[An infant with a black hairy tongue]. / Een zuigeling met een zwarte, harige tong.

At the outpatient clinic, an 8-month-old girl presented with a black hairy tongue. Since 2,5 weeks she used antibiotics because of osteomyelitis in her right humerus. There was no proper oral hygiene. She had no other complaints or abnormalities. The diagnosis 'lingua villosa nigra' was made. This is a benign, self-limiting disorder.

Enterovirus and parechovirus infection in children: a brief overview.

UNLABELLED: Enterovirus and parechovirus are a frequent cause of infection in children. This review is an overview of what is known from enterovirus and parechovirus infection in children and contains information about the epidemiology, pathogenesis, clinical presentation, diagnosis, treatment, and prognosis of enterovirus and parechovirus infection in children. CONCLUSIONS: EV and HPeV infections are a frequent cause of infection in childhood. The clinical presentation is diverse. RT-qPCR is the best way to detect an EV or HPeV. Cerebrospinal fluid, blood and feces have the highest sensitivity for detecting an EV or HPeV. There is no treatment for EV and HPeV infections. Two vaccines against EV 71 are just licensed in China and will be available on the private market. Little is known about the prognosis of EV and HPeV infections. WHAT IS KNOWN: •EV and HPeV are a frequent cause of infection in children. What is new: •This review gives a brief overview over EV and HPeV infection in children.

Prospective assessment of clinical symptoms associated with enterovirus and parechovirus genotypes in a multicenter study in Dutch children.

BACKGROUND: Human non-polio enterovirus (EV) and human parechovirus (HPeV) are important pathogens of viral infection and aseptic meningitis in children. The aim of this study is to prospectively compare the incidence, clinical signs, blood and cerebrospinal fluid in EV and HPeV infected children. OBJECTIVES: To compare the clinical symptoms and laboratory data of children with different EV and HPeV genotypes. STUDY DESIGN: This study is part of a multicenter prospective cohort study. Children were included in 3 different hospitals in The Netherlands from 2008 to 2011. RESULTS: Of 285 included patients, 140 (49%) had EV and 44 (15%) HPeV infection. Of children with EV infection 9 (6%) had EV-A, 109 (78%) EV-B, 12 (9%) had a non-type able EV and in 10 (7%) no genotyping was performed. Of children with HPeV infection, 24 (55%) had HPeV-3, 6 (14%) HPeV-1, 2 (5%) HPeV-4 and 1 (2%) HPeV-6. Meningitis was more frequent in EV than in HPeV infected children (54% vs. 36%, p=0.046), and in EV-B than EV-A infected children (60 vs. 33%). In contrast gastroenteritis was more frequent in HPeV than EV infected children (30% vs. 15%, p=0.030), and significantly more in HPeV-1 than HPeV-3 infected children (p<0.001). CONCLUSIONS: EV infection is more often associated with meningitis and HPeV infection more often with a gastro-enteritis. EV genotype B infection is more often associated with meningitis than EV genotype A infection. HPeV-1 infection was more often associated with gastroenteritis than HPeV-3 infection.

Prospective comparison of the detection rates of human enterovirus and parechovirus RT-qPCR and viral culture in different pediatric specimens.

BACKGROUND: Reverse-transcriptase quantitative real-time polymerase chain reaction (RT-qPCR) has become the gold standard for the diagnosis of human enterovirus (EV) and parechovirus (HPeV) infections. The detection rate of RT-qPCR in different pediatric body specimens has not been compared prospectively in a multicentre study. OBJECTIVES: This study compared the diagnostic detection rates of EV and HPeV RT-qPCR and viral culture in different specimens (feces, nasopharynx, blood, urine and cerebrospinal fluid (CSF)) of pediatric patients. STUDY DESIGN: This prospective, multicenter study performed an EV and HPeV RT-qPCR on nasopharynx, blood, urine, feces and CSF specimens and a viral culture on nasopharynx, feces and CSF specimens in symptomatic children<16 years. RESULTS: Of 285 included children EV was detected in 140 (49%) and HPeV in 44 (15%) children. Both EV and HPeV RT-qPCR had a higher sensitivity and negative predictive value than EV and HPeV viral culture, respectively. EV and HPeV RT-qPCR in feces specimen had the highest sensitivity (99.2% and 95.1%) of all specimens. Pooling results of specimens increased the detection rate for both viruses. CONCLUSION: Of all specimens, RT-qPCR in feces had the highest detection rate for both EV and HPeV in symptomatic pediatric patients. An EV was detected in all EV positive patients if a RT-qPCR was performed on both feces and CSF specimens or in both feces and urine specimens. HPeV was detected in all HPeV positive patients if a RT-qPCR was performed on both feces and CSF specimens, feces and nasopharynx specimens or CSF and nasopharynx specimens.

