The natural history of vertically acquired HCV infection is ill defined. The aim of this study was to outline the natural course of vertical HCV infection in a cohort of untreated children, including ...rate of spontaneous viral clearance, frequency and features of HCV-related autoimmune disorders. Children with vertical HCV infection were prospectively followed from the first month of life with regular clinical and laboratory assessments. Statistical analysis was performed using Prism 5.0. Forty-five children (median age 12 years, interquartile range 6.9–15.5) were studied. Genotype 1 was predominant (53.3 %). Spontaneous viral clearance was achieved by 12 patients (26.7 %) and associated with genotype 3. Alanine-amino-transferase levels were increased in most children in the first 2 years of life with higher values in those who later cleared the infection. All children were asymptomatic for liver disease. Transient elastography (32 patients) showed mild or moderate fibrosis in nine and two cases, respectively. Non-organ-specific autoantibodies were detected in 24 children (53.3 %) independently of viremia; of these, one developed type-1 diabetes. Cryoglobulinemia was associated with genotype 1 infection and found in 15 subjects (33.3 %): two had low C4 levels and persistent proteinuria.
Conclusions
: Vertically acquired HCV infection may result in spontaneous clearance in up to 27 % of children. Resolution of infection is higher with genotype 3, usually occurs in preschool age and persists over time. Chronic infection is generally asymptomatic, although hepatomegaly and mild fibrosis may develop. Autoantibodies and cryoglobulins are frequent, whereas the associated clinical manifestations are rare.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Abstract Purpose This article describes the recommendations of a group of scientific societies concerning the therapeutic approach to immunocompromised children with tuberculosis (TB). Methods Using ...the Consensus Conference method, relevant publications in English were identified by a systematic review of MEDLINE and the Cochrane Database of Systematic Reviews from their inception until December 31, 2014. Findings On the basis of their clinical experience and the published evidence, the group of experts concluded that, although immunosuppressed subjects are at greater risk of developing TB, none of the signs or symptoms is sensitive or specific enough to enable a diagnosis. Immunocompromised patients are at greater risk of developing extrapulmonary forms of TB, especially if they are adolescents, whereas pulmonary forms are more prevalent among younger patients. When TB is suspected, a combination of skin and immunologic tests and other clinical, radiologic, and microbiologic examinations can be used to assess the risk of infection or disease. If the TB diagnosis is confirmed, immunocompromised children should be treated by using a standard regimen with a minimum of 4 drugs for at least 9 to 12 months, during which the tolerability of the drugs and their interactions should be carefully evaluated. Implications It is difficult to diagnose and treat TB in immunocompromised children. Thus, all pediatric patients undergoing immunosuppressive therapy who develop TB should be diagnosed and treated at a TB reference center, which should also be responsible for the recommended follow-up.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background:
Combined antiretroviral therapy (cART) has been associated with a steep decrease in mortality and morbidity in HIV-1 infected children. New antiretroviral molecules and drug classes have ...been developed and the management of HIV-infected children has improved, but recent data on survival are limited.
Methods:
An observational retrospective study investigating changes in mortality and morbidity was conducted on 1,091 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018.
Results:
Three hundred and fifty-four (32%) AIDS events and 26 (2%) deaths occurred overtime. Mortality rates decreased from 0.4/100 person-years in 2001–2006 to 0.27/100 person-years in 2007–2012 and 0.07/100 person-years in 2013–2018. Notably, 92% of the dead children were born in Italy, but only 50% were followed-up since birth or within three months of age. Seventy three percent of children had started cART at age ≥6 months; 23% were treated for <30 days before death. B and C clinical events progressively decreased (
P
< 0.0001). Opportunistic infections significantly decreased over time, but still were the most common events in all the periods (6.76/100 person-years in 2013–2018). In the last period, severe bacterial infections were the most common ones. Cancer rates were 0.07/100; 0.17/100; 0.07/100 person-years in the three periods, respectively.
Conclusions:
Progressive reductions both in mortality and in rates of class B and C clinical events and OIs have been observed during the cART era. However, deaths were still registered; more than half of dead children were enrolled after birth and had belatedly started cART.
