Serological testing for Bartonella henselae infections in The Netherlands: clinical evaluation of immunofluorescence assay and ELISA.

Cat-scratch disease (CSD), caused by Bartonella henselae infection, can mimic malignancy and can manifest atypically. Reliable serological testing is therefore of great clinical importance. The diagnostic performance of immunofluorescence assay (IFA) and ELISA was evaluated in a group of Dutch patients with proven CSD (clinical diagnosis confirmed by PCR). Sera of 51 CSD patients and 56 controls (patients with similar symptoms, but who were B. henselae PCR-negative and had an alternative confirmed diagnosis) were tested for anti-B. henselae IgM and IgG by IFA and ELISA. A commercially available IFA test for IgM had a sensitivity of 6%. In-house assays for IgM showed specificities of 93% (IFA) and 91% (ELISA), but with low sensitivities (53% and 65%, respectively). With a specificity of 82% (IFA) and 91% (ELISA), in-house IgG testing showed a significantly higher sensitivity in IFA (67%) than in ELISA (28%, p <0.01). Sensitivity was higher for genotype I (38-75%) than for genotype II (7-67%) infections, but this was only statistically significant for IgG ELISA (p <0.05). In conclusion, detection of IgM against B. henselae by in-house ELISA and IFA was highly specific for the diagnosis of CSD. The high seroprevalence in healthy individuals limits the clinical value of IgG detection for diagnosing CSD. Given the low sensitivity of the serological assays, negative serology does not rule out CSD and warrants further investigation, including PCR. Adding locally isolated (e.g., genotype II) B. henselae strains to future tests might improve the sensitivity.

Community-acquired pathogens associated with prolonged coughing in children: a prospective cohort study.

A 2-year prospective study was performed of children with prolonged coughing to investigate the frequency of different respiratory pathogens, the rate of mixed infections, and possible differences in severity of disease between single and mixed infections. Sera from 135 children (136 episodes of prolonged coughing lasting 1-6 weeks) were tested for antibodies to different viruses and bacteria. Swabs were taken for culture and PCR to detect different viral and bacterial pathogens. One or more pathogens were found in 91 (67%) patients. One infectious agent was found in 49 (36%) patients, two agents in 35 (26%) patients, and more than two agents in seven (5%) patients. The most frequent pathogens encountered were rhinovirus (n = 43; 32%), Bordetella pertussis (n = 23; 17%) and respiratory syncytial virus (n = 15; 11%). The most frequent mixed infection was B. pertussis and rhinovirus (n = 14; 10%). No significant differences in clinical symptoms were observed between patients with or without pathogens; however, patients with mixed infections were significantly older. There was a strong seasonal influence on the number of infections, but not on the number of mixed infections. In children with prolonged coughing, there was a high frequency of mixed infections regardless of the season. However, mixed infection was not associated with increased disease severity. No clinical symptoms were found that allowed discrimination between specific pathogens.

Inherited deficiency of the third component of complement associated with recurrent pyogenic infections, circulating immune complexes, and vasculitis in a Dutch family.

A family is described in which 3/11 children showed a homozygous deficiency of C3, and both parents and six other children had subnormal levels of C3. The three children with selective C3 deficiency suffered repeatedly from bacterial infections, whereas the parents and the other siblings were clinically healthy. During infectious episodes the patients showed a maculopapular skin rash, and at such times immune complexes were present in the serum. Biopsy specimens of the skin lesions showed the picture of leukocytoclastic vasculitis.

The thymus in "bare lymphocyte" syndrome: significance of expression of major histocompatibility complex antigens on thymic epithelial cells in intrathymic T-cell maturation.

