Hospital admission among HIV-exposed uninfected children compared with HIV-unexposed children.

OBJECTIVE: The main objective of this study was, on a national level, to investigate the risk of in-hospital admissions and use of antibiotics during the first 4 years of life among HIV-exposed uninfected (HEU) children compared with a matched control group of HIV-unexposed children. DESIGN: A nationwide register-based cohort study. METHODS: All HEU children born in Denmark from 2000 to 2012 were individually matched to five HIV-unexposed controls. Outcomes were risk of hospital admission (any, because of an infectious disease, observation/nonspecific diagnosis) and use of antibiotics during the first 4 years of life. Incidence rate ratios (IRRs) were estimated using Poisson regression analysis. RESULTS: In total, 317 HEU children and 1581 matched controls were included. HEU children had a three-fold increased risk of overall admissions {incidence rate ratio (IRR) 3.49 [95% confidence interval (CI) 2.98-4.08]}. There was no difference in risk of admission because of infectious diseases [IRR 1.11 (95% CI 0.73-1.70)] and no difference in use of antibiotics [IRR 0.88 (95% CI 0.73-1.04)]. The excess risk per 100 person-years of admission was primarily caused by an increased risk of admission because of observation/nonspecific diagnosis [excess incidence rate 22.6 (95% CI 18.2-27.0), IRR 6.06 (95% CI 4.84-7.61)]. CONCLUSION: HEU children had an increased risk of overall hospital admission mainly due to an increased risk of admission because of observation/nonspecific diagnosis. There was no increased risk of admission due to infectious disease. The excess risk of admission among HEU may be related to prophylactic treatment and/or HIV testing rather than somatic disease related to HIV or exposure to antiretroviral therapy.

Clinical characteristics and laboratory findings in Danish children hospitalized with primary Epstein-Barr virus infection.

BACKGROUND: Epstein-Barr virus (EBV) positive infectious mononucleosis (IM) is a common disease in adolescents. However, IM is often considered a rare disease in early childhood. We aimed to describe the classical presentation of adolescent EBV-associated IM compared to EBV infection at younger age. METHODS: All immunocompetent children hospitalized at Hvidovre University Hospital, Copenhagen between 2002 and 2013, who presented with clinical features that prompted a laboratory test for EBV, and who tested positive by presence of EBV-specific antibodies, heterophile antibodies or a positive EBV PCR were included (n = 95). RESULTS: Children aged 1-2 years were the age group most commonly hospitalized with acute EBV infection (27% of the cohort), followed by teenagers aged 14-15 years (23%). Fever, cervical lymphadenopathy, tonsillitis and fatigue were the most common physical findings overall. Dividing the children into three age groups (0-4 years, 5-10 years and 11-15 years) revealed that the oldest age groups significantly more often suffered from headache, tonsillitis, sore throat, abdominal pain and nausea. Young children typically presented with a runny nose, fever, fatigue and cervical adenitis. Compared with children under 5, children aged 5-15 years more often showed lymphocytosis (84% vs 62%), elevated alanine aminotransferase (77% vs 33%) and lactate dehydrogenase (79% vs 44%). CONCLUSION: EBV infection is common in young children, and children less than 3 years of age constitute the largest group of hospitalizations for acute EBV infection. EBV-associated IM should be suspected in febrile children of all ages with tonsillitis, lymphadenopathy, lymphocytosis and elevated liver enzymes.

Absence of novel human parvovirus (PARV4) in Danish mothers and children.

BACKGROUND: The recently discovered human parvovirus 4 (PARV4) is found most frequently in injection drug users, HIV-positive patients, and in haemophiliacs. Studies from Ghana report the finding of PARV4 in plasma from 2 to 12% of children without acute infection, and in nasal secretions and faecal samples. Studies of PARV4 in children from industrialized countries are few. OBJECTIVES: We aimed to describe the occurrence of PARV4 in a population-based birth cohort of 228 Danish mothers and their healthy children who previously participated in a study of respiratory tract infections in infancy. STUDY DESIGN: Children were included over a whole calendar year and were monitored through monthly home visits through the first year of life. Plasma samples for the present study were available from 228 mothers, 176 newborns, and 202 12-months-old children. All samples were analysed for the presence of PARV4 antibodies by enzyme immunoassay, and samples with detectable antibodies were in addition studied by real-time PCR. RESULTS: One (0.4%) of 228 mothers had PARV4 IgG exceeding the cut-off absorbance level and another had borderline IgG reactivity. No mother among these two had an acute infection, as they were IgM and PARV4 DNA negative. All blood samples from newborns and one-year-old children had IgG and IgM reactivity below cut-off. CONCLUSIONS: PARV4 is rare in Danish mothers and infants. Further studies are needed, in both rural and urban settings, to investigate the epidemiology and clinical significance of this novel human parvovirus.

