Comparison of bacterial culture with BioFire® FilmArray® multiplex PCR screening of archived cerebrospinal fluid specimens from children with suspected bacterial meningitis in Nigeria.

BACKGROUND: Diagnosis of bacterial meningitis remains a challenge in most developing countries due to low yield from bacterial culture, widespread use of non-prescription antibiotics, and weak microbiology laboratories. The objective of this study was to compare the yield from standard bacterial culture with the multiplex nested PCR platform, the BioFire® FilmArray® Meningitis/Encephalitis Panel (BioFire ME Panel), for cases with suspected acute bacterial meningitis. METHODS: Following Gram stain and bacterial culture on cerebrospinal fluid (CSF) collected from children aged less than 5 years with a clinical suspicion of acute bacterial meningitis (ABM) as defined by the WHO guidelines, residual CSF specimens were frozen and later tested by BioFire ME Panel. RESULTS: A total of 400 samples were analyzed. Thirty-two [32/400 (8%)] of the specimens were culture positive, consisting of; three Salmonella spp. (2 Typhi and 1 non-typhi), three alpha hemolytic Streptococcus, one Staphylococcus aureus, six Neisseria meningitidis, seven Hemophilus influenzae, 11 Streptococcus pneumoniae and 368 were culture negative. Of the 368 culture-negative specimens, the BioFire ME Panel detected at least one bacterial pathogen in 90 (24.5%) samples, consisting of S. pneumoniae, N. meningitidis and H. influenzae, predominantly. All culture positive specimens for H. influenzae, N. meningitidis and S. pneumoniae also tested positive with the BioFire ME Panel. In addition, 12 specimens had mixed bacterial pathogens identified. For the first time in this setting, we have data on the viral agents associated with meningitis. Single viral agents were detected in 11 (2.8%) samples while co-detections with bacterial agents or other viruses occurred in 23 (5.8%) of the samples. CONCLUSIONS: The BioFire® ME Panel was more sensitive and rapid than culture for detecting bacterial pathogens in CSF. The BioFire® ME Panel also provided for the first time, the diagnosis of viral etiologic agents that are associated with meningoencephalitis in this setting. Institution of PCR diagnostics is recommended as a routine test for suspected cases of ABM to enhance early diagnosis and optimal treatment.

Antibiotic Guidelines for Critically Ill Patients in Nigeria.

BACKGROUND: It is well documented that inappropriate use of antimicrobials is the major driver of antimicrobial resistance. To combat this, antibiotic stewardship has been demonstrated to reduce antibiotic usage, decrease the prevalence of resistance, lead to significant economic gains and better patients' outcomes. In Nigeria, antimicrobial guidelines for critically ill patients in intensive care units (ICUs), with infections are scarce. We set out to develop antimicrobial guidelines for this category of patients. METHODS: A committee of 12 experts, consisting of Clinical Microbiologists, Intensivists, Infectious Disease Physicians, Surgeons, and Anesthesiologists, collaborated to develop guidelines for managing infections in critically ill patients in Nigerian ICUs. The guidelines were based on evidence from published data and local prospective antibiograms from three ICUs in Lagos, Nigeria. The committee considered the availability of appropriate antimicrobial drugs in hospital formularies. Proposed recommendations were approved by consensus agreement among committee members. RESULTS: Candida albicans and Pseudomonas aeruginosa were the most common microorganisms isolated from the 3 ICUs, followed by Klebsiella pneumoniae, Acinetobacter baumannii, and Escherichia coli. Targeted therapy is recognized as the best approach in patient management. Based on various antibiograms and publications from different hospitals across the country, amikacin is recommended as the most effective empiric antibiotic against Enterobacterales and A. baumannii, while colistin and polymixin B showed high efficacy against all bacteria. Amoxicillin-clavulanate or ceftriaxone was recommended as the first-choice drug for community-acquired (CA) CA-pneumonia while piperacillin-tazobactam + amikacin was recommended as first choice for the treatment of healthcare-associated (HA) HA-pneumonia. For ventilatorassociated pneumonia (VAP), the consensus for the drug of first choice was agreed as meropenem. Amoxycillin-clavulanate +clindamycin was the consensus choice for CAskin and soft tissue infection (SSIS) and piperacillin-tazobactam + metronidazole ±vancomycin for HA-SSIS. Ceftriaxone-tazobactam or piperacillin-tazobactam + gentamicin was consensus for CA-blood stream infections (BSI) with first choice+regimen for HA-BSI being meropenem/piperacillin-tazobactam +amikacin +fluconazole. For community-acquired urinary tract infection (UTI), first choice antibiotic was ciprofloxacin or ceftriaxone with a catheter-associated UTI (CAUTI) regimen of first choice being meropenem + fluconazole. CONCLUSION: Data from a multicenter three ICU surveillance and antibiograms and publications from different hospitals in the country was used to produce this evidence-based Nigerian-specific antimicrobial treatment guidelines of critically ill patients in ICUs by a group of experts from different specialties in Nigeria. The implementation of this guideline will facilitate learning, continuous improvement of stewardship activities and provide a baseline for updating of guidelines to reflect evolving antibiotic needs.

