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The outbreak of COVID-19 resulted in a decrease in tuberculosis notification rates globally. We compared tuberculosis incidence rates and disease severity in children seen in our centre prior and during COVID-19 pandemic.We performed a cohort study enrolling children aged under 18 years who received a diagnosis of tuberculosis (January 1st, 2010-December 31st, 2021) at our Pediatric Infectious Diseases Unit. Disease severity was evaluated based on: the classification proposed by Wiseman et al., smear positivity, presence of symptoms at presentation, lung cavitation, extrapulmonary disease, respiratory failure and need for intensive care support. Overall, 168 children (50.6% female, median age 69 months, IQR 95.4) received a diagnosis of tuberculosis, 156 (92.8%) between 2010–2019, before COVID-19 outbreak, and 12 (7.2%) between 2020–2021, during the pandemic. The annual tuberculosis notification rate dropped by 73% in 2021 (0.38/100000, 95%CI 0.1–0.96) compared with 2019 (1.46/100000, 95%CI 0.84–2.37). Compared to the pre-pandemic period, the proportion of children classified as severe was higher in 2020–2021 (5, 41.6% vs 23, 15.7%, p = 0.006) with a higher rate of respiratory failure (2, 16.7%, vs 4, 2.6%, p = 0.01) and an increased need for intensive care support (1, 8.3% vs 1, 0.6%, p = 0.01). Conclusion: During COVID-19 pandemic we observed a reduction in tuberculosis notification rate in pediatric population and a significant increase in disease severity. This scenario may be the consequence of a delay in diagnosis and an underreporting of cases, rather than the effect of a reduced transmission of tuberculosis. Children reached health-care services only in the need of urgent medical attention. What is Known:• COVID-19 pandemic had a huge impact on national health care systems, resulting in a reduction of access to medical care. What is New:• In Campania Region, Italy, a low tuberculosis incidence country, we witnessed a 75% reduction in tuberculosis notification rate during pandemic. In parallel we demonstrated a significant increase in disease severity, suggesting that the reduction in notification rate may be attributed to an underreporting of cases and consequential diagnostic delay, rather than a reduced transmission of infection.

Aims: Undue concerns about the consequences of fever and its inappropriate management have been documented worldwide among physicians. However, no data exist on medical students. We investigated the perception, knowledge and attitude towards childhood fever among final-year medical students. Methods: Between June and September 2021, final-year medical students of six Italian universities were invited to complete an online survey on their conceptions and attitude towards pharmacological and non-pharmacological management of childhood fever. History of relevant personal or second-hand experience with childhood fever was also addressed. Both quantitative and qualitative approaches were used. Results: Of 1095 (69%) final-year medical students, 756 completed the survey. Many students believe that high fever might cause brain damage, would recommend physical methods and alternate two drugs for fever. Most students do not think that fever has mainly beneficial effects. In Northern Italy, students are less likely to believe that fever might lead to brain damage (OR 0.55, 95% CI 0.33-0.94), and in Southern Italy students are more likely to advise physical methods (OR 1.77, 95% CI 1.22-2.57) and less likely to believe that fever has mainly beneficial effects (OR 0.55, 95% CI 0.39-0.77). History of a relevant personal episode of fever during childhood was not associated with these outcomes. Conclusions: Misconceptions about fever are common among final-year medical students in Italy. Cultural factors rather than individually learned traits might underlie these beliefs. Medical students are a promising target for educational interventions to improve childhood fever management.

The pathophysiology of SARS-CoV-2-associated diarrhea is unknown. Using an experimental model validated for rotavirus-induced diarrhea, we investigated the effects of SARS-CoV-2 on transepithelial ion fluxes and epithelial integrity of human intestinal cells. The effect of the antidiarrheal agent diosmectite on secretion was also evaluated following its inclusion in COVID-19 management protocols.We evaluated electrical parameters (intensity of short-circuit current [hiSARS-CoV-2 induced an increase inSARS-CoV-2 induces calcium-dependent chloride secretion and oxidative stress without damaging intestinal epithelial structure. The effects are largely induced by the spike protein and are significantly reduced by diosmectite. SARS-CoV-2 should be added to the list of human enteric pathogens.