Low Prevalence of Parvovirus 4 in HIV-infected Children in Denmark.

Parvovirus 4 (PARV4) has been associated with HIV infection in adults. We examined plasma samples from 46 HIV-infected 0-year-old to 16-year-old children for the presence of PARV4. Four children (8.7%) had detectable PARV4 IgG and 1 had IgM. The result of PARV4 polymerase chain reaction was found to be negative in all patients. PARV4 seropositivity was associated with low CD4 count but not with HIV viral load.

Neonatal hepatitis as first manifestation of hyperimmunoglobulinemia d syndrome.

Hyper IgD syndrome (HIDS) is a rare metabolic autoinflammatory syndrome characterised by recurrent febrile episodes, accompanied by various inflammatory symptoms. We present a case of severe HIDS in a young girl, whose symptoms started in the neonatal period with hepatomegaly, hepatitis, thrombocytopenia, and conjugated hyperbilirubinemia. From the age of five months, the child had recurrent febrile episodes, stomatitis, adenitis, and persistent hepatomegaly. The diagnosis of HIDS was established when she was three years and eight months old. This case report suggests that HIDS should be included in the differential diagnosis of neonatal hepatitis and conjugated hyperbilirubinemia.

[Salmonella is a rare cause of meningitis in infants]. / Salmonella er en sjælden årsag til meningitis hos nyfødte.

In developed countries, invasive disease caused by non typhoidal Salmonella spp. is rare. Here we present a Danish case of Salmonella enterica serovar Enteritidis (S. Enteritidis) meningitis in an infant who had no underlying diseases. The child had had no known expositions, and the source of the infection was never identified. The chance of finding uncommon microorganisms as cause of invasive infections such as meningitis and the choice of initial empiric antimicrobial treatments is discussed.

Clinical characteristics of children with Mycoplasma pneumoniae infection hospitalized during the Danish 2010-2012 epidemic.

INTRODUCTION: Mycoplasma pneumoniae is a common cause of community-acquired pneumonia. Pneumonia may be the most severe manifestation of respiratory M. pneumoniae infection. The most typical symptoms in children are cough and wheezing, which are often accompanied by upper respiratory tract manifestations mimicking viralrespiratory syndromes. MATERIAL AND METHODS: This was a retrospective descriptive study. We included all children hospitalized at the Department of Paediatrics, Hvidovre Hospital, Denmark, from 1 August 2010 through May 2012 who tested positive for M. pneumoniae by polymerase chain reaction (PCR). Clinical data were obtained from the medical charts. RESULTS: A total of 671 PCR analyses for M. pneumoniae were performed of which 102 tested positive (15%). Our study included 101 M. pneumoniae-positive children with a median age of six years (range: 57 days-16 years). The cases were distributed throughout the year, but with a peak from October to January. 43% were five years or younger, with 18% being 0-1 years old and almost 7% being less than one year old. Only 17% were 11-16 years old. 58% of the patients reported more than seven days of fever and/or cough prior to admission. In all, 65 of 101 M. pneumoniae-positive children were discharged within 24 hours of admission. CONCLUSION: M. pneumoniae should be kept in mind as a cause not only of community-acquired pneumonia, but also of milder respiratory infections in children younger than five years. PCR from a nasal or throat swap is an easy, reliable and quick diagnostic test in infants and children. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Challenges in diagnosing tuberculosis in children.

INTRODUCTION: Clinical investigations of childhood tuberculosis (TB) are challenged by the paucibacillary nature of the disease and the difficulties in obtaining specimens. We investigated the challenges in diagnosing TB in children in a low-incidence country. MATERIAL AND METHODS: The data were retrieved retrospectively from the paediatric departments at Danish university hospitals from April 2004 to March 2009 using the diagnosis code A15.0-A19.9 in children below the age of 15 years. RESULTS: A total of 54 children were identified of whom 13 were native Danes. The remaining immigrants were from a range of countries, the majority from Somalia. In all, 44 children had pulmonary TB and the proportion of extrapulmonary TB was higher among immigrants than among Danes. The cardinal symptoms were fever, weight loss and cough. In 41 cases (76%), a combination of a positive tuberculin skin test, an abnormal chest X-ray and the clinical presentation led to initiation of treatment. TB diagnosis was confirmed later by culture in 29 cases. The median number of days from contact to the healthcare system to treatment initiation was two days for 23 children who were part of contact tracing and seven days for the remaining children. All children but one completed treatment, and three patients were retreated due to relapse. Side effects to treatment were observed in 20 cases. None of the patients died. CONCLUSION: The majority of the children affected with TB were foreign-born with a higher proportion of extrapulmonary TB. The microbiological confirmation was low. A rapid onset of treatment was closely related to known, recent exposure.

