Accelerated aging in perinatally HIV-infected children: clinical manifestations and pathogenetic mechanisms

BACKGROUND: Premature aging and related diseases have been documented in HIV-infected adults. Data are now emerging also regarding accelerated aging process in HIV-infected children. METHODS: A narrative review was performed searching studies on PubMed published in English language in 2004-2017, using appropriate key words, including "aging", "children", "HIV", "AIDS", "immunosenescence", "pathogenesis", "clinical conditions". RESULTS: Premature immunosenescence phenotype of B and T cells in HIV-infected children is mediated through immune system activation and chronic inflammation. Ongoing inflammation processes have been documented by increased levels of pathogen-associated molecular patterns (PAMPS), increased mitochondrial damage, higher levels of pro-inflammatory cytokines, and a positive correlation between sCD14 levels and percentages of activated CD8+ cells. Other reported features of premature aging include cellular replicative senescence, linked to an accelerated telomeres shortening. Finally, acceleration of age-associated methylation pattern and other epigenetic modifications have been described in HIV-infected children. All these features may favor the clinical manifestations related to premature aging. Lipid and bone metabolism, cancers, cardiovascular, renal, and neurological systems should be carefully monitored, particularly in children with detectable viremia and/or with CD4/CD8 ratio inversion. CONCLUSION: Aging processes in children with HIV infection impact their quality and length of life. Further studies regarding the mechanisms involved in premature aging are needed to search for potential targets of treatment

Systematic review and meta-analysis on the utility of Interferon-gamma release assays for the diagnosis of Mycobacterium tuberculosis infection in children: A 2013 update

BACKGROUND: Previous meta-analyses regarding the performance of interferon-gamma release assays (IGRAs) for tuberculosis diagnosis in children yielded contrasting results, probably due to different inclusion/exclusion criteria. METHODS: We systematically searched PubMed, EMBASE and Cochrane databases and calculated pooled estimates of sensitivities and specificities of QuantiFERON-TB Gold In Tube (QFT-G-IT), T-SPOT.TB, and tuberculin skin test (TST). Several sub-analysis were performed: stratification by background (low income vs. high income countries); including only microbiological confirmed TB cases; including only studies performing a simultaneous three-way comparison of the three tests, and including immunocompromised children. RESULTS: Overall, 31 studies (6183 children) for QFT-G-IT, 14 studies (2518 children) for T-SPOT.TB and 34 studies (6439 children) for TST were included in the analyses. In high income countries QFT-G-IT sensitivity was 0.79 (95%IC: 0.75-0.82) considering all the studies, 0.78 (95%CI:0.70-0.84) including only studies performing a simultaneous three-way comparison and 0.86 (95%IC 0.81-0.90) considering only microbiologically confirmed studies. In the same analyses T-SPOT.TB sensitivity was 0.67 (95%IC 0.62-0.73); 0.76 (95%CI: 0.68 to 0.83); and 0.79 (95%IC 0.69-0.87), respectively. In low income countries QFT-G-IT pooled sensitivity was significantly lower: 0.57 (95%IC:0.52-0.61), considering all the studies, and 0.66 (95%IC 0.55-0.76) considering only microbiologically confirmed cases; while T-SPOT.TB sensitivity was 0.61 (95%IC 0.57-0.65) overall, but reached 0.80 (95%IC 0.73-0.86) in microbiologically confirmed cases. In microbiologically confirmed cases TST sensitivity was similar: 0.86 (95%IC 0.79-0.91) in high income countries, and 0.74 (95%IC 0.68-0.80) in low income countries. Higher IGRAs specificity with respect to TST was observed in high income countries (97-98% vs. 92%) but not in low income countries (85-93% vs. 90%). CONCLUSIONS: Both IGRAs showed no better performance than TST in low income countries

Clinical peculiarities of tuberculosis

The ongoing spread of tuberculosis (TB) in poor resource countries and the recently increasing incidence in high resource countries lead to the need of updated knowledge for clinicians, particularly for pediatricians. The purpose of this article is to provide an overview on the most important peculiarities of TB in children. Children are less contagious than adults, but the risk of progression to active disease is higher in infants and children as compared to the subsequent ages. Diagnosis of TB in children is more difficult than in adults, because few signs are associated with primary infection, interferon-gamma release assays and tuberculin skin test are less reliable in younger children, M. tuberculosis is more rarely detected in gastric aspirates than in smears in adults and radiological findings are often not specific. Treatment of latent TB is always necessary in young children, whereas it is recommended in older children, as well as in adults, only in particular conditions. Antimycobacterial drugs are generally better tolerated in children as compared to adults, but off-label use of second-line antimycobacterial drugs is increasing, because of spreading of multidrug resistant TB worldwide. Given that TB is a disease which often involves more than one member in a family, a closer collaboration is needed between pediatricians and clinicians who take care of adults