CONTEXTE: Il est bien établi que l'utilisation inappropriée des antimicrobiens est le principal moteur de la résistance aux antimicrobiens. Pour lutter contre ce phénomène, il a été démontré que la bonne gestion des antibiotiques permettait de réduire l'utilisation des antibiotiques, de diminuer la prévalence de la résistance, de réaliser des gains économiques significatifs et d'améliorer les résultats pour les patients. Au Nigéria, les directives antimicrobiennes pour les patients gravement malades dans les unités de soins intensifs (USI), souffrant d'infections, sont rares. Nous avons entrepris d'élaborer des lignes directrices sur les antimicrobiens pour cette catégorie de patients. MÉTHODES UTILISÉES: Un comité de 12 experts, composé de microbiologistes cliniques, d'intensivistes, de médecins spécialistes des maladies infectieuses, de chirurgiens et d'anesthésistes, a collaboré à l'élaboration de lignes directrices pour la prise en charge des infections chez les patients gravement malades dans les unités de soins intensifs nigérianes. Les lignes directrices sont basées sur des données publiées et des antibiogrammes prospectifs locaux provenant de trois unités de soins intensifs de Lagos, au Nigeria. Le comité a pris en compte la disponibilité des médicaments antimicrobiens appropriés dans les formulaires des hôpitaux. Les recommandations proposées ont été approuvées par consensus entre les membres du comité. RÉSULTATS: Candida albicans et Pseudomonas aeruginosa étaient les microorganismes les plus fréquemment isolés dans les trois unités de soins intensifs, suivis par Klebsiella pneumoniae, Acinetobacter baumannii et Escherichia coli. La thérapie ciblée est reconnue comme la meilleure approche pour la prise en charge des patients. Sur la base de divers antibiogrammes et publications provenant de différents hôpitaux du pays, l'amikacine est recommandée comme l'antibiotique empirique le plus efficace contre les entérobactéries et A. baumannii, tandis que la colistine et la polymixine B se sont révélées très efficaces contre toutes les bactéries. L'amoxicilline-clavulanate ou la ceftriaxone ont été recommandées comme médicaments de premier choix pour les pneumonies communautaires, tandis que la pipéracilline-tazobactam + amikacine ont été recommandées comme médicaments de premier choix pour le traitement des pneumonies associées aux soins. Pour les pneumonies acquises sous ventilation mécanique (PAV), le consensus sur le médicament de premier choix est le méropénem. L'amoxycilline-clavulanate +clindamycine était le choix consensuel pour les infections de la peau et des tissus mous et la pipéracilline-tazobactam + métronidazole ±vancomycine pour les infections de la peau et des tissus mous. HA-SSIS. Ceftriaxone-tazobactam ou pipéracilline-tazobactam + gentamicine a fait l'objet d'un consensus pour les infections de la circulation sanguine de l'AC (BSI), le premier choix de régime pour les HA-BSI étant le méropénem/pipéracilline-tazobactam +amikacine +fluconazole. Pour les infections urinaires communautaires, l'antibiotique de premier choix était la ciprofloxacine ou la ceftriaxone, le régime de premier choix pour les infections urinaires associées à un cathéter étant le meropenem +fluconazole. CONCLUSION: Les données issues d'une surveillance multicentrique de trois unités de soins intensifs, d'antibiogrammes et de publications de différents hôpitaux du pays ont été utilisées par un groupe d'experts de différentes spécialités nigérianes pour élaborer ces lignes directrices sur le traitement antimicrobien des patients gravement malades dans les unités de soins intensifs, fondées sur des données probantes et spécifiques au Nigeria. La mise en œuvre de ces lignes directrices facilitera l'apprentissage, l'amélioration continue des activités de gestion et fournira une base de référence pour la mise à jour des lignes directrices afin de refléter l'évolution des besoins en antibiotiques. Mots clés: Antimicrobiens, Résistance aux antimicrobiens, Gestion des antibiotiques, Lignes directrices, Soins intensifs, Unité de soins intensifs, Infections associées aux soins de santé.