A 380-kb Duplication in 7p22.3 Encompassing the LFNG Gene in a Boy with Asperger Syndrome.

De novo genomic aberrations are considered an important cause of autism spectrum disorders. We describe a de novo 380-kb gain in band p22.3 of chromosome 7 in a patient with Asperger syndrome. This duplicated region contains 9 genes including the LNFG gene that is an important regulator of NOTCH signaling. We suggest that this copy number variation has been a contributive factor to the occurrence of Asperger syndrome in this patient.

Detection of enterovirus RNA in cerebrospinal fluid: comparison of two molecular assays.

Enterovirus (EV) and human parechovirus (HPeV) are a major cause of infection in childhood. A rapid diagnostic test may improve the management of patients with EV and HPeV infection. The aim of this study is to evaluate the performance of the GeneXpert enterovirus assay (GXEA) for detection of EV RNA compared to a user-developed reverse-transcriptase (RT) quantitative real-time PCR (qPCR) in routine clinical practice. Also a RT-qPCR assay for detection of HPeV RNA in different clinical samples was developed and evaluated. Cerebrospinal fluid (CSF) from 232 patients suspected for meningitis was collected and tested for EV and HPeV using RT-qPCR assays. In parallel an aliquot of the samples was tested using the GXEA and viral culture. EV RNA was detected in 22 (19.0%) and 28 (24.1%) of 116 samples using the GXEA and RT-qPCR assay, respectively. EV was isolated from 10 of 116 (8.6%) samples by viral culture. GXEA had a sensitivity, specificity, positive predictive value and negative predictive value of 82.1%, 100%, 100% and 96.2%, respectively. In this study, molecular assays were superior to viral culture for detecting EV RNA in CSF. GXEA showed a high specificity but a lower sensitivity for the detection of EV RNA compared to the RT-qPCR assay.

Respiratory atopic disease, Ascaris-immunoglobulin E and tuberculin testing in urban South African children.

BACKGROUND: Epidemiological relation of intestinal helminth infection and atopic disease, both associated with a T-helper (Th) 2 immune response, is controversial, as it has been reported that helminth infection may either suppress or pre-dispose to atopic disease. This relation has not been tested in an area with a high burden of Mycobacterium tuberculosis (MTB) infection, a known Th1-stimulating infection. OBJECTIVE: To study the association of intestinal helminth infection and atopic disease in a community where helminth infection is endemic and MTB infection is high. METHODS: Three-hundred and fifty-nine randomly selected children aged 6-14 years from a poor urban suburb were tested with allergy questionnaire, skin prick test (SPT) to common aeroallergens, Ascaris-specific IgE (Ascaris-sIgE), fecal examination for pathogenic intestinal helminths and tuberculin skin testing (TST). Histamine bronchoprovocation was tested in the group of children aged 10 years and older. RESULTS: were corrected for demographic variables, socioeconomic status, parental allergy, environmental tobacco smoke (ETS) exposure in the household, recent anthelminthic treatment and for clustering in the sampling unit. Results Ascaris-sIgE was elevated in 48% of children, Ascaris eggs were found in 15% and TST was positive in 53%. Children with elevated Ascaris-sIgE had significantly increased risk of positive SPT to aeroallergens, particularly house dust mite, atopic asthma (ever and recent), atopic rhinitis (ever and recent) and increased atopy-related bronchial hyper-responsiveness. In children with negative TST (<10 mm), elevated Ascaris-sIgE was associated with significantly increased risk of atopic symptoms (adjusted odds ratio (OR(adj)) 6.5; 95% confidence interval (CI) 1.9-22.4), whereas in those with positive TST (>/=10 mm) this association disappeared (OR(adj) 0.96; 95% CI 0.4-2.8). CONCLUSIONS: These results suggest that immune response to Ascaris (Ascaris-sIgE) may be a risk factor of atopic disease in populations exposed to mild Ascaris infection and that MTB infection may be protective against this risk, probably by stimulation of anti-inflammatory networks.

