The clinical presentation, treatment and outcome of serologically confirmed paediatric Lyme disease in the Republic of Ireland over a 5-year period: a retrospective cohort study.

Lyme disease (LD) is the most common tick-borne illness in Europe. Population-based studies in European children are few. This study aimed to assess the incidence, clinical presentation, treatment and outcome of serologically confirmed paediatric LD in the Republic of Ireland over a 5-year period. A retrospective review of records from accredited laboratories performing Borrelia burgdorferi serological testing was undertaken. Proformas were distributed to clinicians of children and adolescents with positive Lyme serology. Data were requested regarding clinical presentation, treatment and outcome. Updated NICE guidelines were used to classify clinical cases. Serology testing for B. burgdorferi was performed on 2908 samples. Sixty-three (2.2%) children were two-tier positive, generating a crude annual incidence rate of 1.15/100,000. Proformas were returned for 55 (87%) and 47 met clinical and laboratory criteria for LD. Twenty-seven (57%) presented with non-focal symptoms (erythema migrans and/or influenza-like symptoms), and 20 (43%) with focal symptoms (cranial nerve involvement, 11; CNS involvement, 8; arthritis, 1). Median age at presentation was 8.2 (2.5-17.9) years. Seventeen (36%) acquired LD overseas. Twenty-five (83%) of the remaining 30 children acquired infection in the West/Northwest of Ireland. Full resolution of symptoms was reported in 97% of those with available data. Serologically confirmed LD in children is relatively rare in the Republic of Ireland. Ninety-eight percent of children tested were seronegative. Of the seropositive cases, 40% could have been diagnosed based on clinical findings alone. Neurological presentations (40%) were common. Full resolution of symptoms occurred in almost all (97%) where data were available.

A case report of multiple cerebral abscess formation complicating serogroup B Neisseria meningitidis meningitis.

BACKGROUND: Invasive meningococcal disease (IMD) presenting with meningitis causes significant mortality and morbidity. Suppurative complications of serogroup B meningococcal sepsis are rare and necessitate urgent multidisciplinary management to mitigate long-term morbidity or mortality. CASE PRESENTATION: We present a rare case of invasive meningococcal disease in a 28-month old boy complicated by multiple abscess formation within a pre-existing antenatal left middle cerebral artery territory infarct. Past history was also notable for cerebral palsy with right hemiplegia, global developmental delay and West syndrome (infantile spasms). Two craniotomies were performed to achieve source control and prolonged antimicrobial therapy was necessary. The patient was successfully discharged following extensive multidisciplinary rehabilitation. CONCLUSIONS: Longstanding areas of encephalomalacia in the left MCA distribution may have facilitated the development of multiple meningococcal serogroup B abscess cavities in the posterior left frontal, left parietal and left temporal lobes following an initial period of cerebritis and meningitis. A combination of chronic cerebral hypoperfusion and some degree of pre-existing necrosis in these areas, may also have facilitated growth of Neisseria meningitidis, leading ultimately to extensive cerebral abscess formation following haematogenous seeding during meningococcemia. In this case report we review similar cases of cerebral abscess or subdural empyema complicating serogroup B meningococcal meningitis.

Epidemiology of an upsurge of invasive group A streptococcal infections in Ireland, 2012-2015.

OBJECTIVES: Group A streptococcus (GAS) is responsible for mild to very severe disease. The epidemiology of an upsurge in invasive GAS (iGAS) infections in Ireland, 2012-2015 was investigated. METHODS: Epidemiological typing of iGAS (n = 473) isolates was performed and compared to non-invasive (n = 517) isolates. Clinical data of notified iGAS was obtained from the national infectious disease information system. RESULTS: Annual incidences of iGAS cases (n = 561) were 2.33-3.66 per 100,000 population. Bacteraemia was the most common clinical presentation (75%) followed by focus without bacteraemia (19%) and necrotizing faciitis (7%). Streptococcal toxic shock syndrome occurred in 19% of presentations. The main invasive emm types in rank order were emm1, emm3, emm28, emm12 and emm89 whereas emm4, emm28, emm3, emm12, emm89 and emm1 predominated in non-invasive infections. Invasive emm1 and emm3 showed annual fluctuations (15-48% and 4-37%, respectively) and predominated in most clinical presentations of iGAS. Superantigens speA, speG, speJ was associated with iGAS disease and, speC, speI and ssa with non-invasive infections. There was 4.3% erythromycin and 5.6% tetracycline resistance. The main resistant types were emm11, emm28 and emm77. CONCLUSIONS: Cyclic increases in emm1 and emm3 occurred during the iGAS upsurge. Continued surveillance of GAS is therefore essential given the epidemiological changes that occur in a short time period.