Human Immunodeficiency Virus (HIV) infected children have a 30–70% chance of being incompletely immunized and may not respond serologically with the same magnitude or durability as uninfected children. The aim of the study was to describe the rate of protective antibodies titre and the persistence of the response against four recommended vaccinations in HIV infected children and adolescents. A two-phase observational study was performed in which protective IgG antibodies to measles, mumps, rubella and hepatitis B were determined and monitored for 12 and 24 months, in 26 perinatally HIV-infected children. The rate of protection for rubella and hepatitis B was significantly lower in the HIV group compared to the control group (92% vs. 65% for rubella and 78.4% vs. 45.4% for hepatitis B, p &lt, 0.05). Children who received primary vaccination after initiating combination antiretroviral therapy (cART) had a higher rate of response. Seronegative patients who received a booster dose of vaccine had a good immunological response. HIV infection is associated with a lower response to vaccines against rubella and hepatitis. The beginning of cART before vaccination may be associated with a better response. The evaluation of the serological response is crucial in children with HIV infection in order to evaluate the protection of vaccine preventable diseases.

Overcrowding, the unavailability of personal protective equipment, and transmission between health care workers are the main causes of the rapid spread of coronavirus disease 2019 (COVID-19) in hospital settings. Because children have less severe symptoms than adults, we used tele-medicine (TM) as the main approach to managing subjects younger than 14 years who contacted their primary care paediatrician (PCP). A TM program for suspected paediatric COVID-19 cases was developed by the COVID-19 paediatric referral centre and PCPs in the Campania Region, Italy. A total of 269 cases of suspected COVID-19 were discussed through tele-consultation between PCPs and paediatric infectious disease specialists. The main reason for the initiation of tele-consultation by PCPs was the need for case management advice (n=206, 77%). A total of 203 children were tested for COVID-19, and 139 were positive (73 males, aged 5 years [IQR 1-10]), of whom 103 were managed at home with phone/video monitoring, 17 received a direct medical visit and discharged to home, and 19 were admitted to the COVID-19 unit. The main symptoms were fever (45%) and cough (25%). Thirty-five percent were asymptomatic and detected in family clusters. None had severe clinical outcomes.ConclusionTM is a reliable tool to limit the spread of COVID-19 and might reduce the number of unnecessary visits and hospital admissions. Through tele-consultation with an expert, PCPs can identify at-risk children who need testing and manage most cases remotely. However, standardization of the TM approach and criteria for hospital admission are needed.

Background Multisystem inflammatory syndrome in children (MIS-C) is a rare life-threatening clinical condition that can develop in patients younger than 21 years of age with a history of infection/exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The cardiovascular system is a main target of the inflammatory process that frequently causes myocardial dysfunction, myopericarditis, coronary artery dilation, hypotension, and shock. Multisystem inflammatory syndrome in children-associated myocarditis is usually characterized by fever, tachycardia, non-specific electrocardiogram abnormalities, and left ventricular dysfunction, but serious tachyarrhythmias may also occur. We report two cases of patients with MIS-C-associated myocarditis who developed severe bradycardia. Case summary Two female adolescents with recent history of coronavirus disease 2019 (COVID-19) were initially hospitalized for long-lasting high-grade fever and severe gastrointestinal symptoms. Both patients were diagnosed with MIS-C-associated myocarditis for elevation of markers of myocardial injury (mean highly-sensitive cardiac troponin 2663 pg/mL, mean N-terminal-pro-brain natriuretic peptide 5097 pg/mL) and left ventricular dysfunction, which was subsequently confirmed by cardiac magnetic resonance. Both patients developed a severe sinus bradycardia (lowest heart rate 36 and 42, respectively), which appeared refractory to the treatment with intravenous Methylprednisolone and Immunoglobulins, despite a clinical and biochemical improvement. The use of Anakinra (a recombinant interleukin-1 receptor antagonist), was associated with a rapid improvement of cardiac rhythm and excellent clinical outcome at 6 months of follow-up. Discussion In patients with MIS-C-associated myocarditis, a continuous cardiac monitoring is mandatory to promptly identify potential conduction abnormalities. Adolescents may present bradycardia as a rhythm complication. We experienced a rapid recovery after treatment with Anakinra, to be considered as add-on therapy in cases refractory to standard anti-inflammatory treatment.