Thymic biopsies from two patients with combined immunodeficiency and defective expression of HLA class I and class II antigens on blood mononuclear cells ("bare lymphocyte" syndrome) were investigated. This made possible an evaluation of the significance of HLA antigen expression in a detailed (immuno)histologic study. Both thymuses showed a normal lobular architecture with distinct cortex-medulla areas, well-differentiated epithelium, including ultrastructurally defined subtypes, and Hassall's corpuscles. Normal numbers of lymphoid cells were present and normal T-cell phenotype was found. Using anti-HLA-A,B,C antisera, confluent staining of the medulla (stroma and lymphocytes) was observed. One of the thymuses was found to be negative for HLA class II antigen expression: the other revealed only HLA-DR positivity of nonlymphoid cells in the medulla. These cells were not of epithelial nature as judged from double staining with anti-keratin antibody. There was no expression of HLA-DC/DS. These observations differ from findings in the normal thymus, wherein epithelial cells in the cortex carry HLA class I and class II antigens, and epithelial cells in the medulla express HLA class I, and for a minor part class II antigens. The results indicate a normal sequential acquisition of T-cell differentiation antigens in the thymus of both cases. It is suggested that the expression of HLA class I and class II antigens on epithelial cells in the normal thymus cortex does not play a significant role in the sequential acquisition of differentiation antigens on T lymphocytes.

An outbreak of gastroenteritis due to Escherichia coli 0142 H6 in a neonatal department.

An outbreak of gastroenteritis due to Escherichia coli 0142 H6 in a neonatal ward is described. The epidemic affected 16 of 24 infants (infection-rate 66 per cent), of whom one died due to necrotizing enterocolitis. Administration of antibiotics was of limited value in treatment or in eradicating E. coli 0142 H6 from the stools. Termination of the epidemic was only accomplished by isolating the patients, accompanied by strict hygienic measures, including the use of disposable gloves. Gastroenteritis due to this organism occurred only in prematurely born infants during the first 2 weeks of life.

Effects of single-dose fluticasone on exercise-induced asthma in asthmatic children: a pilot study.

A single high dose of inhaled corticosteroid (ICS) can increase airway caliber in children with asthma attacks and laryngitis subglottica. Presumably the effect is due to the vasoconstrictive and antiedematous properties of topical steroids. Enlarged vessels have been suggested to play a role in the pathophysiology of exercise-induced bronchial obstruction (EIB). To investigate this, we evaluated the effect of a single high dose of fluticasone propionate (FP) on EIB in asthmatic children. Nine children aged 8-16 years with mild to moderate asthma were included. All children had a history of EIB, which was confirmed by an exercise test. None was taking ICS maintenance therapy. The children inhaled either a single dose of 1 mg FP or placebo on 2 separate days within 7-14 days. After inhalation, airway caliber (FEV(1)) was assessed for 4 hr before exercise. Then an exercise challenge was performed on a treadmill to assess EIB (% fall FEV(1)). A significant increase in FEV(1) was observed 1 hr after inhalation of FP compared to placebo. Response to exercise was expressed as maximal % fall in FEV(1) from baseline (% fall) and as area under the curve (AUC) of the 30-min time/response curve. The % fall FEV(1) after exercise and the AUC were significantly reduced when FP was inhaled compared to placebo inhalation (% fall 9.7% vs. 19.2%, respectively, P = 0.038 and AUC 92.0%.min vs. 205.7%.min, respectively, P = 0.03). There was considerable individual variability in reduction of EIB, with 5 out of 9 children having a clinically significant response. We conclude that a single high dose of inhaled FP has an acute protective effect on the bronchial response to exercise in a substantial proportion of asthmatic children.

Carriage of gram-negative bacilli in young Brazilian children with community-acquired pneumonia.

