Persistent synovitis in children with Lyme arthritis: two unusual cases. An immunogenetic approach

We report on two patients with a persistent Lyme arthritis. In addition both had a peculiar disease history. The first patient had oligoarticular juvenile idiopathic arthritis in remission. Five months after an infected tick bite, she developed a relapse of arthritis in the same knee. We considered Lyme borreliosis as the possible trigger for this reactivation. The disease history of the second patient was that of a classical non-responder. After extensive antibiotic treatment osteolytic lesions became visible. MRI images suggested an erosive arthropathy and arthroscopy was used to investigate possible erosive arthritis. Studies on collected material made us consider the following hypothesis. Despite demonstration of a spirochete fragment in a synovial biopsy, the patient recovered without additional antibiotic treatment. Conclusion: delay of antibiotic treatment after appearance of erythema migrans may cause systemic spread of the antigen and predispose to Lyme arthritis. If intra-articular steroids are considered when spontaneous resolution of Lyme arthritis does not occur, magnetic resonance imaging of the affected joint, prior to administration, may provide additional information. The success of synovectomy may be related to removal of undegraded antigenic material which may prolong the inflammation.Abbreviations ELISA enzyme-linked immunosorbent assay - EM erythema migrans - JIA juvenile idiopathic arthritis - LA Lyme arthritis - LD Lyme disease - LIV Lyme index value     

Meningitis due toBorrelia burgdorferi in the initial stage of Lyme disease

Borrelia burgdorferi (B. b.) was isolated from cerebrospinal fluid from two children with aseptic meningitis. Serology forB. b. was initially negative or borderline and became positive during the subsequent course. Children with aseptic meningitis of unknown origin should be re-evaluated within 1 month to detect possible increasing antibody titres toB. b. Aseptic meningitis may be a stage 1 manifestation of Lyme disease.Abbreviations B. b. Borrelia burgdorferi - CSF cerebrospinal fluid - CNS central nervous system - ESR erythrocyte sedimentation rate - IFA immunofluorscence assay     

Lymphoproliferative responses toBorrelia burgdorferi in the diagnosis of Lyme arthritis in children and adolescents

Abstract To assess the contribution of the lymphocyte proliferation assay in response to borrelial antigens to establishing a diagnosis of Lyme arthritis (LA) the response to two strains ofBorrelia burgdorferi was tested in peripheral blood lymphocytes of 103 children and adolescents with arthritis, among them 55 with LA and 48 control patients. Patients with LA had a significantly higher response to borrelial antigens than control patients. However, there were several patients with false positive and false negative test results. Specificity and sensitivity of the test were 78% and 77%. In patients with LA the test may turn positive after antibiotic therapy and remain positive for up to 19 months after the disappearance of arthritis. The test does not aid in prognosis or follow up. In one patient with seronegative LA specific lymphocyte proliferation and polymerase chain reaction for borrelialfla sequences in urine were positive.Conclusion Rarely the lymphocyte proliferation assay may aid in finding the correct diagnosis when clinical presentation and anti-borrelial serology do not match.     

Lyme borreliosis in children

A total of 27 children with clinical symptoms indicative of Lyme borreliosis are described, 21 of which were seropositive. CNS symptoms were found in 17 of the seropositive childen (81%). Of these 21, 7 were CSF negative. Another 3 (with Bell's palsy and/or aseptic meningitis) were initially CSF negative but developed specific CSF titres 80, 65 and 120 days after the first lumbar puncture, respectively. Thus, seropositive children with aseptic meningitis and without initial signs of an infectious aetiology should be checked for a neuroborreliosis even when CSF negative in the first lumbar puncture. Antibiotic therapy undertaken in 26 children showed clinical recovery (Sodium penicillin, 300,000–500,000 units/kg per day for 14 days). One developed residual hypoacusis. Comparison of enzyme-linked immunosorbent assay (ELISA) IgG values from 27 cases with those of 30 healthy controls showed that elevated ELISA titres are a good indication of the disease. However, Lyme borreliosis can only be diagnosed correctly if the clinical symptoms conform with specific titres.Abbreviations Bb Borrelia burgdorferi - CNS central nervous system - CSF cerebrospinal fluid - EBV Epstein-Barr virus - ECM erythema chronicum migrans - ELISA enzyme-linked immunosorbent assay - Ig immunoglobulin - Lb Lyme borreliosis     