Reduced thymic size but no evidence of impaired thymic function in uninfected children born to human immunodeficiency virus-infected mothers.

BACKGROUND: HIV-exposed, uninfected (HIV-EU) infants present hematologic and immunologic abnormalities at birth, and it remains to be clarified whether these abnormalities persist beyond infancy, for instance, affecting vaccination responses. METHODS: Thymic size and thymic output were evaluated in 20 HIV-EU children at 15 months of age and compared with 10 age- and gender-matched controls. Regulatory T-cells (Tregs) and immune activation as well as cytokine profiles were determined, and the antibody response to Haemophilus influenzae Type b (Hib) vaccination was evaluated. RESULTS: Thymic size was significantly lower in HIV-EU children (P = 0.011). However, CD4 and CD8 counts did not differ between HIV-EU and control children. Likewise, thymic output estimated as CD4 cells expressing naive (CD45RA+CD62L+CD27+, P = 0.31) or recent thymic naive (CD45RA+CD27+CD31+, P = 0.13) phenotype, or CD4 cells containing T-cell receptor excision circles (P = 0.47) were comparable. HIV-EU children and controls had similar levels of activated cells (CD4+CD38+HLA-DR+, P = 0.87; CD8+CD38+HLA-DR+, P = 0.22), Tregs (CD4+CD25+CD127(low)FOXP3+, P = 0.53), and naive Tregs (CD4+CD25+CD127(low)FOXP3+CD45RA+CD27+, P = 0.65). Finally, comparable titers of Haemophilus influenzae Type b antibodies in the 2 groups were found (P = 0.43). CONCLUSION: The study demonstrates reduced thymic size in HIV-EU children compared with children born to HIV-negative mothers, but no evidence of impaired thymic function, immune regulation, or antibody vaccination response was detected, suggesting that no qualitative immune deficits persist in HIV-EU children at 15 months of age.

Properdin deficiency associated with recurrent otitis media and pneumonia, and identification of male carrier with Klinefelter syndrome.

Properdin is an initiator and stabilizer of the alternative complement activation pathway (AP). Deficiency of properdin is a rare X-linked condition characterized by increased susceptibility to infection with Neisseria meningitidis associated with a high mortality rate. We report properdin deficiency in a large Pakistani family. The index cases were found by screening for immunodeficiency due to a history of recurrent infections. This revealed absent AP activity, but normal classical and lectin pathway activity. Sequencing of the properdin gene (PFC) revealed a novel frameshift mutation. When all available relatives (n=24) were screened for the mutation, four affected males, four female carriers and a male heterozygous carrier were identified. He was subsequently diagnosed with Klinefelter syndrome. A questionnaire revealed a striking association between properdin deficiency and recurrent otitis media (P=0.0012), as well as recurrent pneumonia (P=0.0017). This study is the first to show a significant association between properdin deficiency and recurrent infections.

Long-term effectiveness of highly active antiretroviral therapy (HAART) in perinatally HIV-infected children in Denmark.

The long-term impact of highly active antiretroviral therapy (HAART) on HIV-1 infected children is not well known. The Danish Paediatric HIV Cohort Study includes all patients <16 y of age with HIV-1 infection in Denmark. We report the complete follow-up from 1996 to 2005 of 49 perinatally infected children treated with HAART. Initial HAART included 2 nucleoside reverse-transcriptase inhibitors in combination with either a protease inhibitor (n =38) or a non-nucleoside reverse-transcriptase inhibitor (n =12). 19 (39%) patients were previously treated with mono- or dual therapy. Baseline characteristics were median CD4 percentage 14% and HIV-RNA viral load 4.9 log(10). Within the first 12 weeks of therapy approximately 60% achieved HIV-RNA viral load <500 copies/ml, and this remained stable for up to 8 y, although many children changed the components of HAART. The proportion of children with CD4 percentage >25% increased to 60-70% over the y of treatment. For the total cohort, 245 patient-y of observation were available with only 1 death. During our observation period there were no signs of a waning impact. The challenge remains to maintain a high adherence to therapy as the children grow into adolescence and develop more independence from family and health care staff.

