Pediatric Infectious Diseases Research Articles

Zero-dose children in Latin America: analysis of the problem and possible solutions

Introduction Zero-dose children (ZDC) are defined as those that have never been reached by routine immunization services. In Latin America, almost 2.7 million infants younger than 1 year of age, have incomplete vaccination schedules, and vaccine preventable diseases such as measles or polio have increase worldwide. ZDC are reported to reside in high risk and fragile settings, including remote-rural areas, urban slums, and conflict-affected areas. Identifying the problem and settings in each country is mandatory to propose possible solutions to the immunization coverage situation. Areas covered In November 2023, a group of experts of the Latin America Society of Pediatric Infectious Diseases (SLIPE) analyzed the global and regional reality of ZDC, and present in this document an updated reality of the Latin American region and the weight of the possible interventions to overcome this problem. Expert commentary Communication is a key element to improve vaccination coverage, as it is quality and use of vaccination data. Campaigns that deliver targeted and effective messages to communities and families, provide education about vaccination, avoid missed vaccination opportunities, and coordinate efforts across different sectors and communities, among other strategies, could improve the current immunization situation.

Planetary Health: What You Need to Know as a Pediatric Infectious Diseases Doctor.

Planetary Health: What You Need to Know as a Pediatric Infectious Diseases Doctor.

Nigel Klein: paediatric infectious diseases expert who correctly hypothesised that children could have breaks from HIV treatment

Nigel Klein: paediatric infectious diseases expert who correctly hypothesised that children could have breaks from HIV treatment

Ocular toxocariasis masquerading as toxoplasmosis: a case report and literature review

Background: False-negative and false-positive results in Toxoplasma serology are possible, and this could be misleading. Here, we report the case of a boy with Toxocara-associated panuveitis who was initially treated for toxoplasmosis owing to false-positive Toxoplasma immunoglobulin M (IgM) serology. Case Presentation: A nine-year-old boy presented with intermittent headaches and blurred vision in the left eye. Close contact with domesticated animals was remarkable in the patient’s history. Upon examination, vision was 20/400 in the left eye. Slit-lamp examination revealed anterior chamber cells and flare without keratic precipitates, with vitreous cells and veils, optic disc edema, and a blurred fundus appearance. A systemic investigation revealed the presence of anti-Toxoplasma IgM antibodies. Treatment was initiated using topical cycloplegic and corticosteroid eye drops, in addition to oral trimethoprim/sulfamethoxazole. Oral corticosteroids were also administered. As the inflammation resolved, an inferior tractional detachment was detected on fundus examination, leading to the ultimate diagnosis of ocular toxocariasis. An enzyme-linked immunosorbent assay was positive for serum Toxocara antibodies. A fourteen-day course of oral albendazole was ordered by the pediatric infectious disease service because of the concern for visceral larva migrans, while topical eye drops were continued and oral prednisone was tapered. One month later, visual acuity in the left eye had improved to 20/70. The anterior chamber inflammation resolved; however, some vitreous cells and optic disc edema persisted. The inferior tractional detachment was much better visualized, and a peripheral granuloma was observed. Four months later, without any oral or topical medications, the patient’s visual acuity had improved to 20/30 and his eye had no active inflammation. The patient has been followed up for two years and has never developed any other lesions. Conclusions: False-positive results on Toxoplasma serology and diffuse vitritis from toxocariasis that limited retinal visualization complicated the initial diagnosis in this case. In diagnosing the etiology of uveitis, ocular examination and detailed history taking should be emphasized, as laboratory results may be misleading.

