Homozygous TNNI3 frameshift variant in a consanguineous family with lethal infantile dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is characterized by dilatation of the left ventricle, systolic dysfunction, and normal or reduced thickness of the left ventricular wall. It is a leading cause of heart failure and cardiac death at a young age. Cases with neonatal onset DCM were correlated with severe clinical presentation and poor prognosis. A monogenic molecular etiology accounts for nearly half of cases. FAMILY DESCRIPTION: Here, we report a family with three deceased offspring at the age of 1 year old. The autopsy of the first deceased infant revealed a DCM. The second infant presented a DCM phenotype with a severely reduced Left Ventricular Ejection Fraction (LVEF) of 10%. Similarly, the third infant showed a severe DCM phenotype with LVEF of 30% as well, in addition to eccentric mitral insufficiency. RESULTS: Exome sequencing was performed for the trio (the second deceased infant and her parents). Data analysis following the autosomal dominant and recessive patterns of inheritance was carried out along with a mitochondrial pathways-based analysis. We identified a homozygous frameshift variant in the TNNI3 gene (c.204delG; p.(Arg69AlafsTer8)). This variant has been recently reported in the ClinVar database in association with cardiac phenotypes as pathogenic or likely pathogenic and classified as pathogenic according to ACMG. CONCLUSION: Genetic counseling was provided for the family and a prenatal diagnosis of choronic villus was proposed in the absence of pre-implantation genetic diagnosis possibilities. Our study expands the case series of early-onset DCM patients with a protein-truncating variant in the TNNI3 gene by reporting three affected infant siblings.

Epidemiological and bacterial profile of childhood meningitis in Tunisia.

The worldwide burden of disease of bacterial meningitis remains high, despite the decreasing incidence following introduction of routine vaccination campaigns.The aim of our study was to evaluate the epidemiological and bacteriological profile of paediatric bacterial meningitis (BM) in Tunisian children, during the period 2003-2019, following the implementation of Haemophilus influenzae type b (Hib) vaccine (April 2011) and before 10-valent pneumoccocal conjugate vaccine (PCV10) introduction to the childhood immunization program.All bacteriologically confirmed cases of BM admitted to children's hospital of Tunis were recorded (January 2003 to April 2019). Serogroups of Neisseria meningitidis (Nm) and serotypes of Streptococcus pneumoniae (Sp) and H. influenzae (Hi) and antibiotic resistance were determined using conventional and molecular methods.Among 388 cases, the most frequent species were Sp (51.3%), followed by Nm (27.5%) and Hi (16.8%). We observed a significant decrease in Hi BM rate during the conjugated Hib vaccine use period (P < 0.0001). The main pneumococcal serotypes were 14, 19F, 6B, 23F and 19A and the serotype coverage of PCV10, PCV13, PCV15 and PCV20 was 71.3 and 78.8%, 79.4 and 81.9% respectively. The most frequent Nm serogroup was B (83.1%). Most Hi strains were of serotype b (86.9%). High levels of resistance were found: Sp and Nm to penicillin (respectively 60.1 and 80%) and Hi to ampicillin (42.6%). All meningococcal and Hi isolates were susceptible to third-generation cephalosporins and 7.2% of pneumococcal strains had decreased susceptibility to these antibiotics.The Hib conjugate vaccine decreased the rate of BM. Sp dominated the aetiology of BM in children in Tunisia. Conjugate vaccines introducing decreases not only BM cases but also antimicrobial resistance.

Retrospective Analysis of Clinical Characteristics and Disease Outcomes in Children and Adolescents Hospitalized Due to COVID-19 Infection in Tunisia.