A review of the recent advances on Lassa fever with special reference to molecular epidemiology and progress in vaccine development

Lassa fever, a viral hemorrhagic fever caused by the Lassa virus (LASV), is endemic in West Africa and is associated with high morbidity and mortality. At least three of the four proposed seven lineages of LASV are found in Nigeria, where the multimammate rat, Mastomys natalensis, serves as the primary reservoir. Endemic countries report approximately 200,000 infections and 5,000 deaths annually, with Nigeria experiencing thousands of infections and hundreds of deaths including healthcare workers. The aim of this review is to provide scientific information for better understanding of the evolutionary biology, molecular epidemiology, pathogenesis, diagnosis, and prevention of Lassa fever in Nigeria and other endemic regions worldwide, which can lead to improved control efforts and reduce morbidity and mortality from recurrent epidemics. To achieve this aim, observational studies such as case series, cross-sectional and cohort studies published between December 2017 and September 2022 were searched for on various online databases including Google Scholar, Africa Journals Online (AJOL), Research Gates, PubMed, PMIC, NCDC, and WHO websites. Although the origin and evolutionary history, and the transmission dynamics of Lassa virus have been revealed through recent. molecular epidemiological studies, the factors that drive the evolution of the virus remain unclear. Genetic changes in the viral genome may have enabled the virus to adapt to humans. Diagnosis of Lassa fever has also advanced from basic serological tests to more sophisticated methods such as quantitative real time polymerase chain reaction (qRT-PCR) and sequencing, which are particularly useful for identifying outbreak strains. Several vaccines, including recombinant vesicular stomatitis virus (rVSV), virus-like particle (VLP), and DNA-based vaccines, have shown promise in animal models and some have progressed to phase 2 clinical trials. Preventing and controlling Lassa fever is critical to safeguard the health and well-being of affected communities. Effective measures such as rodent control, improved sanitation, and early detection and isolation of infected individuals are essential for reducing transmission. Ongoing research into the genetic and ecological factors that drive the evolution of Lassa virus is necessary to reduce the impacts of Lassa fever.

A review of the current diphtheria outbreaks

Corynebacterium diphtheriae is responsible for both endemic and epidemic diphtheria. The predisposing factor for this disease is the failure to immunize during childhood. Humans are the only hosts of the organism and is present in the upper respiratory tract. The organism is transmitted via airborne route and can cause respiratory obstruction and heart failure because of the exotoxin it produces. There is presently a resurgence of diphtheria outbreaks in Nigeria. The Nigeria Center for Disease Control (NCDC) was notified of suspected diphtheria outbreaks in Lagos and Kano States, Nigeria, in December 2022 and has been issuing monthly reports since that time. This review of the diphtheria outbreaks following online database searches on PubMed and Google Scholar as well as the NCDC/WHO websites and grey literatures, describes the current trend of the outbreaks globally, elucidated the different strains of Corynebacterium responsible for the outbreaks, identified the recent vaccine formulation developed to tackle the outbreaks, and provide information on vaccine delivery and efficacy studies in the country and globally.

