Response to pneumococcal conjugate and polysaccharide vaccination in children with rheumatic disease.

Children with rheumatic disease and compromised immune system have an increased risk of infection. Streptococcus pneumoniae is a frequent pathogen, and immunization is recommended. In this study, we investigated whether immunocompromised children with rheumatic disease do respond to pneumococcal immunization with 13-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine. The study was conducted at two tertiary referral hospitals in Denmark from 2015 to 2018. Patients with rheumatic disease and compromised immune system aged 2-19 years were eligible. Patients were vaccinated with 13-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine. A blood sample was collected before vaccination and after each vaccination. IgG antibodies were quantified for twelve serotypes. Seroprotection for each serotype was defined as IgG ≥0.35 µg/mL. A total of 27 patients were enrolled. After the conjugate vaccine, an increase in antibody titres compared with pre-vaccination was found for all serotypes and 9/12 were significant. After the polysaccharide vaccine, the antibody titres for all serotypes but one was seen to increase but none reached significance. The proportion of patients protected before immunization ranged from 20.8% to 100% for the individual serotypes. Odds ratio for achieving seroprotection after the conjugate vaccine was >1 for 10/12 serotypes but only significant for three serotypes. After the polysaccharide vaccine, the odds ratio was >1 for 9/12 serotypes but none reached significance. In conclusion, children with rheumatic disease and compromised immune system respond to pneumococcal immunization with 13-valent pneumococcal conjugate vaccine and maintain antibody levels upon subsequent immunization with 23-valent pneumococcal polysaccharide vaccine.

Response to influenza vaccination in immunocompromised children with rheumatic disease: a prospective cohort study.

BACKGROUND: Prevention of illness due to infection by influenza viruses is important for children with rheumatic diseases. Biological disease modifying antirheumatic drugs have become increasingly important in the treatment of juvenile idiopathic arthritis, and combinations of immunosuppressive drugs are used for the treatment of systemic disorders, which increase the risk of secondary immunodeficiency. Therefore, we investigated whether children with rheumatic disease can mount a protective antibody response after influenza immunization. METHODS: The prospective multicentre cohort study was conducted in Denmark during the influenza season 2015-2016. Children with rheumatic disease aged six months to 19 years were eligible. Controls were immunologically healthy children. A blood sample was collected before and after vaccination and analysed by haemagglutination inhibition (HI) assay for the 2015-2016 influenza vaccine-strains. In case of flu-like symptoms the child was tested for influenza. For statistical analyses the patients were grouped according to medical treatment or disease. RESULTS: A total of 226 patients and 15 controls were enrolled. No differences were found for the increase of antibodies from pre-vaccine to post-vaccine between the groups in our primary analyses: A/Cal H1N1pdm09 (p = 0.28), A/Swi H3N2 (p = 0.15) and B/Phu Yamagata (p = 0.08). Only when combining patients across groups a lower increase in antibodies was found compared to controls. Among all patients the pre-vaccine rates for seroprotection using the HI-titer cut-off ≥ 40 were 93.1-97.0 % for all three strains. For seroprotection using the HI-titer cut-off ≥ 110 the pre-vaccine rates for all patients were 14.9-43.6 % for all three strains and an increase in the proportions of patients being seroprotected after vaccination was found for A/Cal H1N1pdm09 and A/Swi H3N2. None of the children with flu-like symptoms tested positive for the vaccine strains. CONCLUSIONS: Children with rheumatic diseases increase in antibody titres after influenza immunization, however, it remains uncertain whether a protective level is achieved.

[Indirect effects of the COVID-19 pandemic on mortality of mothers and children in low- and middle-income countries].

The COVID-19 pandemic may not only increase mortality due to the virus but also due to the indirect effects. The disease continues to ravage health and economic metrics globally, which is likely to increase maternal and under five-year child mortality in low- and middle-income countries. This review highlights key areas of concern for maternal and under five-year child mortality due to the indirect effects of the COVID-19 pandemic in low- and middle-income countries.

