Paediatric tuberculosis (TB) is a substantial threat among infectious diseases, particularly considering the high risk of extrapulmonary tuberculosis (EPTB), severe forms of the disease, and the ...spreading of drug-resistant strains. Describing the characteristics of children with EPTB and those with drug-resistant tuberculosis (DR-TB) and analysing the role of second-line drugs could facilitate the management of these cases. This retrospective study was conducted on 271 children diagnosed with active TB disease (44 EPTB cases, 9 DR-TB cases), originating from diverse geographic areas, who were referred to the infectious disease unit at Meyer Children's Hospital, Florence, Italy, from 2006 to 2022. In most patients, the management of therapies was complicated by the impossibility to obtain drug susceptibility testing (DST) results, which improved over the years: 17/154 (11.04%) children had DST results between 2006 and 2013, and 50/117 (42.73%,
< 0.001) between 2014 and 2022. Second-line drugs were not exclusively administered to DR-TB cases, but also to EPTB cases (20/44, 45.45%). Drugs were generally well tolerated; adverse events occurred in 13 children (13/271, 4.80%) and were generally mild and reversable. Therapies were successful in 267 children (98.52%) considered cured, while 4 (1.48%) presented sequelae. Both univariate and multivariate logistic regression analyses were conducted to investigate factors associated with EPTB, DR-TB, and second-line drugs administration. Originating from Asia emerged as a risk factor associated with both EPTB and DR-TB (
= 0.013 and
= 0.045, respectively). The introduction of GeneXpert tests has significantly improved TB diagnosis and the obtaining of DST results. The administration of second-line therapies should be limited primarily to DR-TB cases, but it is possible that these drugs may also be beneficial in selected EPTB cases.
Spondylodiscitis (SD) is the concurrent infection of the intervertebral disc and the adjacent vertebral bodies. Currently, there is a substantial lack of structured reviews about this topic. The aim ...of this study was to systematically review the available literature in order to determine the main features of pediatric SD. A systematic search of MEDLINE database was performed, according to the PRISMA guideline recommendations. Clinical features, laboratory data, radiological signs, treatments strategies, and outcomes were summarized. Studies' quality assessments were performed using the JBI Critical Appraisal Checklists. A total of 35 retrospective studies were analyzed and 340 children were identified. The most frequently affected age class was 0.5-4 years. The most affected site was the lumbar spine. The most commonly reported symptoms were back pain (37.97%) and refusal to walk/to stand/to sit (49.79%). The most frequently identified pathogen was
(n = 33). The most used antibiotics were third generation cephalosporins. The intravenous therapy duration range was 1-25 weeks, the oral therapy duration range was 5 days-36 months. Surgery was used in 5.88% of children. In 29 cases clinical sequelae were documented. This study provides the main features of pediatric SD; it also emphasizes the significant gaps in the literature regarding this topic.
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
Introduction: Neonatal sepsis represents a major cause of morbidity and mortality in neonates. No diagnostic test has been demonstrated to be sufficiently accurate to confirm or exclude neonatal ...sepsis. This study aimed to evaluate the diagnostic accuracy of presepsin (P-SEP) for neonatal sepsis.
Areas covered: A systematic review of literature was performed on Medline and EMBASE. A meta-analysis was performed to calculate pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic of P-SEP for neonatal sepsis. Eight studies were included, involving 636 neonates. Pooled sensitivity and specificity were 0.90 and 0.90, respectively. The pooled DOR was 120.94, and the Area Under Curve (AUC) was 0.968, indicating a high level of diagnostic accuracy. Using cut-off values <600 ng/L, sensitivity reached 0.93, with a specificity of 0.81 and AUC 0.8195, while using a threshold >600 ng/L, sensitivity was 0.87 and specificity 0.97, with higher diagnostic accuracy (AUC 0.976). Significant heterogeneity was found between studies.
Expert commentary: Diagnostic accuracy of P-SEP resulted high in detecting neonatal sepsis. Even though it cannot be recommended as a single diagnostic test, P-SEP could be a helpful and valuable biomarker in neonates with suspected sepsis.
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.
Introduction: The management of children with fever without apparent sources (FWAS) is difficult. This study aimed to evaluate the diagnostic accuracy of procalcitonin (PCT) in detecting serious or ...invasive bacterial infection (SBI or IBI) in children with FWAS.