Mycobacterium tuberculosis infection may protect against allergy in a tuberculosis endemic area.

BACKGROUND: Epidemiological studies have shown an inverse relation of mycobacterial infection and the frequency of allergic diseases and asthma. Recent evidence suggests that allergic inflammation may be inhibited in the presence of chronic and persistent infections, such as that by Mycobacterium tuberculosis (MTB). The relation of tuberculin skin test (TST) size, an accepted marker of MTB infection and the frequency of allergic disease symptoms has not been reported from an area where MTB infection is endemic. OBJECTIVE: To investigate the association of TST and allergic disease symptoms, in children living in a tuberculosis (TB) endemic area. METHODS: In this cross-sectional study, 841 children aged 6-14 years from randomly selected household addresses in two poor communities of Cape Town, South Africa, were investigated with TST and standardized International Study on Asthma and Allergies in Childhood-based questionnaire on allergic disease symptoms. RESULTS: Children with positive TST (> or =10 mm) were significantly less likely to have allergic disease symptoms, in particular allergic rhinitis (AR) (adjusted odds ratio 0.43; 95% confidence interval 0.24-0.79) than those with negative TST. This association remained significant after adjusting for possible confounders and correcting for the effect of clustering (>1 child per household address) in the sample. There was a significant inverse linear trend in the relation of TST size in millimetre and the frequency of allergic disease symptoms, in particular AR (P<0.001). CONCLUSIONS: These results of inverse association of strong TST reaction and allergic disease symptoms in children from a TB endemic area are in support of the hypotheses that allergic inflammation may be inhibited by chronic infections, such as MTB.

The prevalence of symptoms associated with pulmonary tuberculosis in randomly selected children from a high burden community.

BACKGROUND: Diagnosis of childhood tuberculosis is problematic and symptom based diagnostic approaches are often promoted in high burden settings. This study aimed (i) to document the prevalence of symptoms associated with tuberculosis among randomly selected children living in a high burden community, and (ii) to compare the prevalence of these symptoms in children without tuberculosis to those in children with newly diagnosed tuberculosis. METHODS: A cross sectional, community based survey was performed on a 15% random sample of residential addresses. A symptom based questionnaire and tuberculin skin test (TST) were completed in all children. Chest radiographs were performed according to South African National Tuberculosis Control Program guidelines. RESULTS: Results were available in 1415 children of whom 451 (31.9%) were TST positive. Tuberculosis was diagnosed in 18 (1.3%) children. Of the 1397 children without tuberculosis, 253 (26.4%) reported a cough during the preceding 3 months. Comparison of individual symptoms (cough, dyspnoea, chest pain, haemoptysis, anorexia, weight loss, fatigue, fever, night sweats) in children with and without tuberculosis revealed that only weight loss differed significantly (OR = 4.5, 95% CI 1.5 to 12.3), while the combination of cough and weight loss was most significant (OR = 5.4, 95% CI 1.7 to 16.9). Children with newly diagnosed tuberculosis reported no symptoms in 50% of cases. CONCLUSION: Children from this high burden community frequently reported symptoms associated with tuberculosis. These symptoms had limited value to differentiate children diagnosed with tuberculosis from those without tuberculosis. Improved case definitions and symptom characterisation are required when evaluating the diagnostic value of symptoms.

Well defined symptoms are of value in the diagnosis of childhood pulmonary tuberculosis.