A review of the recent advances on Lassa fever with special reference to molecular epidemiology and progress in vaccine development

Lassa fever, a viral hemorrhagic fever caused by the Lassa virus (LASV), is endemic in West Africa and is associated with high morbidity and mortality. At least three of the four proposed seven lineages of LASV are found in Nigeria, where the multimammate rat, Mastomys natalensis, serves as the primary reservoir. Endemic countries report approximately 200,000 infections and 5,000 deaths annually, with Nigeria experiencing thousands of infections and hundreds of deaths including healthcare workers. The aim of this review is to provide scientific information for better understanding of the evolutionary biology, molecular epidemiology, pathogenesis, diagnosis, and prevention of Lassa fever in Nigeria and other endemic regions worldwide, which can lead to improved control efforts and reduce morbidity and mortality from recurrent epidemics. To achieve this aim, observational studies such as case series, cross-sectional and cohort studies published between December 2017 and September 2022 were searched for on various online databases including Google Scholar, Africa Journals Online (AJOL), Research Gates, PubMed, PMIC, NCDC, and WHO websites. Although the origin and evolutionary history, and the transmission dynamics of Lassa virus have been revealed through recent molecular epidemiological studies, the factors that drive the evolution of the virus remain unclear. Genetic changes in the viral genome may have enabled the virus to adapt to humans. Diagnosis of Lassa fever has also advanced from basic serological tests to more sophisticated methods such as quantitative real time polymerase chain reaction (qRT-PCR) and sequencing, which are particularly useful for identifying outbreak strains. Several vaccines, including recombinant vesicular stomatitis virus (rVSV), virus-like particle (VLP), and DNA-based vaccines, have shown promise in animal models and some have progressed to phase 2 clinical trials. Preventing and controlling Lassa fever is critical to safeguard the health and well-being of affected communities. Effective measures such as rodent control, improved sanitation, and early detection and isolation of infected individuals are essential for reducing transmission. Ongoing research into the genetic and ecological factors that drive the evolution of Lassa virus is necessary to reduce the impacts of Lassa fever

La fièvre de Lassa, une fièvre hémorragique virale causée par le virus de Lassa (LASV), est endémique en Afrique de l'Ouest et est associée à une morbidité et une mortalité élevées. Au moins trois des quatre lignées proposées de LASV se trouvent au Nigeria, où le rat multimammaire, Mastomys natalensis, sert de réservoir principal. Les pays endémiques signalent environ 200,000 infections et 5,000 décès par an, le Nigéria connaissant des milliers d'infections et des centaines de décès, y compris des travailleurs de la santé. L'objectif de cette revue est de fournir des informations scientifiques pour une meilleure compréhension de la biologie évolutive, de l'épidémiologie moléculaire, de la pathogenèse, du diagnostic et de la prévention de la fièvre de Lassa au Nigeria et dans d'autres régions endémiques du monde, ce qui peut conduire à des efforts de contrôle améliorés et réduire la morbidité et la mortalité des épidémies récurrentes. Pour atteindre cet objectif, des études observationnelles telles que des séries de cas, des études transversales et de cohorte publiées entre décembre 2017 et septembre 2022 ont été recherchées sur diverses bases de données en ligne, notamment Google Scholar, Africa Journals Online (AJOL), Research Gate, PubMed, PMIC, Sites Web du NCDC et de l'OMS. Bien que l'origine et l'histoire évolutive, ainsi que la dynamique de transmission du virus de Lassa aient été révélées par des études épidémiologiques moléculaires récentes, les facteurs qui déterminent l'évolution du virus restent flous. Des modifications génétiques du génome viral pourraient avoir permis au virus de s'adapter à l'homme. Le diagnostic de la fièvre de Lassa est également passé des tests sérologiques de base à des méthodes plus sophistiquées telles que la réaction quantitative en chaîne par polymérase en temps réel (qRTPCR) et le séquençage, qui sont particulièrement utiles pour identifier les souches épidémiques. Plusieurs vaccins, y compris le virus recombinant de la stomatite vésiculeuse (rVSV), les particules pseudo-virales (VLP) et les vaccins à base d'ADN, se sont révélés prometteurs dans des modèles animaux et certains ont progressé vers des essais cliniques de phase 2. La prévention et le contrôle de la fièvre de Lassa sont essentiels pour préserver la santé et le bien-être des communautés touchées. Des mesures efficaces telles que le contrôle des rongeurs, l'amélioration de l'assainissement et la détection et l'isolement précoces des personnes infectées sont essentielles pour réduire la transmission. Des recherches continues sur les facteurs génétiques et écologiques qui déterminent l'évolution du virus de Lassa sont nécessaires pour réduire les impacts de la fièvre de Lassa.