Lyme Disease in a 12-year-old Girl

ABSTRACT. We report the case of a 12-year-old girl with erythema chronicum migrans, aseptic meningitis and knee arthralgia. Rise of specific antibody titre against an Ixodes ricinus spirochaete was demonstrated. Circulating immune complexes and high levels of Clr-Cis-CIIA complexes indicating activation of the complement system via the classical pathway were found. The clinical features and the laboratory findings warranted a diagnosis of Lyme disease.     

Evaluation of the polymerase chain reaction for the detection ofBorrelia burgdorferi in cerebrospinal fluid of children with acute peripheral facial palsy

Neuroborreliosis occasionally represents a diagnostic problem, especially in the early stage of the infection. The polymerase chain reaction (PCR) offers an attractive alternative to antibody testing. The aim of our study was to investigate the diagnostic potential of PCR in comparison to antibody tests in CSF of children with facial palsy. In contrast to other manifestations of neuroborreliosis, facial palsy is a welldefined clinical entity in which CSF findings allow an early distinction according to aetiology. The study included 17 children with neuroborreliosis, defined by the detection of specific IgM antibodies in CSF, and 20 children with facial palsy of unknown cause. Primers used for the nested PCR were generated from conserved sequences of the OspA-gene. Most of the cases in both subgroups have been examined within a few days after the onset of the paresis. Only in 2 out of 17 cases with neuroborreliosis could specific DNA be amplified. The PCR gave negative results in all cases of the control group.Conclusion The IgM capture ELISA is superior to PCR to support the clinical diagnosis of neuroborreliosis.     

Epidemiology and clinical management of tuberculosis in children in Canada

Although often regarded as a foreign disease, latent tuberculosis or tuberculosis disease will be encountered in many clinical situations by the Canadian child health practitioner. There are key differences between tuberculosis in children and adults. In the present article, the changing epidemiology of tuberculosis in children in Canada and around the world, the pathogenesis of infection, diagnostic tests, and clinical management of childhood latent tuberculosis and tuberculosis disease are reviewed.     

Detection ofBorrelia burgdorferi by nested polymerase chain reaction in cerebrospinal fluid and urine of children with neuroborreliosis

Diagnosis of neuroborreliosis is often difficult since history and clinical presentation may be non-specific and serological tests may initially be negative. We therefore tested the polymerase chain reaction (PCR) for the detection of borrelial sequences in CSF and urine samples of consecutive children with neuroborreliosis seen in a single summer season. Four of eight children were negative in serum for antibodies toBorrelia burgdorferi. Two of eight children were PCR-positive in CSF and one other child was positive in urine. In two out of four children PCR was the only laboratory test confirming the clinical diagnosis. All children recovered after treatment with third generation cephalosporins. When seven of eight children were re-examined 6 months later all were healthy and antibodies toB. burgdorferi were detected in their serum. PCR may assist the paediatrician in establishing a diagnosis of neuroborreliosis; however, a negative result does not rule out neuroborreliosis. PCR is an adjunct, but no substitute for clinical judgement and serology.     