BACKGROUND: The diagnosis of childhood pulmonary tuberculosis presents a major challenge as symptoms traditionally associated with tuberculosis are extremely common in children from endemic areas. The natural history of tuberculosis in children shows that progressive disease is associated with symptoms which have a persistent, non-remitting character. The aims of this study were to investigate whether improved symptom definition is possible in a clinical setting, and whether use of these well defined symptoms has improved value in the diagnosis of childhood pulmonary tuberculosis. METHODS: A prospective, community based study was conducted in two suburbs of Cape Town, South Africa. All children (<13 years) presenting to the local community clinic with a cough of >2 weeks duration, were referred to the investigator. Parents completed a symptom based questionnaire, whereafter reported symptoms were characterised in a standard fashion. RESULTS: Of the 151 children enrolled, 21 (15.6%) reported symptoms with a persistent, non-remitting character. Tuberculosis was diagnosed in 16 (10.5%) children, all of whom reported these symptom characteristics. A persistent, non-remitting cough was reported in 15/16 (93.8%) children with tuberculosis and in 2/135 (1.5%) children without tuberculosis, indicating a specificity of 98.5% (135/137). Persistent fatigue of recent onset was also sensitive (13/16, 81.3%) and specific (134/135, 99.3%). Persistent fever and/or chest pain were exclusively reported in children with tuberculosis, but were present in only 4/16 (25.0%) children with tuberculosis. CONCLUSION: The use of well defined symptoms is feasible, even in resource limited settings, and may offer significantly improved value in the diagnosis of childhood pulmonary tuberculosis.

Inverse association between Mycobacterium tuberculosis infection and atopic rhinitis in children.

BACKGROUND: The association between Mycobacterium tuberculosis (MTB) infection and atopy remains controversial. AIM: To investigate the association between MTB infection and atopic rhinitis in children living in a high TB incidence area. METHODS: In this cross-sectional study 418 children aged 6-14 years from an established epidemiological research-site in a poor urban community were invited to participate. They were assessed for allergic rhinitis (ISAAC questionnaire) and skin responses to tuberculin and eight environmental allergens. The presence of a BCG scar was documented, intestinal parasites and total and Ascaris lumbricoides-specific IgE levels were measured. Atopic rhinitis was defined, using the new World Allergy Organization (WAO) definition, as reported allergic rhinitis and a positive skin prick test (SPT > or =3 mm) to any allergen. RESULTS: Among the 337 children enrolled 10.4% had allergic rhinitis, 17.5% a positive SPT and 53% a positive tuberculin skin test (TST > or =10 mm). Children with a positive TST were significantly less likely to have recent atopic rhinitis (OR(adjusted) 0.06; 95% CI 0.007-0.5) than those with a negative TST. SPTs were significantly more common in children with negative TST who had recent allergic rhinitis (OR(adj) 34.0; 95% CI 7.6-152.6), but not in children with positive TST and recent allergic rhinitis (OR(adj) 0.6; 95% CI 0.07-5.2). CONCLUSIONS: MTB infection seems to reduce the prevalence of atopic rhinitis, and influences SPT reactivity in children with allergic rhinitis from a high TB incidence area.

The association of prolonged breastfeeding and allergic disease in poor urban children.

The fact that breastfeeding may protect against allergic disease remains controversial, with hardly any reports from developing countries. This study investigated the association between allergic disease in children and prolonged breastfeeding. Data were collected from a 15% random sample of households from two poor suburbs of Cape Town, South Africa. Parents completed a validated International Study on Asthma and Allergies in Childhood questionnaire on allergic diseases for children aged 6-14 yrs. Other questions included breastfeeding duration, maternal smoking and parental allergy. Results were adjusted for possible confounders and for possible clustering within the household. Out of the 861 children included in the study, allergic disease in general, and hay fever in particular, were significantly less frequent in those with prolonged (> or =6 months) breastfeeding. There was a significant linear inverse association between breastfeeding duration and allergic disease in children without allergic parents, but not in children with an allergic predisposition. In conclusion, these results from a developing country suggest a protective effect of prolonged breastfeeding on the development of allergic disease, particularly hay fever, in children born to nonallergic parents. This protective effect was not found in children with an allergic predisposition.

The burden of childhood tuberculosis: a public health perspective.