A review of the epidemiology, diagnosis, treatment, vaccines and economic impact of human monkeypox (Mpox) outbreaks

The current monkeypox outbreak is a public health emergency of international concern and is coming in the wake of the SARS-CoV-2 pandemic. Human monkeypox is a viral zoonotic infection caused by monkeypox virus, an enveloped double-stranded DNA virus of the genus Orthopoxvirus and family Poxviridae that also contain smallpox, cowpox, Orf, and vaccinia viruses. Online databases including PubMed, Google Scholar and Web of Science were searched to obtain relevant publications on the epidemiology, treatment, vaccines and the economic impacts of the current monkeypox (Mpox) outbreak.

A systematic review of clinical characteristics, co-morbidities and outcomes of COVID-19 in children and adolescents

Background: COVID-19 is a major global health challenge that has affected all age groups and gender, with over 5 million deaths reported worldwide to date. The objective of this study is to assess available information on COVID-19 in children and adolescents with respect to clinical characteristics, co-morbidities, and outcomes, and identify gaps in the literatures for appropriate actions. Methodology: Electronic databases including Web of Science, PubMed, Scopus, and Google Scholar were searched for observational studies such as case series, cross-sectional and cohort studies published from December 2019 to September 2021, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guide. Data extracted included (i) patient demography (age and gender), (ii) clinical characteristics including vaccination status and presence of co-morbidities, (iii) clinical management including the use of sequential organ failure assessment (SOFA) scores, oxygen requirement, use of mechanical ventilation, and (iv) disease outcomes including length of hospital and intensive care unit (ICU) admission, recovery, complications with sequelae, or death. Data were analyzed using descriptive statistics. Results: A total of 11 eligible studies were included with a total of 266 children and adolescents; 137 (51.5%) females and 129 (48.5%) males. The mean age of the children was 9.8 years (range of 0 ­ 19 years), and children ≥ 6 years were more affected (40.7%) than age groups 1 ­ 5 years (31.9%) and < 1 year (27.4%). The major co-morbidities were respiratory diseases including pre-existing asthma (3.4%), neurologic conditions (3.4%) and cardiac pathology (2.3%). Majority (74.8%, 199/266) of the patients were discharged without sequelae, 0.8% (2/266) were discharged with sequalae from one study, and mortality of 1.9% (5/266) was reported, also from one study. SOFA scores of patients at admission were not stated in any of the study, while only one study reported patient vaccination status. Conclusion: It is recommended that safe vaccines for children < 1 year of age should be developed in addition to other preventive measures currently in place. SOFA scores should be used to assess risk of COVID-19 severity and monitor prognosis of the disease, and vaccination status of children should be documented as this may impact the management and prognosis of the disease.

A point-prevalence survey of carbapenem-resistant Enterobacteriaceae in two different cities in Kuwait and Nigeria

Background: The family Enterobacteriaceae belongs to the order Enterobacterales, a large diverse group of Gramnegative, facultatively anaerobic bacteria that sometimes cause multidrug-resistant infections which treatment options are often challenging. They are the leading cause of nosocomial bloodstream infection (BSI) and urinary tract infections (UTI). The objective of the study was to carry out a point-prevalence survey of antimicrobial resistance and carbapenem-resistant Enterobacteriaceae (CRE) clinical isolates in two hospitals in Kuwait and Nigeria. Methodology: Clinically significant bacterial isolates of patients from Kuwait and Nigeria, identified by VITEK-2 and MALDI-TOF mass spectrometry analysis were studied. Susceptibility testing of selected antibiotics was performed using E-test and broth dilution methods. Genes encoding carbapenemase, ß-lactamases, and extended-spectrum ßlactamases (ESBLs) were detected by conventional PCR and sequencing, and whole genome sequencing (WGS) analyses. Results: Of 400 isolates from Kuwait and Nigeria, 188 (47.0%) and 218 (54.5%) were Escherichia coli and 124 (31.0%) and 116 (29.0%) Klebsiella pneumoniae, respectively. The prevalence of CRE was 14.0% in Kuwait and 8.0% in Nigeria. The resistance rates of CRE isolates against colistin and tigecycline in Kuwait were 6.6% versus 25.0%, and in Nigeria were 14.2% versus 14.2%, respectively. blaOXA-181 gene was the commonest in CRE isolates in Kuwait and blaNDM-7 in Nigeria. The commonest ESBL gene among the CRE isolates was blaCTX-M-15 in both countries. AmpC resistance genes were present in only Kuwait isolates and mediated by blaEBC, blaCIT and blaDHA. WGS analysis of 12 selected CRE isolates with carbapenem MICs>32µg/ml but no detectable genes from conventional PCR, revealed the presence of multidrug efflux pump genes such as major facilitator superfamily antibiotic efflux pump and resistance-nodulation-cell division antibiotic efflux pump groups. Conclusion: The prevalence of CRE was higher among isolates from Kuwait than Nigeria and the genes encoding resistance in CRE were different. The presence of efflux pump was a main mechanism of resistance in most of the Nigerian CRE isolates.

