevalent in estuarine and coastal environments due to substantial terrestrial input, aquaculture effluent, and... (Review)
Review
Antibiotics and antibiotic resistance genes (ARGs) are prevalent in estuarine and coastal environments due to substantial terrestrial input, aquaculture effluent, and sewage discharge. In this article, based on peer-reviewed papers, the sources, spatial patterns, driving factors, and environmental implications of antibiotics and ARGs in global estuarine and coastal environments are discussed. Riverine runoff, WWTPs, sewage discharge, and aquaculture, are responsible for the prevalence of antibiotics and ARGs. Geographically, pollution due to antibiotics in low- and middle-income countries is higher than that in high-income countries, and ARGs show remarkable latitudinal variations. The distribution of antibiotics is driven by antibiotic usage and environmental variables (heavy metals, nutrients, organic pollutants, etc.), while ARGs are affected by antibiotics residues, environmental variables, microbial communities, and mobile genetic elements (MGEs). Antibiotics and ARGs alter microbial communities and biogeochemical cycles, as well as pose threats to marine organisms and human health. Our results provide comprehensive insights into the transport and environmental behaviors of antibiotics and ARGs in global estuarine and coastal environments.
Topics: Anti-Bacterial Agents; Drug Resistance, Microbial; Genes, Bacterial; Humans; Metals, Heavy; Sewage
PubMed: 33676219
DOI: 10.1016/j.scitotenv.2021.146009