Phenotype, genotype, and mating type determination in oral Candida albicans isolates from pediatric patients with neutropenia.

BACKGROUND: The most frequent species of Candida to infect and colonize patients with neutropenia is still Candida albicans. This study aimed to provide detailed information on the phenotype, genotype, and mating type of oral C. albicans isolated from neutropenic pediatric patients, and to investigate how these characteristics are related. METHODS: Two hundred fifty-four oral samples from patients under 18 years old with neutropenia and malignancies were collected from January to October 2021. Samples were cultured on CHROMagar Candida. Isolates of C. albicans were identified with the germ tube test, chlamydospore production on cornmeal agar, and PCR-RFLP. Genotyping of C. albicans isolates was carried out by amplifying the 25S rDNA gene with specific CAINT-L and CA-INT-R primers. MTLa1 and MTLα1 primers were used to identify each mating type. Yeast peptone dextrose supplemented with phloxine B was used to identify different phenotypes. RESULTS: Ninety-two (36%) patients were positive for C. albicans. The mean age of patients was 7.85. Fifty-three (58.9%) isolates demonstrated type A, 15 (16.7%) type B, 15 (16.7%) types D/E, and 7 (7.7%) type C. Three isolates each (3.3%) were homozygous for MTLa or homozygous for MTLα. All of the MTL-homozygous isolates were genotype A. There was a significant correlation between patients' underlying disease and genotype (p = 0.036). There was a significant correlation between mating type and genotype (p = 0.000). CONCLUSION: Most of the isolates exhibited a white phenotype, noted in the literature as the most virulent. Moreover, heterozygous strains were frequent and may play a role in Candida colonization.

Population structure, susceptibility profile, phenotypic and mating properties of Candida tropicalis isolated from pediatric patients.

BACKGROUND: Candida tropicalis is one of the most frequently isolated species and is commonly associated with nosocomial infections, hematological malignancy, neutropenia, and urinary tract infections. AIMS: This study aims to genotype C. tropicalis strains isolated from pediatric patients admitted to two hospitals in Ahvaz, Iran. We provide a vision of the genotypes, mating types, enzymatic activity, phenotypes, and antifungal susceptibility profile of these isolates. METHODS: Candida tropicalis isolates were collected from various clinical (Oral, urine, wound, and bronchoalveolar lavage) and environmental sources between November 2020 and November 2021. Primitively, samples were cultured on CHROMagar Candida. All isolates were identified by sequencing the Internal Transcribed Spacer (ITS) region for precise identification. Isolates were genotyped by six microsatellite markers specific for C. tropicalis. Antifungal susceptibility profiles were determined against eight antifungal agents according to CLSI M27 standards. The phenotype of each C. tropicalis isolate was assessed using yeast peptone dextrose agar supplemented with phloxine B. Mating types of C. tropicalis isolates were determined using MTLa1 and MTL2 specific primers. RESULTS: Species identification revealed 46 C. tropicalis strains. Among them, 39 different genotypes were detected that have split into 34 singletons and five clusters. Twenty isolates were the non-wild type for itraconazole and posaconazole. Four isolates were multidrug-resistant. The activity of hemolysin and esterase enzyme was very strong among all isolates. Mating type and phenotype were not significantly correlated with genotypes (p = 0.721 and p = 0.135, respectively). CONCLUSIONS: To conclude, tested populations were moderately differentiated with high gene flow. One cluster of isolates among different hospitals was identified, and three clusters were from different cities.

Pediatric candiduria, epidemiology, genotype distribution and virulence factors of Candida albicans.

The presence of Candida species in urine may be due to colonization of this species in the bladder, urinary catheter, and perineum. Candida albicans has been the most commonly isolated from urine samples in patients with candiduria. Several virulence factors include adhesion to host cells, secreted extracellular enzymes, phenotype switching, and biofilm formation are contributing to the pathogenicity of C. albicans. ABC genotyping is the method based on the determination of 25s rDNA and C. albicans is divided into four genotypes include A, B, C, and E. We aimed to identify Candida species from pediatrics and evaluate extracellular enzyme activities, phenotype switching, biofilm formation, and genotyping in isolates. Urine samples collected, cultured, and yielded yeasts were identified. Phenotype switching, biofilm formation, enzymatic patterns, and genotyping of 50 isolates of C. albicans were evaluated. The Genotyping pattern was compared with extracellular enzymes, biofilm formation, and phenotype switching pattern. 16.2% of urine cultures were positive for the different Candida species. The most common species was C. albicans, followed by C. glabrata. Out of 50 isolates of C. albicans, 72% and 28% isolates were recognized as genotypes A and C. All isolates were produced extracellular enzymes and biofilm formation. In conclusion, candiduria with high colony counts is still a challenge in Iranian pediatrics. Genotype A was the predominant genotype among C. albicans strains. There is a statistical difference between esterase and genotypes of C and A C. albicans.

