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Biomedical subjects

J F Schellekens

Publications and source records attributed to J F Schellekens.

At least 19 recordsLinked to original sources

[Doubling of the number of cases of tick bites and lyme borreliosis seen by general practitioners in the Netherlands].

OBJECTIVE: To obtain detailed information about the current geographical distribution and incidence of tick bites and Lyme borreliosis in the Netherlands and to identify regional differences in the ecological risk factors that might be involved. DESIGN: Retrospective questionnaire study. SETTING: All Dutch general practitioner's (GP) practices. METHODS: In April 2002, all GPs in the Netherlands were asked to complete a short questionnaire on the number of cases of tick bites and erythema migrans seen in 2001 and the size of their practice. Associations with possible risk factors were determined at the municipal level. Results were compared with the results of a similar study done in 1995. RESULTS: The response of the GPs was 64.5% (4730/7330). Together, all GPs reported seeing approximately 61,000 patients in 2001 with tick bites and 12,000 patients with erythema migrans. The incidence of erythema migrans was estimated at 73 per 100,000 inhabitants. There were obvious risk areas. At the municipal level, tick bites and erythema migrans were positively associated with the area covered by forest, sandy soil, the number of roe deer and tourism. There was a negative association with the degree of urbanisation. Increases in tourism in areas with many ticks, new forests in urban regions and an increased number of horses were positively associated with the increase in tick bites and erythema migrans since 1994. CONCLUSION: The number of patients with tick bites and erythema migrans seen by GPs in the Netherlands had doubled between 1994 and 2001. This increase may be attributed partly to changes in ecological risk factors and human behaviour. The number of cases of Lyme borreliosis may be reduced by giving prophylactic information annually about ticks and ways to remove them, plus additional education of patients about the recognition of erythema migrans.

Animals↗

Subclinical Legionella infection in workers near the source of a large outbreak of Legionnaires disease.

A survey was conducted of exhibitors at a 1999 floral trade show, where a whirlpool spa on display caused a large outbreak of legionnaires disease (LD). In total, 742 exhibitors without LD returned a questionnaire on their whereabouts during the fair and their health afterward and supplied blood samples for the detection of IgM and IgG antibodies against Legionella pneumophila. The exhibitors had higher average antibody levels than did the general population. The closer to the whirlpool that the exhibitors worked, the higher their antibody levels. Both high-normal and high titer levels were found more frequently among workers with more exposure, suggesting that serosurveys among potentially exposed subjects are a valuable tool for outbreak investigation. Some differences in health complaints were observed between the more and less exposed groups, as estimated by the workplace location, but few differences were found between groups with different antibody levels.

Adult↗

A model based evaluation of the 1996-7 pertussis epidemic in The Netherlands.

In The Netherlands a strong epidemic outbreak of pertussis took place in 1996-7. Here we investigate the possible causes of the epidemic, using an age-structured epidemic model. Motivated by the observation that during the epidemic the number of cases in vaccinated children had increased considerably compared to the preceding period, we focus on two vaccination related changes. First, we consider the possibility that the potency of the vaccine decreased so that it confers protection for a shorter period of time in newly vaccinated children. Second, we consider the possibility that at a certain point in time the duration of protection after vaccination decreased for all individuals. This may be the case if the pathogen population changed such that the current vaccine confers less protection. A comparison of the observed and simulated age-distribution of infections indicates that the second scenario is more in line with the observed pattern of the 1996-7 epidemic. We discuss the implications of this conclusion for B. pertussis circulation, and for the design of vaccination programmes in the face of a polymorphic B. pertussis population that may adapt itself to vaccination.

Adolescent↗

Potentially virulent strains and high colony counts of group A beta-haemolytic streptococci in pharyngitis patients having a delayed recovery or a complication.

T serotyping and M and exotoxin genotyping were performed on strains from 367 streptococcal pharyngitis patients in Dutch general practice. Potentially virulent strains of group A beta-haemolytic streptococci, such as T1M1 and T3M3 subtypes and strains expressing speA and speC, and a high number of colony counts did not occur more frequently in the 166 (45%) more seriously ill patients, defined as those who showed a delayed recovery or a complication.

Adult↗

Immunoglobulin A-mediated protection against Bordetella pertussis infection.

