Elisabetta Venturini

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.ConclusionData 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.

Tuberculosis in childhood: a systematic review of national and international guidelines

BackgroundPaediatric tuberculosis (TB) represents a major public health concern worldwide. About 1 million children aged less than 15 years develop TB each year, contributing to 3-25% of the total TB caseload. The aim of this review is to evaluate national and international guidelines concerning tuberculosis in childhood and compare them in terms of diagnosis and treatment strategies.MethodsA literature search of the Pubmed database was performed from January 2000 to August 2013, using the terms “tuberculosis” and “children”. The search was limited to guidelines and consensus conferences, human species and full text availability, with no language restrictions.ResultsTwenty-seven national and international guidelines are identified. Several discrepancies on the diagnosis workup of TB are underlined. The main points of disagreement are represented by the interpretation of tuberculin skin test (TST) result and the recommendations on the use of TST and/or interferon-gamma release assay (IGRA) for the diagnosis of TB infection. Otherwise, all guidelines are in agreement that a microbiological confirmation should always be sought. Similarly, susceptibility drug testing and genotyping should be performed whenever it is possible on the basis of resources availability. On the contrary, the use of nucleic acid amplification tests (NAATs) for the M. tuberculosis detection is still controversial. A general consensus exists, otherwise, on TB treatment and only minor discrepancies are evidenced, such as the recommendations on daily or intermittent treatment regimens.ConclusionsDespite advances in TB diagnostic tools have been reached during the last decade, a lack of uniformity in their availability, indication and interpretation has relevant consequences for clinical practice. Further studies need to be performed to clarify this issue and identify a reliable and reproducible diagnostic workup. Moreover, future studies should analyze the drug metabolism and the efficacy of intermittent dosing regimes in childhood, as well as new treatment regimens in order to improve the therapy compliance.

Update of the 2009 Italian Pediatric Society Guidelines about management of fever in children.

BACKGROUND In 2009, the Italian Pediatric Society developed national guidelines for management of fever in children for health care providers and parents/caregivers; an update of these guidelines was scheduled after 2 years. OBJECTIVE This article summarizes the update of Italian guidelines on managing fever in children, focusing specifically on measuring body temperature and using antipyretic agents. METHODS Relevant publications in English and Italian were identified through searches of MEDLINE and the Cochrane Database of Systematic Reviews from January 1, 2008, to May 1, 2012. On the basis of consensus of a multidisciplinary expert panel, evidence levels and strength of recommendations were reviewed. RESULTS Axillary temperature measurement using a digital thermometer is recommended in children younger than 4 weeks. In the hospital or ambulatory care setting, axillary temperature measurement using a digital or infrared thermometer (tympanic or skin contact or nocontact) is recommended in children older than 4 weeks. Paracetamol and ibuprofen are the only antipyretic drugs recommended for use in children; however, combined or alternating use of these agents is not recommended. CONCLUSIONS Recent scientific evidence mainly supports previous recommendations. The aim of the present article was to support pediatric knowledge and stimulate application of guidelines in daily clinical practice.

Effectiveness and safety of the A-H1N1 vaccine in children: A hospital-based case - Control study

Objective To verify whether vaccination against the A-H1N1 virus in the paediatric population was effective in preventing the occurrence of influenza-like illness (ILI) or was associated with adverse events of special interest. Design, setting and patients A case–control analysis was performed as part of surveillance of children hospitalised through the emergency departments of eight paediatric hospitals/wards for ILI, neurological disorders, non-infectious muco-cutaneous diseases and vasculitis, thrombocytopaenia and gastroduodenal lesions. Results Among 736 children enrolled from November 2009 to August 2010, only 25 had been vaccinated with the pandemic vaccine. Out of 268 children admitted for a diagnosis compatible with the adverse events of special interest, six had received the A-H1N1 vaccine, although none of the adverse events occurred within the predefined risk windows. Only 35 children out of 244 admitted with a diagnosis of ILI underwent laboratory testing: 11 were positive and 24 negative for the A-H1N1 virus. None of the A-H1N1 positive children had received the pandemic vaccine. The OR of ILI associated with any influenza vaccination was 0.9 (95% CI 0.1 to 5.5). Conclusions The study provides additional information on the benefit–risk profile of the pandemic vaccine. No sign of risk associated with the influenza A-H1N1 vaccine used in Italy was found, although several limitations were observed: in Italy, pandemic vaccination coverage was low, the epidemic was almost over by mid December 2009 and the A-H1N1 laboratory test was performed only during the epidemic phase (in <10% of children). This study supports the importance of the existing network of hospitals for the evaluation of signals relevant to new vaccines and drugs.

Vitamin D and tuberculosis: a review on a hot topic

Abstract The aim of this study is to critically summarize the available data on the correlation between vitamin D level and tuberculosis (TB) infection. A literature search covering English language articles published up to 20 October 2014 was conducted in MEDLINE database. Three hundred ninety-seven articles were initially identified, of which 147 studies were initially selected, and other 13 pertinent studies were included. A significant association between low vitamin D levels and susceptibility to TB infection has been found.

Interferon-gamma release assay sensitivity in children younger than 5 years is insufficient to replace the use of tuberculin skin test in western countries.