Lyme neuroborreliosis in children: Report of nine cases and a review of the literature

Lyme neuroborreliosis is a bacterial infection caused by the dissemination and proliferation of a Borrelia species in the central nervous system. Neuroborreliosis occurs after transmission of the pathogen from an infected tick to a human host during a tick bite. We report nine cases of pediatric neuroborreliosis collected by the National Observatory of Pediatric Bacterial Meningitis in France between 2001 and 2012. The nine children, aged 4–13 years, were identified in northern and eastern France and had the following clinical features: meningeal irritation alone or with facial palsy, or isolated facial palsy. All cases showed anti-Borrelia antibodies in cerebrospinal fluid or serum, or with a positive Borrelia PCR in the CSF. The outcome was favorable in all cases after a 2- to 3-week course of third-generation cephalosporin. On the basis of these nine pediatric cases, this study provides an update on the epidemiology, pathophysiology, diagnostic strategy, and treatment of neuroborreliosis, with insight into the specific features of pediatric neuroborreliosis and the difficulties encountered in the diagnosis of this infection.     

Demonstration ofBorrelia burgdorferi infection in a child with Guillain-Barré syndrome

A 4.5-year-old child suffered from rapidly evolving motor weakness with paresthesia and radicular pain in both legs, accompanied by an isolated elevation of protein levels in CSF. Isoelectric focusing revealed oligoclonal IgG produced in the cerebrospinal compartment only. The diagnosis of Guillain-Barré syndrome was confirmed by electrophysiological studies. High antibody titres againstBorrelia burgdorferi in the serum and specific antibodies in the CSF were demonstrable by ELISA and immunoblotting.B. burgdorferi specific DNA fragments were demonstrated in urine and CSF by means of a nested polymerase chain reaction (PCR), thus providing the borrelial aetiology and indicatingB. burgdorferi infection. Complete recovery was observed after treatment with high dose immunoglobulin and ceftriaxone and control urine specimens were PCR negative.     

From genes to vaccine: A breakthrough in the prevention of meningococcal group B disease

Although safe and effective vaccines exist for meningococcal serogroups A, C, W-135 and Y, no vaccine is available for routine use against disease caused by serogroup B (MenB). Consequently, MenB is now the most common cause of invasive meningococcal disease in Canada. MenB causes more than 80% of invasive meningococcal disease in infants and can occur at any age. The mortality and morbidity rates related to this disease are very high. Vaccine development against MenB has been hampered by the fact that MenB polysaccharide is not immunogenic in humans. Although vaccines derived from the outer membrane vesicle have been effective in controlling MenB outbreaks, such vaccines protect against the outbreak strain only. A new vaccine development strategy, reverse vaccinology, has led to the identification of genes coding for surface-exposed proteins, which are able to induce bactericidal antibodies against a broad range of MenB strains. A new vaccine containing a combination of these proteins has been tested in different age groups, in several clinical trials. The data available provide hope that control of MenB through routine vaccination will soon be possible.     

Staphylococcus aureus bloodstream infections in children: A population-based assessment

BACKGROUND:

Although Staphylococcus aureus is a major cause of bloodstream infections, population-based data on these infections in children are limited.

OBJECTIVE:

To describe the epidemiology of S aureus bacteremia in children.

METHODS:

Population-based surveillance for all incident S aureus bacteremias was conducted among children (18 years of age or younger) living in the Calgary Health Region (Alberta) from 2000 to 2006.

RESULTS:

During the seven-year study, 120 S aureus bloodstream infections occurred among 119 patients; 27% were nosocomial, 18% health care associated and 56% community acquired. The annual incidence was 6.5/100,000 population and 0.094/1000 live births. A total of 52% had a significant underlying condition, and this was higher for nosocomial cases. Bone and joint (40%), bacteremia without a focus (33%), and skin and soft tissue infections (15%) were the most common clinical syndromes. Infections due to methicillin-resistant S aureus were uncommon (occurring in one infection) and three patients (2.5%) died.

CONCLUSIONS:

S aureus bacteremia is an important cause of morbidity in the paediatric age group. Underlying medical conditions and implanted devices are important risk factors. Methicillin-resistant S aureus and mortality rates are low.     

Increase in invasive Streptococcus pneumoniae infections in children with sickle cell disease since pneumococcal conjugate vaccine licensure

Invasive pneumococcal disease (IPD) in children with sickle cell disease has decreased with prophylactic penicillin, pneumococcal polysaccharide vaccine, and pneumococcal protein-conjugate vaccine usage. We report 10 IPD cases since pneumococcal protein-conjugate vaccine licensure, including a recent surge of non-vaccine serotypes. IPD continues to be a serious risk in sickle cell disease.     