Poor Head Growth Is Associated with Later Mental Delay among Vietnamese Preterm Infants: A Follow-up Study.

BACKGROUND: Preterm infants in low- and middle-income countries are at high risk of poor physical growth, but their growth data are still scarce. OBJECTIVES: To describe the growth of Vietnamese preterm infants in the first 2 years, and to compare with references: World Health Organization (WHO) child growth standards, and healthy Southeast Asian (SEA) infants. Further, to assess the association between growth in the first year and neurodevelopment at 2 years corrected age (CA). METHODS: We conducted a cohort study to follow up preterm infants discharged from a neonatal intensive care unit for 2 years. Weight, length and head circumference (HC) were measured at 3, 12 and 24 months CA. Neurodevelopment was assessed using Bayley Scales of Infant and Toddler Development-3rd Edition at 24 months CA. RESULTS: Over 90% of the cohort showed catch-up weight at 3 months CA. Weight and length were comparable to healthy SEA but were lower than WHO standards. HC was significantly smaller than those of WHO standards with HC Z-scores steadily decreasing from -0.95 at 3 months CA to -1.50 at 24 months CA. Each one decrement of HC Z-score from 3 to 12 months CA was associated with nearly twice an increase in odds of mental delay at 24 months CA (odds ratio 1.89; 95% confidence interval 1.02-3.50). CONCLUSION: Vietnamese preterm infants exhibited early catch-up weight but poor head growth, which was associated with later delays in mental development. Our findings support the importance of HC measures in follow-up for preterm infants.

Rates of rehospitalisation in the first 2 years among preterm infants discharged from the NICU of a tertiary children hospital in Vietnam: a follow-up study.

OBJECTIVES: To describe the characteristics of rehospitalisation in Vietnamese preterm infants and to examine the time-to-first-readmission between two gestational age (GA) groups (extremely/very preterm (EVP) vs moderate/late preterm (MLP)); and further to compare rehospitalisation rates according to GA and corrected age (CA), and to examine the association between potential risk factors and rehospitalisation rates. DESIGN AND SETTING: A cohort study to follow up preterm infants discharged from a neonatal intensive care unit (NICU) of a tertiary children's hospital in Vietnam. PARTICIPANTS: All preterm newborns admitted to the NICU from July 2013 to September 2014. MAIN OUTCOMES: Rates, durations and causes of hospital admission during the first 2 years. RESULTS: Of 294 preterm infants admitted to NICU (all outborn, GA ranged from 26 to 36 weeks), 255 were discharged alive, and 211 (83%) NICU graduates were followed up at least once during the first 2 years CA, of whom 56% were hospital readmitted. The median (IQR) of hospital stay was 7 (6-10) days. Respiratory diseases were the major cause (70%). Compared with MLP infants, EVP infants had a higher risk of first rehospitalisation within the first 6 months of age (p=0.01). However, the difference in risk declined thereafter and was similar from 20 months of age. There was an interaction in rehospitalisation rates between GA and CA. Longer duration of neonatal respiratory support and having older siblings were associated with higher rehospitalisation rates. Lower rates of rehospitalisation were seen in infants with higher cognitive and motor scores (not statistically significant in cognitive scores). CONCLUSIONS: Hospital readmission of Vietnamese preterm infants discharged from NICU was frequent during their first 2 years, mainly due to respiratory diseases. Scale-up of follow-up programmes for preterm infants is needed in low-income and middle-income countries and attempts to prevent respiratory diseases should be considered.

Neurodevelopment at 2 years corrected age among Vietnamese preterm infants.

