Biology subjects

Ihekweazu, C.

Publications and source records attributed to Ihekweazu, C..

8 recordsLinked to original sources

bioRxiv2024

Whole genome Sequencing Reveals Enterobacter hormaechei as a key Bloodstream Pathogen in six tertiary care hospitals in southwestern Nigeria.

Enterobacter spp. are an important cause of healthcare-associated bloodstream infections uncommonly reported in Africa. This study used whole genome sequencing (WGS) to characterise Enterobacter spp. from hospitals in Nigerias antimicrobial resistance (AMR) surveillance system. Blood-culture isolates of Enterobacter from six such tertiary-care hospitals recovered between 2014 and 2020 were re-identified and antimicrobial susceptibility-tested using VITEK2. Illumina technology provided whole genome sequences for genome nomenclature, antimicrobial resistance gene prediction, Single Nucleotide Polymorphism (SNP) phylogeny, and multi-locus sequence typing via publicly available bioinformatics pipelines. Initial biochemical delineation often misclassified Enterobacter, necessitating whole-genome sequencing for accurate classification. Among 98 Enterobacter received, Enterobacter hormaechei subspecies xiangfangensis predominated (43), followed by other E. hormachei subspecies (18), E. cloacae (26), E. roggenkampii (4), E. bugandensis (3), E. kobei (2), E. asburiae (1) and E. cancerogenous (1). Cephalosporins, aminoglycoside, chloramphenicol, macrolide, and carbapenem resistance in E. hormaechei was attributed to known resistance genes. They belonged to clusters III, IV, and VIII based on hsp60 typing and clades A, B, C, and D according to Sutton and Cos nomenclature. These isolates and other Enterobacter species recently reported from Nigeria reveal extensive E. hormaechei diversity, as well as clusters representing potential outbreaks. Enterobacter hormaechei, often misidentified and rarely reported from Nigeria, is this studys most common blood culture isolated Enterobacter spp. Uncovering underappreciated species as important bloodstream pathogens and retrospective detection of likely outbreaks emphasise the value of genomic surveillance in resource-limited settings. DATA SUMMARYAll sequence reads were submitted to the European Nucleotide Archive (ENA) under the project ID PRJEB29739 (https://www.ebi.ac.uk/ena/browser/view/PRJEB29739). Accessions can be found in Table S1. IMPACT STATEMENTAccurate identification of Enterobacter is essential in healthcare settings as misidentification can lead to selecting antimicrobials to the genus is intrinsically resistant resistant before susceptibility testing results are available. Also, misidentification can compromise microbiology support for infection prevention and control. We show that E. hormaechei, which is never reported from clinical laboratories in Nigeria, is frequently misidentified using conventional methods like tube- or strip biochemical testing and VITEK systems. Whole genome sequence data demonstrates that E. hormaechei and E. cloacae are the most common Enterobacter isolated from bloodstream infections in Nigeria. Enhanced identification methods for surveillance play pivotal roles in improving patient care, optimising antibiotic stewardship, and combating the evolving challenges posed by this pathogen. Overall, this study reveals the effectiveness of WGS in correctly identifying this important pathogen.

microbiology↗

bioRxiv2024

Nationwide surveillance identifies yellow fever and chikungunya viruses transmitted by various species of Aedes mosquitoes in Nigeria