Prevalence and Risk Factors for Hearing Loss in Neonates Admitted to the Neonatal Intensive Care Unit: A Hospital Study.

INTRODUCTION: Hearing loss is one of the most common congenital disabilities in neonates. The aims of this study were to investigate the prevalence of hearing loss and identify the most significant risk factor in neonates hospitalized at the Neonatal Intensive Care Unit (NICU). METHODS: This cross-sectional study involved 530 neonates admitted to NICU Abuzar Hospital with risk factors for hearing loss based on Joint Committee of Infant Hearing (JCIH). The hearing screening tests include transient evoked otoacoustic emissions (TEOAES) and the automated auditory brain stem response (AABR). For infants with abnormal AABR and TEOAE results, the Auditory Brainstem Response (ABR) and Auditory Steady-State Responses (ASSR) tests were performed. RESULT: Of 530 infants, 27 (5.09%) were diagnosed with different types of hearing loss. Ototoxic drugs, hyperbilirubinemia requiring exchange transfusion, asphyxia, low weight birth, Apgar score < 5, and a kinship marriage of parents were significant risk factors for hearing loss in our study population. CONCLUSION: Due to the high prevalence of hearing loss in the NICU, it is recommended that a hearing screening program be performed for all infants admitted to the NICU. Implement a comprehensive plan for neonatal hearing screening for early detection and intervention of hearing loss is essential.

Risk Factors for Otitis Media in Children Referred to Abuzar Hospital in Ahvaz: A Case-Control Study.

Introduction Otitis media is one of the most common causes of infection in preschool children. The most damaging complication of otitis media is temporary or permanent hearing loss. This study aimed to determine the important risk factors for otitis media. Methods In this case-control study, 625 children aged six months to seven years were examined from winter to spring 2020, and 53 children with otitis media were allocated to the case group and the same number to the control group. The chi-square test was used to identify the risk factors affecting otitis media, and the risk factors were compared between the case and control groups. Logistic regression was used to investigate the relationship between the incidence of otitis media and risk factors. Results Bivariate analysis revealed the following primary risk factors for otitis media: using pacifiers or bottle feeding, working mother, seasonal rhinitis, allergic rhinitis, tonsillopharyngitis, rhinorrhea, and adenoid hypertrophy (P<0.05). In logistic regression analysis, using pacifiers or bottle feeding (odds ratio [OR]=0.156, P=0.000), working mother (OR=0.226, P=0.000), seasonal rhinitis (OR=0.175, P=0.000), allergic rhinitis (OR=5.20, P=0.000) and adenoid hypertrophy (OR=1.57, P=0.000) were identified as the most important risk factors. Conclusion Adenoid hypertrophy and allergic rhinitis increased the risk of otitis media more than the other risk factors. Therefore, pediatricians should increase their awareness of the existence of these risk factors in a patient, and take the appropriate diagnostic steps and implement therapeutic care to prevent language and speech complications.

Identifying medication errors in neonatal intensive care units: a two-center study.

BACKGROUND: This study aimed to assess the types and frequency of medication errors in our NICUs (neonatal intensive care units). METHODS: This descriptive cross-sectional study was conducted on two neonatal intensive care units of two hospitals over 3 months. Demographic information, drug information and total number of prescriptions for each neonate were extracted from medical records and assessed. RESULTS: A total of 688 prescriptions for 44 types of drugs were checked for the assessment of medical records of 155 neonates. There were 509 medication errors, averaging (SD) 3.38 (+/- 5.49) errors per patient. Collectively, 116 neonates (74.8%) experienced at least one medication error. Term neonates and preterm neonates experienced 125 and 384 medication errors, respectively. The most frequent medication errors were wrong dosage by physicians in prescription phase [WU1] (142 errors; 28%) and not administering medication by nurse in administration phase (146 errors; 29%). Of total 688 prescriptions, 127 errors were recorded. In this regard, lack of time and/or date of order were the most common errors. CONCLUSIONS: The most frequent medication errors were wrong dosage and not administering the medication to patient, and on the quality of prescribing, lack of time and/or date of order was the most frequent one. Medication errors happened more frequently in preterm neonates (P < 0.001). We think that using computerized physician order entry (CPOE) system and increasing the nurse-to-patient ratio can reduce the possibility of medication errors.