BACKGROUND: Preterm infants are at risk of neurodevelopmental delay, but data on long-term outcomes in low-income and middle-income countries remain scarce. OBJECTIVES: To examine neurodevelopment using Bayley Scales of Infant and Toddler Development-3rd edition (Bayley-III) and neurological findings in 2-year-old preterm infants, and to compare with healthy Vietnamese infants. Further, to assess factors associated with neurodevelopmental impairment. DESIGN AND SETTING: Cohort study to follow up preterm infants discharged from a neonatal intensive care unit (NICU) of a tertiary children's hospital in Vietnam. PARTICIPANTS: Infants born at <37 weeks of gestational age. MAIN OUTCOMES: Bayley-III assessment and neurological examination at 2-year corrected age (CA) compared with healthy Vietnamese infants. RESULTS: Of 294 NICU preterm infants, Bayley-III scores of all 184/243 (76%) survivors at 2 years CA were significantly lower than those of healthy Vietnamese peers in all three domains: cognition (mean (SD): 84.5 (8.6) vs 91.4 (7.5), p<0.001), language (mean (SD): 88.7 (12.5) vs 95.9 (11.9), p<0.001) and motor (mean (SD): 93.1 (9.0) vs 96.8 (9.3), p=0.003). The mean differences in Bayley-III scores between preterm and healthy Vietnamese infants were -6.9 (-9.1 to -4.7), -7.2 (-10.5 to -3.8) and -3.7 (-6.1 to -1.2) for cognitive, language and motor scores, respectively. The prevalence of neurodevelopmental impairment was 17% for cognitive, 8% for language and 4% for motor performance. In total, 7% were diagnosed with cerebral palsy. Higher maternal education was positively associated with infant neurodevelopment (OR 0.32, 95% CI 0.11 to 0.94). CONCLUSIONS: Vietnamese preterm infants in need of neonatal intensive care showed poor neurodevelopment at 2 years. Higher maternal education was positively associated with infant neurodevelopment. Standard follow-up programmes for preterm infants should be considered in low-resource settings.

Antibody response to vaccination after haematopoietic cell transplantation in children using a reduced dose schedule-A retrospective cohort study.

Children receiving HCT loose protective immunity to vaccines received pre-HCT. Therefore, revaccination post-HCT is of major importance. In Denmark, a vaccination schedule with fewer doses post-HCT has been used, including two doses for diphtheria, tetanus, polio, measles, mumps, and rubella, and one dose only for Haemophilus influenzae type B. The background for this was the presumption that post-HCT immunization constituted booster vaccination of donor immunity. Our objective was to evaluate the proportion of children protected after the scheduled vaccination programme. A nationwide retrospective cohort study of all children who have received an HCT in Denmark during 1994-2012. Antibody levels were analysed in blood samples drawn before and after vaccination, and the probability of achieving protection after the scheduled immunization programme was estimated. A total of 198 children were included. The protection post-immunization was as follows: diphtheria 75.3%, tetanus 89.1%, polio 97.7%, and Haemophilus influenzae type B 94.8%. For diphtheria and tetanus, the probability of achieving protection increased to 93.8% and 97.3%, respectively, after a third dose. For measles, mumps, and rubella, the probability of achieving protection was 89.4%, 80.9%, and 94.2%, respectively. In conclusion, our findings support a more extensive vaccination schedule including three doses for diphtheria and tetanus which are in line with current international guidelines.

Lipoprotein cholesterol fractions are related to markers of inflammation in children and adolescents with juvenile idiopathic arthritis: a cross sectional study.