Infection with Bordetella pertussis, the causative agent of pertussis (whooping cough) in humans, is followed by the production of antibodies of several isotypes, including immunoglobulin A (IgA). Little is known, however, about the role of IgA in immunity against pertussis. Therefore, we studied targeting of B. pertussis to the myeloid receptor for IgA, FcalphaRI (CD89), using either IgA purified from immune sera of pertussis patients or bispecific antibodies directed against B. pertussis and FcalphaRI (CD89 BsAb). Both IgA and CD89 BsAb facilitated FcalphaRI-mediated binding, phagocytosis, and bacterial killing by human polymorphonuclear leukocytes (PMNL) and PMNL originating from human FcalphaRI-transgenic mice. Importantly, FcalphaRI targeting resulted in enhanced bacterial clearance in lungs of transgenic mice. These data support the capacity of IgA to induce anti-B. pertussis effector functions via the myeloid IgA receptor, FcalphaRI. Increasing the amount of IgA antibodies induced by pertussis vaccines may result in higher vaccine efficacy.

Animals↗

[An outbreak of scarlet fever, impetigo and pharyngitis caused by the same Streptococcus pyogenes type T4M4 in a primary school].

UNLABELLED: EPIDEMIC: Following the notification of an unusual number of scarlet fever cases within the same primary school, the epidemiological and clinical features of the outbreak were investigated. Questionnaire information about the cases was collected from parents and general practitioners per telephone. Throat specimens were taken, before and after treatment, for culturing and specific typing of streptococci was performed to determine transmission. Within a period of one month, 21 schoolchildren in a class of 29 pupils, with a mean age of 5 years, presented with symptoms caused by streptococcal infection (attack rate: 72%). Eight had scarlet fever, 5 suffered from impetigo and 8 had pharyngitis. A further 6 children, outside of this class, had complaints of scarlet fever, impetigo or pharyngitis. For 90% (26/29) of the schoolchildren a throat culture was established. Twelve positive cultures of the same strain of beta-haemolytic group A streptococcus, T4M4 exotoxin C gene positive, were found. The advice given was to treat all positive children for 3 days with azithromycin to prevent complications and further spreading of the disease. After two weeks only one child, that had not taken the antibiotics, still had a positive throat culture. No further cases or complications were reported. DISCUSSION: The pattern of the outbreak was typical of a person-to-person transmission. This was confirmed by typing of the isolates. The results of this study demonstrate the importance of mandatory notification of infectious clusters by institutions, such as schools, as introduced in the new Dutch Infectious Disease Act. On the one hand, the notification gives the municipal health authority the opportunity to analyse source and transmission dynamics and on the other to prevent disease and complications.

Bacterial Typing Techniques↗

Waning immunity and sub-clinical infection in an epidemic model: implications for pertussis in The Netherlands.

In The Netherlands, an epidemic outbreak of pertussis took place in 1996-1997. Understanding of the causes of the epidemic is hampered by the fact that many cases of infection with Bordetella pertussis go by unnoticed, and by the fact that immunity against infection does not last lifelong. Motivated by these observations, we develop and analyze an age-structured epidemic model that takes these factors into account. A distinction is made between infection in immunologically naive individuals, and infection in individuals whose immune system has been primed before by infection or vaccination. While the former often lead to severe symptoms and thus are more often diagnosed and notified, the latter are largely sub-clinical. The main questions are: (1) to what extent do sub-clinical infections contribute to the circulation of B. pertussis; and (2) what might be the causes for the recent epidemic? To answer these questions, we first present a new method to estimate the force of infection from notification data. The method is applied to the 1988-1995 case notification data from The Netherlands. Estimates of the force of infection vary greatly, depending on the rate at which immunity is lost, and on the fraction of sub-clinical infections. For the 1988-1995 period, our analysis indicates that if immunity is lost at a small rate and if a majority of infections is sub-clinical, the contribution of infection in adults to the transmission process cannot be neglected. Our results furthermore indicate that a decrease in the duration of protection after vaccination due to a change in the pathogen is the most likely factor to account for the 1996-1997 epidemic.

Adolescent↗

Invasive group A streptococcal disease in the Netherlands: evidence for a protective role of anti-exotoxin A antibodies.