BACKGROUND: Gram-negative bacilli are not infrequently encountered as etiologic organisms of pneumonia in children in warm-climate countries. OBJECTIVES: To investigate the nasopharyngeal carriage rate and antimicrobial susceptibility patterns of gram-negative bacilli colonizing children with community-acquired pneumonia in Fortaleza, Brazil. METHODS: A single nasopharyngeal specimen was collected from children 2 months to 5 years of age presenting at one of the three children's hospitals in Fortaleza and fulfilling the World Health Organization criteria for pneumonia. Randomly recruited healthy children from public daycare centers and immunization clinics served as controls. RESULTS: The study included 912 children, 482 (53%) with pneumonia and 430 (47%) controls. Aerobic gram-negative bacilli were seen in 79 (16%) of the 482 children with pneumonia and 51 (12%) of the 430 healthy controls. Nonfermentative gram-negative bacilli were seen in 85 (18%) of children with pneumonia and 54 (13%) of healthy controls. Neither gender, nutritional status, season, previous hospital admission nor antibiotic use was associated with carriage with gram-negative bacilli. However, pneumonia was associated with increased carriage, whereas concomitant colonization with Streptococcus pneumoniae or Haemophilus influenzae was associated with decreased carriage with gram-negative bacilli. Only 36% of all Escherichia species and 76% of all Klebsiella isolates were susceptible to cotrimoxazole; 90% of all Acinetobacter species were susceptible to gentamicin. CONCLUSION: Nasopharyngeal carriage with gram-negative bacilli, in particular with Acinetobacter species, is common and associated with a clinical diagnosis of community-acquired pneumonia in children in Fortaleza, Brazil.

Autoimmunity and inner ear disorders: an immune-complex mediated sensorineural hearing loss.

An immune-complex mediated form of autoimmune disease is described with the inner ear as one of its target organs. Around 40 dB bilateral sensorineural hearing loss improved on short-term corticosteroid therapy to normal levels. This case report is presented against the background of a general survey on autoimmunity and inner ear diseases. Cellular and humoral immune reactions may be etiologic moments in an audiovestibular dysfunction of autoimmune character.

[Guidelines in bacterial meningitis in children]. / Richtlijnen bacteriële meningitis bij kinderen.

A committee of the Scientific Council of the National Organization for Quality Assurance in Hospitals has published a report on the diagnosis and management of children with meningitis. Agreement was achieved on the diagnostic investigations that should precede antibiotic treatment, and on the prognosis and follow-up of children recovered from meningitis. No agreement was reached on the role of cephalosporins and aminoglycosides in the antibiotic treatment of bacterial meningitis. Furthermore there was no consensus on the prophylactic administration of rifampicin to family members of patients with meningitis caused by Neisseria meningitidis or Haemophilus influenzae. The arguments pro and contra are mentioned and considered.

[Favorable effects of vitamin A in measles infection]. / Gunstige effecten van vitamine A bij mazeleninfectie.

The recent measles epidemic that hit the Netherlands in 1999 resulted in numerous hospitalisations and several fatalities, and resembled the previous epidemic of 1987-1988 in numbers and severity. The triple (parotitis epidemica, measles, and rubella) vaccine used in the nationwide, free-of-charge immunization programme is highly effective, but is not accepted for ideological reasons by specific groups in the Dutch community. High oral doses of vitamin A have been shown to reduce mortality and pulmonary and gastrointestinal complications of measles in children in developing countries, but this treatment option is little known to physicians in the Netherlands. The appropriate dose regimens for safe administration of vitamin A in complicated measles are: age under 6 months 50,000 IU, age between 6 months and 2 years 100,000 IU, and age over 2 years 200,000 IU, administered by mouth upon admission. A repeated dose can be administered on the following day. In the Netherlands, and elsewhere, universal measles immunisation remains the first goal in the fight against this highly contagious disease.

[CBO-guideline 'Bacterial meningitis']. / CBO-richtlijn 'Bacteriële meningitis'.