Vitamin D status and predictors of hypovitaminosis D in internationally adopted children

To evaluate vitamin D status in internationally adopted children at first medical evaluation in Italy and to identify possible risk factors for hypovitaminosis D in this population.25-hydroxyvitamin D [25(OH)D] levels were analyzed in internationally adopted children consecutively recruited at one Italian Center between 2010 and 2014 as part of the first screening protocol. Demographic, clinical and laboratory data were prospectively collected. Serum 25(OH)D levels <10 ng/mL, <20 ng/mL, and <30 ng/mL were used to define severe vitamin D deficiency, vitamin D deficiency and hypovitaminosis D, respectively.962 internationally adopted children (median age: 5.47 years; IQR:3.14-7.93) were included in the study. Median 25(OH)D level was 22.0 ng/mL (IQR:15.0-30.0 ng/mL); 710/962 (73.8%) children showed hypovitaminosis D (<30 ng/mL), 388/962 (40.3%) had vitamin D deficiency (<20 ng/dL), and 92/962 (9.6%) had severe vitamin D deficiency (<10ng/mL). No case of clinical rickets was observed. Hypovitaminosis D was particularly frequent (>90%) in children adopted from Ethiopia, Peru, India, Bulgaria and Lithuania. At multivariate analysis an increased risk of hypovitaminosis D was found to be associated with: age ≥ 6 years, time spent in Italy ≥ 3 months, blood sample taken in winter, spring or fall, compared to summer. Gender, ethnicity/continent of origin, tubercular infection, intestinal parassitosis and BMI-z-score < -2 were not associated with vitamin D status.Hypovitaminosis D is common in internationally adopted children, from all ethnic group. The evaluation of serum 25(OH)D level could be useful early after the adoption to promptly start vitamin D supplementation/treatment if needed

Update on the management of acute pharyngitis in children

Streptococcal pharyngitis is a very common pathology in paediatric age all over the world. Nevertheless there isn't a joint agreement on the management of this condition. Some authors recommend to perform a microbiological investigation in suspected bacterial cases in order to treat the confirmed cases with antibiotics so to prevent suppurative complications and acute rheumatic fever. Differently, other authors consider pharyngitis, even streptococcal one, a benign, self-limiting disease. Consequently they wouldn't routinely perform microbiological tests and, pointing to a judicious use of antibiotics, they would reserve antimicrobial treatment to well-selected cases. It has been calculated that the number of patients needed to treat to prevent one complication after upper respiratory tract infections (including sore throat), was over 4000

Tuberculosis and HIV co-infection in children

HIV is the top and tuberculosis is the second leading cause of death from infectious disease worldwide, with an estimated 8.7 million incident cases of tuberculosis and 2.5 million new HIV infections annually. The World Health Organization estimates that HIV prevalence among children with tuberculosis, in countries with moderate to high prevalence, ranges from 10 to 60%. The mechanisms promoting susceptibility of people with HIV to tuberculosis disease are incompletely understood, being likely caused by multifactorial processes. Paediatric tuberculosis and HIV have overlapping clinical manifestations, which could lead to missed or late diagnosis. Although every effort should be made to obtain a microbiologically-confirmed diagnosis in children with tuberculosis, in reality this may only be achieved in a minority, reflecting their paucibacillary nature and the difficulties in obtain samples. Rapid polymerase chain reaction tests, such as Xpert MTB/RIF assay, are increasingly used in children. The use of less or non invasive methods of sample collection, such as naso-pharyngeal aspirates and stool samples for a polymerase chain reaction-based diagnostic test tests and mycobacterial cultures is promising technique in HIV negative and HIV positive children. Anti-tuberculosis treatment should be started immediately at diagnosis with a four drug regimen, irrespective of the disease severity. Moreover, tuberculosis disease in an HIV infected child is considered to be a clinical indication for initiation of antiretroviral treatment. The World Health Organization recommends starting antiretroviral treatment in children as soon as anti-tuberculosis treatment is tolerated and within 2- 8 weeks after initiating it. The treatment of choice depends on the child’s age and availability of age-appropriate formulations, and potential drug interactions and resistance. Treatment of multi-drug resistant tuberculosis in HIV-infected children follows same principles as for HIV uninfected children. There are conflicting results on effectiveness of isoniazid preventive therapy in reducing incidence of tuberculosis disease in children with HIV. CONCLUSION: Data on HIV/TB co-infection in children are still lacking. There are on-going large clinical trials on the prevention and treatment of TB/HIV infection in children that hopefully will help to guide an evidence-based clinical practice in both resource-rich and resource-limited settings