Community-associated methicillin-resistant Staphylococcus aureus in Indigenous communities in Canada

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have emerged as a significant issue in some Indigenous communities (including First Nations, Inuit and Métis) in Canada. Primarily associated with skin and soft-tissue infections, this organism can also result in significant morbidity and mortality. Canadian and American guidelines for managing CA-MRSA infections have been published. The specific epidemiology, microbiology and susceptibility patterns, and the social/environmental circumstances of CA-MRSA infections in Indigenous communities need to be considered for strategies to reduce transmission. While reducing household crowding and improving in-home potable water supply are optimal strategies to reduce the impact of this illness, implementing Canadian guidelines along with increased prevention strategies are recommended as interim measures.     

Peptic ulcer disease in children

Peptic ulcer disease is uncommon in children with an estimated frequency of 1 case in 3000 hospital admissions. In children, peptic ulcer disease is usually classified as either primary or secondary depending on the underlying pathology. Helicobacter pylori infection of the stomach is the commonest cause of primary peptic ulcers. Other causes of primary ulcers include those caused by rare conditions of acid hypersecretion such as Zollinger–Ellison syndrome; G-Cell hyperplasia; systemic mastocytosis; short bowel syndrome; and hyperparathyroidism. Secondary ulcers occur more often in younger children. They have a worse prognosis and are usually associated with physiological stress and systemic illness such as sepsis, head trauma, burns, sickle cell disease, type I diabetes, systemic lupus erythematosus and drug therapy. Upper gastrointestinal endoscopy is the investigation of choice for children with suspected peptic ulcer disease. Triple therapy given twice daily with a proton-pump inhibitor plus two antibiotics (e.g. Metronidazole plus Amoxicillin or Amoxicillin plus Clarithromycin) for two weeks will eradicate H. pylori and heal ulcers in the majority of cases.     

A sentinel fatal paediatric case of community-associated methicillin-resistant Staphylococcus aureus in Canada

Community-associated methicillin-resistant Staphylococcus aureus is an established pathogen in many centres in the United States, but has yet to establish a firm foothold in Canada. In the present article, the authors report, to their knowledge, Canada’s first fatal paediatric case of invasive disease due to community-associated methicillin-resistant S aureus and review its pathogenesis, epidemiology and treatment.     

Polymerase chain reaction detection of Kingella kingae in children with culture-negative septic arthritis in eastern Ontario

BACKGROUND:

The bacterium Kingella kingae may be an under-recognized cause of septic arthritis in Canadian children because it is difficult to grow in culture and best detected using molecular methods.

OBJECTIVES:

To determine whether K kingae is present in culture-negative joint fluid specimens from children in eastern Ontario using polymerase chain reaction (PCR) detection methods.

METHODS:

K kingae PCR testing was performed using residual bacterial culture-negative joint fluid collected from 2010 to 2013 at a children’s hospital in Ottawa, Ontario. The clinical features of children with infections caused by K kingae were compared with those of children with infections caused by the ‘typical’ septic arthritis bacteria, Staphylococcus aureus and Streptococcus pyogenes.

RESULTS:

A total of 50 joint fluid specimens were submitted over the study period. Ten were culture-positive, eight for S aureus and two for S pyogenes. Residual joint fluid was available for 27 of the 40 culture-negative specimens and K kingae was detected using PCR in seven (25.93%) of these samples. Children with K kingae were significantly younger (median age 1.7 versus 11.3 years; P=0.01) and had lower C-reactive protein levels (median 23.8 mg/L versus 117.6. mg/L; P=0.01) than those infected with other bacteria.

CONCLUSIONS:

K kingae was frequently detected using PCR in culture-negative joint fluid specimens from children in eastern Ontario. K kingae PCR testing of culture-negative joint samples in children appears to be warranted.