BackgroundSince its reemergence in 2017, yellow fever (YF) has been active in Nigeria. The Nigeria Centre for Disease Control (NCDC) has coordinated responses to the outbreaks with the support of the World Health Organization (WHO). The National Arbovirus and Vectors Research Centre (NAVRC) handles the vector component of these responses. This study sought to identify the vectors driving YF transmission and any of the targeted arboviruses and their distribution across states. MethodsEggs, larvae and pupae as well as adult mosquitoes were collected in observational, analytical, and cross-sectional surveys conducted in sixteen YF outbreak states between 2017 and 2020. Adult mosquitoes (field-collected or reared from immature stages) were morphologically identified, and arboviruses were detected using RT-qPCR at the African Centre of Excellence for Genomics of Infectious Diseases (ACEGID). ResultsAedes mosquitoes were collected in eleven of the sixteen states surveyed and the mosquitoes in nine states were found infected with arboviruses. A total of seven Aedes species were collected from different parts of the country. Aedes aegypti was the most dominant (51%) species, whereas Aedes africanus was the least (0.2%). Yellow fever virus (YFV) was discovered in 33 ([~]26%) out of the 127 Aedes mosquito pools. In addition to YFV, the Chikungunya virus (CHIKV) was found in nine pools. Except for Ae. africanus, all the Aedes species tested positive for at least one arbovirus. YFV-positive pools were found in six (6) Aedes species while CHIKV-positive pools were only recorded in two Aedes species. Edo State had the most positive pools (16), while Nasarawa, Imo, and Anambra states had the least (1 positive pool). Breteau and house indices were higher than normal transmission thresholds in all but one state. ConclusionIn Nigeria, there is a substantial risk of arbovirus transmission by Aedes mosquitoes, with YFV posing the largest threat at the moment. This risk is heightened by the fact that YFV and CHIKV have been detected in vectors across outbreak locations. Hence, there is an urgent need to step up arbovirus surveillance and control activities in the country. Author summaryEpidemics of arboviral infections are fast becoming the norm across Africa, especially in Nigeria, where sporadic epidemics of Aedes-borne Yellow Fever (YF) have been on the rise since 2017. A nationwide surveillance was conducted to detect the arboviruses and the vectors transmitting them during large YF outbreaks across Nigeria. Aedes mosquitoes collected from 57 local government areas/outbreak locations, covering 16 out of the 36 states in Nigeria, were reared to adulthood, morphologically identified to species level and assayed using qRT-PCR to detect six epidemiologically important arboviruses (Dengue, Chikungunya (CHIKV), Zika, YF, West Nile and Onyong nyong). Seven Aedes species (including Ae. aegypti, Ae. albopictus, Ae. circumluteolus, Ae. vittatus, Ae. simpsoni complex, Ae. luteocephalus, and Ae. africanus), were caught, with Ae. aegypti and Ae. albopictus the most widespread and predominant. Only YF and CHKV were found in mosquito pools from 9 states, with only Ae. aegypti pools positive for CHKV, while YF virus was found predominantly in this species and Ae. albopictus. This study provides a baseline for widespread distribution of the major Aedes vectors, and their arboviral transmission profiles, which can enhance evidence-based control measures, and strengthen nationwide surveillance systems to forestall future outbreaks of public health magnitude.

zoology↗

bioRxiv2023

Putative APOBEC3 deaminase editing in MPXV as evidence for sustained human transmission since at least 2016.

Mpox is often described as being endemic in West and Central Africa as a zoonotic disease that transmits through contact with the reservoir rodent host, likely a species of African squirrel. In May 2022, human cases of Mpox were detected spreading internationally beyond countries with known endemic reservoirs. At time of writing, 84,700 confirmed cases have been reported in 110 countries. When the first cases from 2022 were sequenced, it was seen that they shared 42 single nucleotide differences from the closest mpox virus (MPXV) genome sampled in 2018. This number of changes within 3-4 years is unexpectedly large and points to a much greater evolutionary rate than expected for a poxvirus. Strikingly, most nucleotide changes are of a specific type - a dinucleotide change from TC->TT or its reverse complement GA->AA. This mutation type is characteristic of the action of APOBEC3 deaminases; host-enzymes with reported antiviral function. Analysis of MPXV genomes sampled from 2017 to 2022 showed further evidence of TC->TT mutation pattern enrichment, with 93% of transmitted single nucleotide mutations since 2017 consistent with APOBEC3 editing. Assuming APOBEC-editing is characteristic of MPXV infection in human hosts, we propose an APOBEC clock that - at a rate of ~6 APOBEC3 mutations per year - estimates MPXV has been circulating in humans since 2016. This evolutionary pattern of host-enzyme editing has implications for the longer-term fitness of the virus in this epidemic as such mechanisms are primarily antiviral in function, but in the context of a poxvirus also provide a source of variation that may conceivably facilitate adaptation.

evolutionary biology↗

bioRxiv2023

High genetic diversity and blaNDM-1 prevalence among Acinetobacter baumannii in Nigerian hospitals