Due to low susceptibility of coronavirus disease of 2019 (COVID-19) in children, limited studies are available regarding COVID-19 in the pediatric population in Tunisia. The current study evaluated the incidence, clinical characteristics, and outcomes of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection among children hospitalized at Béchir Hamza Children's Hospital. A retrospective cohort analysis was conducted using the hospital database between March 2020 and February 2022 with children aged ≤15 years with SARS-CoV-2 infection (confirmed by RT-PCR). A total of 327 COVID-19 hospitalized patients with a mean age of 3.3 years were included; the majority were male. Neurological disease (20%) was the most common comorbidity, while fever (95.3%) followed by cough (43.7%) and dyspnea (39.6%) were the most frequent symptoms reported. Severe disease with oxygen requirement occurred in 30% of the patients; 13% were admitted in the Intensive Care Unit. The overall incidence rate of COVID-19 hospitalization (in Tunis governorates) was 77.02 per 100,000 while the inpatient case fatality rate was 5% in the study population. The most prevalent circulating variant during our study period was Delta (48.8%), followed by Omicron (26%). More than 45% of the study population were <6 months and one-fourth (n = 25, 26.5%) had at least one comorbidity. Thus, the study findings highlight the high disease burden of COVID-19 in infants.

Critically ill infants with SARS-COV-2 delta variant infection.

BACKGROUND: SARS-CoV-2 is described to cause mild to moderate symptoms in children. To date, clinical data and symptoms of the Delta variant in pediatric patients are lacking. AIM: To describe clinical characteristics and outcomes of infants admitted in the pediatric intensive care unit (PICU) during the period of Delta variant predominance. METHODS: We performed a retrospective study, between June 23, 2021 and August 16, 2021. We included children aged under 15 years, admitted to PICU with severe and critical form of SARS-CoV-2 infection as confirmed by RT-PCR. We reviewed medical records for all patients. RESULTS: During the study period, 20 infants were included. The median age was 47 days (IQR: 26.5-77). The sex ratio was 0.8 (9 males). No underlying medical conditions were noted. Parents were not vaccinated. Respiratory involvement was the main feature to be observed in our cohort. Eleven patients had pediatric acute respiratory distress (PARDS) with a median oxygen saturation index (OSI) of 9 (IQR: 7-11). PARDS was mild in 4 cases, moderate in 5 cases and severe in 2 cases. Hemodynamic instability was observed in 4 cases. The main radiological finding was ground glass opacities in 11 cases. Seventeen patients were mechanically ventilated and 3 of them were escalated to high-frequency oscillatory ventilation. The median duration of mechanical ventilation was 6 days (IQR 2.5-12.5). The remaining patients were managed with high flow nasal cannula. Four patients died. CONCLUSION: We report herein a case series of very young infants, with no comorbidities, and with a life-threatening illness due to SARS-CoV-2 Delta variant.

Severe and critical SARS-COV-2 delta variant infection in infants without underlying medical conditions.

We report herein a case series of infants, with no comorbidities, who developed a life-threatening illness due to the SARS-CoV-2 Delta variant. We retrospectively reviewed the medical records of children, aged under 15 years, admitted to PICU, during the peak of Delta infection, between June 23 and August 16 2021, with severe and critical forms of SARS-CoV-2 infection, confirmed by RT-PCR. Twenty infants were included, the median age was 47 days (IQR: 26.5-77) and sex ratio was 0.8. No underlying medical conditions were noted. Parents were not vaccinated. Respiratory involvement was the main feature observed. Eleven patients had paediatric acute respiratory distress (PARDS) with a median oxygen saturation index (OSI) of 9 (IQR: 7-11). PARDS was mild in four, moderate in five, and severe in two cases. Hemodynamic instability was observed in 4 cases. The main radiological finding was ground glass opacities in 11 cases. Seventeen patients were mechanically ventilated, and three of them were escalated to high-frequency oscillatory ventilation. The median duration of mechanical ventilation was 6 days (IQR 2.5-12.5). The remaining patients were managed with high-flow nasal cannula. Four patients died.

High flow nasal cannula therapy versus continuous positive airway pressure and nasal positive pressure ventilation in infants with severe bronchiolitis: a randomized controlled trial.