Neisseria meningitidis and Streptococcus pneumoniae are the most frequent causes of bacterial meningitis. The incidence of Haemophilus meningitis in the Netherlands is low due to successful Haemophilus influenzae type b vaccination. This implies that there is no need to take account into this microorganism in using initial empiric antimicrobial therapy for bacterial meningitis. Vomiting (especially children), headache, fever, and a stiff neck characterize acute bacterial meningitis. However, even without these signs a patient may still have acute bacterial meningitis. The characteristics in neonates are less specific. An emergency lumbar puncture should be performed in all patients with meningeal irritation or other signs of bacterial meningitis. Examination of the CSF is not indicated for convulsive children (between the ages of 6 months and 6 years) who do not exhibit other clinical signs. In patients who respond adequately to the treatment, it is not necessary to examine the CSF again. Papilloedema or focal neurological symptoms contraindicate a lumbar puncture in patients with bacterial meningitis, until CT results justify that it can be performed safely. Antibiotic treatment should not be delayed until after the CT. General practitioners should treat their patients with suspected meningococcus infection by admitting them to the hospital without first injecting antibiotics. In the Netherlands, patients with suspected pneumococcus meningitis may still be treated with benzylpenicillin. Patients with bacterial meningitis have no fluid restrictions; only in case of the syndrome of inadequate secretion of antidiuretic hormone is fluid reduction indicated. The physician is responsible for prescribing prophylaxis to family members. The Regional Health Services organize chemoprophylaxis for classmates. The latter is only indicated if at least 2 related cases occur in one month.

[Respiratory syncytial virus infections and preventive options]. / Infectie met respiratoir syncytieel virus en mogelijkheden voor preventie.

Respiratory syncytial virus (RSV) is the most prominent pathogen found in respiratory tract infections in children and the most important cause of bronchiolitis in the first two years of life. In the Netherlands approximately 2000 children are admitted each winter season. A serious course is mostly seen in children younger than 3 months, (ex-)prematures, children with bronchopulmonary dysplasia or congenital cardiac anomalies, children with cystic fibrosis younger then 2 years and children with impaired T cell immunity; such cases not rarely require intensive care. Treatment (fluid, nutrition, bronchodilator agents, corticosteroids, oxygen and ventilation) is usually symptomatic. Antiviral therapy is only indicated in immunodeficient patients. For prevention by passive immunization palivizumab was recently registered in the Netherlands, a monoclonal antibody against RSV that has to be administered intramuscularly from the start of the RSV season (15 mg per kg bodyweight once a month during five months). In a number of large-scale American multicenter studies both the number of hospital admissions related to RSV infection and the mean duration of hospital stay showed a statistically significant reduction in high-risk children who had been treated with palivizumab. Palivizumab appears to be indicated in children from the categories with an increased risk for serious RSV disease.

[Enterobacter cloacae epidemic on a neonatal intensive care unit due to the use of contaminated thermometers]. / Enterobacter cloacae-epidemie op een neonatale intensive-care-unit door gebruik van besmette thermometers.

From December 1999 to March 2000 a nosocomial outbreak of multiresistant Enterobacter cloacae occurred in the neonatal intensive care unit (NICU) at the VU Medical Center, Amsterdam, the Netherlands. Twenty-six patients were infected or colonized with this strain resistant to third generation cephalosporins and with decreased sensitivity for aminoglycosides. Three neonates experienced sepsis with E. cloacae with serious clinical symptoms and two of them died. Comparison of the Enterobacter isolates by amplified-fragment length polymorphism indicated that this outbreak was caused by the spread of a single strain. Infection control precautions were initiated in order to stop further spread; barrier precautions, enforcement of hand disinfection and cohorting of colonized patients. A multidisciplinary crisis team coordinated these infection control precautions and informed all persons involved. Analysis of antibiotic usage in 1999 showed an increase in the use of third generation cephalosporins from November onwards. Due to the resistance pattern of the epidemic strain the use of third generation cephalosporins was discontinued in February 2000. At the end of February the NICU was temporarily closed. The epidemic strain of E. cloacae was isolated from one digital rectal thermometer. Patient use of thermometers and disposable coverings for rectal thermometers were introduced to eliminate this possible means of spread. No spread of multiresistant E. cloacae was found following the introduction of these interventions. Once all the neonates had been transferred, the NICU was disinfected and reopened in March.

[Invasive infection with Haemophilus influenzae type b in spite of complete vaccination]. / Invasieve infectie met Haemophilus influenzae type b ondanks volledige vaccinatie.

