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1.
J Infect Dev Ctries ; 18(4): 550-555, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38728649

ABSTRACT

INTRODUCTION: Pakistan has been experiencing an extensively drug-resistant (XDR) outbreak of typhoid for some years. We sought to evaluate how the COVID-19 pandemic impacted typhoid epidemiology in Pakistan, from the beginning of the pandemic in 2020 through the end of 2022, and the reduction of COVID-19 cases. METHODOLOGY: We compared national public COVID-19 data with retrospectively obtained patient data of confirmed S. Typhi isolates between January 2019 and December 2022 from Shaukat Khanum Memorial Cancer Hospital and Research Centre and the hospital's extended network of laboratory collection centers across Pakistan. RESULTS: We observed that during the early onset of the COVID-19 pandemic and COVID-19 peaks, typhoid positivity generally decreased. This suggests that restrictions and non-pharmaceutical interventions that limited social interactions and promoted good sanitation and hygiene practices had a positive secondary effect on typhoid. This led to an overall yearly decrease in typhoid positivity between 2019 to 2021. However, the percentage of S. Typhi cases isolated that were ceftriaxone-resistant continued to increase, suggesting the continued dominance of XDR typhoid in Pakistan. In 2022, with the alleviation of pandemic restrictions, we observed increased typhoid positivity and COVID-19 and typhoid positivity started to follow similar trends. CONCLUSIONS: Given the continued presence of COVID-19 along with XDR typhoid in Pakistan, it will be imperative to use differential testing to ensure that the epidemiology of each reported is accurate, the spread of each it contained, and that antibiotics are not misused. The use of approved vaccinations will lessen the burden of both diseases.


Subject(s)
COVID-19 , Salmonella typhi , Typhoid Fever , Typhoid Fever/epidemiology , Pakistan/epidemiology , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Salmonella typhi/drug effects , Salmonella typhi/isolation & purification , Retrospective Studies , SARS-CoV-2 , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology
2.
PLoS Negl Trop Dis ; 18(4): e0012132, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38630840

ABSTRACT

BACKGROUND: Typhoid fever is a common cause of febrile illness in low- and middle-income countries. While multidrug-resistant (MDR) Salmonella Typhi (S. Typhi) has spread globally, fluoroquinolone resistance has mainly affected Asia. METHODS: Consecutively, 1038 blood cultures were obtained from patients of all age groups with fever and/or suspicion of serious systemic infection admitted at Mnazi Mmoja Hospital, Zanzibar in 2015-2016. S. Typhi were analyzed with antimicrobial susceptibility testing and with short read (61 strains) and long read (9 strains) whole genome sequencing, including three S. Typhi strains isolated in a pilot study 2012-2013. RESULTS: Sixty-three S. Typhi isolates (98%) were MDR carrying blaTEM-1B, sul1 and sul2, dfrA7 and catA1 genes. Low-level ciprofloxacin resistance was detected in 69% (43/62), with a single gyrase mutation gyrA-D87G in 41 strains, and a single gyrA-S83F mutation in the non-MDR strain. All isolates were susceptible to ceftriaxone and azithromycin. All MDR isolates belonged to genotype 4.3.1 lineage I (4.3.1.1), with the antimicrobial resistance determinants located on a composite transposon integrated into the chromosome. Phylogenetically, the MDR subgroup with ciprofloxacin resistance clusters together with two external isolates. CONCLUSIONS: We report a high rate of MDR and low-level ciprofloxacin resistant S. Typhi circulating in Zanzibar, belonging to genotype 4.3.1.1, which is widespread in Southeast Asia and African countries and associated with low-level ciprofloxacin resistance. Few therapeutic options are available for treatment of typhoid fever in the study setting. Surveillance of the prevalence, spread and antimicrobial susceptibility of S. Typhi can guide treatment and control efforts.


Subject(s)
Anti-Bacterial Agents , Ciprofloxacin , Drug Resistance, Multiple, Bacterial , Genotype , Microbial Sensitivity Tests , Salmonella typhi , Typhoid Fever , Humans , Salmonella typhi/genetics , Salmonella typhi/drug effects , Salmonella typhi/isolation & purification , Salmonella typhi/classification , Ciprofloxacin/pharmacology , Drug Resistance, Multiple, Bacterial/genetics , Anti-Bacterial Agents/pharmacology , Typhoid Fever/microbiology , Typhoid Fever/epidemiology , Tanzania/epidemiology , Adolescent , Male , Child , Adult , Young Adult , Female , Child, Preschool , Whole Genome Sequencing , Middle Aged , Infant , Aged
3.
BMC Microbiol ; 23(1): 25, 2023 01 21.
Article in English | MEDLINE | ID: mdl-36681806