As part of a nationwide surveillance in The Netherlands during 1994-1997, 53 patients with invasive group A streptococcal (GAS) infections were evaluated for medical history, symptoms, and outcome. Patients' isolates were tested for the production of pyrogenic exotoxins A (SPE-A) and B (SPE-B). Acute-phase sera from all patients and convalescent sera from 12 patients were investigated for the presence of antibodies against SPE-A and SPE-B. Twenty-three patients developed toxic shock-like syndrome and 16 died. Absence of antibodies against SPE-A and/or SPE-B was a risk factor for developing invasive streptococcal disease. Toxic shock and mortality were associated with a lack of anti-SPE-A antibodies (P<.025). Anti-SPE-A antibodies were found in convalescent sera from all patients infected by speA-positive isolates. Virtually all invasive speA-positive streptococci expressed SPE-A protein in vitro. Thus antibodies against SPE-A appeared vital for mediating the outcome of invasive GAS disease in this population.

Adolescent↗

Specificity and sensitivity of high levels of immunoglobulin G antibodies against pertussis toxin in a single serum sample for diagnosis of infection with Bordetella pertussis.

Laboratory confirmation of pertussis by culture, PCR, or detection of antibody increase in paired sera is hampered by low sensitivity in the later stages of the disease. Therefore, we investigated whether, and at which level, concentrations of immunoglobulin G (IgG) antibodies against pertussis toxin (PT), IgG-PT, in a single serum sample are indicative of active or recent pertussis. IgG-PT, measured by enzyme-linked immunosorbent assay in units per milliliter, was analyzed in 7,756 sera collected in a population-based study in The Netherlands, in the sera of 3,491 patients with at least a fourfold increase of IgG-PT, in paired sera of 89 patients with positive cultures and/or PCR results, and in the sera of 57 patients with clinically documented pertussis with a median follow-up of 1.4 years. We conclude that, independently of age, IgG-PT levels of at least 100 U/ml are diagnostic of recent or active infection with Bordetella pertussis. Such levels are present in less than 1% of the population and are reached in most pertussis patients within 4 weeks after disease onset and persist only temporarily.

Adolescent↗

An epidemic of pertussis among elderly people in a religious institution in The Netherlands.

An epidemic of pertussis is described among elderly people in a religious institution in the Netherlands in 1992. Subjects were evaluated for their vaccination status and for history and presence of respiratory symptoms. Specimens were collected for culture, polymerase chain reaction, and serological evaluation. None of the 75 residents and 19 of 24 nonresident personnel had been vaccinated against pertussis. The overall attack rate of clinical pertussis, defined as persistent cough lasting at least 2 weeks, was 49%. In five subjects with clinical pertussis, either culture or polymerase chain reaction or both were positive for Bordetella pertussis. A significant (at least 4-fold) change in specific antibody titre was observed in 85% (41/48) and 20% (10/49) of subjects with and without clinical pertussis, respectively (P < 0.0001, chi-square 41.1). The attack rate of laboratory-confirmed pertussis was 42% (41/98). This rate was 5% (1/19), 20% (1/5), and 53% (39/74) in vaccinated personnel, nonvaccinated personnel, and nonvaccinated residents, respectively (not significant). Among residents aged between 55-74 years and 75-94 years, the attack rates were 47% (17/36) and 58% (22/38), respectively (relative risk=0.8; 95% confidence interval 0.5-1.3). Four of 75 residents (5%) died from intracranial bleeding, while they were symptomatic for pertussis. It is concluded that the attack rate of pertussis was high among nonvaccinated elderly and that pertussis tended to increase with age. There may be a considerable risk of mortality from pertussis in this population. Physicians should be alert to the diagnosis of pertussis in the elderly with nocturnal and prolonged periods of coughing.

Adult↗

Clinical evaluation of guidelines and two-test approach for lyme disease.

OBJECTIVE: The diagnosis of Lyme disease should be based on objective clinical signs and symptoms. In a clinical study, we have evaluated whether the recommended two-step approach for serodiagnosis of Lyme disease is useful in daily clinical practice and can influence clinical decision making. METHODS: The signs and symptoms of patients with ongoing musculoskeletal complaints, assumed by their referring physician or themselves to be attributable to active or chronic Lyme disease, and of patients diagnosed as having Lyme disease, were evaluated. On the basis of clinical evaluation only, patients were classified into three groups: previous Lyme disease, active Lyme disease and no Lyme disease. Antibodies to Borrelia burgdorferi were determined by means of an enzyme-linked immunosorbent assay (ELISA), followed, when positive, by immunoblotting. RESULTS: One hundred and three patients (41 males and 62 females, mean age 48.7 yr) participated in the study. Of the 49 patients classified as previous Lyme disease, 25 (51%) had antibodies to B. burgdorferi. All 10 patients with active Lyme disease had positive antibodies and 12 of the 44 patients (27%) classified as no Lyme disease had positive antibodies. No statistically significant differences were found between the percentage of positive immunoblots from patients with previous Lyme disease (72%) and patients with active Lyme disease (100%). In the group of no Lyme disease, five out of 12 patients had a negative immunoblot. Concerning serological testing, immunoblotting could have added additional information. However, immunoblotting did not influence clinical decision making in this group of patients. CONCLUSION: Immunoblotting did not influence clinical decision making for the 47 patients with antibodies to B. burgdorferi in this study.