Documento nacional de consenso de monitorización terapéutica de antibióticos y antifúngicos en el paciente pediátrico y neonatal de la Sociedad Española de Farmacia Hospitalaria (SEFH) y la Sociedad Española de Infectología Pediátrica (SEIP)

Therapeutic monitoring of antibiotics and antifungals based on pharmacokinetic and pharmacodynamic param- eters, is a strategy increasingly used for the optimization of therapy to improve efficacy, reduce the occurrence of toxicities, and prevent the selection of antimicrobial resistance, particularly in vulnerable patients including neonates and the critical or immunocompromised host.In neonates and children, infections account for a high percentage of hospital admissions and anti-infectives are the most used drugs. However, pediatric pharmacokinetic and pharmacodynamic studies and the evidence regarding the efficacy and safety of some newly marketed antibiotics and antifungals -usually used off-label in pediatrics- to determine the optimal drug dosage regimens are limited. It is widely known that this population presents important differences in the pharmacokinetic parameters (especially in drug clearance and volume of distribution) in comparison with adults that may alter antimicrobial exposure and, therefore, compromise treat- ment success. In addition, pediatric patients are more susceptible to potential adverse drug effects and they need closer monitoring.The aim of this document, developed jointly between the Spanish Society of Hospital Pharmacy (SEFH) and the Spanish Society of Pediatric Infectious Diseases (SEIP), is to describe the available evidence on the indications for therapeutic drug monitoring of antibiotics and antifungals in newborn and pediatric patients and to provide prac- tical recommendations for therapeutic drug monitoring in routine clinical practice to optimize pharmacokinetic and pharmacodynamic parameters, efficacy and safety of antibiotics and antifungals in the pediatric population.

Clinical guideline highlight for the hospitalist: Diagnosis and management of acute bacterial arthritis in children.

Clinical Practice Guideline by the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA): 2023 Guideline on Diagnosis and Management of Acute Bacterial Arthritis RELEASE DATE: January 1, 2024 PRIOR VERSION(S): n/a DEVELOPER: Pediatric Infectious Diseases Society (PIDS), Infectious Diseases Society of America (IDSA) FUNDING SOURCE: PIDS and IDSA TARGET POPULATION: Children with suspected or confirmed acute bacterial arthritis.

Integration and validation of host transcript signatures, including a novel 3-transcript tuberculosis signature, to enable one-step multiclass diagnosis of childhood febrile disease

BackgroundWhole blood host transcript signatures show great potential for diagnosis of infectious and inflammatory illness, with most published signatures performing binary classification tasks. Barriers to clinical implementation include validation studies, and development of strategies that enable simultaneous, multiclass diagnosis of febrile illness based on gene expression.MethodsWe validated five distinct diagnostic signatures for paediatric infectious diseases in parallel using a single NanoString nCounter® experiment. We included a novel 3-transcript signature for childhood tuberculosis, and four published signatures which differentiate bacterial infection, viral infection, or Kawasaki disease from other febrile illnesses. Signature performance was assessed using receiver operating characteristic curve statistics. We also explored conceptual frameworks for multiclass diagnostic signatures, including additional transcripts found to be significantly differentially expressed in previous studies. Relaxed, regularised logistic regression models were used to derive two novel multiclass signatures: a mixed One-vs-All model (MOVA), running multiple binomial models in parallel, and a full-multiclass model. In-sample performance of these models was compared using radar-plots and confusion matrix statistics.ResultsSamples from 91 children were included in the study: 23 bacterial infections (DB), 20 viral infections (DV), 14 Kawasaki disease (KD), 18 tuberculosis disease (TB), and 16 healthy controls. The five signatures tested demonstrated cross-platform performance similar to their primary discovery-validation cohorts. The signatures could differentiate: KD from other diseases with area under ROC curve (AUC) of 0.897 [95% confidence interval: 0.822–0.972]; DB from DV with AUC of 0.825 [0.691–0.959] (signature-1) and 0.867 [0.753–0.982] (signature-2); TB from other diseases with AUC of 0.882 [0.787–0.977] (novel signature); TB from healthy children with AUC of 0.910 [0.808–1.000]. Application of signatures outside of their designed context reduced performance. In-sample error rates for the multiclass models were 13.3% for the MOVA model and 0.0% for the full-multiclass model. The MOVA model misclassified DB cases most frequently (18.7%) and TB cases least (2.7%).ConclusionsOur study demonstrates the feasibility of NanoString technology for cross-platform validation of multiple transcriptomic signatures in parallel. This external cohort validated performance of all five signatures, including a novel sparse TB signature. Two exploratory multi-class models showed high potential accuracy across four distinct diagnostic groups.