Background: In comparison with adults, severe acute respiratory syndrome (SARS-CoV-2) infection in children has a milder course. The management of children with suspected or confirmed coronavirus disease (COVID-19) needs to be appropriately targeted. Methods: We designed a hub-and-spoke system involving a Hub Centre to provide relevant healthcare information, based on the use of telemedicine and stringent admission criteria. Result: Between March and April 2020, the Hub Centre managed a total of 119 children (62 males, 52%; median age, 5.5 years; interquartile range [IQR], 2; 10) with suspected or confirmed COVID-19. Of the 119 children, 90 were managed in cooperation with family paediatricians and 29 with hospital-based physicians. In total, 8 (6.7%) children were hospitalised, with a median length of hospital stay of 10 days (IQR, 8.5 days; range, 4–22 days). Conclusion: case-by-case management allows a global evaluation in which the clinical condition is one determinant in medical decision-making along with the use of isolation to prevent the spread of COVID-19 among family members and cohabitants, and biocontainment measures. Large centres could coordinate paediatric COVID-19 cases through telemedicine, taking advantage of the generally milder presentation in children but also considering their dependence on adults and risk of infection spreading.

Objective: Clinical and psychological HIV-related problems peak during adolescence, which coincides with transition of children and adolescents infected from mothers from pediatric to adult reference centers for HIV infection. Transition often is done without specific programs. We wanted to explore transition as an opportunity to increase the efficacy of care and the psychological well-being through a specific program. Methods: Thirteen vertically infected patients aged 13-20 years were followed up for 24 months by pediatricians, infectious disease specialists, a psychologist, and a nurse. Interventions consisted in joint clinic, simplification of therapy, patient group discussions, HIV infection explanations, and psychological support, lasting 12 months. Efficacy was measured by viro-immunological outcomes and adherence to therapy and psychological tests. Clinical, viro-immunological, and psychological evaluations were performed at 0 (T0) and 12 months (T12) and 6 months after transition to an adult center (T18). Psychological outcomes were assessed using standardized questionnaires for quality of life and self-esteem. Results: In 11/13 participants, pills administrations/day were significantly reduced. Patients with undetectable viral load and CD4+ >25% increased from 61 to 77% and from 61 to 74%, respectively. Six months after transition, all patients exhibited an undetectable viral load. Adolescents' awareness of the severity of the disease and the risk of sexual transmission was generally poor. Patients classified with "severe" psychological distress according to the quality of life index decreased from 38 to 15% and well-being increased. Similar results were observed 6 months after the transition to adult care. No effect was observed on self-esteem index. Conclusions: Specific protocols for transition should be developed to optimize resilience and psychological well-being, including routine psychological support for adolescents with HIV infection transiting from pediatric to adult centers for HIV infection.

Background Ascites can develop as a consequence of a number of diseases in childhood. Despite chronic liver disease is the most common cause, several conditions can lead to ascites also in the absence of liver dysfunction. As non-cirrhotic ascites shows a high degree of overlapping sign and symptoms it is still a challenge for physicians. Case presentation A 8-year-old Caucasian girl was referred for fever, vomit and diarrhea occurred over the past few weeks. Physical examination showed timpanitic distension of the abdomen with marked tenderness and increased abdominal wall rigidity. Abdominal imaging showed diffuse ascites and thickened omentum and bowel wall. Blood tests showed increased C- reactive protein levels and decreased lymphocyte count. Specific treatment for inflammatory bowel disease was started. Persisting of ascites required additional investigations. Positive tuberculin skin test and Interferon Gamma release assay (IGRA) as well as increased Ca125 serum concentrations were found. Computed tomography scan showed mediastinal and mesenteric adenopathies and diffuse smooth thickening of the omentum with significant enhancement (omental cake-like). Ascitic fluid analysis revealed high leucocytes and protein levels. Presumptive diagnosis of peritoneal tuberculosis (PTB) was made. Antituberculous treatment resulted in the resolution of ascites and normalization of lymphocyte count and Ca125 serum concentrations. Conclusions PTB is still possible in low-prevalence countries. As it is a great mimicker of other abdominal pathology whose treatment might worsen tuberculosis progression, clinical suspicion and adequate screening are required to avoid unnecessary interventions and delayed treatment. Ca125 is a non-specific marker of peritoneal inflammation but it might be helpful in monitoring the treatment response.