ABSTRACT

Typhoid fever is transmitted by ingestion of polluted water, contaminated food, and stool of typhoid-infected individuals, mostly in developing countries with poor hygienic environments. To find novel therapeutic targets and inhibitors, We employed a subtractive genomics strategy towards Salmonella Typhi and the complete genomes of eight strains were primarily subjected to the EDGAR tool to predict the core genome (n = 3207). Human non-homology (n = 2450) was followed by essential genes identification (n = 37). The STRING database predicted maximum protein-protein interactions, followed by cellular localization. The virulent/immunogenic ability of predicted genes were checked to differentiate drug and vaccine targets. Furthermore, the 3D models of the identified putative proteins encoded by the respective genes were constructed and subjected to druggability analyses where only "highly druggable" proteins were selected for molecular docking and simulation analyses. The putative targets ATP-dependent CLP protease proteolytic subunit, Imidazole glycerol phosphate synthase hisH, 7,8-dihydropteroate synthase folP and 2,3-bisphosphoglycerate-independent phosphoglycerate mutase gpmI were screened against a drug-like library (n = 12,000) and top hits were selected based on H-bonds, RMSD and energy scores. Finally, the ADMET properties for novel inhibitors ZINC19340748, ZINC09319798, ZINC00494142, ZINC32918650 were optimized followed by binding free energy (MM/PBSA) calculation for ligand-receptor complexes. The findings of this work are expected to aid in expediting the identification of novel protein targets and inhibitors in combating typhoid Salmonellosis, in addition to the already existing therapies.


Subject(s)
Anti-Bacterial Agents , Salmonella typhi , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Endopeptidase Clp , Genomics , Molecular Docking Simulation , Salmonella typhi/drug effects , Salmonella typhi/genetics , Typhoid Fever
4.
World J Microbiol Biotechnol ; 38(11): 190, 2022 Aug 16.
Article in English | MEDLINE | ID: mdl-35972699

ABSTRACT

Multi-drug resistance (MDR) in Salmonella is one of the major reasons for foodborne outbreaks worldwide. Decreased susceptibility of Salmonella Typhi to first-line drugs such as ceftriaxone, ciprofloxacin, and azithromycin has raised concern. Reduced outer membrane proteins (OMPs) permeability and increased efflux pump transportation are considered to be the main reasons for the emergence of antibiotic resistance in Salmonella. The present study aimed to assess the expression of OMPs at sub-lethal concentrations of ceftriaxone in S. Typhi (Sl5037/BC, and Sl05). The S. Typhi strains were exposed to sub-MIC and half of the sub-MIC concentrations of ceftriaxone at three different time intervals (0 min, 40 min, and 180 min) and analyzed for differential expression of OMPs. Further, the expression variation of OMP encoding genes (yaeT, ompX, lamb, ompA, and ybfM) in response to ceftriaxone was evaluated using real-time PCR. The genes like lamB, ompX, and yaeT showed significant downregulation (p < 0.05) compared to the control without antibiotic exposure, whereas ybfM and ompA showed a moderate downregulation. The expression of omp genes such as lamB, ompA, ompX, ybfM, and yaeT were found to be low in the presence of ceftriaxone, followed by time and dose-dependent. The study provides insights into the possible involvement of OMPs in drug resistance of S. Typhi, which could help develop a therapeutic strategy to combat MDR isolates of S. Typhi.


Subject(s)
Anti-Bacterial Agents , Bacterial Outer Membrane Proteins , Ceftriaxone , Salmonella typhi , Anti-Bacterial Agents/pharmacology , Bacterial Outer Membrane Proteins/metabolism , Ceftriaxone/pharmacology , Drug Resistance, Bacterial , Microbial Sensitivity Tests , Salmonella typhi/drug effects
5.
Clin Infect Dis ; 74(12): 2234-2237, 2022 07 06.
Article in English | MEDLINE | ID: mdl-34626469

ABSTRACT

We report the persistent circulation of third-generation cephalosporin resistant Salmonella Typhi in Mumbai, linked to the acquisition and maintenance of a previously characterized IncX3 plasmid carrying the ESBL gene blaSHV-12 and the fluoroquinolone resistance gene qnrB7 in the genetic context of a triple mutant also associated with fluoroquinolone resistance.