Viral etiology and incidence of acute gastroenteritis in young children attending day-care centers.

BACKGROUND: The purpose of the study was to investigate the frequency, morbidity and cause of acute gastroenteritis in children attending day-care centers in Denmark. METHODS: Children with acute diarrhea (> or =2 consecutive loose stools in 24 hours, with duration of < or =7 days), recruited from 19 day-care centers, were included. Gastroenteritis viruses, group A rotavirus, sapoviruses, noroviruses and astroviruses were detected with reverse transcription-polymerase chain reaction assays. In addition, stool specimens were cultured for bacterial pathogens. Children who were brought to the clinic with acute diarrhea underwent a medical evaluation, including an estimation of dehydration. RESULTS: Two hundred seven children (median age, 20.1 months; range, 9-44 months) were enrolled. During the 6-month study period, 98 diarrheal episodes in 95 children were reported. Of these, 48 were reported retrospectively in telephone interviews. The incidence of acute diarrheal episodes was 0.08 episode per child per month. A viral etiologic agent was identified in 69% of cases. Rotaviruses were identified in 17 cases (40%), sapoviruses in 8 (19%) and astroviruses in 3 (7%). One patient had a coinfection with rotavirus and astrovirus. Campylobacter jejuni was detected in 2 patients and Clostridium difficile was found in 5 patients, all coinfected with a virus. In clinical assessments, 9 patients (18%) showed signs of dehydration and were given oral rehydration solution; 6 of these were hospitalized. CONCLUSIONS: Acute diarrhea among children attending day-care centers was common in wintertime. Rotaviruses were, expectedly, the most common causative agents, but sapoviruses were second to rotaviruses as etiologic agents in this population.

Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis.

OBJECTIVE: To determine whether probiotic lactobacilli may alleviate small intestinal inflammation and strengthen the intestinal barrier function in children with atopic dermatitis. STUDY DESIGN: In a double-blinded, placebo-controlled, cross-over study, probiotic lactobacilli (Lactobacillus rhamnosus 19070-2 and L reuteri DSM 12246) were administered for 6 weeks to 41 children with moderate and severe atopic dermatitis. Gastrointestinal symptoms were registered before and during treatment and small intestinal permeability was measured by the lactulose-mannitol test. RESULTS: During Lactobacillus supplementation, there was a significant decrease in the frequency of gastrointestinal symptoms (39% during the placebo period versus 10% during active treatment, P=.002). There was a positive association between the lactulose to mannitol ratio and the severity of the eczema (r=0.61, P=.02 after placebo and r=0.53, P=.05 after active treatment). After probiotic treatment, the lactulose to mannitol ratio was lower (0.073) than after placebo (0.110, P=.001). CONCLUSIONS: Impairment of the intestinal mucosal barrier appears to be involved in the pathogenesis of atopic dermatitis. The study suggests that probiotic supplementation may stabilize the intestinal barrier function and decrease gastrointestinal symptoms in children with atopic dermatitis.

Tick-borne encephalitis in childhood--consensus 2004.

Tick-borne encephalitis (TBE) is a communicable disease caused by a flavi-virus, ticks being the main vectors. The nervous system is affected, four clinical features of different severity are observed: meningitis, meningoencephalitis, meningoencephalomyelitis, meningoradiculoneuritis. TBE is a preventable disease, which is rapidly becoming a growing public health problem in Europe. So far no causal treatment is possible but an efficient, safe vaccination is available. During the 6th meeting of the International Scientific Working Group on TBE with the main conference issue "Tick-borne encephalitis in childhood" an international consensus was achieved. In countries where TBE is endemic--and not prevented by immunization--both children and adults are affected. The disease in children is generally milder, although severe illness may occur and even lead to permanent impairment of the quality of life due to neuropsychological sequelae. Therefore immunization should be offered to all children living in or traveling to endemic areas.

Effect of probiotic Lactobacillus strains in children with atopic dermatitis.