Key Points Question Are chilblain-like lesions of the toes associated with SARS-CoV-2 infection or is the association merely temporal? Findings This case series of 17 adolescents found that chilblain-like lesions of the toes emerged during the COVID-19 pandemic in otherwise healthy adolescents without signs of SARS-CoV-2 infection or other inflammatory, autoimmune, or thrombophilic phenomena. Meaning These results suggest that chilblain-like lesions are not associated with systemic or localized SARS-CoV-2 infection., Importance Chilblain-like lesions have been one of the most frequently described cutaneous manifestations during the COVID-19 pandemic. Their etiopathogenesis, including the role of SARS-CoV-2, remains elusive. Objective To examine the association of chilblain-like lesions with SARS-CoV-2 infection. Design, Setting, and Participants This prospective case series enrolled 17 adolescents who presented with chilblain-like lesions from April 1 to June 30, 2020, at a tertiary referral academic hospital in Italy. Main Outcomes and Measures Macroscopic (clinical and dermoscopic) and microscopic (histopathologic) analysis contributed to a thorough understanding of the lesions. Nasopharyngeal swab, serologic testing, and in situ hybridization of the skin biopsy specimens were performed to test for SARS-CoV-2 infection. Laboratory tests explored signs of systemic inflammation or thrombophilia. Structural changes in peripheral microcirculation were investigated by capillaroscopy. Results Of the 17 adolescents (9 [52.9%] male; median [interquartile range] age, 13.2 [12.5-14.3] years) enrolled during the first wave of the COVID-19 pandemic, 16 (94.1%) had bilaterally localized distal erythematous or cyanotic lesions. A triad of red dots (16 [100%]), white rosettes (11 [68.8%]), and white streaks (10 [62.5%]) characterized the dermoscopic picture. Histologic analysis revealed a remodeling of the dermal blood vessels with a lobular arrangement, wall thickening, and a mild perivascular lymphocytic infiltrate. SARS-CoV-2 infection was excluded by molecular and serologic testing. In situ hybridization did not highlight the viral genome in the lesions. Conclusions and Relevance This study delineated the clinical, histologic, and laboratory features of chilblain-like lesions that emerged during the COVID-19 pandemic, and its findings do not support their association with SARS-CoV-2 infection. The lesions occurred in otherwise healthy adolescents, had a long but benign course to self-resolution, and were characterized by a microvascular remodeling with perivascular lymphocytic infiltrate but no other signs of vasculitis. These results suggest that chilblain-like lesions do not imply a concomitant SARS-CoV-2 infection. Ongoing studies will help clarify the etiopathogenic mechanisms., This case series examines the association of chilblain-like lesions with SARS-CoV-2 infection.

Antibiotic therapy is not necessary for acute diarrhea in children, as rehydration is the key treatment and symptoms resolve generally without specific therapy. Searching for the etiology of gastroenteritis is not usually needed; however, it may be necessary if antimicrobial treatment is considered. The latter is left to the physician evaluation in the absence of clear indications. Antimicrobial treatment should be considered in severely sick children, in those who have chronic conditions or specific risk factors or in specific settings. Traveler’s diarrhea, prolonged diarrhea, and antibiotic-associated diarrhea may also require antibiotic therapy. Depending on the severity of symptoms or based on risk of spreading, empiric therapy may be started while awaiting the results of microbiological investigations. The choice of antibiotic depends on suspected agents, host conditions, and local epidemiology. In most cases, empiric therapy should be started while awaiting such results. Empiric therapy may be started with oral co-trimoxazole or metronidazole, but in severe cases parenteral treatment with ceftriaxone or ciprofloxacin might be considered.

Background Diarrhea is a severe complication in HIV-1-infected patients with Trans-activator of transcription (HIV-1 Tat) protein being recognized as a major underlying cause. Beside its direct enterotoxic effects, Tat protein has been recently shown to affect enteric glial cell (EGC) activity. EGCs regulate intestinal inflammatory responses by secreting pro-inflammatory molecules; nonetheless, they might also release immune-regulatory factors, as palmytoilethanolamide (PEA), which exerts anti-inflammatory effects by activating PPARα receptors. We aimed at clarifying whether EGCs are involved in HIV-1 Tat-induced diarrhea and if PEA exerts antidiarrheal activity. Methods Diarrhea was induced by intracolonic administration of HIV-1 Tat protein in rats at day 1. PEA alone or in the presence of peroxisome proliferator-activated receptor (PPAR) antagonists was given intraperitoneally from day 2 to day 7. S100B, iNOS, NF-kappaB, TLR4 and GFAP expression were evaluated in submucosal plexi, while S100B and NO levels were measured in EGC submucosal plexi lysates, respectively. To verify whether PEA effects were PPARα-mediated, PPARα−/− mice were also used. After 7 days from diarrhea induction, endogenous PEA levels were measured in submucosal plexi homogenates deriving from rats and PPARα−/− mice. Results HIV-1 Tat protein induced rapid onset diarrhea alongside with a significant activation of EGCs. Tat administration significantly increased all hallmarks of neuroinflammation by triggering TLR4 and NF-kappaB activation and S100B and iNOS expression. Endogenous PEA levels were increased following HIV-1 Tat exposure in both wildtype and knockout animals. In PPARα−/− mice, PEA displayed no effects. In wildtype rats, PEA, via PPARα-dependent mechanism, resulted in a significant antidiarrheal activity in parallel with marked reduction of EGC-sustained neuroinflammation. Conclusions EGCs mediate HIV-1 Tat-induced diarrhea by sustaining the intestinal neuroinflammatory response. These effects are regulated by PEA through a selective PPARα-dependent mechanism. PEA might be considered as an adjuvant therapy in HIV-1-induced diarrhea. Electronic supplementary material The online version of this article (10.1186/s12974-018-1126-4) contains supplementary material, which is available to authorized users.