Areas covered: A systematic review of literature from 2007 to 2017 was performed on Medline. Twelve studies were included, involving 7,260 children with FWAS and analyzing the diagnostic performance of PCT. Four meta-analyses were performed to calculate pooled sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic curve for PCT in detecting SBI and IBI, at two different thresholds. Considering IBI, PCT sensitivity and specificity at a threshold of 0.5 ng/mL were 0.82 and 0.86, respectively; at a threshold of 2 ng/mL sensitivity and specificity were 0.61 and 0.94, respectively. In detecting SBI, PCT performance was lower, with 55% sensitivity and 85% specificity at a threshold of 0.5 ng/mL, and 30% sensitivity and 95% specificity at a threshold of 2 ng/mL.
Expert commentary: Considering IBI, results showed high diagnostic accuracy for PCT. Conversely, PCT performance in diagnosis of SBI was poor. These findings suggest that PCT level determination could be helpful in detecting meningitis, bacteremia and sepsis in children with FWAS.
BACKGROUND:The incidence of drug-resistant forms of tuberculosis (DR-TB) and the number of children treated with second-line drugs (SLDs) are increasing. However, limited amount of information is ...available regarding the use of SLDs in this population.
METHODS:To describe the treatment of pediatric TB with SLDs and factors associated with use of SLDs in children with and without documented DR-TB, records of pediatric TB patients referred to a center in Italy from 2007 to 2018 were reviewed retrospectively.
RESULTS:Of 204 children diagnosed with active TB during the study period, 42 were treated with SLDs because of confirmed or probable drug resistance (42.8%), adverse reactions to first-line drugs (7.1%), central nervous system involvement (11.9%) or unconfirmed possible drug resistance (38.1%). There were no deaths or adverse reactions to SLDs reported. Treatment was successful in 85.2% children treated with first-line drugs and 92.9% children treated with SLDs. After adjusting for calendar period, the only factor associated with DR-TB was <2 years old odds ratio (OR)5.24 for <2 years vs. 5–18 years; P = 0.008. Factors associated with treatment with SLDs were TB at 2 or more sites (OR11.30; P < 0.001), extrapulmonary TB (OR8.48; P < 0.001) or adverse reactions to first-line drugs (OR7.48; P = 0.002). No differences were noted in age or region of origin.
CONCLUSIONS:A substantial proportion of TB children were treated with SLDs. The main reason for using SLDs was failure of a first-line drug regimen, suggesting possible DR-TB and underestimation of DR-TB in children. The use of SLD regimens was associated with a high success rate and good tolerability profile.
•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
BACKGROUND:Strategies for prevention of HIV-1 mother-to-child transmission (PMTCT) have been continuously optimized. However, cases of vertical transmission continue to occur in high income ...countries.
OBJECTIVES:To investigate changes in PMTCT strategies adopted by Italian clinicians over time and to evaluate risk factors for transmission.
METHODS:Data from mother-child pairs prospectively collected by the Italian Register, born in Italy in 1996-2016, were analyzed. Risk factors for MTCT were explored by logistic regression analyses.
RESULTS:6,503 children (348 infections) were included. In our cohort, the proportion of children born to foreign mothers increased from 18.3% (563/3078) in 1996-2003 to 66.2% (559/857) in 2011-2016 (P<0.0001). Combination neonatal prophylaxis (CNP) use significantly (P<0.0001) increased over time, reaching 6.3% (56/857) after 2010, and it was largely (4.2%) adopted in early preterm infants. The proportion of vaginal deliveries in women with undetectable viral load (VL) increased over time, and was 9.9% (85/857) in 2011-2016; no infection occurred among them. In children followed up since birth MTCT rate was 3.5% (96/2783) in 1996-2003; 1.4% (36/2480) in 2004-2010, and 1.1% (9/835) in 2011-2016. At multivariate analysis, factors associated with MTCT were vaginal delivery with detectable or missing VL or non-elective caesarean delivery, prematurity, breastfeeding, lack of maternal or neonatal ART, detectable maternal VL, age at first observation. Previously described increased risk for offspring of immigrant women was not confirmed.
CONCLUSION:Risk for MTCT in Italy is ongoing, even in recent years, underling the need for implementation of the current screening program in pregnancy. Large CNP use in preterm infants was observed, even if data on safety and efficacy in prematures are poor.
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