A M van Furth

VU University Amsterdam, Amsterdamo, North Holland, Netherlands

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Publications (55)83.47 Total impact

  • 05/2014; 2(1):12-20. DOI:10.6000/2292-2598.2014.02.01.2
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    ABSTRACT: Tuberculous meningitis (TBM) is a severe complication of tuberculosis (TB) predominantly affecting young children. Early initiation of treatment is important to prevent morbidity and mortality associated with TBM, emphasising the importance of early diagnosis. Among the most promising new methods for diagnosing TB are antigen-detection assays based on the detection of lipoarabinomannan (LAM). To evaluate the diagnostic value of a commercial, antigen-capture enzyme-linked immunosorbent assay (ELISA) test based on the detection of LAM in urine for the early diagnosis of TBM in children. A cross-sectional study in which urine samples from paediatric patients with suspected TBM attending the Tygerberg Children's Hospital, Cape Town, South Africa, were tested for LAM. Complete data were available for 50 of 56 patients with suspected TBM. TBM was diagnosed in 21 (42%) patients and excluded in 29 (58%). The LAM ELISA had a sensitivity of 4.8% and a specificity of 93.1%. Serial measurements in the first 2 weeks after treatment initiation did not improve test performance. We have shown that urinary LAM detection was of little value for the diagnosis of TBM in a cohort of paediatric patients with suspected TBM.
    The International Journal of Tuberculosis and Lung Disease 02/2014; 18(2):205-10. DOI:10.5588/ijtld.13.0526 · 2.76 Impact Factor
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    ABSTRACT: Over 90% of the population is infected with the Epstein-Barr virus (EBV). Following primary infection, the virus remains latent in B-lymphocytes. In isolated cases, especially in immunocompromised patients, the Epstein-Barr virus can result in a chronic active infection (CAEBV).
    Nederlands tijdschrift voor geneeskunde 01/2014; 158:A7608.
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    ABSTRACT: In 2004, a model identifying children at risk of academic or behavioural limitations after bacterial meningitis (BM) was presented. Risk factors were: male gender, low birth weight, lower educational level of the father, Streptococcus pneumoniae, lower cerebrospinal fluid (CSF) leukocyte count, delay between admission and start of antibiotics, dexamethasone <2 days, seizures and prolonged fever. The aim of this study was to validate that prediction model in an independent cohort. Academic or behavioural limitations were determined in 93 Dutch school-age BM survivors. Risk factors for limitations were obtained from medical files. Validation was performed by applying the model in the cohort, then assessing discrimination and goodness of fit. Multiple imputation techniques were used to deal with missing values. Although fit of the model appeared good when it came to similarity of expected and observed cases (p-value of the Hosmer-Lemeshow test 0.24-0.57), discrimination was poor. Area Under the Curve (AUC) of the Receiver Operated Characteristics (ROC) curve of the model was 0.83 (95% CI: 0.77-0.89) in the development cohort and 0.53 (95% CI: 0.41-0.65) in the validation cohort. External validation of the model was unsuccessful. It is not suitable for implementation in practice. This article is protected by copyright. All rights reserved.
    Acta Paediatrica 08/2013; 102(12). DOI:10.1111/apa.12407 · 1.84 Impact Factor
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    ABSTRACT: 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. 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. 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. 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. 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.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 08/2013; 58(2). DOI:10.1016/j.jcv.2013.07.017 · 3.47 Impact Factor
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    ABSTRACT: Tuberculosis is a global health issue with annually about 1.5 million deaths and 2 billion infected people worldwide. Extra pulmonary tuberculosis comprises 13% of all cases of which tuberculous meningitis is the most severe. It has a high mortality and is often diagnosed once irreversible neurological damage has already occurred. Development of diagnostic and treatment strategies requires a thorough understanding of the pathogenesis of tuberculous meningitis. This disease is characterized by the formation of a cerebral granuloma, which is a collection of immune cells that attempt to immunologically restrain, and physically contain bacteria. The cytokine tumor necrosis factor-α is known for its important role in granuloma formation. Because traditional experimental animal studies exploring tuberculous meningitis are difficult and expensive, another approach is needed to begin to address this important and significant disease outcome. Here, we present an in silico model capturing the unique immunological environment of the brain that allows us to study the key mechanisms driving granuloma formation in time. Uncertainty and sensitivity analysis reveal a dose-dependent effect of tumor necrosis factor-α on bacterial load and immune cell numbers thereby influencing the onset of tuberculous meningitis. Insufficient levels result in bacterial overgrowth, whereas high levels lead to uncontrolled inflammation being detrimental to the host. These findings have important implications for the development of immuno-modulating treatment strategies for tuberculous meningitis.