Despite the effectiveness of combined anti-retroviral therapy, human immunodeficiency virus (HIV) infected-patients frequently report diarrhea and neuropsychological deficits. It is claimed that the viral HIV-1 Trans activating factor (HIV-1 Tat) protein is responsible for both diarrhea and neurotoxic effects, but the underlying mechanisms are not known. We hypothesize that colonic application of HIV-1 Tat activates glial cells of the enteric nervous system (EGCs), leading to a neuroinflammatory response able to propagate to the central nervous system. We demonstrated that HIV-1 Tat-induced diarrhea was associated with a significant activation of glial cells within the colonic wall, the spinal cord and the frontal cortex, and caused a consistent impairment of the cognitive performances. The inhibition of glial cells activity by lidocaine, completely abolished the above-described effects. These observations point out the role of glial cells as putative effectors in HIV-1 Tat-associated gastrointestinal and neurological manifestations and key regulators of gut-brain signaling.

Background: Clostridium difficile toxin A is responsible for colonic damage observed in infected patients. Drugs able to restore Clostridium difficile toxin A-induced toxicity have the potential to improve the recovery of infected patients. Cannabidiol is a non-psychotropic component of Cannabis sativa, which has been demonstrated to protect enterocytes against chemical and/or inflammatory damage and to restore intestinal mucosa integrity. Objective:The purpose of this study was to evaluate (a) the anti-apoptotic effect and (b) the mechanisms by which cannabidiol protects mucosal integrity in Caco-2 cells exposed to Clostridium difficile toxin A. Methods: Caco-2 cells were exposed to Clostridium difficile toxin A (30 ng/ml), with or without cannabidiol (10−7–10−9 M), in the presence of the specific antagonist AM251 (10−7 M). Cytotoxicity assay, transepithelial electrical resistence measurements, immunofluorescence analysis and immunoblot analysis were performed in the different experimental conditions. Results: Clostridium difficile toxin A significantly decreased Caco-2 cells’ viability and reduced transepithelial electrical resistence values and RhoA guanosine triphosphate (GTP), bax, zonula occludens-1 and occludin protein expression, respectively. All these effects were significantly and concentration-dependently inhibited by cannabidiol, whose effects were completely abolished in the presence of the cannabinoid receptor type 1 (CB1) antagonist, AM251. Conclusions:Cannabidiol improved Clostridium difficile toxin A-induced damage in Caco-2 cells, by inhibiting the apoptotic process and restoring the intestinal barrier integrity, through the involvement of the CB1 receptor.

Disclosure of the HIV status to infected children is often delayed due to psychosocial problems in their families. We aimed at improving the quality of life in families of HIV-infected children, thus promoting disclosure of the HIV status to children by parents. Parents of 17 HIV-infected children (4.2-18 years) followed at our Center for pediatric HIV, unaware of their HIV status, were randomly assigned to the intervention group (8 monthly sessions of family group psychotherapy, FGP) or to the control group not receiving psychotherapy. Changes in the Psychological General Well-Being Index (PGWB-I) and in the Short-Form State-Trait Anxiety Inventory (Sf-STAI), as well as the HIV status disclosure to children by parents, were measured. Ten parents were assigned to the FGP group, while 7 parents to the controls. Psychological well-being increased in 70% of the FGP parents and none of the control group (p=0.017), while anxiety decreased in the FGP group but not in controls (60% vs. 0%, p=0.03). HIV disclosure took place for 6/10 children of the intervention group and for 1/7 of controls. Family group psychotherapy had a positive impact on the environment of HIV-infected children, promoting psychological well-being and the disclosure of the HIV status to children.

