Whole-Cell and Acellular Pertussis Vaccine: Reflections on Efficacy.

Pertussis is a common respiratory infection caused by the bacterium Bordetella pertussis. Although most cases occur in developing countries, it is considered endemic globally. The World Health Organization estimates there are 20-40 million cases of pertussis annually. Pertussis vaccines played a pivotal role in reducing the burden of pertussis disease as well as infant morbidity and mortality. Although the two forms of pertussis vaccine are effective, each has its advantages and drawbacks. This review aims to review the current knowledge on pertussis vaccines, emphasizing vaccine effectiveness in different populations within a community. Clinical trials have shown favorable vaccine efficacy with acellular pertussis (aP)vaccine. However, observational and population-level studies showed that introducing at least a single dose of whole-cell pertussis (wP) vaccine within the routine immunization schedule is associated with better disease protection and a longer duration of immunity. On the other hand, wP vaccine is more reactogenic and associated with higher adverse events. Therefore, the selection of vaccine should be weighed against the effectiveness, reactogenicity, and cost-effectiveness. Due to its safety profile, aP vaccine can be offered to wider population groups. Booster adolescent and pregnant immunization programs have been implemented globally to control outbreaks and protect vulnerable infants. Due to the variable effectiveness performance of both vaccines, different countries adopted distinctive immunization programs. Determining the right vaccination approach depends on financial consideration, immunization program infrastructure, adverse event monitoring, and pertussis surveillance in the community.

SARS-CoV-2 Clinical Characteristics and Viral Shedding in Kuwait.

OBJECTIVES: We aimed to describe the clinical characteristics of SARS-CoV-2 infection and estimate viral shedding duration in respiratory specimens. METHODS: A retrospective cohort study was performed from February 25 to March 25, 2020. In Kuwait, all suspected coronavirus disease 2019 (COVID-19) cases, contacts of cases, and returning travelers were systematically tested for SARS-CoV-2 by RT-PCR. All infected persons, regardless of symptoms, were hospitalized and serially tested until they had two negative results. Descriptive statistics and regression analyses were performed. RESULTS: Two hundred seven cases of SARS-CoV-2 infection were included in this study. About half of the cases were asymptomatic and 1.9% died. The median time to negative RT-PCR was 22 days. Increasing age, ARDS, and low peripheral white blood cell count were associated with prolonged PCR positivity. CONCLUSION: Predictors for prolonged RT-PCR positivity included increasing age, ARDS, and low white blood cell count. The findings of this study may aid in better understanding of the epidemiology of SARS-CoV-2 infection and molecular testing dynamics.

The Pediatric COVID-19 Registry in Kuwait: Methodology and Results of Pilot Phase.

OBJECTIVE: Establishing a pediatric COVID-19 registry in Kuwait (PCR-Q8) was deemed imperative during the pandemic to study children infected with severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) focusing on mode of presentation, therapeutic interventions, disease severity, and early outcomes. This manuscript describes the rapid establishment of the PCR-Q8 registry showcasing an infrastructure of the development process and presents the results of the pilot phase. SUBJECT AND METHODS: The registry was developed and implemented using the general key steps from a resource titled "Registries for Evaluating Patient Outcomes: A User's Guide" as a guide for best practice, experience from a previously established pediatric diabetes registry in Kuwait and several other COVID-19 registries developed globally. During the pilot phase, a convenience sample of 120 children was included, of whom 66 (55%) were male. RESULTS: Experience and expertise from other COVID-19 registries; guidance provided by the World Health Organization; and effective collaboration and cooperation between the stakeholders, study group, and data enterers during these challenging times were critical for the development and implementation of the registry. Our results were similar to international reports which showed that most children presented with mild disease (69.2%), majority (70.2%) had normal chest X-ray, and the most common symptom at presentation was fever (77%). CONCLUSION: We anticipate the development of PCR-Q8 to be a stepping-stone for more in-depth investigation of SARS-CoV-2 infection in children in Kuwait and for the establishment of other registries.

Clinical characteristics of pediatric SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) in Kuwait.