    Journal of Theoretical Biology 03/2013; 328. DOI:10.1016/j.jtbi.2013.03.008 · 2.30 Impact Factor
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    Tijdschrift voor kindergeneeskunde 02/2013; 81(1). DOI:10.1007/s12456-013-0075-1
  • D H Visser, J F Schoeman, A M VAN Furth
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    ABSTRACT: Tuberculous meningitis (TBM) is a severe complication of tuberculosis and occurs mainly during early childhood. The incidence rate of TBM varies with season, and serum vitamin D levels, which are dependent on sunlight, might play a role. We studied the association between TBM incidence rate and hours of sunshine in Cape Town, South Africa and found a significant association between the incidence rate of TBM and hours of sunshine 3 months earlier (incidence rate ratio per 100 sunshine hours 0·69, 95% confidence interval 0·54-0·88, P=0·002). The association supports the hypothesis that vitamin D might play a role in the pathophysiology of TBM. Further prospective studies in which vitamin D status is measured are necessary to determine causality.
    Epidemiology and Infection 05/2012; 141(3):1-4. DOI:10.1017/S0950268812001045 · 2.49 Impact Factor
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    ABSTRACT: 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.
    Journal of virological methods 01/2012; 179(1):104-7. DOI:10.1016/j.jviromet.2011.10.007 · 1.88 Impact Factor
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    ABSTRACT: In children, neuroborreliosis often manifests itself as cranial neuritis (particularly facial palsy) or aseptic meningitis. Presentation with torticollis and simple partial seizures resulting from diffuse leptomeningeal inflammation is rare. A seven-year-old boy who had developed torticollis and partial seizures, lost weight and was complaining of tiredness was seen by a paediatric neurologist. A brain and spinal cord MRI showed diffuse leptomeningeal enhancement, in combination with a hyperintense cervical cord lesion. Laboratory testing of serum and cerebrospinal fluid confirmed the diagnosis of neuroborreliosis. The boy was treated with intravenous ceftriaxone for 30 days and made a full recovery. As illustrated by this case neuroborreliosis can manifest itself atypically with torticollis, seizures and diffuse leptomeningeal enhancement due to inflammation. If there is leptomeningeal enhancement on MRI then neuroborreliosis should be included in the differential diagnosis. In childhood neuroborreliosis can be successfully treated and the prognosis is good.
    Nederlands tijdschrift voor geneeskunde 01/2012; 156(51):A5157.
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    ABSTRACT: The susceptibility, severity and prognosis of infectious diseases depend on the ability of the host immune system to respond to pathogens. Genetic variation of immune response genes is associated with susceptibility to and severity of infectious diseases. Bacterial meningitis (BM) is a serious and life-threatening infectious disease of the central nervous system (CNS). Despite adequate antibiotic treatment and immunization strategies, mortality remains high, especially in developing countries. Streptococcus pneumoniae and Neisseria meningitidis are the two most common causative microorganisms of BM worldwide. The pathogenesis of BM starts with mucosal bacterial colonization, followed by invasion and survival of bacteria in the bloodstream, crossing of the blood-brain barrier, finally causing infection in the CNS, where host defense is less adequate. Host defense to BM starts with a complex cascade of pathogen recognition and subsequent intracellular signaling causing transcription of genes leading to the production of inflammatory mediators. Although this immune reaction is essential for killing microbes, it is also associated with damage to healthy cells and thus adverse disease outcome. This review provides an overview of the pathogenesis of invasive pneumococcal disease and invasive meningococcal disease related to the influence of genetic variation in genes involved in innate immunity, focusing on BM.
    Genes and immunity 04/2011; 12(5):321-34. DOI:10.1038/gene.2011.20 · 3.79 Impact Factor
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    ABSTRACT: Meningitis may cause inflammation of the cochlea, which may result in deafness and also in rapid obliteration ofthe cochlea with fibrous tissue or even ossification, conditions that obstruct the placement ofa cochlear implant. In the first of two cases of postmeningitis deafness, in a boy aged 6 months and a girl aged 1 year and 9 months, ignorance about the time of audiological follow-up threatened the options for restoration of hearing. In the other case, a long diagnostic programme and an unsuccessful attempt at cochlear implantation caused a long delay in optimal restoration of hearing. Both cases illustrate the difficulties in connection with postmeningitis deafness in relation to the option of a cochlear implant operation. To increase the chances of a successful implantation, the time span between meningitis and audiological and radiological follow-up must be short. Auditory brain stem responses (ABR) and MRI are the keystones of the work-up.