Adolescent↗

[2 patients with atypical manifestations of cat-scratch disease].

In 2 boys aged 8 years and 10 months, respectively, uncommon manifestations of cat scratch disease were seen. The first patient had acute encephalopathy: coma and generalized tonic-clinic convulsions. The second patient was presented with fever and peripheral lymphadenopathy in combination with hypodense lesions in the liver on ultrasound. Diagnosis was established on the clinical picture and the positive results of serological testing of antibody titres for Bartonella henselae. Both patients recovered completely within 2 months.

Antibodies, Bacterial↗

The geographical distribution of tick bites and erythema migrans in general practice in The Netherlands.

BACKGROUND: Lyme disease is caused by Borrelia burgdorferi which is transmitted in Europe by the tick ixodes ricinus. Erythema migrans is a skin lesion which is pathognomonic of Lyme disease. A retrospective study was carried out to determine the geographical distribution of the occurrence of tick bites and erythema migrans in the Netherlands and to identify ecological risk factors. METHODS: In April 1995, all general practitioners (GPs) in the Netherlands were asked to complete a postal questionnaire on the number of tick bites and erythema migrans case-patients seen in 1994 and the size of the practice. Reminders were sent to non-responders. Information on ecological risk factors by local government area was obtained from a geographical information system. RESULTS: The response rate was 79.9%. In 1994, GPs reported seeing approximately 33,000 patients with tick bites and 6500 with erythema migrans. The incidence rate of erythema migrans was estimated at 4.3 per 10,000 population. Ecological risk factors for both tick bites and erythema migrans were the proportion of the area covered by woods, sandy soil, dry uncultivated land, the number of tourist-nights per inhabitant and sheep population density. The cattle population density was a risk factor for erythema migrans. CONCLUSIONS: Using simple methods, a crude estimate of the incidence rate of erythema migrans was obtained rapidly, and high risk areas were identified. Lyme disease appears to be an important problem in the Netherlands.

Animals↗

Pitfalls and fallacies of cat scratch disease serology: evaluation of Bartonella henselae-based indirect fluorescence assay and enzyme-linked immunoassay.

The diagnostic value of the detection of immunoglobulin G (IgG) and IgM by Bartonella henselae-based indirect fluorescence assay (IFA) and enzyme-linked immunoassay (EIA) for the diagnosis of cat scratch disease (CSD) was evaluated. The IFA was performed either with B. henselae that was cocultivated for a few hours with Vero cells or with noncocultivated B. henselae as the antigen. Additionally, the performance of a Bartonella PCR hybridization assay based on the 16S rRNA gene was determined and compared with those of the serologic assays. The study group consisted of 45 patients suspected of suffering from CSD by fulfilling one or more of the classical criteria. The specificities of the immunoassays were set at > or = 95% by analysis of sera from 60 healthy blood donors. It is shown that the sensitivities of the IgG assays are very low (40.9% for the IFA with noncocultivated B. henselae as antigen) and that those of the IgM assays are higher (71.4% for the EIA) for patients who fulfilled two or more criteria for CSD. The IgM EIA showed the highest sensitivity: 71.4% in patients with two or more criteria for CSD and 80.6% for patients with a positive Bartonella PCR result. The results indicate that the specificities of both IFA and EIA IgG serologies and the sensitivity of the IFA IgM serology need to be improved. The PCR hybridization assay showed a sensitivity of 86.4% for patients who fulfilled two or more criteria for CSD and 100% for seven patients who fulfilled three or more criteria. The kinetics of IgG and IgM antibody production were studied in 18 patients with CSD on the basis of a positive B. henselae IFA IgM serology. The results indicate that there is no standard course of anti-B. henselae IgG and IgM production in patients with CSD, because some patients produced high levels of both IgG and IgM, others produced only high levels of IgM, and a few patients produced only low levels of antibodies.

