Fluoroquinolone-resistant typhoid, South Africa.
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ABSTRACT:
SUBMITTER: Keddy KH
PROVIDER: S-EPMC2954527 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Typhoid fever is notifiable in South Africa but clinical notification is notoriously poor. South Africa has an estimated annual incidence rate of 0.1 cases per 100,000 population of culture-confirmed typhoid fever, decreased from 17 cases per 100,000 population in the 1980s. This work was undertaken to identify the reasons for this decrease and identify potential weaknesses that may result in an increase of observed cases. Culture-confirmed cases, with additional demographic and clinical data have been collected from selected sentinel sites since 2003. Data on contextual factors (gross domestic product [GDP], sanitation, female education, and childhood diarrhea mortality) were collected. National incidence rates of culture-confirmed typhoid fever have remained constant for the past 13 years, with the exception of an outbreak in 2005: incidence was 0.4 per 100,000 population. Paratyphoid fever remains a rare disease. Antimicrobial susceptibility data suggest resistance to ciprofloxacin and azithromycin is emerging. The South African population increased from 27.5 million in 1980 to 55.0 million in 2015: urbanization increased from 50% to 65%, GDP increased from United States Dollar (USD) $2,910 to USD $6,167, access to sanitation improved from 64.4% to 70.0% in the urban population and 26.4% to 60.5% in rural areas. Female literacy levels improved from 74.8% to 92.6% over the period. Improved socioeconomic circumstances in South Africa have been temporally associated with decreasing incidence rates of typhoid fever over a 35-year period. Ongoing challenges remain including potential for large outbreaks, a large immigrant population, and emerging antimicrobial resistance. Continued active surveillance is mandatory.
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Project description:Metagenomics analysis of sewage for surveillance of antimicrobial resistance in South Africa
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Project description:Fluoroquinolones came into widespread use in African countries in the early 2000s, after patents for the first generation of these drugs expired. By that time, quinolone antibacterial agents had been used intensively worldwide and resistant lineages of many bacterial species had evolved. We sought to understand which Gram negative enteric pandemic lineages have been reported from Africa, as well as the nature and transmission of any indigenous resistant clones. A systematic review of articles indexed in the Medline and AJOL literature databases was conducted. We report on the findings of 43 eligible studies documenting local or pandemic fluoroquinolone-resistant enteric clones in sub-Sahara African countries. Most reports are of invasive non-typhoidal Salmonella and Escherichia coli lineages and there have been three reports of cholera outbreaks caused by fluoroquinolone-resistant Vibrio cholerae O1. Fluoroquinolone-resistant clones have also been reported from commensals and animal isolates but there are few data for non-Enterobacteriaceae and almost none for difficult-to-culture Campylobacter spp. Fluoroquinolone-resistant lineages identified in African countries were universally resistant to multiple other classes of antibacterial agents. Although as many as 972 non-duplicate articles refer to fluoroquinolone resistance in enteric bacteria from Africa, most do not report on subtypes and therefore information on the epidemiology of fluoroquinolone-resistant clones is available from only a handful of countries in the subcontinent. When resistance is reported, resistance mechanisms and lineage information is rarely investigated. Insufficient attention has been given to molecular and sequence-based methods necessary for identifying and tracking resistant clones in Africa and more research is needed in this area.
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Project description:Resistance to fluoroquinolones (FQ) is being increasingly reported and found to be mediated by efflux pumps, plasmid-mediated quinolone resistance genes (PMQR) and mutations in gyrA, gyrB, parC and parE. However, studies reporting on FQ resistance mechanisms (FQRM), particularly in Africa, are focused mostly on Salmonella. This study used a whole-genome-based approach to describe FQRM in forty-eight clinical Enterobacteriaceae isolates comprising of Klebsiella pneumoniae (n = 21), Serratia marcescens (n = 12), Enterobacter spp. (n = 10), Citrobacter freundii (n = 3), Escherichia coli (n = 1), and Klebsiella michiganensis (n = 1) with reduced susceptibility to FQ in Enterobacteriaceae. All the isolates exhibited exceptionally high-level resistance (MIC of 4-512mg/L) to all three FQs, which could not be reversed by carbonyl cyanide m-chlorophenyl hydrazine (CCCP), verapamil (VRP) or reserpine (RSP). PMQR genes such as oqxAB (n = 43), aac(6')-Ib-cr (n = 28), and qnr(S1, B1, B2, B9, B49, B66) (n = 23) were identified without transposons or integrons in their immediate environments. Multiple and diverse mutations were found in gyrA (including S83I/Y and T/I83I/T), gyrB, parC and parE, which were clonally specific. There were vertical and horizontal transmission of high-level FQ resistance in Enterobacteriaceae in hospitals in Durban, South Africa, which are mediated by efflux, PMQR genes, and gyrA, gyrB, parC and parE mutations.
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Project description:There is paucity of data regarding the geographical distribution, incidence, and phylogenetics of multi-drug resistant (MDR) Salmonella Typhi in sub-Saharan Africa. Here we present a phylogenetic reconstruction of whole genome sequenced 249 contemporaneous S. Typhi isolated between 2008-2015 in 11 sub-Saharan African countries, in context of the 2,057 global S. Typhi genomic framework. Despite the broad genetic diversity, the majority of organisms (225/249; 90%) belong to only three genotypes, 4.3.1 (H58) (99/249; 40%), 3.1.1 (97/249; 39%), and 2.3.2 (29/249; 12%). Genotypes 4.3.1 and 3.1.1 are confined within East and West Africa, respectively. MDR phenotype is found in over 50% of organisms restricted within these dominant genotypes. High incidences of MDR S. Typhi are calculated in locations with a high burden of typhoid, specifically in children aged <15 years. Antimicrobial stewardship, MDR surveillance, and the introduction of typhoid conjugate vaccines will be critical for the control of MDR typhoid in Africa.
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Project description:Wide-ranging evidence on the occurrence of fluoroquinolone (FQ) resistance genetic determinants in African Salmonella strains is not available. The main objectives of this study were to assess the heterogeneity, estimate pooled proportions and describe the preponderance of FQ-resistance determinants in typhoidal and non-typhoidal Salmonella (NTS) isolates of Africa.Genetic and phenotypic data on 6103 Salmonella isolates were considered. Meta- and frequency analyses were performed depending on the number of studies by category, number of isolates and risks of bias. A random effects model was used to assess heterogeneity and estimate pooled proportions. Relative and cumulative frequencies were calculated to describe the overall preponderance of FQ-resistance determinants in quinolone resistant isolates.The pooled proportion of gyrA mutants (Salmonella enterica serovar Typhi, Salmonella enterica serovar Typhimurium, and Salmonella enterica serovar Enteritidis) was estimated at 5.7% (95% Confidence interval (CI) = 2.6, 9.8; Tau squared (T2) = 0.1105), and was higher in S. Typhi than in S. Typhimurium (odds ratio (OR) = 3.3, 95%CI = 2, 5.7). The proportions of each of gyrB and parC mutants, and strains with Plasmid Mediated Quinolone Resistance genes (qnrA, qnrB and qnrS) were low (? 0.3%). Overall, 23 mutant serotypes were identified, and most strains had mutations at codons encoding Ser83 and Asp87 of gyrA (82%, 95%CI = 78, 86).Mutations at gyrA appear to account for ciprofloxacin non-susceptibility in most clinical Salmonella strains in Africa. The estimates could be harnessed to develop a mismatch-amplification mutation-assay for the detection of FQ-resistant strains in Africa.
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