    Nederlands tijdschrift voor geneeskunde 07/2007; 151(22):1209-13.
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    ABSTRACT: A 7-year-old Indian boy travelling from India to the United Kingdom was brought to the Emergency Clinic of Airport Medical Services at Schiphol airport in Amsterdam, the Netherlands. He had had watery diarrhoea in the aircraft and had lost consciousness. In view of the strong indications for cholera and the rice water-like diarrhoea, he was admitted to the paediatric ward of the VU Medical Centre where intravenous rehydration was carried out. He recovered within three days. A large number of comma-shaped, motile, Gram-negative rods were found in the faeces. After two days, the faeces culture revealed Vibrio cholerae O1 El Tor, serotype Inaba. On the day of the flight, the patient had drunk a litre of water from a bottle that later turned out to have been from the New Delhi water supply. Cholera is rare as an import disease in the Netherlands. Due to the severe dehydration, the infection can run a serious course and even be fatal. The infection is not transmitted from person to person. Therefore, no special measures are needed when a patient with cholera is admitted to hospital.
    Nederlands tijdschrift voor geneeskunde 01/2006; 150(4):210-3.
  • A M van Furth, R J Vermeulen, F B Plötz
    Nederlands tijdschrift voor geneeskunde 10/2005; 149(36):2024-5.
  • A. M. van Furth, T. F. W. Wolfs, N. G. Hartwig
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    ABSTRACT: A recent study by De Gans and Van de Beek in the nejm entitled ‘Dexamethasone in adults with bacterial meningitis’ made the question relevant if children suspected of bacterial meningitis should be treated with dexamethasone. Based on the literature available we advise dexamethasone treatment for children older than two months of age who are suspected of acute bacterial meningitis. Dexamethasone should be given just before, or together with the first dose of (intravenous) antibiotics, in a dosage of 0.6 mg/kg/day in four doses during four days. Naar aanleiding van het artikel ‘Dexamethasone in adults with bacterial meningitis’ door De Gans en Van de Beek in de nejm is de vraag in de actualiteit gekomen of dexamethason ook gegeven moet worden aan kinderen die worden verdacht van bacteriële meningitis. Op basis van de beschikbare literatuur adviseren wij kinderen ouder dan twee maanden bij de verdenking op bacteriële meningitis te behandelen met dexamethason. Dexamethason moet vlak voor, of gelijktijdig met de eerste gift (intraveneuze) antibiotica worden gegeven in een dosering van 0,60 mg/kg/dag in vier doses gedurende vier dagen.
    Tijdschrift voor kindergeneeskunde 06/2005; 73(3):162-164. DOI:10.1007/BF03061569
  • L B van der Mark, A M van Furth
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    ABSTRACT: A 14-year-old boy from Ghana presented with low lumbar pain and loss of neurological function of the legs, due to spinal tuberculosis.
    Nederlands tijdschrift voor geneeskunde 02/2005; 149(2):82.
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    ABSTRACT: To develop a prediction rule to identify postmeningitic children at high risk of academic and behavioural limitations. 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. 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. With a prediction rule based on nine risk factors, postmeningitic children at high risk of developing academic and/or behavioural limitations could be identified. Additional research is required to further validate this prediction rule. In the future, a careful follow-up of high risk children may enhance early detection and treatment of these limitations.
    Acta Paediatrica 11/2004; 93(10):1378-85. DOI:10.1111/j.1651-2227.2004.tb02939.x · 1.84 Impact Factor
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    ABSTRACT: To establish the incidence of sensorineural hearing loss in children who survived non-Haemophilus influenzae type B (Hib) bacterial meningitis, to highlight the actual percentage whose hearing was evaluated, and to develop a prediction rule to identify those who are at risk of hearing loss. In 1999, we compiled a cohort of 628 school-aged children who were born between January 1986 and December 1994 and had survived non-Hib bacterial meningitis between January 1990 and December 1995. Presence of sensorineural hearing loss (>25 dB) was determined, based on information from questionnaires and medical records. Potential risk factors for hearing loss were obtained from medical records; independent predictors were identified using multivariate logistic regression analysis, leading to the formulation of a prediction rule. The incidence of hearing loss was 7%. The hearing of 68% of the children was evaluated as part of their routine follow-up after bacterial meningitis, resulting in the detection of 75% of the cases of hearing loss. The remaining 25% were detected after this follow-up had ended. Using a prediction rule based on 5 factors-duration of symptoms before admission >2 days, absence of petechiae, cerebrospinal fluid glucose level <or=0.6 mmol/L, Streptococcus pneumoniae, and ataxia-62% of the postmeningitic children were selected as being at risk. All cases of hearing loss were in this at-risk group. Hearing loss can be predicted satisfactorily. When the hearing of children who are predicted to be at risk is tested as part of their routine follow-up, no children with hearing loss need be missed.