INTRODUCTION: non-invasive ventilation is widely used in the respiratory management of severe bronchiolitis. METHODS: a randomized controlled trial was carried out in a tertiary pediatric university hospital´s PICU over 3 years to compare between continuous positive airway pressure/nasal positive pressure ventilation (CPAP/NPPV) and high flow nasal cannula (HFNC) devices for severe bronchiolitis. The trial was recorded in the national library of medicine registry (NCT04650230). Patients aged from 7 days to 6 months, admitted for severe bronchiolitis were enrolled. Eligible patients were randomly chosen to receive either HFNC or CPAP/NPPV. If HFNC failed, the switch to CPAP/NPPV was allowed. Mechanical ventilation was the last resort in case of CPAP/NPPV device failure. The primary outcome was the success of the treatment defined by no need of care escalation. The secondary outcomes were failure predictors, intubation rate, stay length, serious adverse events, and mortality. RESULTS: a total of 268 patients were enrolled. The data of 255 participants were analyzed. The mean age was 51.13 ± 34.43 days. Participants were randomized into two groups; HFNC group (n=130) and CPAP/NPPV group (n=125). The success of the treatment was significantly higher in the CPAP/NPPV group (70.4% [61.6%- 78.2%) comparing to HFNC group (50.7% [41.9%- 59.6%])- (p=0.001). For secondary outcomes, lower baseline pH was the only significant failure predictor in the CPAP/NPPV group (p=0.035). There were no differences in intubation rate or serious adverse events between the groups. CONCLUSION: high flow nasal cannula was safe and efficient, but CPAP/ NPPV was better in preventing treatment failure. The switch to CPAP/NPPV if HFNC failed, avoided intubation in 54% of the cases.

Phylogeography and phylogeny of Rhinoviruses collected from Severe Acute Respiratory Infection (SARI) cases over successive epidemic periods in Tunisia.

Rhinoviruses (RV) are a major cause of Severe Acute Respiratory Infection (SARI) in children, with high genotypic diversity in different regions. However, RV type diversity remains unknown in several regions of the world. In this study, the genetic variability of the frequently circulating RV types in Northern Tunisia was investigated, using phylogenetic and phylogeographic analyses with a specific focus on the most frequent RV types: RV-A101 and RV-C45. This study concerned 13 RV types frequently circulating in Northern Tunisia. They were obtained from respiratory samples collected in 271 pediatric SARI cases, between September 2015 and November 2017. A total of 37 RV VP4-VP2 sequences, selected among a total of 49 generated sequences, was compared to 359 sequences from different regions of the world. Evolutionary analysis of RV-A101 and RV-C45 showed high genetic relationship between different Tunisian strains and Malaysian strains. RV-A101 and C45 progenitor viruses' dates were estimated in 1981 and 1995, respectively. Since the early 2000s, the two types had a wide spread throughout the world. Phylogenetic analyses of other frequently circulating strains showed significant homology of Tunisian strains from the same epidemic period, in contrast with earlier strains. The genetic relatedness of RV-A101 and RV-C45 might result from an introduction of viruses from different clades followed by local dissemination rather than a local persistence of an endemic clades along seasons. International traffic may play a key role in the spread of RV-A101, RV-C45, and other RVs.

First Tunisian Cluster Admissions of Critically Ill Patients with Multisystem Inflammatory Syndrome in Children (MIS-C).