The purpose of this study was to evaluate (a) the anti-apoptotic effect and (b) the mechanisms by which cannabidiol protects mucosal integrity in Caco-2 cells exposed toCaco-2 cells were exposed toCannabidiol improved

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.

SummaryA case of visceral disseminated infection by Mycobacterium sherrisii in an African HIV-infected adolescent with multiple abdominal abscesses is reported. Despite multiple drug resistance to first-line antibiotics in vitro, long-term treatment with clarithromycin, moxifloxacin, and clindamycin, together with appropriate antiretroviral treatment, resulted in clinical and radiological cure after 19 months of therapy and follow-up.

Summary Aims : To assess the incidence of intestinal inflammation in children with cystic fibrosis and to investigate whether probiotics decrease it. Study design : In this two-phase, controlled, prospective study, faecal calprotectin was measured by enzyme-linked immunosorbent assay in 30 children with cystic fibrosis, 30 healthy controls and 15 children with active inflammatory bowel disease. Ten children with cystic fibrosis received Lactobacillus GG, and faecal calprotectin was re-measured 4 weeks later. Rectal nitric oxide production was measured with the rectal dialysis bag technique in 20 children with cystic fibrosis, 20 healthy controls and 15 children with inflammatory bowel disease. Five children with cystic fibrosis received Lactobacillus GG and nitric oxide was re-measured 4 weeks later. Results : Mean faecal calprotectin was significantly higher in the two groups of patients than in controls. Abnormal values were detected in 27 of 30 cystic fibrosis and in 15 of 15 inflammatory bowel disease children. Also mean nitric oxide production was increased in both group of patients, and abnormal values were detected in 19 of 20 cystic fibrosis and in 15 of 15 inflammatory bowel disease children. Calprotectin and nitric oxide concentrations were reduced after probiotics administration. Conclusions : Intestinal inflammation is a major feature of cystic fibrosis and is reduced by probiotics. The latter finding suggests that intestinal microflora play a major role in intestinal inflammation in cystic fibrosis children.

Background & Aims Intestinal inflammation is a hallmark of cystic fibrosis (CF). Administration of probiotics can reduce intestinal inflammation and the incidence of pulmonary exacerbations. We investigated the composition of intestinal microbiota in children with CF and analyzed its relationship with intestinal inflammation. We also investigated the microflora structure before and after Lactobacillus GG (LGG) administration in children with CF with and without antibiotic treatment. Methods The intestinal microbiota were analyzed by denaturing gradient gel electrophoresis (DGGE), real-time polymerase chain reaction (RT-PCR), and fluorescence in situ hybridization (FISH). Intestinal inflammation was assessed by measuring fecal calprotectin (CLP) and rectal nitric oxide (rNO) production in children with CF as compared with healthy controls. We then carried out a small double-blind randomized clinical trial with LGG. Results Twenty-two children with CF children were enrolled in the study (median age, 7 years; range, 2–9 years). Fecal CLP and rNO levels were higher in children with CF than in healthy controls (184±146 µg/g vs. 52±46 µg/g; 18±15 vs. 2.6±1.2 µmol/L NO2−, respectively; P

Background: Nutrient malabsorption is a negative prognostic factor in acquired immunodeficiency syndrome and recent studies have shown that pancreatic insufficiency is a codetermining factor of malabsorption. Aims: To evaluate the effectiveness of open-label oral pancreatic enzyme supplementation therapy in acquired immunodeficiency syndrome patients with fat malabsorption. Patients and methods: Twenty-four consecutive patients with human immunodeficiency virus infection and fat malabsorption were recruited (11 males, 13 females; median age, 9.1 years). Faecal fat loss was evaluated by steatocrit assay at entry to the study (T-0), after 2 weeks (T-1) without pancreatic enzyme treatment and after a further 2 weeks (T-2) of treatment with pancreatic extracts (Creon 10 000 at a dose of 1000 units of lipase per gram of ingested dietary fat). Faecal elastase-1 and chymotrypsin were assayed at entry. Results: Six patients (25%) had abnormally low elastase-1 and/or chymotrypsin faecal concentration. In all patients, steatocrit values were elevated at both T-0 and T-1. Five patients proved intolerant to pancreatic enzyme treatment because of the onset of abdominal pain, and therapy was discontinued. In the 19 patients who concluded the study, steatocrit values during pancreatic enzyme treatment (T-2) were significantly lower than at entry (P