    PEDIATRICS 11/2003; 112(5):1049-53. DOI:10.1542/peds.112.5.1049 · 5.30 Impact Factor
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    ABSTRACT: T1- en T2-gewogen magnetische resonantie beeldvorming (mri) van de hersenen is bij uitstek geschikt om de integriteit van de hersenen in beeld te brengen. Diffusiegewogen mri is een nieuwe, veelbelovende techniek die vooral gevoelig is voor verminderde diffusie van water zoals dat gezien wordt bij cytotoxisch oedeem, onder andere in het kader van acute ischemische veranderingen. De waarde van T1-, T2- en diffusiegewogen mri wordt besproken aan de hand van twee patiëntjes met een ernstig neurologisch ziektebeeld. Twee premature neonaten ontwikkelden een Bacillus cereus-infectie van het centraal zenuwstelsel. Op de T1-gewogen mri-beelden waren hyperintense afwijkingen zichtbaar in de gehele supratentoriële witte stof en cortex; deels waren deze afwijkingen hypo-intens op T2-gewogen beelden, passend bij bloed. Op de T2-gewogen mri-beelden was een deels afwijkende cortex zichtbaar; de basale kernen toonden relatief weinig afwijkingen. Op de diffusiegewogen mri-beelden was bij beide kinderen een verhoogd signaal zichtbaar in de basale kernen en de cortex, passend bij cytotoxisch oedeem. Conclusie: Bij een neonatale Bacillus cereus-infectie van het centraal zenuwstelsel kan een zeer ernstige hemorragische meningo-encefalitis optreden. mri is een zeer gevoelige techniek voor het vaststellen van de uitgebreidheid van de schade aan de hersenen. Hierbij heeft diffusiegewogen mri een toegevoegde waarde voor het vaststellen van extra afwijkingen, die meest waarschijnlijk berusten op cytotoxisch oedeem. T1 and T2 weighted mr images of the brain are very suitable to demonstrate the integrity of the infant's brain. Diffusion weighted mri is a new promising technique which is sensitive to conditions with restricted water diffusion, e.g. cytotoxic edema in infection and ischaemia. The value of this new mri technique will be discussed in relation to two patients with severe neurological problems. Two premature infants developed a Bacillus cereus infection of the central nervous system. T1 weighted mri showed a hyperintense signal in the entire cerebral cortex and white matter; some of these areas were hypointense on T2 weighted mri, suggestive of hemorrhage. On T2 weighted mri part of the cortex was abnormal whereas the basal nuclei appeared normal. dwi showed increased signal in basal nuclei and cortex, probably due to cytotoxic edema. Conclusion: Bacillus cereus infection of the central nervous system can lead to a severe hemorrhagic meningo-encephalitis. mri is an excellent technique to investigate the extent of lesions in the brain. Diffusion weighted mri has an additional value in detecting extra lesions most probably due to cytotoxic edema.
    Tijdschrift voor kindergeneeskunde 10/2003; 71(2):201-205. DOI:10.1007/BF03061457
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    ABSTRACT: Reported here is the case of a 5-year old boy with a pyeloureteral junction (PUJ) obstruction and pyelonephritis caused by Actinobaculum schaalii, an Actinomyces-like organism. Pyelonephritis or any other urinary tract infection caused by Actinobaculum schaalii has not been described in children before. The patient responded well to pyeloplasty in combination with antibiotic treatment.
    European Journal of Clinical Microbiology 08/2003; 22(7):438-40. DOI:10.1007/s10096-003-0933-3 · 2.54 Impact Factor

Publication Stats

485 Citations
83.47 Total Impact Points


  • 2013–2014
    • VU University Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 2002–2013
    • VU University Medical Center
      • Department of Pediatrics
      Amsterdamo, North Holland, Netherlands
  • 2003
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Paediatrics
      Amsterdamo, North Holland, Netherlands
  • 1994–1999
    • Leiden University Medical Centre
      • Department of Infectious Diseases
      Leiden, South Holland, Netherlands
  • 1995–1997
    • Leiden University
      Leyden, South Holland, Netherlands
  • 1992–1993
    • HagaZiekenhuis van Den Haag
      's-Gravenhage, South Holland, Netherlands