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a new emerging severe disease that is temporally related to previous exposure to coronavirus infection disease (COVID-19). AIM: To describe the clinical features, laboratory findings, therapies, and outcomes for the first Tunisian cluster admissions of critically ill children with severe MIS-C. METHODS: Retrospective study conducted from November 01 to November 30, 2020According to the WHO definition case, we included eight children aged less than 15 years who were admitted to our pediatric intensive care and met MIS-C criteria. We reviewed all patients' medical records to collect demographic and clinical data, severity scores, laboratory test results, echocardiographic findings, treatment, and outcomes. RESULTS: The median age was 8 years (IQR: 4-10years). All children were previously fit and well. Seven patients were boys. Known exposure to COVID-19 was reported in 4 cases. Fever and gastrointestinal symptoms were reported in all cases. Five patients had marked abdominal pain and were examined by the surgeon for possible appendicitis. Seven patients had diarrhea. On examination, we found rash (n=7), conjunctivitis (n=7), cheilitis (n=5), and meningism (n=3). We reported cardiac dysfunction in 7 cases and shock with hypotension in 3 cases. All patients received immunoglobulins, methylprednisolone, and a low dose of aspirin. No deaths occurred. CONCLUSION: We reported here the first Tunisian cluster admissions of 8 critically ill children with MIS-C to highlight the increase of a new severe emerging disease with evidence of prior COVID-19 infection in older children.

Evaluation of the influenza-like illness surveillance system in Tunisia, 2012-2015.

BACKGROUND: This study was initiated to evaluate, for the first time, the performance and quality of the influenza-like illness (ILI) surveillance system in Tunisia. METHODS: The evaluation covered the period of 2012-2015 and used different data sources to measure indicators related to data quality and completeness, representativeness, timeliness, simplicity, acceptability, flexibility, stability and utility. RESULTS: During the evaluation period, 485.221 ILI cases were reported among 6.386.621 outpatients at 268 ILI sentinel sites. To conserve resources, cases were only enrolled and tested for influenza during times when the number of patients meeting the ILI case definition exceeded 7% (10% after 2014) of the total number of outpatients for the week. When this benchmark was met, five to 10 patients were enrolled and sampled by nasopharyngeal swabs the following week. In total, The National Influenza Center (NIC) received 2476 samples, of which 683 (27.6%) were positive for influenza. The greatest strength of the system was its representativeness and flexibility. The timeliness of the data and the acceptability of the surveillance system performed moderately well; however, the utility of the data and the stability and simplicity of the surveillance system need improvement. Overall, the performance of the Tunisian influenza surveillance system was evaluated as performing moderately well for situational awareness in the country and for collecting representative influenza virologic samples. CONCLUSIONS: The influenza surveillance system in Tunisia provided pertinent evidence for public health interventions related to influenza situational awareness. To better monitor influenza, we propose that ILI surveillance should be limited to sites that are currently performing well and the quality of data collected should be closely monitored and improved.

Predictors of Mortality in Mechanically Ventilated Critical Pertussis in a low Income Country.

BACKGROUND: Critical pertussis is characterized by severe respiratory failure, important leukocytosis, pulmonary hypertension, septic shock and encephalopathy. AIM: To describe the clinical course of critical pertussis, and identify predictors of death at the time of presentation for medical care. METHODOLOGY: Retrospective study conducted in children's hospital Tunisian PICU between 01 January and 31 October 2013. Patients with critical pertussis confirmed by RT-PCR and requiring mechanical ventilation were included. Predictors of death were studied. RESULTS: A total of 17 patients was studied. Median age was 50 days. Mortality was 23%. Predictors risk of mortality were : high PRISM score (Pediatric Risk of Mortality Score) (p=0,007), shock (p=0,002), tachycardia (p=0,005), seizures (p=0,006), altered mental status (p=0,006), elevated WBC count (p=0,003) and hemodynamic support (p=0022). However, the difference did not reach statistical significance in comorbidity, pneumoniae, high pulmonary hypertension or exchange transfusion. Concomitant viral or bacterial co-infection was not related to poor outcome. CONCLUSION: Young infants are at high risk to have critical pertussis. Despite advances in life support and the treatment of organ failure in childhood critical illness, critical pertussis remains difficult to treat.

Neurological variant of Lemierre's Syndrome with purulent meningitis: a case report and literature review.