Clinical presentation of coronavirus disease-2019 (COVID-19) ranges from asymptomatic to severe and life-threatening. National-level registries found that children, generally, have less severe disease when compared with adults. However, most asymptomatically infected children will not present to hospital and may be missed. We aimed to describe the clinical characteristics in pediatric COVID-19 patients in Kuwait, and to estimate the potential duration of viral shedding. A retrospective cohort study was performed in Jaber Alahmad Hospital (JAH) from February 29 to April 30, 2020. During the study period and as part of the public health measures, all severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients from 1 month to 18 years old, regardless of symptoms, were hospitalized at JAH, and were included. Polymerase chain reaction (PCR) negativity was defined as having two consecutive negative PCR results from a respiratory specimen. Descriptive statistics and multivariable regression analyses were performed. We found that 67.9% (95% CI, 59.4%-75.3%) of 134 SARS-CoV-2-infected children were asymptomatic. Median PCR positivity was 15 days and did not vary with symptoms. Among patients who had laboratory investigations and chest imaging, symptomatic infection was associated with elevated C-reactive protein and procalcitonin, and radiographic pneumonia. Asymptomatic SARS-CoV-2 infection is very common in children. Among symptomatic patients, the disease seems to be mild. Children exhibit substantial duration of viral shedding, regardless of symptoms.

Antibiotic Prescription Practice for Pediatric Urinary Tract Infection in a Tertiary Center.

OBJECTIVES: Prescribing antibiotics for suspected urinary tract infection (UTI) is common practice and may lead to unnecessary antibiotic exposure. We aimed to review UTI diagnosis and management in the emergency department and to identify targets for antimicrobial stewardship. METHODS: Single-center, retrospective cohort study of children aged 12 weeks to younger than 18 years discharged from the emergency department with a diagnosis of UTI between October and December 2016. Children with genitourinary malformations were excluded. Clinical information, urine collection method, laboratory findings, and urine culture results were gathered. The sensitivity and specificity of nitrite and leukocyte esterase for UTI diagnosis were calculated. The relationship between urinalysis characteristics and confirmed UTI was examined using logistic regression. RESULTS: A total of 183 children with a median (interquartile range) age of 4.2 (1.1-7.5) years were included; 82.5% were female. Almost all children were discharged home on antibiotics (n = 180, 98%) for a median (interquartile range) duration of 7 (7-10) days. A total of 85 patients (46.4%) received antibiotics despite negative urine cultures leading to 525 unnecessary antibiotic days. The presence of nitrites was the strongest predictor of UTI (odds ratio = 20.22, P < 0.001) and was highly specific. CONCLUSIONS: Current practice in managing suspected pediatric UTIs in our ED resulted in significant and unnecessary antibiotic exposure. We identified targets to reduce unnecessary antibiotic exposure including improving the diagnostic accuracy of UTIs, a process to discontinue antibiotics for negative cultures and standardizing antimicrobial duration.

Low-Cost Polyester-Tipped Three-Dimensionally Printed Nasopharyngeal Swab for the Detection of Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2).

Case identification, isolation, and contact tracing are fundamental strategies used to control the spread of coronavirus disease 2019 (COVID-19). This has led to widespread testing that interrupted the supply chain for testing materials around the world. A prospective study was conducted to compare inexpensive and easily sourced 3-dimensionally (3D)-printed polylactic acid and polyester nasopharyngeal swabs to commercially manufactured swabs for the detection of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). During the study period, 287 laboratory-confirmed hospitalized COVID-19 patients, at multiple stages of their illness, were enrolled. The median age for the study population was 47.6 years (interquartile range [IQR], 34.4 to 56.6 years), and two-thirds (67.6%) of the subjects were male. The median duration of hospitalization, at the time of sampling, was 13 days (IQR, 10 to 16 days). Overall concordance between the prototype and control swabs was 80.8% (Cohen's kappa coefficient, 0.61). Most discrepant results were due to prototype-positive control-negative results. When considering all positive results to be true positives, the prototype swab had a higher sensitivity (90.6% versus 80.8%; 95% confidence interval [CI], 85.7% to 94.0% and 74.7% to 85.7%, respectively; P < 0.015). The cost to produce the prototype swab was estimated to be $0.05 per swab. Polylactic acid 3D-printed polyester-tipped swabs were shown to be effective for nasopharyngeal sample collection. We believe that this design can easily be adopted in countries where commercial swabs are not readily available and can play a vital role in public health efforts for disease control in low-income countries.