Early highly active antiretroviral therapy (HAART), started within the first months of age, has been proven to be the optimal strategy to prevent immunological and clinical deterioration in ...perinatally HIV-infected children. Nevertheless, data about long-term follow-up of early treated children are lacking.
We report data from 40 perinatally HIV-infected-children receiving early HAART, with a median follow-up period of 5.96 years (interquartile range IQR:4.21-7.62). Children were enrolled at birth in the Italian Register for HIV Infection in Children. Comparison with 91 infected children born in the same period, followed-up from birth, and receiving deferred treatment was also provided.
Nineteen children (47.5%) were still receiving their first HAART regimen at last follow-up. In the remaining children the first regimen was discontinued, after a median period of 3.77 years (IQR: 1.71-5.71) because of viral failure (8 cases), liver toxicity (1 case), structured therapy interruption (3 cases), or simplification/switch to a PI-sparing regimen (9 cases). Thirty-nine (97.5%) children showed CD4+ T-lymphocyte values>25%, and undetectable viral load was reached in 31 (77.5%) children at last visit. Early treated children displayed significantly lower viral load than not-early treated children, until 6 years of age, and higher median CD4+ T-lymphocyte percentages until 4 years of age. Twenty-seven (29.7%) not-early treated vs. 0/40 early treated children were in clinical category C at last follow-up (P < 0.0001).
Our findings suggest that clinical, virologic and immunological advantages from early-HAART are long-lasting. Recommendations indicating the long-term management of early treated children are needed.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The worldwide prevalence of hepatitis C virus (HCV) infection in children is 0.05%-0.4% in developed countries and 2%-5% in resource-limited settings, where inadequately tested blood products or ...un-sterile medical injections still remain important routes of infection. After the screening of blood donors, mother-to-child transmission (MTCT) of HCV has become the leading cause of pediatric infection, at a rate of 5%. Maternal HIV co-infection is a significant risk factor for MTCT and anti-HIV therapy during pregnancy seemingly can reduce the transmission rate of both viruses. Conversely, a high maternal viral load is an important, but not preventable risk factor, because at present no anti-HCV treatment can be administered to pregnant women to block viral replication. Caution is needed in adopting obstetric procedures, such as amniocentesis or internal fetal monitoring, that can favor fetal exposure to HCV contaminated maternal blood, though evidence is lacking on the real risk of single obstetric practices. Mode of delivery and type of feeding do not represent significant risk factors for MTCT. Therefore, there is no reason to offer elective caesarean section or discourage breast-feeding to HCV infected parturients. Information on the natural history of vertical HCV infection is limited. The primary infection is asymptomatic in infants. At least one quarter of infected children shows a spontaneous viral clearance (SVC) that usually occurs within 6 years of life. IL-28B polymorphims and genotype 3 infection have been associated with greater chances of SVC. In general, HCV progression is mild or moderate in children with chronic infection who grow regularly, though cases with marked liver fibrosis or hepatic failure have been described. Non-organ specific autoantibodies and cryoglobulins are frequently found in children with chronic infection, but autoimmune diseases or HCV associated extrahepatic manifestations are rare.
To evaluate the impact of highly active antiretroviral therapy (HAART) on cancer incidence in HIV-infected children throughout a 20-year period.
An observational population study was conducted on ...1,190 perinatally HIV-infected children enrolled onto the Italian Register for HIV Infection in Children from 1985 to 2004 and never lost to follow-up (total observation time, 10,037.66 years). Cancer rates were calculated in the pre-HAART (1985 to 1995), early HAART (1996 to 1999), and late HAART (2000 to 2004) periods and compared using Poisson regression adjusted for age. The proportion of HAART-treated children increased from 4.1% in 1996 to 60.4% in 1999 and to 81.5% in 2004. In the same time frame, the proportion of children receiving HAART for at least 2 years increased from 3.1% to 77.0%.