Neonatal outcomes associated with maternal recto-vaginal colonization with extended-spectrum ß-lactamase producing Enterobacteriaceae in Nigeria: a prospective, cross-sectional study.

OBJECTIVES: The objective of this study was to assess the prevalence of maternal recto-vaginal extended-spectrum ß-lactamase producing Enterobacteriacea (ESBL-E) colonization, identify risk factors for maternal and neonatal ESBL-E colonization, and subsequent impact on neonatal mortality. METHODS: A prospective, cross-sectional study was conducted at the University of Abuja Teaching Hospital from April 2016 to May 2017. Maternal-neonatal pairs were screened for ESBL-E exposure at time of delivery. Neonatal mortality was assessed at 28 days. RESULTS: A total of 1161 singleton deliveries were evaluated. In total, 9.7% (113/1161) of mothers and 4.3% (50/1161) of infants had ESBL-E-positive cultures at delivery. Maternal antibiotic exposure was associated with ESBL-E recto-vaginal colonization (18.6% (21/113) vs. 8.4% (88/1048), p < 0.001)). Maternal ESBL-E colonization (adjusted odds ratio (AOR) 14.85; 95% CI 7.83-28.15) and vaginal delivery (AOR 6.35; 95% CI 2.63-17.1) were identified as a risk factor for positive ESBL-E neonatal surface cultures. Neonatal positive ESBL-E surface cultures were a risk factor for neonatal mortality (stillbirths included, AOR 4.84; 95% CI 1.44-16.31). The finding that maternal ESBL-E recto-vaginal colonization appeared protective in regards to neonatal mortality (AOR 0.22; 95% CI .06-0.75) requires further evaluation. CONCLUSIONS: Maternal ESBL-E recto-vaginal colonization is an independent risk factor for neonatal ESBL-E colonization and neonates with positive ESBL-E surface cultures were identified as having increased risk of neonatal mortality.

Group B streptococcal colonization and transmission dynamics in pregnant women and their newborns in Nigeria: implications for prevention strategies.

OBJECTIVES: Because few studies have been conducted on group B Streptococcus (GBS) in Nigeria, we sought to estimate GBS colonization and transmission frequencies for 500 women and their newborns and identify risk factors for both outcomes. METHODS: GBS strains were characterized for antibiotic susceptibilities, capsule (cps) genotype, pilus island profile and multilocus sequence type (ST). RESULTS: In all, 171 (34.2%) mothers and 95 (19.0%) of their newborns were colonized with GBS; the vertical transmission rate was 48.5%. One newborn developed early-onset disease, yielding an incidence of 2.0 cases per 1000 live births (95% CI 0.50-7.30). Rectal maternal colonization (OR 26.6; 95% CI 13.69-51.58) and prolonged rupture of membranes (OR 4.2; 95% CI 1.03-17.17) were associated with neonatal colonization, whereas prolonged membrane rupture (OR 3.4; 95% CI 1.04-11.39) and young maternal age (OR 2.0; 95% CI 1.22-3.39) were associated with maternal colonization. Women reporting four or more intrapartum vaginal examinations (OR 6.1; 95% CI 3.41-10.93) and douching (OR 3.7; 95% CI 2.26-6.11) were also more likely to be colonized. Twelve STs were identified among 35 mother-baby pairs with evidence of transmission; strains of cpsV ST-19 (n = 9; 25.7%) and cpsIII ST-182 (n = 7; 20.0%) predominated. CONCLUSIONS: These data demonstrate high rates of colonization and transmission in a population that does not use antibiotics to prevent neonatal infections, a strategy that should be considered in the future.