Subject(s)
Anti-Bacterial Agents , Drug Resistance, Bacterial , Salmonella typhi , Anti-Bacterial Agents/pharmacology , Cephalosporins/pharmacology , Fluoroquinolones , Humans , India/epidemiology , Microbial Sensitivity Tests , Salmonella typhi/drug effects , Salmonella typhi/genetics , beta-Lactamases/genetics
6.
Microb Drug Resist ; 28(1): 120-126, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34357814

ABSTRACT

Objective: To determine the molecular strain typing and drug resistance pattern of Salmonella enterica serovar Typhi prevalent in Northwest Pakistan. Methodology: A total of 2,138 blood samples of suspected typhoid patients from Northwest Pakistan were collected followed by identification of Salmonella Typhi through biochemical, serological, and species-specific fliC-d gene amplification. These isolates were typed by variable-number tandem repeat (VNTR) profiling and investigated for drug resistance. Results: The overall prevalence of Salmonella Typhi was found to be 8.8% (n = 189). Thirty different VNTR strain types of Salmonella Typhi were detected and the most prevalent strain types were T1 and T4, whereas T27 was less prevalent strain. Among the 189 isolates 175 (92.5%) isolates were multidrug resistant, whereas 12 (5.8%) isolates were extensively drug resistant. Resistance to imipenem in Salmonella Typhi was not observed. Most of the isolates have genes encoding for resistance to fluoroquinolones, including gyrA (n = 164), gyrB (n = 160), parC (n = 164), parE (n = 160), ac(6')-ib-cr (n = 163), qnrS (n = 15), and qnrB (n = 3). Similarly, chloramphinicol (cat; n = 147), azithromycin (msrA; n = 3), and co-trimoxazole (dfrA7; n = 145) resistance genes were detected among Salmonella Typhi isolates. Conclusion: In this study, T1 and T4 type Salmonella Typhi strains were predominantly prevalent in Northwest Pakistan. Antibiotic resistance among Salmonella Typhi isolates were observed. Findings of the study would be helpful to devise an appropriate antibiotic policy to control the emergence of drug-resistant Salmonella Typhi in Pakistan.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Multiple, Bacterial/genetics , Salmonella typhi/drug effects , Salmonella typhi/genetics , Cross Infection/genetics , Genes, Bacterial , Humans , Microbial Sensitivity Tests , Minisatellite Repeats , Molecular Typing , Pakistan , Tertiary Care Centers
7.
Pan Afr Med J ; 40: 58, 2021.
Article in English | MEDLINE | ID: mdl-34795837

ABSTRACT

INTRODUCTION: Marsdenia macrantha is a crucial source of traditional medicine in Northern Namibia. Its roots are used to treat various health conditions ranging from mouth infections to urinary retention. Despite its medicinal application, there is no known knowledge of its therapeutic properties. Thus, we investigated the phytochemical content and antibacterial activity of M. macrantha. METHODS: M. macrantha root extracts were obtained using three different solvents (distilled water, methanol and acetone) - in the soxhlet and maceration extraction methods. Total phytochemical (terpenoid, alkaloid and/or flavonoid) content was determined by spectrophotometry. Antibacterial activity against common foodborne pathogens (Staphylococcus aureus, Escherichia coli and Salmonella typhi) was determined by both well and disc diffusion method. RESULTS: we detected the presence of all the tested phytochemicals. Methanol gave the highest percentage yield of extraction (mean: 13.95 ± standard deviation: 0.41%) followed by water (10.92 ± 0.11%) and acetone (6.85 ± 0.23%), F-ratio=326.71 and p<0.0003. The total content determined showed that M. macrantha root extract contained more flavonoids than alkaloids (mg of standard per grams of the dry material). Antibacterial analyses showed inhibitory activity against all the selected pathogens, with the highest inhibition zone against S. typhi (19.7 ± 0.3 mm) - for the acetone-prepared root extract. There were variations in minimum inhibitory concentrations of the extracts prepared by the different solvents. CONCLUSION: this is the first study demonstrating the presence of phytochemicals and antibacterial properties of M. macrantha roots. Further studies are needed to isolate and characterize the phytochemicals for antibacterial application.


Subject(s)
Anti-Bacterial Agents/pharmacology , Marsdenia/chemistry , Plant Extracts/pharmacology , Alkaloids/isolation & purification , Alkaloids/pharmacology , Anti-Bacterial Agents/isolation & purification , Disk Diffusion Antimicrobial Tests , Escherichia coli/drug effects , Flavonoids/isolation & purification , Flavonoids/pharmacology , Microbial Sensitivity Tests , Phytochemicals/chemistry , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Extracts/chemistry , Plant Roots , Salmonella typhi/drug effects , Solvents/chemistry , Staphylococcus aureus/drug effects , Terpenes/isolation & purification , Terpenes/pharmacology
8.
Pak J Pharm Sci ; 34(3(Supplementary)): 1149-1156, 2021 May.
Article in English | MEDLINE | ID: mdl-34602445