BackgroundAcinetobacter baumannii cause difficult-to-treat infections mostly among immunocompromised patients. Clinically relevant A. baumannii lineages and their carbapenem resistance mechanisms are sparsely described in Nigeria. ObjectiveThis study aimed to characterise the diversity and genetic mechanisms of carbapenem resistance among A. baumannii strains isolated from hospitals in southwestern Nigeria. MethodsWe sequenced the genomes of all A. baumannii isolates submitted to Nigerias antimicrobial resistance surveillance reference laboratory between 2016 - 2020 on an Illumina platform and performed in silico genomic characterisation. Selected strains were sequenced using the Oxford Nanopore technology to characterise the genetic context of carbapenem resistance genes. ResultsThe 86 A. baumannii isolates were phylogenetically diverse and belonged to 35 distinct sequence types (STs), 16 of which were novel. Thirty-eight (44.2%) isolates belonged to none of the known international clones (ICs). Over 50% of the isolates were phenotypically resistant to 10 of 12 tested antimicrobials. Majority (n=54) of the isolates were carbapenem-resistant, particularly the IC7 (100%) and IC9 (>91.7%) strains. blaOXA-23 (34.9%) and blaNDM-1 (27.9%) were the most common carbapenem resistance genes detected. All blaOXA-23 genes were carried on Tn2006 or Tn2006-like transposons. Our findings suggest that the mobilisation of a 10kb Tn125 composite transposon is the primary means of blaNDM-1 dissemination. ConclusionOur findings highlight an increase in blaNDM-1 prevalence and the widespread transposon-facilitated dissemination of carbapenemase genes in diverse A. baumannii lineages in southwestern Nigeria. We make the case for improving surveillance of these pathogens in Nigeria and other understudied settings. ImportanceAcinetobacter baumannii are increasingly clinically relevant due to their propensity to harbour genes conferring resistance to multiple antimicrobials, as well as their ability to persist and disseminate in hospital environments and cause difficult-to-treat nosocomial infections. Little is known about the molecular epidemiology and antimicrobial resistance profiles of these organisms in Nigeria, largely due to limited capacity for their isolation, identification, and antimicrobial susceptibility testing. Our study characterised the diversity and antimicrobial resistance profiles of clinical A. baumannii in southwestern Nigeria using whole-genome sequencing. We also identified the key genetic elements facilitating the dissemination of carbapenem resistance genes within this species. This study provides key insights into the clinical burden and population dynamics of A. baumannii in hospitals in Nigeria and highlights the importance of routine whole-genome sequencing-based surveillance of this and other previously understudied pathogens in Nigeria and other similar settings.

genomics↗

bioRxiv2023

Different Coexisting Mpox Lineages Were Continuously Circulating in Humans Prior to 2022

The origin and hazardous potential of human mpox is obscured by a lack of genomic data between the 2018, when exportations from Nigeria were recorded, and 2022 when the global outbreak started. Here, 18 genomes from patients across southern Nigeria in 2019/20 reveal multiple lineages of Monkeypox virus have achieved sustained human-to-human transmission, co-existing in humans for several years and accumulating mutations consistent with APOBEC3 activity suggesting the virus in humans is now segregated from its natural reservoir. Remarkably, three genomes have disruptions in the A46R gene, which contributes to innate immune modulation. The data demonstrates that the A.2 lineage, multiply exported to North America since 2021 independently of the global outbreak, has persisted in Nigeria for more than two years prior to its latest exportation. One-Sentence SummaryMpox is now a human diseae evolving in humans with multiple variants taking separate paths towards adaptation, some analogous to those of Variola

microbiology↗

bioRxiv2021

Clones and Clusters of Antimicrobial-Resistant Klebsiella from Southwestern Nigeria

IntroductionKlebsiella pneumoniae is a World Health Organization high-priority antibiotic-resistant pathogen. However, little is known about the population structure and evolution of Klebsiella circulating in Nigeria. MethodsWe performed whole genome sequencing (WGS) of 141 Klebsiella isolated between 2016 and 2018 from clinical specimens at 3 antimicrobial-resistance (AMR) sentinel surveillance tertiary hospitals in southwestern Nigeria. We conducted in silico multilocus sequence typing, AMR gene, virulence gene, plasmid, and K and O loci profiling, as well as phylogenetic analyses, using publicly available tools and Nextflow pipelines. ResultsPhylogenetic analysis revealed that the majority of the 134 K. pneumoniae and 5 K. quasipneumoniae isolates from Nigeria characterized are closely related to globally disseminated multidrug-resistant clones. Of the 39 K. pneumoniae sequence types (STs) identified, the most common were ST307 (15%), ST5241 (12%), ST15 (~9%), and ST25 (~6%). ST5241, one of 10 novel STs detected, is a single locus variant of ST636 carrying dfrA14, tetD, qnrS, and oqxAB resistance genes. The extended-spectrum {beta} lactamase (ESBL) gene blaCTX_M-15 was seen in 72 % of K. pneumoniae genomes, while 8% encoded a carbapenemase. Four likely outbreak clusters from one facility, within STs 17, 25, 307, and 5241, were ESBL but not carbapenemase-bearing clones. ConclusionThis study uncovered known and novel K. pneumoniae lineages circulating in Nigeria that include multidrug-resistant ESBL producers. Carbapenemase-producing isolates remain uncommon. WGS retrospectively identified outbreak clusters, pointing to the value of genomic approaches in AMR surveillance for improving infection prevention and control in Nigerian hospitals. summaryWe performed whole genome sequencing (WGS) of 141 Klebsiella isolated in 2016-2018 at 3 antimicrobial-resistance (AMR) sentinel surveillance tertiary hospitals in southwestern Nigeria. This study uncovered known and novel K. pneumoniae lineages circulating in Nigeria that include multidrug-resistant ESBL producers. FUNDINGThis work was supported by Official Development Assistance (ODA) funding from the National Institute of Health Research [16/136/111: NIHR Global Health Research Unit on Genomic Surveillance of Antimicrobial Resistance]. This research was commissioned by the National Institute of Health Research using Official Development Assistance (ODA) funding. INO is an African Research Leader supported by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement that is also part of the EDCTP2 program supported by the European Union. The funders had no role in the content, crafting or submission of this paper. The views expressed in this publication are those of the authors and not necessarily those of the funders or their affiliates. CONFLICT OF INTERESTThe authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

genomics↗

bioRxiv2019

Cholera in Internally Displaced Persons Camps in Borno State--Nigeria, 2017: A qualitative study of the multi-sectorial emergency response to stop the spread of the outbreak