BACKGROUND: The purpose of the study is to determine levels of total cholesterol (TC), low-density, and high-density lipoprotein fractions of cholesterol (LDLc and HDLc), in patients with juvenile idiopathic arthritis (JIA), and relate those to disease activity, overweight, and physical activity (PA), testing the hypothesis that the levels of cholesterol fractions are associated with inflammation as well as with overweight and low PA. METHODS: Two hundred ten patients with JIA were included in this descriptive cross-sectional study. TC, LDLc, HDLc were measured, and associations with clinical disease activity (JADAS27), biomarkers of inflammation (myelo-related protein complex 8/14 (MRP8/14), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR)), body mass index (BMI), waist-to-height ratio (WtH ratio), and PA were explored. RESULTS: Mean values for TC, LDLc, and HDLc in the patients were within the normal range for Danish Children. HDLc was negatively correlated with MRP8/14 (r = -0.343, CI -0.474 to -0.201, p < 0.0005) but was not related to overweight or PA. Neither TC nor LDLc showed any association with inflammation, overweight, or PA. MRP8/14 correlated positively with CRP, JADAS27 and WtH ratio (r = 0.277, CI 0.142 to 0.413, p = 0.001). CONCLUSIONS: Levels of cholesterol fractions in patients with JIA were found within the normal range. Nonetheless, the level of HDLc was negatively associated with the level of the inflammatory marker MRP8/14, which is in accordance with the concept of inflammation as an important driver for premature development of atherosclerosis in JIA. WtH ratio (a measure of central fatness) was not associated to HDLc, but to MRP8/14, suggestive of central fatness as an additional driving factor for the chronic inflammation in JIA.

South Vietnamese Rural Mothers' Knowledge, Attitude, and Practice in Child Health Care.

A study of 600 rural under-five mothers' knowledge, attitude, and practice (KAP) in child care was performed in 4 southern provinces of Vietnam. The mothers were randomly selected and interviewed about sociodemographic factors, health seeking behaviour, and practice of home care of children and neonates. 93.2% of the mothers were literate and well-educated, which has been shown to be important for child health care. 98.5% were married suggesting a stable family, which is also of importance for child health. Only 17.3% had more than 2 children in their family. The mother was the main caretaker in 77.7% of the families. Only 1% would use quacks as their first health contact, but 25.2% would use a private clinic, which therefore eases the burden on the government system. Nearly 69% had given birth in a hospital, 27% in a commune health station, and only 2.7% at home without qualified assistance. 89% were giving exclusive breast feeding at 6 months, much more frequent than in the cities. The majority of the mothers could follow IMCI guideline for home care, although 25.2% did not deal correctly with cough and 38.7% did not deal correctly with diarrhoea. Standard information about Integrated Management of Childhood Illnesses (IMCI) based home care is still needed.

Premature subclinical atherosclerosis in children and young adults with juvenile idiopathic arthritis. A review considering preventive measures.

Many studies show that Juvenile Idiopathic Arthritis (JIA) is associated with early subclinical signs of atherosclerosis. Chronic inflammation per se may be an important driver but other known risk factors, such as dyslipidemia, hypertension, insulin insensitivity, a physically inactive lifestyle, obesity, and tobacco smoking may also contribute substantially. We performed a systematic review of studies through the last 20 years on early signs of subclinical atherosclerosis in children and adolescents with JIA with the purpose of investigating whether possible risk factors, other than inflammation, were considered.We found 13 descriptive cross sectional studies with healthy controls, one intervention study and two studies on adults diagnosed with JIA. Only one study addressed obesity, and physical activity (PA) has only been assessed in one study on adults with JIA and only by self-reporting. This is important as studies on PA in children with JIA have shown that most patients are less physically active than their healthy peers, and as physical inactivity in several large studies of normal schoolchildren is found to be associated with increased clustering of risk factors for cardiovascular disease. It is thus possible that an inactive lifestyle in patients with JIA is an important contributor to development of the subclinical signs of atherosclerosis seen in children with JIA, and that promotion of an active lifestyle in childhood and adolescence may diminish the risk for premature atherosclerotic events in adulthood.

[Individualized treatment of osteoarticular infections in children may shorten the treatment course]. / Individualisering af behandling af osteoartikulære infektioner hos børn kan afkorte behandlingsforløbet.