Impact of decreasing cerebrospinal fluid enterovirus PCR turnaround time on costs and management of children with suspected enterovirus meningitis.

To estimate the impact of implementing in-hospital enterovirus (EV) polymerase chain reaction (PCR) testing of cerebrospinal fluid (CSF) with same-day turn-around-time (TAT) on length-of-stay (LOS), antibiotic use and on cost per patient with suspected EV meningitis, compared with testing at an outside reference laboratory. A model-based analysis using a retrospective cohort of all hospitalized children with CSF EV PCR testing done between November 2013 and 2017. The primary outcome measured was the potential date of discharge if the EV PCR result had been available on the same day. Patients with positive EV PCR were considered for potential earlier discharge once clinically stable with no reason for hospitalization other than intravenous antibiotics. Descriptive statistics and cost-sensitivity analyses were performed. CSF EV PCR testing was done on 153 patients, of which 44 (29%) had a positive result. Median test TAT was 5.3 days (IQR 3.9-7.6). Median hospital LOS was 5 days (IQR 3-12). Most (86%) patients received intravenous antibiotics with mean duration of 5.72 ± 6.51 days. No patients with positive EV PCR had a serious bacterial infection. We found that same-day test TAT would reduce LOS and duration of intravenous antibiotics by 0.50 days (95%CI 0.33-0.68) and 0.67 days (95%CI 0.42-0.91), respectively. Same-day test TAT was associated with a cost reduction of 342.83CAD (95%CI 178.14-517.00) per patient with suspected EV meningitis. Compared with sending specimens to a reference laboratory, performing CSF EV PCR in-hospital with same-day TAT was associated with decreased LOS, antibiotic therapy, and cost per patient.

Isolated cutaneous mucormycosis in a pediatric renal transplant recipient.

Mucormycosis is a rare and potentially life-threatening infection, typically affecting immunocompromised hosts. We report a case of an adolescent boy who developed primary isolated cutaneous mucormycosis in the early period following kidney transplantation. Surgical excision was performed using intraoperative fungal staining to obtain clear margins, followed by topical and systemic antifungal therapy. A skin graft was then applied to the excised area with good healing, and the patient made a full recovery.

Sputum production and salivary microbiome in COVID-19 patients reveals oral-lung axis.

SARS-CoV-2, a severe respiratory disease primarily targeting the lungs, was the leading cause of death worldwide during the pandemic. Understanding the interplay between the oral microbiome and inflammatory cytokines during acute infection is crucial for elucidating host immune responses. This study aimed to explore the relationship between the oral microbiome and cytokines in COVID-19 patients, particularly those with and without sputum production. Saliva and blood samples from 50 COVID-19 patients were subjected to 16S ribosomal RNA gene sequencing for oral microbiome analysis, and 65 saliva and serum cytokines were assessed using Luminex multiplex analysis. The Mann-Whitney test was used to compare cytokine levels between individuals with and without sputum production. Logistic regression machine learning models were employed to evaluate the predictive capability of oral microbiome, salivary, and blood biomarkers for sputum production. Significant differences were observed in the membership (Jaccard dissimilarity: p = 0.016) and abundance (PhILR dissimilarity: p = 0.048; metagenomeSeq) of salivary microbial communities between patients with and without sputum production. Seven bacterial genera, including Prevotella, Streptococcus, Actinomyces, Atopobium, Filifactor, Leptotrichia, and Selenomonas, were more prevalent in patients with sputum production (p<0.05, Fisher's exact test). Nine genera, including Prevotella, Megasphaera, Stomatobaculum, Selenomonas, Leptotrichia, Veillonella, Actinomyces, Atopobium, and Corynebacteria, were significantly more abundant in the sputum-producing group, while Lachnoanaerobaculum was more prevalent in the non-sputum-producing group (p<0.05, ANCOM-BC). Positive correlations were found between salivary IFN-gamma and Eotaxin2/CCL24 with sputum production, while negative correlations were noted with serum MCP3/CCL7, MIG/CXCL9, IL1 beta, and SCF (p<0.05, Mann-Whitney test). The machine learning model using only oral bacteria input outperformed the model that included all data: blood and saliva biomarkers, as well as clinical and demographic variables, in predicting sputum production in COVID-19 subjects. The performance metrics were as follows, comparing the model with only bacteria input versus the model with all input variables: precision (95% vs. 75%), recall (100% vs. 50%), F1-score (98% vs. 60%), and accuracy (82% vs. 66%).

