J.J. Roord

Twenty Years of Pediatric Tuberculous Meningitis: A Retrospective Cohort Study in the Western Cape of South Africa

OBJECTIVE. Tuberculous meningitis is the most severe extrapulmonary complication of tuberculosis, with high morbidity and mortality rates. The objective of this study was to assess the relationship between presenting clinical characteristics and outcome of pediatric tuberculous meningitis. PATIENTS AND METHODS. We present a retrospective cohort study of all of the children diagnosed with tuberculous meningitis in a large university hospital in South Africa between January 1985 and April 2005. We compared demographic, clinical, and diagnostic characteristics with clinical outcome after 6 months of treatment. RESULTS. We included 554 patients. Common characteristics on admission were young age (82%; <5 years), stage II or III tuberculous meningitis (97%), nonspecific symptoms existing for >1 week (58%), poor weight gain or weight loss (91%), loss of consciousness (96%), motor deficit (63%), meningeal irritation (98%), raised intracranial pressure (23%), brainstem dysfunction (39%), and cranial nerve palsies (27%). Common features of tuberculous meningitis on computed tomography scan of the brain were hydrocephalus (82%), periventricular lucency (57%), infarctions (32%), and basal meningeal enhancement (75%). Clinical outcome after 6 months was as follows: normal (16%), mild sequelae (52%), severe sequelae (19%), and death (13%). All of the patients diagnosed with stage I tuberculous meningitis had normal outcome. Factors associated with poor outcome in univariate analyses were as follows: African ethnicity, young age, HIV coinfection, stage III tuberculous meningitis, absence of headache and vomiting, convulsions, decreased level of consciousness, motor deficits, cranial nerve palsies, raised intracranial pressure, brainstem dysfunction and radiographic evidence of hydrocephalus, periventricular lucency, and infarction. Ethnicity, stage of disease, headache, convulsions, motor function, brainstem dysfunction, and cerebral infarctions were independently associated with poor outcome in multivariate logistic regression analysis. CONCLUSIONS. Tuberculous meningitis starts with nonspecific symptoms and is often only diagnosed when brain damage has already occurred. Earlier diagnosis will improve outcome significantly. We were able to identify presenting variables independently associated with poor clinical outcome.

Cost-Effectiveness of Adolescent Pertussis Vaccination for The Netherlands: Using an Individual-Based Dynamic Model

Background Despite widespread immunization programs, a clear increase in pertussis incidence is apparent in many developed countries during the last decades. Consequently, additional immunization strategies are considered to reduce the burden of disease. The aim of this study is to design an individual-based stochastic dynamic framework to model pertussis transmission in the population in order to predict the epidemiologic and economic consequences of the implementation of universal booster vaccination programs. Using this framework, we estimate the cost-effectiveness of universal adolescent pertussis booster vaccination at the age of 12 years in the Netherlands. Methods/Principal Findings We designed a discrete event simulation (DES) model to predict the epidemiological and economic consequences of implementing universal adolescent booster vaccination. We used national age-specific notification data over the period 1996–2000—corrected for underreporting—to calibrate the model assuming a steady state situation. Subsequently, booster vaccination was introduced. Input parameters of the model were derived from literature, national data sources (e.g. costing data, incidence and hospitalization data) and expert opinions. As there is no consensus on the duration of immunity acquired by natural infection, we considered two scenarios for this duration of protection (i.e. 8 and 15 years). In both scenarios, total pertussis incidence decreased as a result of adolescent vaccination. From a societal perspective, the cost-effectiveness was estimated at €4418/QALY (range: 3205–6364 € per QALY) and €6371/QALY (range: 4139–9549 € per QALY) for the 8- and 15-year protection scenarios, respectively. Sensitivity analyses revealed that the outcomes are most sensitive to the quality of life weights used for pertussis disease. Conclusions/Significance To our knowledge we designed the first individual-based dynamic framework to model pertussis transmission in the population. This study indicates that adolescent pertussis vaccination is likely to be a cost-effective intervention for The Netherlands. The model is suited to investigate further pertussis booster vaccination strategies.

Prediction of academic and behavioural limitations in school-age survivors of bacterial meningitis.

Aim: To develop a prediction rule to identify postmeningitic children at high risk of academic and behavioural limitations. Methods: 182 children (mean age 10 y; range 5–14) were selected from a cohort of 674 school‐age survivors of bacterial meningitis. These children had neither meningitis with “complex onset”, nor prior cognitive or behavioural problems, nor severe disease sequelae. On average, 7 y after the meningitis, they were evaluated using an “Academic Achievement Test”, and their parents filled in the “Child Behaviour Checklist”. By reviewing the medical records, potential risk factors for academic and/or behavioural limitations were collected. Independent predictors were identified using multivariate logistic regression analysis, leading to the formulation of a prediction rule. Results: The cumulative incidence of academic and/or behavioural limitations among children who survived bacterial meningitis without severe disease sequelae was 32%. The prediction rule was based on nine independent risk factors: gender, birthweight, educational level of the father, S. pneumoniae, cerebrospinal fluid leukocyte count, delay between admission and start of antibiotics, dexamethasone use, seizures treated with anticonvulsive therapy, and prolonged fever. When 10 was taken as a cut‐off point for the risk score computed using this rule, 76% of the children with limitations could be identified, while 38% of the children in the cohort were selected as at risk for these limitations.