Older studies have suggested that antibiotic treatment for less than 21 days in children with osteoarticular infections is associated with relapse, and therefore traditionally these infections have been treated for six weeks with an intravenous phase of one week. However, four new prospective studies suggest that if the duration of treatment is individualized and made dependent on the clinical response and the C-reactive protein level, the treatment course may be shortened substantially without increasing the risk of relapse or sequelae. This article reviews older and newer literature on this subject.

[Symptoms of severe calciphylaxis in a girl with X-linked hypophosphataemia].

X-linked hypophosphataemia (XLH) is the most common form of hereditary rickets. We present a case report of a girl who was diagnosed with XLH. She was treated with activated vitamin D and phosphate and received several correctives surgical procedures. After a knee surgery, complicated with osteomyelitis, she presented with symptoms of severe calciphylaxis with calcification of several organ systems. Medical therapy was paused and systemic inflammation was treated with steroids and loop diuretics. This case report underlines the necessity of careful dosage of vitamin D and pausing of medical therapy after surgical procedures in patients with XLH.

Neonatal bloodstream infections in a pediatric hospital in Vietnam: a cohort study.

Septicemia and bloodstream infections (BSIs) are major causes of neonatal morbidity and mortality in developing countries. We prospectively recorded all positive blood cultures (BSI) among neonates admitted consecutively to a tertiary pediatric hospital in Vietnam during a 12-month period. Among 5763 neonates, 2202 blood cultures were performed, of which 399 were positive in 385 neonates. Among these, 64 died, 62 in relation to septicemia. Of the BSI isolates, 56% was known pathogenic and 48% was gram-negative bacteria, most frequently Klebsiella spp. (n = 78), Acinetobacter spp. (n = 58) and Escherichia coli (n = 21). Only three Streptococcus spp. were identified, none group B. Resistance against antibiotics applied was common. The mortality was highest in neonates with gram-negative BSI compared with no confirmed BSI and gram-positive BSI (P < 0.01). In this setting, the majority of BSI were likely to have been transmitted from the environment. Improvement of hygienic precautions and systematic BSI surveillance are recommended.

[The risk of infections in internationally adopted children is real]. / Infektionsrisikoen hos internationale adoptivbørn er reel.

Each year approximately 400 internationally adopted children (IAC) come to Denmark from countries with high prevalences of infectious diseases. Former studies of IAC have shown that approximately 1% of the IAC are infected with Hepatitis A, 3-6% with Hepatitis B, mostly asymptomatic infections. 8-27% have gastrointestinal parasites and 1-7% have tuberculosis, but 3-21% have a positive Mantoux test. The studies found none with HIV or HCV and only a few with syphilis. The vaccination status was often deficient and the serology results did not match the vaccination records. All studies conclude that screening of IAC is recommended.

[Anti-TNFalpha treatment of juvenile uveitis]. / Tumornekrosefaktor alpha-haemning som led i behandling af uveitis hos børn.

INTRODUCTION: To present our experience with anti-TNFalpha treatment of juvenile idiopatic arthritis (JIA) associated uveitis. MATERIALS AND METHODS: All 11 children with severe uveitis were monitored between 2001 and 2005. Nine of the children had JIA and a set of twins had a rare hereditary granulomatous disease, Blau's syndrome. The patients were selected and the reason for starting anti-TNFalpha treatment was an insufficient response in the arthritis or uveitis to previous therapy. RESULTS: In all patients the anti-TNFalpha treatment reduced the activity of uveitis. The response to treatment was related to 1) visual acuity and 2) the reduction of systemic immune-suppressing agents. All 11 children are still on anti-TNFalpha treatment. CONCLUSION: Anti-TNFalpha was effective in treating uveitis in all 11 patients. In patients with active uveitis associated JIA not responding to corticosteroids and methotrexate and with declined vision the trend is to start anti-TNFalpha treatment early in the inflammatory disease to prevent long term complications to the eyes. The results indicate a superiority of infliximab over Eternacept in the treatment of uveitis.

Risk factors for acute respiratory tract infections in young Greenlandic children.