Rapid and simultaneous detection of common childhood diarrhea viruses by microfluidic-FEN1-assisted isothermal amplification with ultra-high specificity and sensitivity

Rapid and accurate diagnostic methods are crucial for managing viral gastroenteritis in children, a leading cause of global childhood morbidity and mortality. This study introduces a novel microfluidic-Flap endonuclease 1 (FEN1)-assisted isothermal amplification (MFIA) method for simultaneously detecting major viral pathogens associated with childhood diarrhea—rotavirus, norovirus, and adenovirus. Leveraging the specificity-enhancing properties of FEN1 with a universal dspacer-modified flap probe and the adaptability of microfluidic technology, MFIA demonstrated an exceptional detection limit (5 copies/μL) and specificity in the simultaneous detection of common diarrhea pathogens in clinical samples. Our approach addresses the limitations of current diagnostic techniques by offering a rapid (turn around time <1 h), cost-effective, easy design steps (universal flap design), and excellent detection performance method suitable for multiple applications. The validation of MFIA against the gold-standard PCR method using 150 actual clinical samples showed no statistical difference in the detection performance of the two methods, positioning it as a potential detection tool in pediatric diagnostic virology and public health surveillance. In conclusion, the MFIA method promises to transform pediatric infectious disease diagnostics and contribute significantly to global health efforts combating viral gastroenteritis.

Antibiotics Utilization Pattern in a Children’s Medical Center in North of Iran

Background: The development of a system for rational use of antimicrobials seems mandatory. Furthermore, since hospitals do not share the same bacterial flora and have different patterns of antibiotic therapy the purpose of the present study is to perform a Drug Utilization Evaluation (DUE) on the pattern of antibiotic administration in patients hospitalized in 17 Shahrivar Pediatric Hospital, RASHT, Iran. Methods: In this descriptive cross-sectional study that was conducted in a one-year period (2021-2022), 560 patients were randomly selected and their medication data were collected based on the gender and age as well as the type, dose, duration of antibiotic therapy and the results of bacterial cultures and also susceptibility of the infectious microorganisms. Results: The average age of patients was 53.56 months with 46.9% of them being less than 24 months old. The highest rate of antibiotics administration belonged to the infectious diseases ward (30%) and 33% of antibiotics were prescribed by pediatric infectious diseases specialists. The result of most of the cultures was reported as negative (98.38%), the most prevalent microorganism was Escherichia Coli from urine cultures (2.38%) and Staphylococcus Aureus from sputum cultures (14.28%). The highest prescribed antibiotics were ceftriaxone (51.2%) and vancomycin (45.6%). It was determined the antibiotic stipend was 15.6% of the whole budget for purchasing medicine. Conclusions: It is necessary to develop a guideline regarding the prescription of antibiotics in children's departments, which reduces empiric treatment and the requirement to adjust the drug after a negative culture.

Evaluation of the Bio-Speedy Meningitis/Encephalitis Panel in the Diagnosis of Central Nervous System Infections