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

ABSTRACT 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.

Parental perception of educational, behavioural and general health problems in school-age survivors of bacterial meningitis

Aim: To determine the occurrence of educational, behavioural and general health problems in Dutch school‐age survivors of bacterial meningitis. Methods: A cohort of 680 school‐age survivors of meningitis caused by the most common Gram‐positive and Gram‐negative bacteria was established approximately 6 y after the childrens illness. Children with Haemophilus influenzae type b (Hib) meningitis were excluded because this form of the disease has virtually disappeared. Parents completed questionnaires on educational, behavioural and general health problems. The reference group comprised 304 school‐age siblings and peers. Results: Postmeningitic children were more likely than controls to under achieve at school: 20% vs 5% (odds ratio 5.6; 95% confidence interval 3.0–10.7). The postmeningitic children repeated a year twice as often as the children in the reference group (16% vs 8%, odds ratio: 2.5, 95% confidence interval 1.5–4.2) and were referred to a special‐needs school four times more frequently (8% vs 2%, odds ratio: 5.5; 95% confidence interval 2.0–15.4). Parents also reported more behavioural problems at home. More than half of the postmeningitic children experienced general health problems. The causative pathogen or age at infection had no influence on the relative frequency of educational and behavioural problems, and reduced auditory functioning played only a small part in these problems.

A New Murine Model to Study the Pathogenesis of Tuberculous Meningitis

Tuberculous meningitis (TM) is a severe complication of tuberculosis that mainly occurs during childhood. No murine models are available to study this disease. The purpose of the present study was to develop a murine model to investigate the pathogenesis of TM. Mice were intracerebrally injected with Mycobacterium tuberculosis. Bacilli could be cultured from brain homogenates, and, on histopathological examination, all mice were found to have meningeal cellular infiltration. We found elevated levels of chemoattractants for mononuclear phagocytes and neutrophilic granulocytes. This is the first murine model for TM that can be used for research on the host response to TM, in particular the innate immune response.

Moet de huisarts bij verdenking op een meningokokkeninfectie direct een antibioticum geven

Het klinisch beeld dat wordt veroorzaakt door meningokokken (Neisseria meningitidis) beslaat een zeer uiteenlopend spectrum varierend van fulminant septische shock tot een benigne griepachtig beeld. Meningokokkemie en meningitis zijn de meest voorkomende ziektebeelden.

Infecties met Bartonella henselae; de vele gezichten van kattenkrabziekte

SummaryThe clinical spectrum of cat scratch disease caused by Bartonella henselae is much wider than initially recognised. Three patients are described. A 5 year old girl with axillar lymphadenopathy and negative serology, had a positive polymerase chain reaction (pcr) for Bartonella henselae. An 11 year old girl presenting with convulsions and coma, had Bartonella henselae encephalitis. A 7 year old girl with fever of unknown origin, turned out to have systemic cat scratch disease with liver and spleen abcesses. Bartonella henselae infections should be suspected in patients with an unclear infectious presentation. In case of negative serological results and persistent suspicion of a Bartonella henselae infection, one should obtain a pcr from relevant tissue. Antibiotic treatment is usually not necessary. In severe atypical infections, as in immuno-compromised hosts, macrolides are the drug of choice.samenvattingDoor de toegenomen mogelijkheden om infecties door Bartonella henselae te diagnosticeren, blijkt kattenkrabziekte een breed spectrum aan verschijningsvormen te hebben. We beschrijven drie patiënten. Een 5-jarig meisje met een typische lymfadenitis met negatieve serologie, bleek op grond van een positieve polymerasekettingreactie (pcr) in lymfeklierweefsel toch kattenkrabziekte te hebben. Een 11-jarig meisje met coma en convulsies bij een Bartonella henselae-encefalitis, herstelde restloos. Tot slot bleek een 7-jarig meisje met piekende koorts, lever- en miltabcessen te hebben in het kader van een systemische kattenkrabziekte. Bij bijzondere infectieuze presentaties moet aan atypische vormen van kattenkrabziekte gedacht worden. Bij negatieve serologie en blijvende klinische verdenking op kattenkrabziekte is het raadzaam een pcr op relevant materiaal te verrichten. Antibiotische behandeling van een typische lymfadenitis door een Bartonella henselae is niet nodig. Bij atypische presentatievormen en bij immuungecompromitteerde patiënten met kattenkrabziekte kan behandeling overwogen worden. In dat geval hebben macroliden de voorkeur.