ABSTRACT

As part of our continuous research to understand the interaction mechanism of drug and metallo-elements, heavy metal complexes of azithromycin (AZI) were synthesized with arsenic oxide, lead carbonate and silver chloride salts in molar ratio of 2: 1 (L: M). Synthesized heavy metal complexes have shown good percent yield and characterized through spectroscopic parameters including UV-Visible, TLC, FT-IR, NMR and elemental analysis (CHN). Spectroscopic characterization reveals the binding of ligand AZI with heavy metals in bi-dentate manner involving the hydroxide and 9a-NCH3 group of the aglycone ring of AZI. These newly synthesized heavy metal complexes were evaluated for their antimicrobial response against selected gram positive and gram negative organisms and antifungal species. It was noted that all newly synthesized complexes exhibits increased activity against B.subtilus whereas, AZI itself didn't show any activity, while synthesized complexes have low to moderate response against all the studied organisms. Complex A-M12 possess greater enzymatic response against both urease and alpha chymotrypsin among all the studied complexes. Results obtained were then statistically analyzed through one way ANOVA and Dunnett's test by using SPSS version 20.0 suggesting the significant response of complexes against selected organisms.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Arsenic Trioxide/pharmacology , Azithromycin/pharmacology , Carbonates/pharmacology , Coordination Complexes/pharmacology , Lead/pharmacology , Silver Compounds/pharmacology , Arsenic Trioxide/chemistry , Azithromycin/analogs & derivatives , Azithromycin/chemistry , Bacillus subtilis/drug effects , Candida albicans/drug effects , Carbonates/chemistry , Chymotrypsin/metabolism , Citrobacter/drug effects , Coordination Complexes/chemistry , Disk Diffusion Antimicrobial Tests , Enzyme Assays , Escherichia coli/drug effects , Klebsiella pneumoniae/drug effects , Lead/chemistry , Micrococcus luteus/drug effects , Proteus mirabilis/drug effects , Pseudomonas aeruginosa/drug effects , Salmonella typhi/drug effects , Shigella flexneri/drug effects , Silver Compounds/chemistry , Staphylococcus aureus/drug effects , Streptococcus/drug effects , Urease/metabolism
9.
Elife ; 102021 09 13.
Article in English | MEDLINE | ID: mdl-34515028

ABSTRACT

Background: Understanding the dynamics of infection and carriage of typhoid in endemic settings is critical to finding solutions to prevention and control. Methods: In a 3-year case-control study, we investigated typhoid among children aged <16 years (4670 febrile cases and 8549 age matched controls) living in an informal settlement, Nairobi, Kenya. Results: 148 S. Typhi isolates from cases and 95 from controls (stool culture) were identified; a carriage frequency of 1 %. Whole-genome sequencing showed 97% of cases and 88% of controls were genotype 4.3.1 (Haplotype 58), with the majority of each (76% and 88%) being multidrug-resistant strains in three sublineages of the H58 genotype (East Africa 1 (EA1), EA2, and EA3), with sequences from cases and carriers intermingled. Conclusions: The high rate of multidrug-resistant H58 S. Typhi, and the close phylogenetic relationships between cases and controls, provides evidence for the role of carriers as a reservoir for the community spread of typhoid in this setting. Funding: National Institutes of Health (R01AI099525); Wellcome Trust (106158/Z/14/Z); European Commission (TyphiNET No 845681); National Institute for Health Research (NIHR); Bill and Melinda Gates Foundation (OPP1175797).


Subject(s)
Anti-Bacterial Agents/pharmacology , Carrier State/microbiology , Drug Resistance, Multiple, Bacterial , Salmonella typhi/drug effects , Typhoid Fever/microbiology , Adolescent , Case-Control Studies , Child , Child, Preschool , Female , Humans , Infant , Kenya/epidemiology , Male , Phylogeny , Salmonella typhi/classification , Salmonella typhi/genetics , Salmonella typhi/isolation & purification , Typhoid Fever/drug therapy , Typhoid Fever/epidemiology
10.
J Infect Dis ; 224(12 Suppl 2): S788-S791, 2021 12 20.
Article in English | MEDLINE | ID: mdl-34528685

ABSTRACT

Typhoid is endemic in many countries in South Asia and sub-Saharan Africa. The high burden of this age-old, preventable disease exacerbates constraints on the health systems of these countries. Currently, most patients are treated effectively in the community or outpatient departments, but with rising antimicrobial resistance and the dearth of novel antimicrobials in the horizon, we risk losing our primary defense against typhoid. Extensively drug-resistant Salmonella Typhi is spreading, and azithromycin is the last oral drug to continue treating typhoid in the community. With increasing azithromycin resistance, emergence of pan-oral drug resistant Salmonella Typhi is imminent. The high burden of typhoid is also an underlying cause of the unnecessary use of antimicrobials. In addition to implementing water sanitation and hygiene interventions to prevent typhoid, it is imperative to rapidly roll out typhoid conjugate vaccines in endemic countries. This will not only reduce the burden of typhoid but will also help interrupt the trend of increasing antimicrobial resistance.