Infections of the central nervous system (CNS) can lead to severe outcomes if not accurately diagnosed and treated. The broad spectrum of pathogens involved in CNS infections can make diagnosis challenging. Polymerase chain reaction (PCR) -based multiplex molecular diagnostic panels can rapidly and simultaneously detect multiple neuropathogens in cerebrospinal fluid (CSF). This study was aimed to assess the Bio-Speedy Meningitis/Encephalitis RT-PCR MX-17 panel (Bioeksen, İstanbul, Türkiye), a novel multiplex PCR test, in diagnosing CNS infections. The panel can detect a range of pathogens, including Escherichia coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis, Streptococcus pneumoniae, Streptococcus agalactiae, enterovirus (EV), herpes simplex virus (HSV) 1 and 2, HHV-6, HHV-7, HHV-8, human parechovirus (HPeV), varicella zoster virus (VZV), cytomegalovirus (CMV) and Cryptococcus gatti/neoformans in CSF samples. This retrospective study included 128 CSF samples from 128 patients sent to Bursa Uludağ University Health Application and Research Center Microbiology Laboratory between June 2022 and July 2023 to search for CNS infectious agents. Patient clinical, radiological and laboratory data were collected from the Hospital Information Record System (HIRS). Bacterial pathogens were identified through culture, while viral pathogens were detected in CSF samples using the Fast Track Diagnostics (FTD) multiplex RT-PCR panel (Fast Track Diagnostics Ltd., Luxembourg) for HSV-1, HSV-2, VZV, EV, mumps virus and HPeV. The stored CSF samples were then tested using the BioSpeedy panel and the results were compared with those of the culture and the FTD panel. Pathogens that were detected were considered positive if they were consistent with the patient's symptoms and CSF characteristics according to infectious disease and pediatric infectious disease specialists. Pathogens detected but not supported by the patient's symptoms and CSF characteristics were classified as uncertain clinical relevance (UCR). Out of the 128 patients tested for CNS infectious agents, 44 (34.4%) were diagnosed with a CNS infection. The overall pathogen detection rate with all methods was 43.2% (19/44). The Bio-Speedy panel identified pathogens in 29.5% (13/44) of the patients, followed by the FTD panel (20.5%, 9/44) and culture (9.1%, 4/44). Four bacteria were identified with culture, three of which were also detected by the Bio-Speedy panel. Additionally, six bacteria were identified with Bio-Speedy panel, that were not identified by culture. The FTD panel identified nine viruses, four of which were also identified by Bio-Speedy. In total, the Bio-Speedy panel detected 13 of the 19 positive pathogens (nine bacteria and four viruses: [S.pneumoniae (n= 3), VZV (n= 3), N.meningitidis (n= 2), H.influenzae (n= 2), L.monocytogenes (n= 1), E.coli (n= 1) ve EV (n= 1)]. However, the Bio-Speedy panel identified 15 pathogens [S.pneumoniae (n= 1), E.coli (n= 1), C.gatti/neoformans (n= 1), CMV (n= 8), HHV-6 (n= 3) ve HHV-7 (n= 1)] considered as UCR. The Bio-Speedy identified the causative pathogens in the highest percentage (29.5%) of patients with confirmed CNS infections. Nevertheless, test results should be interpreted based on patient characteristics to ensure appropriate patient management. Using multiple methods and multiplex tests may improve diagnostic accuracy for CNS infections.

Simulation training for residents at the department of pediatric infectious diseases of “Astana medical university”

The article presents the results of the implementation of simulation training for residents of the 1st and 2nd year of study at the Simulation Center of “Astana Medical University”.

Navigating the Med-Peds Maze: Considerations for the Combined Adult and Pediatric Infectious Disease Fellowship Application Process.

Navigating the combined adult and pediatric infectious disease (ID) fellowship application, interview, and matching process requires careful consideration from applicants and programs alike. Currently, it is functional but not streamlined, and as the ID community is facing recruitment and workforce challenges, it is important to be transparent about this process for applicants while emphasizing areas of potential improvement for fellowship programs. As it stands, this process requires foresight from the applicant and coordination between the adult and pediatric fellowship programs. This perspective article provides an anecdote and discusses issues and suggestions for troubleshooting, including, but not limited to: strategic approach to applications, interviews, and ranking, mentorship, geographic preference, and program saturation.

Is there a Role for Hyperbaric Oxygen Therapy in Pediatric Infectious Diseases Practice?

Is there a Role for Hyperbaric Oxygen Therapy in Pediatric Infectious Diseases Practice?