Association between risk of obstructive sleep apnea severity and risk of severe COVID-19 symptoms: insights from salivary and serum cytokines.

Objectives: Obstructive sleep apnea (OSA) can adversely affect the immune response through clinical factors such as hypoxia, inflammation, and sleep disturbance. Since SARS-CoV-2 heavily relies on local and systemic host immune responses, this study aims to examine the links between the severity of OSA risk, cytokine levels, and the severity of symptoms associated with SARS-CoV-2 infection. Methods: Saliva and blood samples from 50 COVID-19 patients and 30 non-infected hospital staff members were collected. Using Luminex multiplex analysis, 65 blood and salivary cytokines were examined from the collected samples. Ordinal logistic regression analysis was utilized to examine the association between the self-reported risk of OSA, assessed through the STOP-Bang questionnaire, and the likelihood of experiencing severe symptoms of COVID-19. Mann-Whitney test was then performed to compare the cytokine levels between individuals with moderate to severe risk of OSA to those with a mild risk of OSA. Results: Ordinal logistic regression analysis revealed that individuals with a moderate to severe risk of OSA were 7.60 times more likely to experience more severe symptoms of COVID-19 compared to those with a mild risk of OSA (OR = 7.60, 95%CI: 3.03, 19.06, p < 0.001). Moreover, among COVID-19-positive patients with a moderate to severe risk of OSA, there was a statistically significant negative correlation with serum IL-6 (p < 0.05), Eotaxin (CCL11) (p = 0.04), and salivary MIP-3α/CCL20 (p = 0.04). In contrast, individuals without COVID-19 who had a moderate to severe risk of OSA exhibited a significant positive correlation with serum IL-6 (p = 0.04). Conclusion: Individuals with moderate to severe risk of OSA were more likely to experience severe COVID-19 symptoms than those with mild risk for OSA. Additional analysis from the present studies revealed distinct patterns of oral and systemic immune responses between individuals with mild and moderate to severe risk of OSA. Findings from the present study underscores the importance of early detection and management of OSA to improve clinical outcomes, particularly when faced with the subsequent superimposed infection such as COVID-19.

Host-microbiome associations in saliva predict COVID-19 severity.

Established evidence indicates that oral microbiota plays a crucial role in modulating host immune responses to viral infection. Following severe acute respiratory syndrome coronavirus 2, there are coordinated microbiome and inflammatory responses within the mucosal and systemic compartments that are unknown. The specific roles the oral microbiota and inflammatory cytokines play in the pathogenesis of coronavirus disease 2019 (COVID-19) are yet to be explored. Here, we evaluated the relationships between the salivary microbiome and host parameters in different groups of COVID-19 severity based on their oxygen requirement. Saliva and blood samples (n = 80) were collected from COVID-19 and from noninfected individuals. We characterized the oral microbiomes using 16S ribosomal RNA gene sequencing and evaluated saliva and serum cytokines and chemokines using multiplex analysis. Alpha diversity of the salivary microbial community was negatively associated with COVID-19 severity, while diversity increased with health. Integrated cytokine evaluations of saliva and serum showed that the oral host response was distinct from the systemic response. The hierarchical classification of COVID-19 status and respiratory severity using multiple modalities separately (i.e. microbiome, salivary cytokines, and systemic cytokines) and simultaneously (i.e. multimodal perturbation analyses) revealed that the microbiome perturbation analysis was the most informative for predicting COVID-19 status and severity, followed by the multimodal. Our findings suggest that oral microbiome and salivary cytokines may be predictive of COVID-19 status and severity, whereas atypical local mucosal immune suppression and systemic hyperinflammation provide new cues to understand the pathogenesis in immunologically compromised populations.

The effect of Telehealth Antimicrobial Stewardship Program (Tele-ASP) on antimicrobial use in a pediatric intensive care unit: Pre- and post-implementation single center study.