Pattern and extent of off-label and unlicensed drug use in neonatal intensive care units in Iran.

BACKGROUND: Many newborns may need to be hospitalized and receive drugs during the first days of their lives. These drugs are fundamentally prescribed as off-label and unlicensed. This study aimed to investigate the amount of these kinds of drugs administered in the Neonatal Intensive Care Units (NICUs) of Abuzar and Imam Khomeini Teaching Hospitals in Ahvaz, Iran. METHODS: This was a 3-month descriptive, cross-sectional study with retrospective nature in which 193 hospitalized newborns were studied. Demographic data were extracted from the patients' files. The drugs were classified as off-label, unlicensed or licensed according to the Pediatric & Neonatal Dosage Handbook (Lexicomp®, 22nd Edition). RESULTS: In total, 1049 prescriptions were registered for the 193 hospitalized newborns (term and preterm). For each newborn, the mean numbers of prescriptions and drugs received were 5.4 and 4.5, respectively. The mean numbers of prescriptions and drugs were greater for preterm newborns. Of the total 1049 prescriptions, 38.1% were off-label and 1.9% were unlicensed. Of the 193 newborns, 85% received at least one off-label or unlicensed prescription. Off-label prescriptions were mostly related to dose (44.8%) and dosing interval (36.5%). Most off-label drugs were antibiotics (mainly Gentamicin). Albuterol was used off-label in 100% of the cases. CONCLUSIONS: The results of the present study show that the prescription of off-label and unlicensed drugs in NICUs is as high in Iran as in other countries. This suggests that it is necessary to provide information to neonatologists to decrease the prescription of off-label and unlicensed drugs.

Association of SP-B gene 9306 A/G polymorphism (rs7316) and risk of RDS.

BACKGROUND: Respiratory distress syndrome (RDS) is a severe pulmonary disease predominantly affects preterm newborns. Polymorphisms of surfactant-protein genes have been mostly evaluated as the candidate contributors in genetics of RDS. However the results are divers in different studies. We aimed at investigating the association of surfactant protein B (SPB) gene 9306 A/G polymorphism (rs7316) with RDS development. METHOD: Three hundred and eighty newborns with gestational age of less than 34 weeks were included in a multicenter case-control study. Respiratory distress (RD) was scored according to Downes' scoring system. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping. RESULT: One hundred and eighty-four neonates showed RDS and 196 did not. Gestational age (GA) was significantly lower in the RDS group compared with the controls. AA genotype and A allele were found more frequently in the RDS group than the controls (96.2% versus 63.8% and 98.1% versus 80.6%, respectively) (p =.0001). CONCLUSIONS: This is the first report of association of SFTPB rs7316 polymorphism with RDS development in Iranian newborns. The current study suggests that GA <28-weeks is the most important factor in predisposition to RDS. Genetic background in terms of SP-B gene might be involved in predisposition to RDS in premature neonates.

Association of SP-C gene codon 186 polymorphism (rs1124) and risk of RDS.

BACKGROUND: Respiratory distress syndrome (RDS) is a severe pulmonary disease that mainly affects preterm neonates. Surfactant-protein genes' polymorphisms have been mostly evaluated as the candidate contributors in genetics of RDS. However, the results are diverse in different populations. We aimed at investigating the association of rs1124 with RDS development. METHOD: Three hundred and thirty five preterm neonates were enrolled in a multicenter case-control study. Respiratory distress (RD) was scored according to Downes' scoring system. Genotyping was performed by PCR-RFLP method. RESULT: One hundred and sixty six neonates showed RDS and 169 did not. Gestational age (GA) was significantly lower in RDS group compared to the controls. In female preterm newborns, AA genotype was found more frequently in RDS group. In RDS group, AA genotype was also associated with milder RD irrespective of gender. In neonates who were born 28-34 weeks, RD appeared to be more severe in the RDS group and males. CONCLUSIONS: This is the first report of association of SFTPC rs1124 polymorphism with RDS development in Iranian newborns. The current study suggests that GA <28-weeks is the most important factor in predisposition to RDS. AA genotype is also, a predisposing factor for the development of RDS in female preterm infants.

Comparison of the Combined versus Conventional Apgar Scores in Predicting Adverse Neonatal Outcomes.

