Epidemiology and Natural History of Childhood-Acquired Chronic Hepatitis C: A Single-Center Long-Term Prospective Study.

OBJECTIVES: To prospectively describe the epidemiology and long-term outcome of childhood-acquired hepatitis C virus (HCV) infection in a large cohort of children followed at a single center. METHODS: All children with chronic HCV infection followed at the Liver Unit of our tertiary Hospital in Florence (Italy) from January 1, 1988, to September 30, 2021, were included in the analysis. RESULTS: The final sample consisted of 163 children (median age at enrollment 4 years, interquartile range (IQR): 10; median age at last follow-up 14 years, IQR: 7). The median duration of follow-up was 86 months (IQR: 112). One hundred twenty-five children were vertically infected and 26 acquired the infection horizontally. Twenty-six of the 125 children who were vertically infected (20.8%) underwent spontaneous clearance of HCV RNA at a median age of 4 years (IQR: 2), whereas all the others remained persistently viremic. One patient was diagnosed with cirrhosis; 2 presented clinically detectable extrahepatic manifestations (chronic urticaria). Thirty-two children (19.6%) received antiviral therapy: 8 out of 32 (25%) were treated with pegylated-interferon alfa-2b [sustained virological response (SVR) 24 weeks after the end of treatment in 7/8]; 24 out of 32 (75%) were treated with direct-acting antivirals (SVR 12 weeks after the end of treatment in 23/24). CONCLUSIONS: The present study describes the largest cohort of children with chronic HCV infection prospectively evaluated with a long follow-up at a single center. HCV infection in children is often a chronic infection that can be cured with modern antiviral therapy. Early treatment could prevent the development of advanced liver disease.

Highly Active Antiretroviral Therapy in an Extremely Low Birth Weight Newborn With in Utero Transmission of HIV.

The management of perinatal HIV infection in preterm infants is hampered by the lack of evidence informing optimal antiretroviral treatment for these vulnerable newborns. We present a case of an extremely preterm infant with HIV infection treated immediately with a 3-drug antiretroviral regimen and achieving stable suppression of HIV plasma viral load.

Severe Typhoid Fever Complicated by Superior Mesenteric and Splenic Vein Thrombosis.

Typhoid fever (Typhoid or enteric fever) is still the most common bacterial bloodstream infection worldwide, caused by Salmonella typhi. The transmission route is indirect through passive vehicles such as contaminated water or food. Main clinical findings are a fever lasting more than three days, abdominal symptoms, leukocytosis, and anemia. Typhoid can cause a wide range of multi-organ complications. We report a particularly severe form of this infection complicated by superior mesenteric vein and splenic vein thrombosis, an extremely uncommon manifestation.

Confidence Distribution for the Ability Parameter of the Rasch Model.

In this paper, we consider the Rasch model and suggest novel point estimators and confidence intervals for the ability parameter. They are based on a proposed confidence distribution (CD) whose construction has required to overcome some difficulties essentially due to the discrete nature of the model. When the number of items is large, the computations due to the combinatorics involved become heavy, and thus, we provide first- and second-order approximations of the CD. Simulation studies show the good behavior of our estimators and intervals when compared with those obtained through other standard frequentist and weakly informative Bayesian procedures. Finally, using the expansion of the expected length of the suggested interval, we are able to identify reasonable values of the sample size which lead to a desired length of the interval.

Prevention of vertical transmission of hepatitis B virus infection.

Hepatitis B virus (HBV) is the leading cause of chronic viral hepatitis. Annually, almost two million children younger than 5 years acquire the infection, mostly through vertical or horizontal transmission in early life. Vertical transmission of HBV is a high efficacy phenomenon ranging, in the absence of any preventive interventions, from 70% to 90% for hepatitis e antigen positive mothers and from 10% to 40% for hepatitis e antigen-negative mothers. Maternal viraemia is a preeminent risk factor for vertical transmission of HBV. Maternal screening is the first step to prevent vertical transmission of HBV. Hepatitis B passive and active immunoprophylaxis at birth together with antiviral treatment of highly viraemic mothers are the key strategies for global elimination of HBV infection. Strategies are needed to promote implementation of birth-dose vaccination and hepatitis B immunoglobulins in low- and middle-income countries where the prevalence of the infection is at the highest.

Treatment of Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis in Children: The Role of Bedaquiline and Delamanid.