Tuberculin skin test, QuantiFERON-TB Gold In-Tube and T-SPOT.TB were performed in 338 children at risk for tuberculosis (TB), including 70 active TB cases. In children <5 years of age, QuantiFERON-TB Gold In-Tube sensitivity was 73.3% [95% confidence interval (CI): 57.5–89.1]; and T-SPOT.TB sensitivity was 59.3% (95% CI: 40.1–77.8); both were inferior to tuberculin skin test sensitivity (90.0%; 95% CI: 79.3–100). In children ≥5 years QuantiFERON-TB Gold In-Tube sensitivity was 92.5% (95% CI: 84.4–100); T-SPOT.TB sensitivity was 73.0% (95% CI: 58.6–87.3) ; and tuberculin skin test sensitivity was 97.5% (95% CI: 92.6–100).Test specificities were similar in all age groups.

Rational use of antibiotics for the management of children's respiratory tract infections in the ambulatory setting: An evidence-based consensus by the Italian Society of Preventive and Social Pediatrics

BACKGROUND Several guidelines for the management of respiratory tract infections in children are available in Italy, as well as in other European countries and the United States of America. However, poor adherence to guidelines and the sustained inappropriate use of antibiotics have been reported. In the outpatient setting, almost half of antibiotics are prescribed for the treatment of common respiratory tract infections. In Italy the antibiotic prescription rate is significantly higher than in other European countries, such as Denmark or the Netherlands, and also the levels of antibiotic resistance for a large variety of bacteria are higher. Therefore, the Italian Society of Preventive and Social Paediatrics organised a consensus conference for the treatment of respiratory tract infections in children to produce a brief, easily readable, evidence-based document. METHODS The conference method was used, according to the National Institute of Health and the National Plan Guidelines. A literature search was performed focusing on the current guidelines for the treatment of airway infections in children aged 1 month-18 years in the ambulatory setting. RESULTS Recommendations for the treatment of acute pharyngitis, acute otitis media, sinusitis, and pneumonia have been summarized. Conditions for which antibiotic treatment should not be routinely prescribed have been highlighted. CONCLUSION This evidence-based document is intended to accessible to primary care pediatricians and general practice physicians in order to make clinical practice uniform, in accordance with the recommendations of the current guidelines.

Self-reported pediatricians' management of the well-appearing young child with fever without a source: first survey in an European country in the anti-pneumococcal vaccine era

BackgroundRecent studies suggest a substantially reduced risk of invasive bacterial infection in children vaccinated with heptavalent pneumococcal conjugate vaccine (PCV). To investigate whether the introduction of PCV might affect clinical decision making, we conducted a cross-sectional survey aimed at Italian Pediatric physicians.ResultsThe study included 348 (46.5%) primary care pediatricians; 251 (36.4%) hospital pediatricians, and 139 (20.1%) pediatric residents. In an hypothetical scenario, a well-appearing 12-month-old child with fever without source would be sent home with no therapy by 60.7% (419/690) of physicians if the child was not vaccinated with PCV. The proportion increased to 74.2% (512/690) if the child had received PCV (P < 0.0001). Also, physicians would obtain blood tests less frequently in the vaccinated than in unvaccinated children (139/690 [20.1%] vs. 205/690 [29.7%]; P < 0.0001), and started empiric antibiotic therapy less frequently (3.0% vs. 7.5%; P < 0.0001). In the hypothetical event that white blood cell count was 17,500/μL, a significantly lower proportion of physicians would ask for erythrocyte sedimentation rate (P < 0.017), C reactive protein (P < 0.0001), blood culture (P = 0.022), and urine analysis or dipstick (P = 0.028), if the child had received PCV. Only one third of participants routinely recommended PCV.ConclusionOur data suggest that implementation of educational programs regarding the proper management of the febrile child is needed.

Pediatric Tuberculosis in Italian Children: Epidemiological and Clinical Data from the Italian Register of Pediatric Tuberculosis

Tuberculosis (TB) is one of the leading causes of death worldwide. Over the last decades, TB has also emerged in the pediatric population. Epidemiologic data of childhood TB are still limited and there is an urgent need of more data on very large cohorts. A multicenter study was conducted in 27 pediatric hospitals, pediatric wards, and public health centers in Italy using a standardized form, covering the period of time between 1 January 2010 and 31 December 2012. Children with active TB, latent TB, and those recently exposed to TB or recently adopted/immigrated from a high TB incidence country were enrolled. Overall, 4234 children were included; 554 (13.1%) children had active TB, 594 (14.0%) latent TB and 3086 (72.9%) were uninfected. Among children with active TB, 481 (86.8%) patients had pulmonary TB. The treatment of active TB cases was known for 96.4% (n = 534) of the cases. Overall, 210 (39.3%) out of these 534 children were treated with three and 216 (40.4%) with four first-line drugs. Second-line drugs where used in 87 (16.3%) children with active TB. Drug-resistant strains of Mycobacterium tuberculosis were reported in 39 (7%) children. Improving the surveillance of childhood TB is important for public health care workers and pediatricians. A non-negligible proportion of children had drug-resistant TB and was treated with second-line drugs, most of which are off-label in the pediatric age. Future efforts should concentrate on improving active surveillance, diagnostic tools, and the availability of antitubercular pediatric formulations, also in low-endemic countries.

Diagnostic features of community‐acquired pneumonia in children: what's new?

To critically summarise the available data on diagnosis of CAP in children, focusing on the newest findings and on the need for new studies.