OBJECTIVES: Assessing the value of the Combined-Apgar score in predicting neonatal mortality and morbidity compared to the Conventional-Apgar. METHODS: This prospective cohort study evaluated 942 neonates (166 very preterm, 233 near term, and 543 term) admitted to a tertiary referral hospital. At 1- and 5-minutes after delivery, the Conventional and Combined Apgar scores were recorded. The neonates were followed, and the following information was recorded: the occurrence of severe hyperbilirubinemia requiring medical intervention, the requirement for mechanical ventilation, the occurrence of intraventricular hemorrhage (IVH), and neonatal mortality. RESULTS: Before adjusting for the potential confounders, a low Conventional (<7) or Combined (<10) Apgar score at 5-minutes was associated with adverse neonatal outcomes. However, after adjustment for the gestational age, birth weight and the requirement for neonatal resuscitation in the delivery room, a depressed 5-minute Conventional-Apgar score lost its significant associations with all the measured adverse outcomes; after the adjustments, a low 5-minute Combined-Apgar score remained significantly associated with the requirement for mechanical ventilation (OR,18.61; 95%CI,6.75-51.29), IVH (OR,4.8; 95%CI,1.91-12.01), and neonatal mortality (OR,20.22; 95%CI,4.22-96.88). Additionally, using Receiver Operating Characteristics (ROC) curves, the area under the curve was higher for the Combined-Apgar than the Conventional-Apgar for the prediction of neonatal mortality and the measured morbidities among all the admitted neonates and their gestational age subgroups. CONCLUSIONS: The newly proposed Combined-Apgar score can be a good predictor of neonatal mortality and morbidity in the admitted neonates, regardless of their gestational age and resuscitation status. It is also superior to the Conventional-Apgar in predicting adverse neonatal outcomes in very preterm, near term and term neonates.

Comparison of the four proposed Apgar scoring systems in the assessment of birth asphyxia and adverse early neurologic outcomes.

OBJECTIVES: To compare the Conventional, Specified, Expanded and Combined Apgar scoring systems in predicting birth asphyxia and the adverse early neurologic outcomes. METHODS: This prospective cohort study was conducted on 464 admitted neonates. In the delivery room, after delivery the umbilical cord was double clamped and a blood samples was obtained from the umbilical artery for blood gas analysis, meanwhile on the 1- , 5- and 10- minutes Conventional, Specified, Expanded, and Combined Apgar scores were recorded. Then the neonates were followed and intracranial ultrasound imaging was performed, and the following information were recorded: the occurrence of birth asphyxia, hypoxic Ischemic Encephalopathy (HIE), intraventricular hemorrhage (IVH), and neonatal seizure. RESULTS: The Combined-Apgar score had the highest sensitivity (97%) and specificity (99%) in predicting birth asphyxia, followed by the Specified-Apgar score that was also highly sensitive (95%) and specific (97%). The Expanded-Apgar score was highly specific (95%) but not sensitive (67%) and the Conventional-Apgar score had the lowest sensitivity (81%) and low specificity (81%) in predicting birth asphyxia. When adjusted for gestational age, only the low 5-minute Combined-Apgar score was independently associated with the occurrence of HIE (B = 1.61, P = 0.02) and IVH (B = 2.8, P = 0.01). CONCLUSIONS: The newly proposed Combined-Apgar score is highly sensitive and specific in predicting birth asphyxia and also is a good predictor of the occurrence of HIE and IVH in asphyxiated neonates.

Prevalence of celiac disease in siblings of Iranian patients with celiac disease.

CONTEXT: Celiac disease, one of the best-known autoimmune human leukocyte antigen-dependent disorders, has a relatively increased prevalence in first-degree relatives. OBJECTIVE: To determine the prevalence of celiac disease in siblings of patients with confirmed celiac disease. METHODS: Siblings of confirmed celiac disease patients in our center were identified and enrolled in this study. Their serum immunoglobulin A and tissue transglutaminase antibody-enzyme-linked immunosorbent assay (anti-tissue transglutaminase, immunoglobulin A, and immunoglobulin G) were measured and multiple endoscopic duodenal biopsy specimens were obtained with parental consensus. Celiac disease was confirmed by observation of characteristic histological changes. RESULTS: A total of 49 children (male, 29; female, 20; age, 2-16 years) with confirmed celiac disease in a pediatric gastroenterology ward were studied from 1999 to 2006. We found 30 siblings (female, 16) all shared in both parents. The only measurement available was for immunoglobulin A tissue transglutaminase antibody. A duodenal biopsy was performed in all 30 siblings. Clinical findings such as abdominal pain, fatigue, growth retardation and diarrhea were found in 53.3% of the completely studied siblings, and positive serology without histological changes was identified in four cases. Both serology and biopsy (confirmed new cases) were positive in 2 of the 30 siblings. CONCLUSION: High prevalence of celiac disease among siblings of patients with confirmed celiac disease necessitates serologic screening (and confirmatory biopsy if indicated) in families having celiac disease. It is advantageous to diagnose the disease as soon as possible because early diagnosis and diet intervention may prevent serious complications such as growth retardation, short stature, chronic diarrhea, and malignancy.