Subject(s)
Salmonella typhi/drug effects , Typhoid Fever/prevention & control , Typhoid-Paratyphoid Vaccines , Vaccines, Conjugate/administration & dosage , Drug Resistance, Bacterial/drug effects , Humans , Typhoid Fever/drug therapy
11.
PLoS Negl Trop Dis ; 15(9): e0009755, 2021 09.
Article in English | MEDLINE | ID: mdl-34529660

ABSTRACT

Little is known about the genetic diversity of Salmonella enterica serovar Typhi (S. Typhi) circulating in Latin America. It has been observed that typhoid fever is still endemic in this part of the world; however, a lack of standardized blood culture surveillance across Latin American makes estimating the true disease burden problematic. The Colombian National Health Service established a surveillance system for tracking bacterial pathogens, including S. Typhi, in 2006. Here, we characterized 77 representative Colombian S. Typhi isolates collected between 1997 and 2018 using pulse field gel electrophoresis (PFGE; the accepted genotyping method in Latin America) and whole genome sequencing (WGS). We found that the main S. Typhi clades circulating in Colombia were clades 2.5 and 3.5. Notably, the sequenced S. Typhi isolates from Colombia were closely related in a global phylogeny. Consequently, these data suggest that these are endemic clades circulating in Colombia. We found that AMR in S. Typhi in Colombia was uncommon, with a small subset of organisms exhibiting mutations associated with reduced susceptibility to fluoroquinolones. This is the first time that S. Typhi isolated from Colombia have been characterized by WGS, and after comparing these data with those generated using PFGE, we conclude that PFGE is unsuitable for tracking S. Typhi clones and mapping transmission. The genetic diversity of pathogens such as S. Typhi is limited in Latin America and should be targeted for future surveillance studies incorporating WGS.


Subject(s)
Salmonella typhi/genetics , Typhoid Fever/epidemiology , Typhoid Fever/microbiology , Anti-Bacterial Agents/pharmacology , Colombia/epidemiology , Drug Resistance, Bacterial/genetics , Population Surveillance , Salmonella typhi/drug effects
12.
PLoS One ; 16(9): e0257744, 2021.
Article in English | MEDLINE | ID: mdl-34582469

ABSTRACT

Sepsis is a syndromic response to infections and is becoming an emerging threat to the public health sector, particularly in developing countries. Salmonella Typhi (S. Typhi), the cause of typhoid fever, is one primary cause of pediatric sepsis in typhoid endemic areas. Extensively drug-resistant (XDR) S. Typhi is more common among pediatric patients, which is responsible for over 90% of the reported XDR typhoid cases, but the majority of antibiotic resistance studies available have been carried out using S. Typhi isolates from adult patients. Here, we characterized antibiotic-resistance profiles of XDR S. Typhi isolates from a medium size cohort of pediatric typhoid patients (n = 45, 68.89% male and 31.11% female) and determined antibiotic-resistance-related gene signatures associated with common treatment options to typhoid fever patients of 18 XDR S. Typhi representing all 45 isolates. Their ages were 1-13 years old: toddlers aging 1-2 years old (n = 9, 20%), pre-schoolers aging 3-5 years old (n = 17, 37.78%), school-age children aging 6-12 years old (n = 17, 37.78%), and adolescents aging 13-18 years old (n = 2, 4.44%). Through analyzing blaTEM1, dhfR7, sul1, and catA1genes for multidrug-resistance, qnrS, gyrA, gyrB, parC, and parE for fluoroquinolone-resistance, blaCTX-M-15 for XDR, and macAB and acrAB efflux pump system-associated genes, we showed the phenotype of the XDR S. Typhi isolates matches with their genotypes featured by the acquisitions of the genes blaTEM1, dhfR7, sul1, catA1, qnrS, and blaCTX-M-15 and a point mutation on gyrA. This study informs the molecular basis of antibiotic-resistance among recent S. Typhi isolates from pediatric septicemia patients, therefore providing insights into the development of molecular detection methods and treatment strategies for XDR S. Typhi.