We report an unusual variant of Lemierre's Syndrome (LS) in a 10-year-old-girl admitted to the intensive care unit for septic shock with meningitis. The primary infection was otitis media. A gram negative bacillus was identified in the direct exam of the purulent ear discharge and the cerebrospinal fluid but cultures were negative. Computerized tomography of the neck revealed a thrombus in the internal jugular vein. Septic shock improved rapidly under supportive treatment. The patient recovered without sequellae after a prolonged duration of parenteral antibiotherapy and hospital stay. Neurologic variants of LS with meningitis, previously reported in the literature, are reviewed.

Prevalence of Bordetella pertussis and Bordetella parapertussis infections in Tunisian hospitalized infants: results of a 4-year prospective study.

The prevalence of pertussis in Tunisia remains undetermined essentially because of the unavailability of a basic laboratory diagnostic service. Specific diagnostic tools were applied for the first time in a Tunisian prospective study in order to get a first estimation of the prevalence of Bordetella pertussis/parapertussis infections and to evaluate their use to determine the epidemiologic characteristics of these infections in Tunisian infants. Between 2007 and 2011, a total of 626 samples from 599 infants aged <1 year with and without pertussoid cough were investigated for the presence of B. pertussis/parapertussis using culture and real-time polymerase chain reaction (PCR). The real-time PCR (RT-PCR) targets include IS481 commonly found in B. pertussis, B. bronchiseptica, and B. holmesii; IS1001 specific of B. parapertussis, in combination with the pertussis toxin promoter region gene (ptx) of B. pertussis; and the recA gene specific of B. holmesii. When possible, patients' household contacts provided nasopharyngeal aspirates (NPAs) for RT-PCR detection of B. pertussis/parapertussis or single-serum samples for anti-PT IgG quantification. All except 1 NPAs were negative by conventional culture, whereas PCR gave positive signals for 126 specimens (21%): B. pertussis, B. parapertussis, and Bordetella spp. were detected in 82%, 6%, and 4% of the samples, respectively. The simultaneous presence of B. pertussis and B. parapertussis was noted in 8% of the cases. Pertussis was reported throughout the year with a peak during the summer of the year 2009. The prevalence of Bordetella infection was 20% between 2007 and 2011. Most of these cases corresponded to patients younger than 6 months who received <3 doses of pertussis vaccine. Among the household contacts enrolled in the study, mothers seemed to be the likely source of infection. This study showed that pertussis is still prevalent in Tunisia and that the disease remains a public health problem affecting not only infants but also adults. Given this situation, sensitive and specific laboratory tests are needed to improve the accuracy of pertussis diagnosis.

Lidocaine toxicity secondary to local anesthesia administered in the community for elective circumcision.

We report three previously healthy infants aged, respectively, 23 days, 6 weeks, and 3 months with systemic lidocaine toxicity following administration of subcutaneous lidocaine for regional anesthesia during an elective circumcision. The patients developed a generalized seizure requiring endotracheal intubation but recovered fully with supportive care. We report the clinical details of these cases as well as a review of lidocaine toxicity.

Community-acquired methicillin-resistant Staphylococcus aureus infections requiring admission to a Tunisian pediatric intensive care unit.

BACKGROUND: There is limited literature describing severe community acquired methicillin-resistant S aureus (CA-MRSA) in children admitted to an intensive care unit. AIM: To review clinical features and outcome of children admitted in a Tunisian pediatric intensive care with CA-MRSA. METHODS: Retrospective chart review of patients coded for CAMRSA over 10 years. RESULTS: There were 14 (0.32% of all admissions) patients identified with severe CA-MRSA. The median age was 3 months (range,0.5-156 months). All patients had pulmonary involvement. Six children (42.8%) developed septic shock. Two (14.3%) patients had multifocal infection with deep venous thrombosis. Two (14.3%) patients died. CONCLUSION: Severe CA-MRSA pneumonia dominated presentation. The mortality of CA-MRSA infection in our series is lower than reported in the literature.

Community-associated methicillin-resistant Staphylococcus aureus infections in a pediatric intensive care unit.