Clinical and epidemiological analysis of intestinal infections in a children's infectious diseases hospital, experience in using the PEWS scale

Purpose of the work: to conduct a clinical-epidemiological analysis of intestinal infections in a pediatric infectious diseases hospital and the effectiveness of the PEWS scale.Materials and methods: a retrospective study was conducted at the Moscow City Clinical Hospital «Communarka» and City Clinical Hospital No. 1 in the pediatric infectious disease departments from June 1, 2023, to August 31, 2023. Laboratory, clinical, and anamnestic data were obtained from the medical information system «EMIAS» and the laboratory information system (LIS) «ALISA». The study analyzed 838 medical records of children with acute respiratory infections.Results: when conducting a statistical analysis of indicators in two groups (group 1 — PEWS ≥ 3 points, recorded at least once during the entire period of hospitalization, group 2 — PEWS from 1 to 2 points, recorded at least once during hospitalization period) no significant differences were observed in terms of etiology, age, day of illness, blood test results, and length of hospital stay. All patients had a moderate form of acute respiratory infection, however, patients with PEWS ≥ 3 points required increased attention from medical staff and had a higher risk of deterioration without additional medical intervention, with the most significant risk in predicting deterioration being related to changes in the cardiovascular system. All children were discharged home in satisfactory condition with PEWS = 0.Conclusion: In our conducted research, for the first time in the Russian Federation, the experience of using the PEWS scale in pediatric practice for patients with gastrointestinal infections was applied with the aim of early detection of the risk of clinical deterioration. It can be assumed that the most significant risk in predicting deterioration in the condition of a child with acute gastrointestinal infection, as well as with acute respiratory infection, is predominantly due to disturbances in the cardiovascular system.

Intersectional inequalities in paediatric infectious diseases: a national cohort study in Sweden

BackgroundIt is well known that socially deprived children are more likely to be hospitalised for infections. Less is known about how different social disadvantages interact. Therefore, we examine intersectional inequalities...

Overcoming Challenges for Non-US International Medical Graduates in Pediatric Infectious Diseases.

International medical graduates (IMGs) in pediatric infectious diseases face unique and complex challenges related to their immigration status. This Perspective provides a review of challenges impacting non-US IMG trainees and early-career faculty, and how the infectious diseases community can respond.

The clinical application and laboratory management of molecular genetic diagnosis in children's hospital

AbstractBackgroundMolecular diagnostic technology is the foundation of precision medicine, which has the advantages of good specificity, high sensitivity, strong targeting, rapiddiagnosis, etc. It has a wide range of applications in the field of pediatrics. However, molecular diagnostic technology is characterized by complicated experimental operation, high difficulty in data analysis and interpretation, in consistent standards among laboratories, and difficult standardization of technical processes. Enhancing the application value of molecular diagnostic technology in pediatrics and promoting the high‐quality development of the discipline requires careful consideration by relevant management and professionals.MethodsThis study firstly outlines the development history of molecular diagnostic technology. Then, it analyzes the application of molecular diagnostic technology in the field of pediatrics. Finally, it explores the countermeasures for the management of molecular diagnostic laboratories.ResultsThis study highlights the importance of molecular diagnostic technology in providing information and decision‐making basis for disease prevention, prediction,diagnosis, treatment and regression. It has a wide range of applications in the molecular diagnosis of pediatric hereditary diseases, malignant tumors and infectious diseases. In addition, the countermeasures for the management of molecular diagnostic laboratories are proposed from the five aspects of laboratory, personnel team construction, standardized management,multidisciplinary cross‐discipline, research and translation, safety managementand ethical supervision, and management upgrading and modernization.ConclusionsMolecular diagnostic technology, as the basis of precision medicine, has become one of the important frontier fields in the development of contemporary pediatric medicine. Enhanced laboratory capacity in molecular diagnostic techniques can improve outcomes in the prevention, prediction, diagnosis, treatment, prognosis and research of pediatricdiseases, and lay the groundwork for child healthcare.

Leading Paediatric Infectious Diseases-Current Trends, Gaps, and Future Prospects in Oral Pharmacotherapeutic Interventions.