Preliminary clinical evidence suggests that Helicobacter pylori may be associated with diarrhea through its vacuolating toxin (VacA). To establish whether VacA induces intestinal secretion, epithelial damage, or both, purified pH-activated VacA was added to Caco-2 cell monolayers mounted in Ussing chambers, and electrical parameters were monitored. Mucosal addition of VacA induced an increase in short circuit current, consistent with enterotoxic effect. The effect was time- and dose-dependent and saturable. It was not found if the toxin was not pH-activated, added to the serosal side, or preheated. In cells preloaded with the Ca2+ buffering compound BAPTA/AM or with the Cl- channel inhibitor 5-nitro-2-3-(3-phenylpropylamino)benzoic acid, short circuit current did not change, indicating that VacA induces activation of Ca2+-dependent Cl- channels. VacA did not show cytopathic effects, as judged by tissue resistance. These results support the hypothesis that H. pylori may be associated with diarrhea through production of VacA.

Oral administration of human serum immunoglobulin reduces the duration of diarrhea and of rotaviral excretion in children. To investigate the in vitro effects of immunoglobulin on virusenterocyte interaction, Caco-2 cells were infected with Rotavirus strain SA11. Immunoglobulin was added prior to and at various times postinfection. Indirect immunofluorescence was performed with an antibody against VP-6 rotaviral antigen. Cell viability and monolayer transepithelial electrical resistance (TEER) were monitored. Immunofluorescence showed a perinuclear distribution in 90% of cells.Rotavirus infection induced a progressive decrease in TEER and a parallel reduction in cell viability, depending on viral load. Preincubation of the virus with immunoglobulin prevented cell infection as judged by immunofluorescence. Immunoglobulin addition to infected cells partially prevented the decrease in TEER and induced a later shift of TEER toward increasing values, suggesting restoration of monolayer's integrity. The efficacy of immunoglobulin depended on its concentration and on the time of its addition. These results indicate that immunoglobulin is effective in preventing infection and in reducing cell damage, through a direct anti-Rotavirus action and may indicate that immunoglobulin should be administered in the early phase of diarrhea, to reduce the severity ofRotavirus infection.

Background There are few and debated data regarding possible differences in the clinical presentations of influenza A/H1N1, A/H3N2 and B viruses in children. This study evaluates the clinical presentation and socio-economic impact of laboratory-confirmed influenza A/H1N1, A/H3N2 or B infection in children attending an Emergency Room because of influenza-like illness. Methods Among the 4,726 children involved, 662 had influenza A (143 A/H1N1 and 519 A/H3N2) and 239 influenza B infection detected by means of real-time polymerase chain reaction. Upon enrolment, systematic recordings were made of the patients' demographic characteristics and medical history using standardised written questionnaires. The medical history of the children was re-evaluated 5-7 days after enrolment and until the resolution of their illness by means of interviews and a clinical examination by trained investigators using standardised questionnaires. During this evaluation, information was also obtained regarding illnesses and related morbidity among households. Results Children infected with influenza A/H1N1 were significantly younger (mean age, 2.3 yrs) than children infected with influenza A/H3N2 (mean age, 4.7 yrs; p < 0.05)) or with influenza B (mean age, 5.2 yrs; p < 0.05). Adjusted for age and sex, children with influenza A/H3N2 in comparison with those infected by either A/H1N1 or with B influenza virus were more frequently affected by fever (p < 0.05) and lower respiratory tract involvement (p < 0.05), showed a worse clinical outcome (p < 0.05), required greater drug use (p < 0.05), and suffered a worse socio-economic impact (p < 0.05). Adjusted for age and sex, children with influenza B in comparison with those infected by A/H1N1 influenza virus had significantly higher hospitalization rates (p < 0.05), the households with a disease similar to that of the infected child (p < 0.05) and the need for additional household medical visits (p < 0.05). Conclusions Disease due to influenza A/H3N2 viral subtype is significantly more severe than that due to influenza A/H1N1 subtype and influenza B virus, which indicates that the characteristics of the different viral types and subtypes should be adequately considered by health authorities when planning preventive and therapeutic measures.