Antibodies, Bacterial↗

[Cat-scratch disease and other infections caused by Bartonella species].

Bartonella henselae, the causative agent of cat-scratch disease, was identified recently by DNA amplification techniques. Several other Bartonellae (most of which were called Rochalimaea before) cause disease in humans: B. bacilliformis (Carrion's disease), B. elizabethae (endocarditis) and B. quintana (bacillary angiomatosis and peliosis, chronic bacteraemia and endocarditis, trench fever). B. henselae is transmitted to humans by scratch or bite of a bacteraemic, but asymptomatic, cat, which event may be followed by regional lymphadenitis (classical cat-scratch disease), bacillary angiomatosis or peliosis of liver and spleen (in immune compromised, e.g. HIV-infected individuals) or chronic bacteraemia and endocarditis (in elderly individuals). The incidence in the Netherlands of cat-scratch disease is > 2/100,000/year. If a Bartonella infection is suspected, specific immuno-assays and polymerase chain reaction assay may be applied for diagnosis. Culture of the organism is difficult. Macrolides and tetracyclines have been shown to be effective in treatment of disseminated infections. The natural (self-limiting) course of regional lymphadenitis however is not affected by antibiotic treatment.

Aged↗

Detection of four species of Borrelia burgdorferi sensu lato in Ixodes ricinus ticks collected from roe deer (Capreolus capreolus) in The Netherlands.

Roe deer (Capreolus capreolus) were investigated for their value as sentinel animals for Lyme borreliosis in the Netherlands. Serum was obtained from 114 roe deer, and 513 Ixodes ricinus, predominantly females (72%), were obtained from 47 animals (41%). The polymerase chain reaction was used to detect DNA of Borrelia burgdorferi sensu lato in a total of 190 ticks, comprising 106 engorged ticks and 84 non-engorged ticks. Borrelia DNA was detected in 24 engorged ticks (23%) and 26 non-engorged ticks (31%). This difference was not significant (P = 0.25). Four species of B. burgdorferi sensu lato were identified in the ticks. B. burgdorferi sensu stricto, Borrelia garinii, Borrelia afzelii and group VS116. B. afzelii was most commonly found and present in 13 mixed infections, and in 28 single infections. Fifteen sera (13%) contained antibodies to Borrelia spp. Ticks are more appropriate sentinel animals for Lyme borreliosis than roe deer, an important host for I. ricinus. Although the viability of borrelia spirochaetes in engorged ticks collected from roe deer was not assessed, a bloodmeal taken from roe deer did not eliminate borrelia spirochaetes from the tick. The relevance of this finding for transovarial transmission of borrelia spirochaetes in ticks is discussed.

Animals↗

Predominance of two Bartonella henselae variants among cat-scratch disease patients in the Netherlands.

Restriction endonuclease analysis of the PCR-amplified 16S-23S rRNA gene spacer region was used to investigate the prevalence of Bartonella henselae variants in samples from cat-scratch disease (CSD) patients. Analysis of spacer PCR fragments from 27 Bartonella DNA-positive samples from Dutch patients with CSD with AluI revealed two restriction fragment length polymorphism (RFLP) patterns, patterns A and B. Twenty samples yielded B. henselae pattern A, and 7 samples yielded B. henselae pattern B. Three samples from North American patients with CSD were shown to contain B. henselae with RFLP pattern B. To be able to detect and differentiate Bartonella DNA in clinical material more sensitively and faster, two B. henselae PCRs which amplify part of the 16S rRNA gene and which can discriminate between two B. henselae variants were developed. Thirty-two of 41 Bartonella DNA-positive samples from Dutch patients with CSD contained type I B. henselae, 7 samples contained type II B. henselae, and two samples were negative in both type-specific PCRs. Two samples from North American patients with CSD both contained type II B. henselae. A 100% correlation was found between the AluI spacer RFLP pattern and the 16S rRNA PCR type. We have shown that Dutch patients with CSD contain a limited number of B. henselae variants, suggesting that, in contrast to systemic bartonellosis, CSD in immunocompetent patients is caused by a limited number of B. henselae variants.

Bartonella henselae↗