Subject(s)
Bacterial Proteins/genetics , Drug Resistance, Multiple, Bacterial , Salmonella typhi/isolation & purification , Sepsis/microbiology , Typhoid Fever/diagnosis , Adolescent , Anti-Bacterial Agents/pharmacology , Child , Child, Preschool , Cohort Studies , Female , Humans , Infant , Male , Point Mutation , Salmonella typhi/drug effects , Salmonella typhi/genetics
13.
Infect Genet Evol ; 96: 105093, 2021 12.
Article in English | MEDLINE | ID: mdl-34592414

ABSTRACT

In view of widespread isolation of fluoroquinolone (FQ) resistant Salmonella enterica serovar Typhi globally, third generation cephalosporins (ceftriaxone) are used as alternative drugs for treatment of typhoid fever in recent years. But reports on emergence of third generation cephalosporin resistant S. Typhi have been documented from various countries including India posing threat in future use of this drug for typhoid treatment. Here, we report on genomic analysis of a third generation cephalosporin resistant S. Typhi strain isolated for the first time from Eastern India, Kolkata during 2019. The study strain was phenotypically resistant to ceftriaxone, ampicillin. Whole genome sequencing revealed the presence of conjugative IncX3 plasmid carrying blaSHV-12 gene on it. The study strain belongs to H58 haplotype (4.3.1.2) and ST1 type. Comparison of phylogenetic analysis of the study strain with other cephalosporin resistant S. Typhi strains across the world revealed that three strains isolated from Western part of India during 2016 were its closest neighbours. Hence close monitoring of cephalosporin resistant S. Typhi strains are of great importance to control the furure use of this antibiotic for the treatment of typhoid fever.


Subject(s)
Anti-Bacterial Agents/pharmacology , Ceftriaxone/pharmacology , Drug Resistance, Multiple, Bacterial/genetics , Salmonella typhi/genetics , Haplotypes , India , Microbial Sensitivity Tests , Phylogeny , Salmonella typhi/drug effects , Typhoid Fever/microbiology , Whole Genome Sequencing
14.
J Infect Dis ; 224(12 Suppl 2): S883-S889, 2021 12 20.
Article in English | MEDLINE | ID: mdl-34550365

ABSTRACT

Resistance to commonly available antimicrobials is a major threat to the fight against endemic bacterial diseases in sub-Saharan Africa, with a majority of the population unable to afford alternative effective antimicrobial options for management of these diseases. Diseases such as typhoid, cholera, and invasive nontyphoidal Salmonella are among the key enteric infections endemic in most parts of sub-Saharan Africa, especially in displaced populations and among the urban populations living in overcrowded informal settlements. Here, we explore the prevalence and the genomic epidemiology of these infections and the growing problem of multidrug resistance, including emerging resistance to the last line of treatment for these infections. Prevalence rates to commonly available antimicrobials, including ampicillin, chloramphenicol, cotrimoxazole, and tetracycline, now range between 65% and 80%, while 15%-20% of recently studied isolates show reduced susceptibility to fluoroquinolones and emerging resistance to extended-spectrum ß-lactams mediated by the CTX-M-15 gene carried on a highly mobile genetic element. The high prevalence of multidrug-resistant isolates including resistance to reserve antibiotics, calls for enhanced control and management options. It will be important for governments in the region to enhance the implementation of national action plans, as guided by the global action plan championed by the World Health Organization, to combat the threat of antimicrobial resistance. However, to yield meaningful results, these efforts will require a strong commitment and enhancement at all levels of healthcare in order. In addition, the use of World Health Organization-approved vaccines in the short to medium term and improvement of water and sanitation in the long term will reduce the burden of disease and antimicrobial resistance in the region.


Subject(s)
Anti-Bacterial Agents/pharmacology , Cholera/drug therapy , Drug Resistance, Bacterial/drug effects , Salmonella enterica/drug effects , Typhoid Fever/drug therapy , Anti-Bacterial Agents/therapeutic use , Cholera/epidemiology , Gastrointestinal Microbiome , Genomics , Humans , Kenya/epidemiology , Microbial Sensitivity Tests , Prevalence , Salmonella typhi/drug effects , Salmonella typhi/genetics , Typhoid Fever/epidemiology
15.
J Med Microbiol ; 70(8)2021 Aug.
Article in English | MEDLINE | ID: mdl-34356003