A resistance of A/H1N1 influenza viruses to oseltamivir has recently emerged in a number of countries. However, the clinical and socioeconomic importance of this resistance has not been precisely defined. As children have the highest incidence of influenza infection and are at high risk of severe disease, the aim of this study was to evaluate the clinical importance and the impact on the households of oseltamivir-resistant seasonal A/H1N1 influenza virus in an otherwise healthy pediatric population. A total of 4,726 healthy children younger than 15 years with influenza-like illness were tested for influenza viruses by real-time polymerase chain reaction in the winters of 2007-2008 and 2008-2009 in Italy. The influenza A virus-positive samples underwent neuraminidase gene analysis using pyrosequencing to identify mutations H275Y and N294 S in A/H1N1, and E119V, R292K, and N294 S in A/H3N2. Among the A/H1N1 subtypes, the H275Y mutation was found in 2/126 samples taken in 2007-2008 (1.6%) and in all 17 samples (100%; p < 0.0001) taken in 2008-2009. No other mutation was identified in any of the A/H1N1 or A/H3N2 influenza viruses. No significant differences were found in terms of clinical importance or impact on the households between the children with oseltamivir-resistant seasonal A/H1N1 influenza virus and those with the wild-type. The spread of H275Y-mutated A/H1N1 seasonal influenza virus is a common phenomenon and the clinical importance and impact on the households of the mutated virus is similar to that of the wild-type in an otherwise healthy pediatric population.

The mechanisms of diarrhea due to rotavirus infection in humans are not fully understood; no specific therapy is available, but orally administered human serum immunoglobulins are effective in blocking stool output. We aimed to investigate the effect of rotavirus on ion transport and the role of NSP4 in human-derived enterocytes, and to test the efficacy of human serum immunoglobulin in a model of rotavirus infection. Soon after infection, rotavirus induces active chloride secretion in enterocytes. This effect is evident before viral replication leads to cell damage and correlates with NSP4 production. Inhibition of NSP4 prevents the early secretory phase but not cell damage. Incubation with human serum immunoglobulin blocks both ion secretion and cell damage. Rotavirus exerts an early NSP4-dependent ion secretion and subsequent tissue damage. The combined enterotoxic and cytotoxic effects may be responsible for the increased severity of diarrhea due to rotavirus infection, and both are counteracted by human serum immunoglobulin.

AIMS: Iodine supplementation of parenterally fed infants recommended by ESPGHAN is 1 microg/kg/day. To assess nutritional and thyroid status of children on parenteral nutrition (PN) through urinary iodine concentration (UIC). PATIENTS AND METHODS: Children (1-17 yrs), undergoing PN and receiving an iodine supply of 1 microg/kg/day, were enrolled from 2000 to 2007. RESULTS: We observed 15 children (10 males, mean age 76.53+/-60.4 months) on PN from 14 to 84 weeks (mean 38.5+/-21.4). Ten were on TPN and five on PPN; nine had short bowel syndrome (SBS) and six had other intestinal diseases requiring PN. Iodine supply in TPN ranged between 1 and 1.6 microg/kg/day (mean 1.1+/-0.3 microg/kg/day), while in PPN it ranged from 2.3 to 2.8 microg/kg/day (mean 2.6+/-0.7 microg/kg/day). We found an inverse correlation between duration of PN in months and UIC (P=0.05). Four weeks after PN onset, UIC

Summary Background There is conflicting evidence as to whether ursodeoxycholic acid (UDCA) reduces the incidence of parenteral nutrition-associated cholestasis. Aim To investigate the efficacy of UDCA on parenteral nutrition-associated cholestasis in children with intestinal failure due to short bowel syndrome or to other causes. Methods Children with cholestasis received 30 mg/kg/day UDCA. Improvement or normalization of parenteral nutrition-associated cholestasis was evaluated at 6 months of therapy and at the last follow-up. In a subgroup of children, serum UDCA levels were measured while receiving UDCA and after 4 weeks withdrawal. Results Twelve children were treated with UDCA. Full remission or partial improvement of parenteral nutrition-associated cholestasis occurred in 11 of 12 children. In three of four children, withdrawal of UDCA was associated with a rebound rise of cholestasis. Only one of 12 treated children showed no improvement and in this patient, in contrast to four other patients, plasma levels of UDCA did not increase during treatment. Conclusions Ursodeoxycholic acid was effective in controlling parenteral nutrition-associated cholestasis. The efficacy of UDCA also in children with short bowel is related to intestinal absorption.