Paediatric infectious diseases contribute significantly to global health challenges. Conventional therapeutic interventions are not always suitable for children, as they are regularly accompanied with long-standing disadvantages that negatively impact efficacy, thus necessitating the need for effective and child-friendly pharmacotherapeutic interventions. Recent advancements in drug delivery technologies, particularly oral formulations, have shown tremendous progress in enhancing the effectiveness of paediatric medicines. Generally, these delivery methods target, and address challenges associated with palatability, dosing accuracy, stability, bioavailability, patient compliance, and caregiver convenience, which are important factors that can influence successful treatment outcomes in children. Some of the emerging trends include moving away from creating liquid delivery systems to developing oral solid formulations, with the most explored being orodispersible tablets, multiparticulate dosage forms using film-coating technologies, and chewable drug products. Other ongoing innovations include gastro-retentive, 3D-printed, nipple-shield, milk-based, and nanoparticulate (e.g., lipid-, polymeric-based templates) drug delivery systems, possessing the potential to improve therapeutic effectiveness, age appropriateness, pharmacokinetics, and safety profiles as they relate to the paediatric population. This manuscript therefore highlights the evolving landscape of oral pharmacotherapeutic interventions for leading paediatric infectious diseases, crediting the role of innovative drug delivery technologies. By focusing on the current trends, pointing out gaps, and identifying future possibilities, this review aims to contribute towards ongoing efforts directed at improving paediatric health outcomes associated with the management of these infectious ailments through accessible and efficacious drug treatments.

Natural History and Management of Hepatitis C in Children: 25 Years Experience of a Reference Center in Northern Italy.

Hepatitis C virus (HCV) infection natural history and management in the pediatric population are still debated. We retrospectively evaluated the outcome of a HCV pediatric population managed at the Pediatric Infectious Disease Unit of Luigi Sacco Hospital (Milan, Italy) from January 1997 to January 2022 (median follow-up 10 years) and we focused on the role of new drugs and transient elastography. Fifty-seven patients were enrolled: 8 (14%) had a spontaneous clearance, 33 were treated (58%), 7 (12%) were not treated because they were under 12 years old and 9 were lost at follow-up. HCV RNA was undetectable in all treated patients at the end of therapy, after 12 weeks (SVR12) and for the rest of their follow-up. All patients treated underwent elastography before and 1 year after therapy. Median stiffness pretherapy was 5.6 kPa, and 9 patients (16%) had abnormal transient elastography (>7 kPa, median 8.7 kPa). Median stiffness after treatment in the abnormal group was 6.8 kPa. Direct-acting antiviral agents are a safe and effective therapy for HCV chronic infection in the pediatric population. Liver elastography is normal in many vertically infected children before 12 years, but, when abnormal, it shows a significant improvement after direct-acting antiviral agent treatment. Further studies are needed to evaluate the role of elastography at diagnosis and follow-up in children.

Risk Factors for Pediatric Critical COVID-19: A Systematic Review and Meta-Analysis.

Risk stratification is a cornerstone of the Pediatric Infectious Diseases Society COVID-19 treatment guidance. This systematic review and meta-analysis aimed to define the clinical characteristics and comorbidities associated with critical COVID-19 in children and adolescents. Two independent reviewers screened the literature (Medline and EMBASE) for studies published through August 31, 2023, that reported outcome data on patients aged ≤21 years with COVID-19. Critical disease was defined as an invasive mechanical ventilation requirement, intensive care unit admission, or death. Random-effects models were used to estimate pooled odds ratios (OR) with 95% confidence intervals (CI), and heterogeneity was explored through subgroup analyses. Among 10,178 articles, 136 studies met the inclusion criteria for review. Data from 70 studies, which collectively examined 172,165 children and adolescents with COVID-19, were pooled for meta-analysis. In previously healthy children, the absolute risk of critical disease from COVID-19 was 4% (95% CI, 1%-10%). Compared with no comorbidities, the pooled OR for critical disease was 3.95 (95% CI, 2.78-5.63) for the presence of one comorbidity and 9.51 (95% CI, 5.62-16.06) for ≥2 comorbidities. Key risk factors included cardiovascular and neurological disorders, chronic pulmonary conditions (excluding asthma), diabetes, obesity, and immunocompromise, all with statistically significant ORs > 2.00. While the absolute risk for critical COVID-19 in children and adolescents without underlying health conditions is relatively low, the presence of one or more comorbidities was associated with markedly increased risk. These findings support the importance of risk stratification in tailoring pediatric COVID-19 management.