Acute respiratory infections cause considerable morbidity among Inuit children, but there is very little information on the risk factors for these infections in this population. To identify such factors, the authors performed a prospective community-based study of acute respiratory infections in an open cohort of 288 children aged 0-2 years in the town of Sisimiut, Greenland. Between July 1996 and August 1998, children were monitored weekly, and episodes of upper and lower respiratory tract infections were registered. Risk factor analyses were carried out using a multivariate Poisson regression model adjusted for age. Risk factors for upper respiratory tract infections included attending a child-care center (relative risk = 1.7 compared with home care) and sharing a bedroom with adults (relative risk = 2.5 for one adult and 3.1 for two adults). Risk factors for lower respiratory tract infections included being a boy (relative risk = 1.5), attending a child-care center (relative risk = 3.3), exposure to passive smoking (relative risk = 2.1), and sharing a bedroom with children aged 0-5 years (relative risk = 2.0 for two other children). Breastfeeding tended to be protective for lower respiratory tract infections. The population-attributable risk of lower respiratory tract infections associated with passive smoking and child-care centers was 47% and 48%, respectively. The incidence of acute respiratory infections among Inuit children may be reduced substantially through public health measures.

[Reflex dystrophy affects children, too]. / Børn får også refleksdystrofi.

Reflex dystrophy or Complex Regional Pain Syndrome (CRPS) is a neuropathic pain condition in a limb after a trauma. Pain is not limited to one or more dermatomes and there is a disproportion between the intensity of the pain and the eliciting trauma. Among physicians in Denmark it is not common knowledge that CRPS also affects children. It is not described in paediatric textbooks and until 1978 there were only eight published case reports. CRPS is seen in older children and teenagers and the pain is often located in a leg. CRPS is more common among girls than boys (approx. 4:1). Lack of knowledge of CRPS in children often results in a fairly long delay between the onset of symptoms and the diagnosis. Physiotherapy is an important part of the treatment of CRPS but concomitant pain treatment is often required in order to make physiotherapy possible. Sympathetic nerve block with intravenous regional guanethedine block or an epidural blockade is used. A number of analgesics may also be used. The treatment should be administered by a multi-disciplinary team. The incidence of CRPS in children in Denmark is unknown but the condition is probably under-diagnosed. Early diagnosis and active treatment may reduce the duration of the condition considerably.

Ocular complications and visual outcome in juvenile chronic arthritis: a 25-year follow-up study.

OBJECTIVE: Assessment of longterm ophthalmic outcome in juvenile chronic arthritis (JCA) with emphasis on visual acuity and identification of disease-related parameters associated with rheumatic eye affection. MATERIAL: Sixty-five adults (52 females, 13 males) with a history of or still active JCA were assessed an average of 26.7 years after disease onset. METHODS: Cross-sectional, longterm, follow-up study including complete ophthalmological and rheumatological examinations. RESULTS: Evidence of ocular complications was found in 13 subjects (20%): 10 had had recurrent iritis, two band keratopathy, and one diplopia due to rheumatoid eye muscle involvement. The three single eyes with poor sight (<0.1) were all in the complication subgroup. Binocularly, all but one patient scored at least 6/9 as best corrected visual acuity; one, however, had severe glaucoma-impaired visual fields. The refractive range was -8.12 to +6.0 D. There were no cases of keratoconjunctivitis sicca. Iritis was associated with early disease onset (p = 0.02), longer disease duration (p = 0.02) and a positive antinuclear antibodies (ANA) (p = 0.02). CONCLUSION: Ophthalmic complications were recorded in 20% of the study group, primarily in ANA positive patients with pauciarticular onset JCA. In addition to the two patients with severely affected bilateral visual status (3%), one of the 65 patients had acquired unilateral blindness. Half of the complications were late in that they were first recorded after the age of 16 years. Otherwise, the findings were in keeping with other studies of visual prognosis using non-selected series.