ABSTRACT

Introduction. Fluoroquinolone (FQ) resistant Salmonella are classified as high priority pathogens by WHO. FQ resistance among Salmonella Typhi has emerged rapidly and is predominantly mediated by mutations in the topoisomerase genes gyrA, and parC. Mutations in GyrA result in classical FQ resistance (DCS-NAR) i.e. decreased susceptibility to ciprofloxacin (MIC of 0.12 to 0.5 µg ml-1) (DCS) and resistance to nalidixic acid (NAR). Previously a nalidixic acid disc test was proposed for detection of DCS. Recently isolates with non-classical FQ resistance caused by plasmid-mediated quinolone resistance (PMQR) and mutations in GyrB have emerged. These mechanisms also result in DCS but are nalidixic acid susceptible (NAS) and thus pose diagnostic challenges. CLSI and EUCAST have recommended use of 5 µg pefloxacin discs for detection of DCS in Salmonella.Hypothesis. The CLSI and EUCAST recommendations for use of 5 µg pefloxacin for detection of DCS has not been validated on typhoidal Salmonella and resistance mediated by GyrB mutation in Salmonella species.Aim. The aim of the present study was to validate the performance of the 5 µg pefloxacin discs to detect isolates of S. Typhi with DCS with special reference to GyrB mutations.Methodology. A total of 180 clinical isolates of Salmonella Typhi (2005-2014) were investigated for genetic mechanisms of resistance. Zone diameters for nalidixic acid (30µg), ciprofloxacin (5µg) and pefloxacin (5µg) and minimum inhibitory concentration (MIC) for ciprofloxacin were determined using CLSI guidelines. Performance of the three discs was evaluated to detect FQ resistance in S. Typhi.Results. Topoisomerase mutations in GyrB +/ ParC and GyrB were detected in 112 and 34 isolates respectively. Different mutations have a varied effect on the MIC for ciprofloxacin. The current breakpoints for susceptible (≤0.06 µg ml-1) and non-susceptible (≥0.125 µg ml-1), failed to detect all isolates with a resistance mechanism. Performance of both ciprofloxacin and pefloxacin discs were excellent compared to nalidixic acid in differentiating isolates with non-classical resistance mediated by GyrB from wild-type.Conclusion. The pefloxacin disc can be used to detect FQ resistance among S. Typhi. This is the first report of validation of pefloxacin for detection of FQ resistance in S. Typhi mediated by GyrB mutation.


Subject(s)
DNA Gyrase/genetics , Drug Resistance, Bacterial/drug effects , Fluoroquinolones/pharmacology , Pefloxacin/pharmacology , Salmonella typhi/drug effects , Anti-Bacterial Agents/pharmacology , Ciprofloxacin/pharmacology , DNA Topoisomerase IV/genetics , Drug Resistance, Bacterial/genetics , Humans , Microbial Sensitivity Tests , Mutation , Nalidixic Acid/pharmacology , Salmonella typhi/genetics , Salmonella typhi/isolation & purification , Topoisomerase II Inhibitors/pharmacology , Typhoid Fever/microbiology
16.
Microb Genom ; 7(8)2021 08.
Article in English | MEDLINE | ID: mdl-34370659

ABSTRACT

The emergence of antimicrobial resistance (AMR) to first- and second-line treatment regimens of enteric fever is a global public-health problem, and routine genomic surveillance to inform clinical and public-health management guidance is essential. Here, we present the prospective analysis of genomic data to monitor trends in incidence, AMR and travel, and assess hierarchical clustering (HierCC) methodology of 1742 isolates of typhoidal salmonellae. Trend analysis of Salmonella Typhi and S. Paratyphi A cases per year increased 48 and 17.3%, respectively, between 2016 and 2019 in England, mainly associated with travel to South Asia. S. Paratyphi B cases have remained stable and are mainly associated with travel to the Middle East and South America. There has been an increase in the number of S. Typhi exhibiting a multidrug-resistant (MDR) profile and the emergence of extensively drug resistant (XDR) profiles. HierCC was a robust method to categorize clonal groups into clades and clusters associated with travel and AMR profiles. The majority of cases that had XDR S. Typhi reported recent travel to Pakistan (94 %) and belonged to a subpopulation of the 4.3.1 (H58) clone (HC5_1452). The phenotypic and genotypic AMR results showed high concordance for S. Typhi and S. Paratyphi A, B and C, with 99.99 % concordance and only three (0.01 %) discordant results out of a possible 23 178 isolate/antibiotic combinations. Genomic surveillance of enteric fever has shown the recent emergence and increase of MDR and XDR S. Typhi strains, resulting in a review of clinical guidelines to improve management of imported infections.


Subject(s)
Anti-Bacterial Agents , Phylogeny , Salmonella typhi/classification , Salmonella typhi/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/pharmacology , Child , Child, Preschool , Drug Resistance, Bacterial , England , Female , Genotype , Humans , Infant , Infant, Newborn , Male , Middle Aged , Middle East , Pakistan , Salmonella typhi/drug effects , Typhoid Fever/epidemiology , Typhoid Fever/microbiology , Young Adult
18.
Molecules ; 26(16)2021 Aug 15.
Article in English | MEDLINE | ID: mdl-34443531