BACKGROUND: Overuse or misuse of antimicrobials is common in pediatric intensive care units (PICU) and may be associated with poor clinical outcomes. Although an antimicrobial stewardship program (ASP) has been found to improve this practice, the required expertise in infectious diseases may be limited in some centers. We aimed to evaluate the effect of telehealth ASP on the rate of PICU antimicrobial use in a center without a local Infectious Diseases consultation service. METHODS: A retrospective cohort study was performed between October 1st, 2018, and October 31st, 2020, in Farwaniya Hospital PICU, a 20-bed unit. All pediatric patients who were admitted to PICU and received systemic antimicrobials during the study period were included and followed until hospital discharge. The ASP team provided weekly prospective audit and feedback on antimicrobial use starting October 8th, 2019. A pediatric infectious diseases specialist joined the ASP rounds remotely. Descriptive analyses and a pre-post intervention comparison of days of therapy (DOT) were used to assess the effectiveness of the ASP intervention. RESULTS: There were 272 and 156 PICU admissions received systemic antimicrobial before and after the initiation of ASP, respectively. Bronchiolitis and pneumonia were the most common admission diagnoses, together compromising 60.7% and 61.2% of cases pre- and post-ASP. The requirement for respiratory support was higher post-ASP (76.5% vs. 91.5%, p < 0.001). Average monthly antimicrobial use decreased from 922 (95%CI 745-1000) to 485 DOT/1000 patient-days (95%CI 246-722, P < 0.05). A decline in DOT was observed across most antibiotic classes, except for ceftriaxone. No effect on the length of PICU stay, length of hospitalization, or mortality was observed. Most (89.7%) ASP recommendations were followed either fully or partially. CONCLUSION: In settings where Infectious Diseases consultation services are unavailable, PICU telehealth ASP can be effectively implemented and associated with significantly reducing antimicrobial use.

A Narrative Review of Healthcare-Associated Gram-Negative Infections Among Pediatric Patients in Middle Eastern Countries.

INTRODUCTION: Gram-negative bacteria (GNB) have become prominent across healthcare and community settings due to factors including lack of effective infection control and prevention (ICP) and antimicrobial stewardship programs (ASPs), GNB developing antimicrobial resistance (AMR), and difficulty treating infections. This review summarizes available literature on healthcare-associated infections (HAIs) in Middle Eastern pediatric patients. METHODS: Literature searches were performed with PubMed and Embase databases. Articles not reporting data on GNB, HAIs, pediatric patients, and countries of interest were excluded. RESULTS: The searches resulted in 220 publications, of which 49 met the inclusion criteria and 1 additional study was identified manually. Among 19 studies across Egypt reporting GNB prevalence among pediatric patients, Klebsiella species/K. pneumoniae and Escherichia coli were typically the most common GNB infections; among studies reporting carbapenem resistance and multidrug resistance (MDR), rates reached 86% and 100%, respectively. Similarly, in Saudi Arabia, Klebsiella spp./K. pneumoniae and E. coli were the GNB most consistently associated with infections, and carbapenem resistance (up to 100%) and MDR (up to 75%) were frequently observed. In other Gulf Cooperation Council countries, including Kuwait, Oman, and Qatar, carbapenem resistance and MDR were also commonly reported. In Jordan and Lebanon, E. coli and Klebsiella spp./K. pneumoniae were the most common GNB isolates, and AMR rates reached 100%. DISCUSSION: This review indicated the prevalence of GNB-causing HAIs among pediatric patients in Middle Eastern countries, with studies varying in reporting GNB and AMR. Most publications reported antimicrobial susceptibility of isolated GNB strains, with high prevalence of extended-spectrum beta-lactamase-producing K. pneumoniae and E. coli isolates. A review of ASPs highlighted the lack of data available in the region. CONCLUSIONS: Enhanced implementation of ICP, ASPs, and AMR surveillance is necessary to better understand the widespread burden of antimicrobial-resistant GNB and to better manage GNB-associated HAIs across Middle Eastern countries.

Host-Microbiome Associations in Saliva Predict COVID-19 Severity.