Five patients, 4 boys and 1 girl aged 13-41 months, developed invasive Haemophilus influenzae type b (Hib) disease (2 epiglottitis, 3 meningitis) despite full (or at least 3 times) vaccination. At admission as well during convalescence, 3 out of 5 had IgG anti Hib antibody levels < or = 5 U/ml. Serum immunoglobulin levels, including IgG subclasses, as well as complement were normal in all cases. In 2 of the 3, booster vaccinations with Hib conjugate vaccine elicited adequate antibody titres. Since the incorporation of the conjugated Hib polysaccharide tetanus toxoid vaccine (HibTT) in the National Vaccination Programme in the Netherlands, the number of invasive infections caused by Hib has dropped significantly. Causes of Hib conjugate vaccine failures are mostly unknown. In about one-third of the cases serum immunoglobulin levels are deficient, most often IgG2 or IgM. Susceptibility to Hib infection is in part also genetically determined. In the follow-up of Hib vaccine failures, anti Hib antibody titres should be determined. Booster vaccinations may be necessary.

[Cytokines]. / Cytokines.

Cytokines are relatively small polypeptides that are essential components of inflammatory reactions and immunologic processes. They are produced by a great variety of cells. The molecular biology revolution of the seventies and eighties has enabled investigators to elucidate the structure of cytokines and to unravel their spectrum of activity. Cytokines play a central role in the pathogenesis of infectious diseases and in the regulation of the immune system. Tumor necrosis factor (TNF) and interleukin-I (IL-I) were found to be responsible for most of the symptoms of infectious diseases, from fever to septic shock. In addition, TNF and IL-I are probably indispensable for repair of tissue damage. IL-2 is the pivotal cytokine for the regulation of the immune system; it is produced by CD4-positive T-cells and essential for the proliferation of T-lymphocytes in general and crucial for the induction of cytotoxic T-cells. Studies to define the therapeutic possibilities of cytokines are in progress.

[Bacterial meningitis in young children. Current viewpoints in pathogenesis, treatment and prevention]. / Bacteriële meningitis bij jonge kinderen. Nieuwe inzichten in pathogenese, behandeling en preventie.

Bacterial meningitis is frequently diagnosed in children below the age of five years. Recently our understanding of the pathophysiology of meningitis has been enhanced by several innovative studies. In addition the development and future application of conjugate vaccines against H. influenzae, N. meningitidis, and S. pneumoniae will result in a substantial reduction of morbidity and mortality in patients with meningitis caused by these microorganisms. This review will discuss the current status on the epidemiology, pathophysiology, prevention and treatment of meningitis.

[Cephalosporins: microbiological and pharmacokinetic properties, application to pediatrics]. / Cefalosporines: microbiologische en farmacokinetische eigenschappen, toepassingsgebieden in de pediatrie.

Many cephalosporins are presently available for clinical use. Although the cephalosporins are excellent antimicrobial agents for many infectious diseases in childhood, they have not replaced the older antibiotic regiments. In fact they offer the pediatrician a broader range of choices in treatment. This article gives a review on microbiological and pharmacokinetic properties of cephalosporins and an indication for the use of cephalosporins in pediatric therapy.

[Typhoid fever in childhood]. / Febris typhoidea op de kinderleeftijd.

Typhoid fever is an uncommon disease in the Netherlands. Acquisition occurs mainly during holidays in an endemic area. The history of three children, admitted in the summer of 1985, will be discussed, in one of them the disease had a complicated course. A short review of the literature is given, especially regarding pathogenesis, diagnosis and treatment. Cultures of blood, faeces and bone-marrow are essential for diagnosis. Bone marrow culture remains the most effective method for recovery of the causative agent, especially in children who previously were treated with antibiotics. Chloramphenicol still is the drug of choice in treatment. Vaccination with the oral typhoid vaccine of children who intend to visit an endemic area is recommended.