ABSTRACT

The aim of the study was to determine the chemical profile, antioxidant properties and antimicrobial activities of Heterotrigona itama bee bread from Malaysia. The pH, presence of phytochemicals, antioxidant properties, total phenolic content (TPC) and total flavonoid content (TFC), as well as antimicrobial activities, were assessed. Results revealed a decrease in the pH of bee bread water extract (BBW) relative to bee bread ethanolic extract (BBE) and bee bread hot water extract (BBH). Further, alkaloids, flavonoids, phenols, tannins, saponins, terpenoids, resins, glycosides and xanthoproteins were detected in BBW, BBH and BBE. Also, significant decreases in TPC, TFC, DPPH activity and FRAP were detected in BBW relative to BBH and BBE. We detected phenolic acids such as gallic acid, caffeic acid, trans-ferulic acid, trans 3-hydroxycinnamic acid and 2-hydroxycinnamic acid, and flavonoids such as quercetin, kaempferol, apigenin and mangiferin in BBE using high-performance liquid chromatography analysis. The strongest antimicrobial activity was observed in Klebsilla pneumonia (MIC50 1.914 µg/mL), followed by E. coli (MIC50 1.923 µg/mL), Shigella (MIC50 1.813 µg/mL) and Salmonella typhi (MIC50 1.617 µg/mL). Bee bread samples possess antioxidant and antimicrobial properties. Bee bread contains phenolic acids and flavonoids, and could be beneficial in the management and treatment of metabolic diseases.


Subject(s)
Anti-Infective Agents/pharmacology , Antioxidants/pharmacology , Bees/chemistry , Propolis/pharmacology , Alkaloids/chemistry , Animals , Anti-Infective Agents/chemistry , Antioxidants/chemistry , Chromatography, High Pressure Liquid , Escherichia coli/drug effects , Escherichia coli/pathogenicity , Flavonoids/chemistry , Glycosides/chemistry , Hymenoptera/chemistry , Phenols/chemistry , Propolis/chemistry , Salmonella typhi/drug effects , Salmonella typhi/pathogenicity , Saponins/chemistry , Shigella/drug effects , Shigella/pathogenicity , Tannins/chemistry , Terpenes/chemistry
19.
J Infect Dis ; 224(12 Suppl 2): S775-S780, 2021 12 20.
Article in English | MEDLINE | ID: mdl-34453548

ABSTRACT

In 2016, a whole-genome sequence (WGS)-based genotyping framework (GenoTyphi) was developed and provided a phylogenetically informative nomenclature for lineages of Salmonella Typhi, the etiological agent of typhoid fever. Subsequent surveillance studies have revealed additional epidemiologically important subpopulations, which require the definition of new genotypes and extension of associated software to facilitate the detection of antimicrobial resistance (AMR) mutations. Analysis of 4632 WGS provide an updated overview of the global S Typhi population structure and genotyping framework, revealing the widespread nature of haplotype 58 ([H58] 4.3.1) genotypes and the diverse range of genotypes carrying AMR mutations.


Subject(s)
Drug Resistance, Bacterial/genetics , Salmonella typhi/genetics , Typhoid Fever/microbiology , Anti-Bacterial Agents/pharmacology , Genotype , Haplotypes , Humans , Phylogeny , Polymorphism, Single Nucleotide , Salmonella typhi/drug effects , Salmonella typhi/isolation & purification , Typhoid Fever/epidemiology , Whole Genome Sequencing
20.
Future Microbiol ; 16: 731-739, 2021 07.
Article in English | MEDLINE | ID: mdl-34236261

ABSTRACT

Aim: To determine the prevalence of multidrug (MDR) and extensively drug-resistant (XDR) pathogens from pediatric blood samples Methods: In total, 4543 children's blood samples were processed in the BacT/ALERT system. Confirmation of the isolates and MIC was determined in VITEK® 2 system. Molecular identification of blaIMP, blaVIM and blaOXA-48 was done by PCR. Results: Of 4543 blood cultures, 458 (10%) were positive for bacterial growth and Salmonella Typhi (415; 90%) remained the primary pathogens. Antibiogram revealed 208 (50.1%) and 137 (33%) were MDR and XDR S. Typhi, respectively. Klebsiella pneumoniae displayed 46% resistance to imipenem. One hundred twelve (81.7%) XDR Typhi were positive for blaCTXM, whereas 14 (66.6%) blaVIM were found in carbapenem-resistant bacteria. Conclusion: A high prevalence of MDR and XDR pathogens was found in peads blood culture.


Subject(s)
Drug Resistance, Multiple, Bacterial , Salmonella typhi/isolation & purification , Sepsis , Carbapenems/pharmacology , Child , Humans , Pakistan/epidemiology , Public Health , Salmonella typhi/drug effects , Sepsis/diagnosis , Sepsis/microbiology
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