BACKGROUND: Recent studies suggest that oral bacteriotherapy with probiotics might be useful in the management of atopic dermatitis (AD). OBJECTIVE: The purpose of this investigation was to evaluate the clinical and anti-inflammatory effect of probiotic supplementation in children with AD. METHODS: In a double-blind, placebo-controlled, crossover study, 2 probiotic Lactobacillus strains (lyophilized Lactobacillus rhamnosus 19070-2 and Lactobacillus reuteri DSM 122460) were given in combination for 6 weeks to 1- to 13-year-old children with AD. The patients' evaluations were registered after each intervention (ie, better, unchanged, or worse). The clinical severity of the eczema was evaluated by using the scoring atopic dermatitis (SCORAD) score. As inflammatory markers, eosinophil cationic protein in serum and cytokine production by PBMCs were measured. RESULTS: After active treatment, 56% of the patients experienced improvement of the eczema, whereas only 15% believed their symptoms had improved after placebo (P =.001). The total SCORAD index, however, did not change significantly. The extent of the eczema decreased during active treatment from a mean of 18.2% to 13.7% (P =.02). The treatment response was more pronounced in allergic patients (at least one positive skin prick test response and elevated IgE levels), and in this group the SCORAD score decreased (P =.02 compared with nonallergic patients). During active treatment, serum eosinophil cationic protein levels decreased (P =.03). No significant changes in the production of the cytokines IL-2, IL-4, IL-10, or IFN-gamma were found. CONCLUSIONS: A combination of L rhamnosus 19070-2 and L reuteri DSM 122460 was beneficial in the management of AD. The effect was more pronounced in patients with a positive skin prick test response and increased IgE levels.

Effect of probiotic Lactobacillus strains in young children hospitalized with acute diarrhea.

BACKGROUND: Oral bacteriotherapy promotes recovery from acute childhood diarrhea, but few strains have been shown to have therapeutic potentials. We examined the effect of two newly identified probiotic Lactobacillus strains in acute childhood diarrhea. METHODS: Sixty-nine children were randomized during hospitalization for acute diarrhea to receive a mixture of Lactobacillus rhamnosus 19070-2 and Lactobacillus reuteri DSM 12246, 10(10) colony-forming units of each strain or placebo twice daily for 5 days. Before selection of these stains their potential probiotic characteristics were demonstrated in vitro and in healthy volunteers. RESULTS: In patients receiving probiotics, the diarrheal phase was reduced by 20%. The duration of diarrhea was 82 h in the treatment group vs. 101 h in the control group (not significant, P = 0.07). However, 3 of 30 patients from the treatment group vs. 13 of 39 from the control group still had loose stools at the end of the study period (P = 0.03). In patients with diarrhea for <60 h before start of treatment (early intervention), a clear effect of the probiotics was demonstrated (80 h in the treatment group vs. 130 h in the control group, P = 0.003). After early intervention, the length of hospitalization was reduced by 48% (3.5 vs. 1.7 days, P = 0.03). At the end of the intervention, rotavirus antigen was found in 12% of patients from the treatment group vs. 46% from the control group (P = 0.02). CONCLUSIONS: The two probiotics, L. rhamnosus 19070-2 and L. reuteri DSM 12246, ameliorated acute diarrhea in hospitalized children and reduced the period of rotavirus excretion. Oral bacteriotherapy was associated with a reduced length of hospital stay. The beneficial effects were most prominent in children treated early in the diarrheal phase.

Effect of probiotic Lactobacillus strains on acute diarrhea in a cohort of nonhospitalized children attending day-care centers.

BACKGROUND: Certain strains of lactobacilli have been shown to promote recovery from rotavirus enteritis in hospitalized children. Few studies have examined the effect of probiotics in nonhospitalized children with mild diarrhea. METHODS: We studied in a randomized placebo-controlled trial the effect of lyophilized Lactobacillus rhamnosus 19070-2 and Lactobacillus reuteri DSM 12246, 10(10) colony-forming units of each strain twice daily for 5 days, on acute diarrhea in children in a cohort of children recruited from local day-care centers. The duration of diarrhea and assessment of stool consistency were recorded by the parents. RESULTS: In patients treated with the selected Lactobacillus strains, the mean duration of diarrhea after intervention was reduced (76 h in patients treated with probiotics vs. 116 h in the placebo group; P = 0.05). In patients with diarrhea for <60 h before start of treatment (early intervention), a more pronounced effect of probiotics was found. The time to recovery after early treatment was 79 h vs. 139 h in the placebo group (P = 0.02); 1 of 17 patients treated early vs. 6 of 13 in the control group still had loose stools 120 h after start of treatment (P = 0.03). CONCLUSIONS: In children from day-care centers with mild gastroenteritis, the combination of L. rhamnosus 19070-2 and L. reuteri DSM 12246 was effective in reducing the duration of diarrhea.