Established evidence indicates that oral microbiota plays a crucial role in modulating host immune responses to viral infection. Following Severe Acute Respiratory Syndrome Coronavirus 2 - SARS-CoV-2 - there are coordinated microbiome and inflammatory responses within the mucosal and systemic compartments that are unknown. The specific roles that the oral microbiota and inflammatory cytokines play in the pathogenesis of COVID-19 are yet to be explored. We evaluated the relationships between the salivary microbiome and host parameters in different groups of COVID-19 severity based on their Oxygen requirement. Saliva and blood samples (n = 80) were collected from COVID-19 and from non-infected individuals. We characterized the oral microbiomes using 16S ribosomal RNA gene sequencing and evaluated saliva and serum cytokines using Luminex multiplex analysis. Alpha diversity of the salivary microbial community was negatively associated with COVID-19 severity. Integrated cytokine evaluations of saliva and serum showed that the oral host response was distinct from the systemic response. The hierarchical classification of COVID-19 status and respiratory severity using multiple modalities separately (i.e., microbiome, salivary cytokines, and systemic cytokines) and simultaneously (i.e., multi-modal perturbation analyses) revealed that the microbiome perturbation analysis was the most informative for predicting COVID-19 status and severity, followed by the multi-modal. Our findings suggest that oral microbiome and salivary cytokines may be predictive of COVID-19 status and severity, whereas atypical local mucosal immune suppression and systemic hyperinflammation provide new cues to understand the pathogenesis in immunologically naïve populations.

A Pediatric Investigators Collaborative Network on Infections in Children (PICNIC) multi-centre Canadian descriptive analysis of Haemophilus influenzae bacteremia in children: Emerging serotypes.

Background: There has been dramatic reduction in Haemophilus influenzae serotype b (Hib) since introduction of Hib vaccines, but children still experience serious invasive Haemophilus influenzae (Hi) disease caused by various serotype and non-typeable bacteria. The object of this study was to describe the serotype distribution and clinical spectrum of Hi bacteremia in children admitted to Canadian hospitals. Methods: All children with Hi bacteremia admitted 2013 through 2017 to 10 centres across Canada were included. Demographic, clinical, treatment and outcome data were collected. Results: Haemophilus influenzae bacteremia occurred in 118 children of median age 12 months (inter-quartile range: 7-48 months). Forty-three (36%) isolates were non-typeable (NTHi) and 8 were not typed. Of the 67 typeable (THi), Hia (H. influenzae serotype a) (n=36, 54%), Hif (serotype f) (n=19, 26%) and Hib (serotype b) (n=9, 13%) dominated. The THi was more likely than NTHi bacteremia to present as meningitis (p<0.001), particularly serotype a (p=0.04) and less likely to present as pneumonia (p<0.001). Complicated disease (defined as intensive care unit admission, need for surgery, long-term sequelae or death) occurred in 31 (26%) cases and were more likely to have meningitis (p<0.001) than were those with uncomplicated disease. Conclusion: In the era of efficacious conjugate Hib vaccines, NTHi, Hia and Hif have emerged as the leading causes of invasive Hi in Canadian children, with Hia being most likely to result in meningitis and complicated disease. A vaccine for all NTHi and THi would be ideal, but knowledge of the current disease burden from circulating strains will inform prioritization of vaccine targets.

Potential Strategies to Control the Risk of Antifungal Resistance in Humans: A Comprehensive Review.

Fungal infections are becoming one of the main causes of morbidity and mortality in people with weakened immune systems. Mycoses are becoming more common, despite greater knowledge and better treatment methods, due to the regular emergence of resistance to the antifungal medications used in clinical settings. Antifungal therapy is the mainstay of patient management for acute and chronic mycoses. However, the limited availability of antifungal drug classes limits the range of available treatments. Additionally, several drawbacks to treating mycoses include unfavourable side effects, a limited activity spectrum, a paucity of targets, and fungal resistance, all of which continue to be significant issues in developing antifungal drugs. The emergence of antifungal drug resistance has eliminated accessible drug classes as treatment choices, which significantly compromises the clinical management of fungal illnesses. In some situations, the emergence of strains resistant to many antifungal medications is a major concern. Although new medications have been developed to address this issue, antifungal drug resistance has grown more pronounced, particularly in patients who need long-term care or are undergoing antifungal prophylaxis. Moreover, the mechanisms that cause resistance must be well understood, including modifications in drug target affinities and abundances, along with biofilms and efflux pumps that diminish intracellular drug levels, to find novel antifungal drugs and drug targets. In this review, different classes of antifungal agents, and their resistance mechanisms, have been discussed. The latter part of the review focuses on the strategies by which we can overcome this serious issue of antifungal resistance in humans.