Introduction/BackgroundIn August 2017, a cholera outbreak started in Muna Garage IDPs camp, Borno State-Nigeria, and >5000 cases occurred in six local government areas. This qualitative study evaluated perspectives about the emergency response to this outbreak.\n\nMethods/FindingsWe conducted 39 key informant interviews and focused group discussions, and reviewed 21 documents with participants involved with surveillance, water-sanitation-hygiene, case management, oral cholera vaccine, communications, logistics, and coordination. Qualitative data analysis used thematic techniques comprising key-words-in-context, word-repetition, and key-sector-terms.\n\nAuthorities were alerted quickly, but outbreak declaration took 12 days due to a 10 day delay waiting for culture confirmation. Outbreak investigation revealed several potential transmission channels, but a leaking latrine around the index cases house was not repaired for >7 days.\n\nUse of chlorine disinfectant was initially not accepted by the community due to rumors that it would sterilize women. This could have been avoided with improved community consultation. Initially, key messages were communicated in Hausa, although Kanuri was the primary language; later this was corrected. Planning would have benefited using exercise drills to identify weaknesses, and inventory sharing to avoid stock outs.\n\nThe response by the Rural Water Supply and Sanitation Agency was perceived to be slow and an increased risk from Eid El Jabir festival with increased movement and food sharing was not recognized. Case management was provided at treatment centers, but some partners were concerned that their work was recognized asking, \"who gets the glory and the data?\"\n\nOCV was provided to nearly one million people and it distribution benefited from a robust polio vaccine structure; however, logistical problems related to payment of staff needed resolution.\n\nInitial coordination was thought to be slow, but improved by activating an Emergency Operations Centre. The Borno Ministry of Health used an Incident Management System to coordinate multi-sectoral response activities.\n\nThese were informed by daily reviews of epi curves and geo-coordinate maps. The synergy between partners and government improved when each recognized the governments leadership role.\n\nConclusions/SignificanceDespite a timely alert of the outbreak, the delayed declaration led to a slowed initial response, but this improved during the course of the outbreak. OCV distribution was efficient and benefited from the OPV infrastructure. Improvements in laboratory capacity are urgently needed.\n\nAuthor SummaryIn August 2017, a cholera outbreak started in the Muna Garage Internally Displaced Persons (IPDs) camp in Borno State, Nigeria. By October, it appeared in six local government areas with a total of 5,340 cases reported including 61 deaths. We evaluated the perspectives of the emergency response by the government of Nigeria and implementing partners to stop the outbreak. We conducted 39 interviews and group discussions and also studied 21 documents related to the outbreak response. We found that epidemiologic surveillance timely alerted the health authorities about the outbreak, but the outbreak was declared 12 days later, awaiting for culture confirmation. This led to delays in the initial response. We also observed that conditions in the IDPs camps like overflowing latrines, overcrowding, and open defecation were highly favorable to cholera transmission. Improved IDP camp conditions are needed to prevent cholera and other water born infections and strengthened laboratory capacity is needed to enable a more rapid response.

epidemiology↗

bioRxiv2019

Real-time Metagenomic Analysis of Undiagnosed Fever Cases Unveils a Yellow Fever Outbreak in Edo State, Nigeria

We report here the use of metagenomic sequencing to identify and characterize yellow fever virus (YFV) in a cluster of undiagnosed febrile patients from Edo State, Nigeria. Yellow fever, an acute mosquito-borne viral haemorrhagic fever, re-emerged in Nigeria in 2017 after decades of relative control.1 Once a major public health concern in the region,2 the prolonged absence of yellow fever has left a gap in knowledge about circulating virus and lowered clinical suspicion for a disease whose spectrum overlaps with endemic infections (e.g., malaria and Lassa fever). In this context, metagenomic sequencing can be a powerful tool for identifying and tracking pathogens causing infectious disease.3\n\nPlasma samples from thirteen epidemiologically-linked patients with unexplained, often fatal, fever were sent from Irrua Specialist Teaching Hospital to the African Center of Excellence for Genomics of ...

genomics↗