INTRODUCTION: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection is an increasing problem worldwide. In developing countries, there is little data on CA-MRSA infection in children. This study reviewed the clinical features and outcomes of children admitted in a Tunisian pediatric intensive care unit with severe CA-MRSA infections. METHODOLOGY: Retrospective chart review of patients coded for CA-MRSA over 10 years. RESULTS: There were 14 (0.32% of all admissions) patients identified with severe CA-MRSA infections. The median age was three months (range, 0.5-156 months). All patients had pulmonary involvement. Six children (42.8%) developed septic shock. Two (14.3%) patients had multifocal infection with deep venous thrombosis. Two (14.3%) patients died. CONCLUSIONS: Severe CA-MRSA pneumonia dominated presentation. The mortality of CA-MRSA infection in our series is lower than that previously reported.

Management of meconium aspiration syndrome with highfrequency oscillatory ventilation.

BACKGROUND: High-frequency oscillatory ventilation (HFOV) has been advocated for use to improve lung inflation while potentially decreasing lung injury. There were few data on the early use of HFOV in hypoxemic term neonates. AIM: To evaluate the effectiveness of HFOV, used as the initial mode of ventilation, in neonates with severe meconium aspiration syndrome (MAS). METHODS: In a tertiary care paediatric intensive care unit, 17 term neonates with severe MAS were managed with HFOV, used as the initial mode of ventilation, and prospectively evaluated. Ventilator settings, blood gases, oxygenation index (OI) and alveolar-arterial oxygen difference (P(A-a)O2) were prospectively recorded during HFOV treatment and compared at the multiple time intervals. RESULTS: Target ventilation was easily achieved with HFOV. Initiation of HFOV caused a significant decrease in FIO2, achieved as early as 1 hour (from 0.93 ± 0.11 to 0.78 ± 0.25; p=0.031) and the improvement was sustained during the 1-32 hours period. There were a significant decreases in P (A-a) O2 and OI, respectively, at 4 hours (from 562.5 ± 71.7 to 355.4 ± 206 mm Hg; p=0.03) and 8 hours (from 23.3±17 to 14.6±16.3; p=0.04), that were sustained up to 16 and 40 hours . Three neonates (17.6%) developed pneumothorax on HFOV. One patient required oxygen support at 28 days. No significant others complications associated with HFOV were detected. Sixteen infants (94 %) were successfully weaned from HFOV and 15 (88%) survived to hospital discharge. CONCLUSION: Use of HFOV as the initial mode of ventilation in neonates with severe MAS is an effective strategy.

Datura stramonium L. poisoning in a geophagous child: a case report.

Datura stramonium L. (DS) is a wild-growing plant widely distributed and easily accessible. It contains a variety of toxic anticholinergic alkaloids such as atropine, hyoscamine, and scopolamine. Voluntary or accidental ingestion can produce severe anticholinergic poisoning. We report an unusual case of DS intoxication occurring in a geophagous young child after accidental ingestion of the plant. Our case is original because of the young age of the victim and the underlying geophagia facilitating the occurrence of poisoning.

The new health legacy: when pertussis becomes a heritage transmitted from mothers to infants.

Despite high vaccination coverage rates, there has been a gradual increase in reported pertussis cases. Although whooping cough affects all ages, young infants continue to suffer the greatest pertussis disease burden. Adolescents and adults are the primary source of infection for young babies. In this paper, we report two cases involving the likely transmission of pertussis from mothers to infants in Tunisia.

Fatal subdural empyema caused by Streptococcus constellatus and Actinomyces viscosus in a child--case report.

Group milleri streptococci that colonize the mouth and the upper airways are generally considered to be commensal. In combination with anaerobics, they are rarely responsible for brain abscesses in patients with certain predisposing factors. Mortality in such cases is high and complications are frequent. We present a case of fatal subdural empyema caused by Streptococcus constellatus and Actinomyces viscosus in a previously healthy 7-year-old girl.