Comparative phylodynamics reveals the evolutionary history of SARS-CoV-2 emerging variants in the Arabian Peninsula.

Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to be responsible for an unprecedented worldwide public health and economic catastrophe. Accurate understanding and comparison of global and regional evolutionary epidemiology of novel SARS-CoV-2 variants are critical to guide current and future interventions. Here, we utilized a Bayesian phylodynamic pipeline to trace and compare the evolutionary dynamics, spatiotemporal origins, and spread of five variants (Alpha, Beta, Delta, Kappa, and Eta) across the Arabian Peninsula. We found variant-specific signatures of evolution and spread that are likely linked to air travel and disease control interventions in the region. Alpha, Beta, and Delta variants went through sequential periods of growth and decline, whereas we inferred inconclusive population growth patterns for the Kappa and Eta variants due to their sporadic introductions in the region. Non-pharmaceutical interventions imposed between mid-2020 and early 2021 likely played a role in reducing the epidemic progression of the Beta and the Alpha variants. In comparison, the combination of the non-pharmaceutical interventions and the rapid rollout of vaccination might have shaped Delta variant dynamics. We found that the Alpha and Beta variants were frequently introduced into the Arab peninsula between mid-2020 and early 2021 from Europe and Africa, respectively, whereas the Delta variant was frequently introduced between early 2021 and mid-2021 from East Asia. For these three variants, we also revealed significant and intense dispersal routes between the Arab region and Africa, Europe, Asia, and Oceania. In contrast, the restricted spread and stable effective population size of the Kappa and the Eta variants suggest that they no longer need to be targeted in genomic surveillance activities in the region. In contrast, the evolutionary characteristics of the Alpha, Beta, and Delta variants confirm the dominance of these variants in the recent outbreaks. Our study highlights the urgent need to establish regional molecular surveillance programs to ensure effective decision making related to the allocation of intervention activities targeted toward the most relevant variants.

Incidence of SARS-CoV-2 reinfection in a paediatric cohort in Kuwait.

OBJECTIVE: Subsequent protection from SARS-CoV-2 infection in paediatrics is not well reported in the literature. We aimed to describe the clinical characteristics and dynamics of SARS-CoV-2 PCR repositivity in children. DESIGN: This is a population-level retrospective cohort study. SETTING: Patients were identified through multiple national-level electronic COVID-19 databases that cover all primary, secondary and tertiary centres in Kuwait. PARTICIPANTS: The study included children 12 years and younger between 28 February 2020 and 6 March 2021. SARS-CoV-2 reinfection was defined as having two or more positive SARS-CoV-2 PCR tests done on a respiratory sample, at least 45 days apart. Clinical data were obtained from the Pediatric COVID-19 Registry in Kuwait. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary measure is to estimate SARS-CoV-2 PCR repositivity rate. The secondary objective was to establish average duration between first and subsequent SARS-CoV-2 infection. Descriptive statistics were used to present clinical data for each infection episode. Also, incidence-sensitivity analysis was performed to evaluate 60-day and 90-day PCR repositivity intervals. RESULTS: Thirty paediatric patients with COVID-19 had SARS-CoV-2 reinfection at an incidence of 1.02 (95% CI 0.71 to 1.45) infection per 100 000 person-days and a median time to reinfection of 83 (IQR 62-128.75) days. The incidence of reinfection decreased to 0.78 (95% CI 0.52 to 1.17) and 0.47 (95% CI 0.28 to 0.79) per person-day when the minimum interval between PCR repositivity was increased to 60 and 90 days, respectively. The mean age of reinfected subjects was 8.5 (IQR 3.7-10.3) years and the majority (70%) were girls. Most children (55.2%) had asymptomatic reinfection. Fever was the most common presentation in symptomatic patients. One immunocompromised experienced two reinfection episodes. CONCLUSION: SARS-CoV-2 reinfection is uncommon in children. Previous confirmed COVID-19 in children seems to result in a milder reinfection.