Prevalence of celiac disease in siblings of Iranian patients with celiac disease / Prevalência de doença celíaca em filhos de pais iranianos com doença celíaca

CONTEXT: Celiac disease, one of the best-known autoimmune human leukocyte antigen-dependent disorders, has a relatively increased prevalence in first-degree relatives. OBJECTIVE: To determine the prevalence of celiac disease in siblings of patients with confirmed celiac disease. METHODS: Siblings of confirmed celiac disease patients in our center were identified and enrolled in this study. Their serum immunoglobulin A and tissue transglutaminase antibody-enzyme-linked immunosorbent assay (anti-tissue transglutaminase, immunoglobulin A, and immunoglobulin G) were measured and multiple endoscopic duodenal biopsy specimens were obtained with parental consensus. Celiac disease was confirmed by observation of characteristic histological changes. RESULTS: A total of 49 children (male, 29; female, 20; age, 2-16 years) with confirmed celiac disease in a pediatric gastroenterology ward were studied from 1999 to 2006. We found 30 siblings (female, 16) all shared in both parents. The only measurement available was for immunoglobulin A tissue transglutaminase antibody. A duodenal biopsy was performed in all 30 siblings. Clinical findings such as abdominal pain, fatigue, growth retardation and diarrhea were found in 53.3 percent of the completely studied siblings, and positive serology without histological changes was identified in four cases. Both serology and biopsy (confirmed new cases) were positive in 2 of the 30 siblings. CONCLUSION: High prevalence of celiac disease among siblings of patients with confirmed celiac disease necessitates serologic screening (and confirmatory biopsy if indicated) in families having celiac disease. It is advantageous to diagnose the disease as soon as possible because early diagnosis and diet intervention may prevent serious complications such as growth retardation, short stature, chronic diarrhea, and malignancy.

CONTEXTO: A doença celíaca, uma das mais conhecidas enfermidades autoimunes humanas, leucocitária antígeno-dependente, tem prevalência relativamente maior em parentes de primeiro grau. OBJETIVO: Determinar a prevalência de doença celíaca em irmãos de pacientes confirmadamente celíacos, filhos dos mesmos pais. MÉTODOS: Os irmãos de pacientes com doença celíaca confirmada no Department of Pediatrics, Ahvaz Jundishapur University of Medical Sciences, em Ahvaz, Iran, foram identificados e incluídos no estudo. A imunoglobulina A sérica e o anticorpo transglutaminase tecidual por ensaio imunoenzimático (anti-transglutaminase tecidual, imunoglobulina A e imunoglobulina G) foram medidos e múltiplas biopsias endoscópicas duodenais foram obtidas com o consenso dos pais. A doença celíaca foi confirmada pela observação das características histológicas. RESULTADOS: Um total de 49 crianças (29 do sexo masculino; 20 do sexo feminino; de 2 a 16 anos) com diagnóstico confirmado de doença celíaca em uma enfermaria de gastroenterologia pediátrica foi estudado de 1999 a 2006. Encontraram-se 30 irmãos (16 do sexo feminino) e todos compartilhavam os mesmos pais dos pacientes. A única medida disponível foi do anticorpo tecidual imunoglobulina A transglutaminase. A biopsia duodenal foi realizada em todos os 30 irmãos. As manifestações clínicas como dor abdominal, fadiga, retardo do crescimento e diarréia foram encontradas em 53,3 por cento dos irmãos estudados completamente, e a sorologia positiva sem alterações histológicas foi identificada em quatro casos. Ambas, sorologia e biopsia (novos casos confirmados) foram positivas em 2 dos 30 irmãos. CONCLUSÕES: A prevalência de doença celíaca entre irmãos de pais confirmadamente celíacos exige triagem sorológica e biopsia de confirmação, se indicada, em familiares com doença celíaca. Diagnosticar a doença o mais rápido possível traz vantagens, pois o diagnóstico precoce e a intervenção dietética podem prevenir complicações graves, como retardo do crescimento, baixa estatura, diarreia crônica e malignidade.