Overall, 35 cancers occurred. Cancer rates were 4.49 (95% CI, 2.37 to 6.64), 4.09 (95% CI, 1.68 to 6.50), and 0.76 (95% CI, 0.00 to 1.80) per 1,000 children per year in 1985 to 1995, 1996 to 1999, and 2000 to 2004, respectively. Notably, there was no significant difference comparing the periods from 1985 to 1995 and 1996 to 1999 (P = .081). By contrast, cancer rates were significantly lower in the period from 2000 to 2004 than in 1996 to 1999 (P < .0001). Results were confirmed by separately analyzing data from children observed from birth (P = .418 for 1985 to 1995 v 1996 to 1999; P = .001 for 1996 to 1999 v 2000 to 2004).
Dramatically reduced cancer rates were observed only in the late HAART period in parallel to the increasing proportion of children receiving HAART therapy.
Highlights • RT-PCR is considered to be a useful, and powerful method for HPeV detection. • The optimization and standardization of Real Time PCR assay are mandatory. • Pediatric gastroenteritis ...remains the second cause of child mortality worldwide.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Gastroenteritis is a common disease in children. It is characterized by diarrhea, vomiting, abdominal pain, and fever. Sapovirus (SaV) is a causative agent of acute gastroenteritis, but it causes ...milder illness than do rotavirus and norovirus. There is high variability in the analytical performance of quantitative PCR-based assays among clinical laboratories. This study developed a reverse transcription real-time PCR method to detect SaV in fecal specimens collected from children under 5-years-old with acute gastroenteritis. Of 137 episodes of acute gastroenteritis, 15 (10.9%) were associated with SaV genomic detection, with a median viral load of 6.6(log
10
) ± 7.1(log
10
) genomes/mg fecal specimens. There was a significant difference in detection rate between males and females (9.48% (13/15) vs. 1.46% (2/15), p = 0.0232). Among the 15 SaV-positive cases, 6 were also positive for rotavirus. Viral RNA recovery rate ranged from 46% to 77% in the manual RNAzol protocol and from 31% to 90% in the automated Maxwell protocol. We also studied whether human genomic DNA influences the sensitivity of the assay: its presence caused a decrease in PCR sensitivity. The development of a laboratory-designed real-time PCR TaqMan assay for quantitative detection of SaV and the optimization and standardization of this assay, using stools of children with acute gastroenteritis, are described.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Peripartum HIV-RNA is the strongest factor influencing vertical transmission of HIV.•When HIV-RNA is <50 copies/mL, ART discontinuation is the strongest risk factor.•Intrapartum ZDV has no effect on ...transmission in women with HIV RNA <50 copies/mL.•The administration of unnecessary zidovudine may be perceived as a stigma.•Study of the U=U concept in mother-child couple could help fight stigma.
Intravenous administration of zidovudine (ZDV) during labour is a key step for vertical HIV transmission (VT) prevention, but there is no evidence of benefit when maternal HIV-RNA at delivery is <50 copies/mL. The aim of this study is evaluating the appropriateness of intrapartum ZDV use in Italy.
Observational study including mother-infant pairs with perinatal HIV exposure during 2002-2019, enrolled in the Italian Register for HIV Infection in Children. Univariable and multivariable logistic regression were used to evaluate factors associated with VT.
A total of 3,861 infants, born from 3,791 pregnancies were included. The frequency of ZDV use was 79.9%, 92.1%, 93.7% and 92.8% when HIV-RNA was not available, ≥400 copies, between 50 and 399 copies, and <50 copies/mL. Thirty-three out of 3861 (0.85%) infants were subsequently diagnosed with HIV, 25/3861 (0.6%) of them born to mothers receiving intrapartum ZDV, and 31 (93.9%) to mothers with HIV-RNA ≥50 copies/mL or not available. In women with HIV-RNA < 50 copies/mL, ART discontinuation during pregnancy was the strongest risk factor for VT (odds ratio, OR, 23.1, 95%CI 2.4-219.3), while a higher gestational age (OR 0.6, 95%CI 0.4-0.8) and PEP administration to the newborn (aOR 0.004, 95%CI <0.0001-0.4) were protective factors. Intrapartum ZDV administration did not influence the final outcome in this group.
In ART era, more transmission events may occur in utero, limiting value of intrapartum ZDV, particularly for women with suppressed HIV-RNA load. More attention to the HIV-RNA testing of mothers before delivery may avoid unnecessary ZDV use.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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