Multidrug-resistant (MDR) tuberculosis (TB) has been emerging at an alarming rate over the last few years. It has been estimated that about 3% of all pediatric TB is MDR, meaning about 30,000 cases each year. Although most children with MDR-TB can be successfully treated, up to five years ago effective treatment was associated with a high incidence of severe adverse effects and patients with extensively drug-resistant (XDR) TB had limited treatment options and no standard regimen. The main objective of this manuscript is to discuss our present knowledge of the management of MDR- and XDR-TB in children, focusing on the characteristics and available evidence on the use of two promising new drugs: bedaquiline and delamanid. PubMed was used to search for all of the studies published up to November 2020 using key words such as "bedaquiline" and "delamanid" and "children" and "multidrug-resistant tuberculosis" and "extensively drug-resistant tuberculosis". The search was limited to articles published in English and providing evidence-based data. Although data on pediatric population are limited and more studies are needed to confirm the efficacy and safety of bedaquiline and delamanid, their use in children with MDR-TB/XDR-TB appears to have good tolerability and efficacy. However, more evidence on these new anti-TB drugs is needed to better guide their use in children in order to design effective shorter regimens and reduce adverse effects, drug interactions, and therapeutic failure.

Congenital Cytomegalovirus Infection: Update on Diagnosis and Treatment.

Congenital cytomegalovirus (cCMV) infection is the most common congenital viral infection and is the leading non-genetic cause of sensorineural hearing loss (SNLH) and an important cause of neurodevelopmental disabilities. The risk of intrauterine transmission is highest when primary infection occurs during pregnancy, with a higher rate of vertical transmission in mothers with older gestational age at infection, while the risk of adverse fetal effects significantly increases if fetal infection occurs during the first half of pregnancy. Despite its prevalence and morbidity among the neonatal population, there is not yet a standardized diagnostic test and therapeutic approach for cCMV infection. This narrative review aims to explore the latest developments in the diagnosis and treatment of cCMV infection. Literature analysis shows that preventive interventions other than behavioral measures during pregnancy are still lacking, although many clinical trials are currently ongoing to formulate a vaccination for women before pregnancy. Currently, we recommend using a PCR assay in blood, urine, and saliva in neonates with suspected cCMV infection. At present, there is no evidence of the benefit of antiviral therapy in asymptomatic infants. In the case of symptomatic cCMV, we actually recommend treatment with oral valganciclovir for a duration of 12 months. The effectiveness and tolerability of this therapy option have proven effective for hearing and neurodevelopmental long-term outcomes. Valganciclovir is reserved for congenitally-infected neonates with the symptomatic disease at birth, such as microcephaly, intracranial calcifications, abnormal cerebrospinal fluid index, chorioretinitis, or sensorineural hearing loss. Treatment with antiviral drugs is not routinely recommended for neonates with the mildly symptomatic disease at birth, for neonates under 32 weeks of gestational age, or for infants more than 30 days old because of insufficient evidence from studies. However, since these populations represent the vast majority of neonates and infants with cCMV infection and they are at risk of developing late-onset sequelae, a biomarker able to predict long-term sequelae should also be found to justify starting treatment and reducing the burden of CMV-related complications.

SARS-CoV-2 infection in children in Parma.

not available.

Clinical utility of beta-hydroxybutyrate measurement in the management of physiological ketosis at home in children under 5.

AIM: To verify the possible advantages of 3- ß-hydroxybutyrate (3HB) measurement compared to urinary assay of ketones during an intercurrent disease managed at home. METHODS: Twelve Pediatricians were asked to enroll at least 4 patients aged 3 to 5 years, affected by an intercurrent illness and showing at least one of symptoms reliable to ketosis. Recruited patients were submitted to the simultaneous assay of 3HB in capillary blood and ketones in urine at 3 (T3) and 6 hours (T6) from the first measurement (T0). For urinary and blood ketone detection commercial tests were used. RESULTS: Thirty-eight children (4.36±2.60 years old; 25 boys) were enrolled into the study. At T0 all children showed 3HB levels (1.2-3.2 mmol/L), but only 10 of them (26.3%) associated also urinary ketone bodies (2 to 4+). In response to 3 hour treatment (T3) with a glucose solution, 3HB values decreased in 19 (0,8-1,8 mmol/L) and normalized in 13 children (<0.2 mmol/L); while ketonuria disappeared in only 2 patients, it was confirmed in 8 and appeared (4+) the first time in the remaining 28 children. At T6 3HB levels fell definitively within the normal range in all children, while ketonuria was still present (2+) in 9 patients (23%). The pediatricians reported two limitations about blood 3HB dosage compared to the urinary test: the invasiveness of capillary blood collection, and the cost of supplies for finger pricking, reagent strips and reflectance meter. CONCLUSIONS: 3HB monitor in capillary blood is more effective and clinically more useful in diagnosing and managing of an ongoing ketosis in children with a mild infective disease than ketones detection in the urine. These advantages are mitigated by the cost of 3HB measurement.