The burden of childhood tuberculosis (TB) reflects recent transmission within a community and the level of TB control achieved within the adult (maintenance host) population. Children contribute little to the maintenance of the TB epidemic, but they may suffer severe TB-related morbidity and mortality. This review describes the main determinants of the burden of childhood TB within a particular community. Basic infectious disease principles identify the community, and not the individual, as the central entity that sustains an epidemic. The prevalence of TB is determined by the community's exposure to Mycobacterium tuberculosis, and their vulnerability to developing disease following exposure. The main variables that influence both exposure and vulnerability are discussed. Multiple variables are linked to poverty, and it is their cumulative effect, rather than the exact degree of poverty, that seems most important. Diligent contact tracing and the use of preventive chemotherapy will reduce the TB-related suffering of children. The burden of childhood TB, however, is a reflection of our ability to control the epidemic; this remains the ultimate challenge. Current efforts to control the TB epidemic aim to reduce transmission by treating sputum smear-positive adults, while very little emphasis is placed on reducing the vulnerability of high-burden communities. Successful control of the epidemic is the most effective way to reduce the burden of childhood TB, but this will require a holistic approach that acknowledges the importance of sustainable poverty alleviation.

The clinical epidemiology of childhood pulmonary tuberculosis: a critical review of literature from the pre-chemotherapy era.

The pre-chemotherapy literature represents an impressive body of evidence that clarifies important epidemiological concepts in childhood tuberculosis. Reports describe the major transitions in tuberculosis, from exposure to infection and from infection to disease (morbidity and mortality), without the influence of chemotherapy. Children with household exposure to a sputum smear-positive source case experienced the greatest risk of becoming infected and of developing subsequent disease. Household exposure to a sputum smear-negative source case or non-household exposure still posed an appreciable, although greatly reduced, risk. Infection in children less than 2 years of age indicated a probable household source case. The majority of older children who were infected did not have a household source identified, and presumably became infected in the community. The annual risk of infection (ARI) was not constant across all ages, but seemed to increase during periods of widening social contact. Infants and adolescents were the groups at highest risk for disease development and death following primary infection.

The natural history of childhood intra-thoracic tuberculosis: a critical review of literature from the pre-chemotherapy era.

The pre-chemotherapy literature documented the natural history of tuberculosis in childhood. These disease descriptions remain invaluable for guiding public health policy and research, as the introduction of effective chemotherapy radically changed the history of disease. Specific high-risk groups were identified. Primary infection before 2 years of age frequently progressed to serious disease within the first 12 months without significant prior symptoms. Primary infection between 2 and 10 years of age rarely progressed to serious disease, and such progression was associated with significant clinical symptoms. In children aged >3 years the presence of symptoms represented a window of opportunity in which to establish a clinical diagnosis before serious disease progression. Primary infection after 10 years of age frequently progressed to adult-type disease. Early effective intervention in this group will reduce the burden of cavitating disease and associated disease transmission in the community. Although the pre-chemotherapy literature excluded the influence of human immune deficiency virus (HIV) infection, recent disease descriptions in HIV-infected children indicate that immune-compromised children behave in a similar fashion to immune immature children (less than 2 years of age). An important concept deduced from the natural history of tuberculosis in childhood is that of relevant disease. Deciding which children to treat may be extremely difficult in high-prevalence, low-resource settings. The concept of relevant disease provides guidance for more effective public health intervention.

[Missed infections in immigrant children]. / Gemiste pathogenen bij immigrerende kinderen.

Three African children who migrated to the Netherlands developed serious infections after they arrived. The first patient, a girl of 3 years adopted from the Zaire, was discovered to be a chronic hepatitis B carrier. Advice to vaccinate her whole adoption family was not followed. Her adoptive mother became infected with hepatitis B. The second patient, an Ethiopian girl of 13 years, was not adequately screened for infections on arrival. She was a chronic hepatitis B carrier and infected her adoptive mother. Seven years later she developed pulmonary tuberculosis with cavity formation and infected four contacts. The third patient, a 15-year-old political refugee from Zaire, who developed paediatric aids and later died of it, was not screened according to the screening protocol advised for immigrating children. All immigrating children should be fully and adequately screened for infectious diseases upon arrival in the Netherlands.

[Borrelia lymphocytoma ('winter ears') in children]. / Borrelia-lymfocytoom ('winteroren') bij kinderen.

Two cases of Borrelia lymphocytoma are reported. The skin lesions were located on the ear margin or lobe. They were swollen, red and painful on touching. Serum titres of antibodies to Borrelia burgdorferi were elevated in both cases. Spirochaetal cultures from skin biopsies taken from the lesions were unsuccessful. Both patients responded very well to antibiotic treatment.