Clinical Utility of Polymerase Chain Reaction Testing for Streptococcus pneumoniae in Pediatric Cerebrospinal Fluid Samples: A Diagnostic Accuracy Study of More Than 2000 Samples From 2004 to 2015.

The aim of this retrospective study was to review the diagnostic accuracy of real-time polymerase chain reaction (PCR) testing of cerebrospinal fluid (CSF) samples for Streptococcus pneumoniae DNA in comparison with traditional bacterial culture. The hypothesis was that PCR is more sensitive than culture and would detect more cases of pneumococcal meningitis, particularly in children treated with antimicrobials before CSF sampling occurred. Patients younger than 16 years of age who had a CSF sample tested for S. pneumoniae DNA by PCR between 2004 and 2015 were included. A total of 2025 samples were included, and the PCR had a sensitivity of 100% and specificity of 98% for the detection of S. pneumoniae DNA in comparison with culture. Of the 28 culture negative/PCR positive cases, 25 (89%) were probable meningitis cases and only 3 (11%) were suspected false positive results. Nineteen (76%) of the 25 probable cases required ICU admission, and 3 died (12%). Six different serotypes were found in the culture positive patients (18C, 6B, 14, 22F, 7F and 33F). This study demonstrates that PCR testing of CSF samples for S. pneumoniae is sensitive and specific when compared with culture. PCR is particularly useful in detecting those cases where culture is negative, perhaps relating to pre-CSF sampling administration of antimicrobials.

Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: A large patient cohort study.

BACKGROUND: Activated phosphoinositide 3-kinase δ syndrome (APDS) is a recently described combined immunodeficiency resulting from gain-of-function mutations in PIK3CD, the gene encoding the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ). OBJECTIVE: We sought to review the clinical, immunologic, histopathologic, and radiologic features of APDS in a large genetically defined international cohort. METHODS: We applied a clinical questionnaire and performed review of medical notes, radiology, histopathology, and laboratory investigations of 53 patients with APDS. RESULTS: Recurrent sinopulmonary infections (98%) and nonneoplastic lymphoproliferation (75%) were common, often from childhood. Other significant complications included herpesvirus infections (49%), autoinflammatory disease (34%), and lymphoma (13%). Unexpectedly, neurodevelopmental delay occurred in 19% of the cohort, suggesting a role for PI3Kδ in the central nervous system; consistent with this, PI3Kδ is broadly expressed in the developing murine central nervous system. Thoracic imaging revealed high rates of mosaic attenuation (90%) and bronchiectasis (60%). Increased IgM levels (78%), IgG deficiency (43%), and CD4 lymphopenia (84%) were significant immunologic features. No immunologic marker reliably predicted clinical severity, which ranged from asymptomatic to death in early childhood. The majority of patients received immunoglobulin replacement and antibiotic prophylaxis, and 5 patients underwent hematopoietic stem cell transplantation. Five patients died from complications of APDS. CONCLUSION: APDS is a combined immunodeficiency with multiple clinical manifestations, many with incomplete penetrance and others with variable expressivity. The severity of complications in some patients supports consideration of hematopoietic stem cell transplantation for severe childhood disease. Clinical trials of selective PI3Kδ inhibitors offer new prospects for APDS treatment.

Human IFNAR2 deficiency: Lessons for antiviral immunity.

Type I interferon (IFN-α/ß) is a fundamental antiviral defense mechanism. Mouse models have been pivotal to understanding the role of IFN-α/ß in immunity, although validation of these findings in humans has been limited. We investigated a previously healthy child with fatal encephalitis after inoculation of the live attenuated measles, mumps, and rubella (MMR) vaccine. By targeted resequencing, we identified a homozygous mutation in the high-affinity IFN-α/ß receptor (IFNAR2) in the proband, as well as a newborn sibling, that rendered cells unresponsive to IFN-α/ß. Reconstitution of the proband's cells with wild-type IFNAR2 restored IFN-α/ß responsiveness and control of IFN-attenuated viruses. Despite the severe outcome of systemic live vaccine challenge, the proband had previously shown no evidence of heightened susceptibility to respiratory viral pathogens. The phenotype of IFNAR2 deficiency, together with similar findings in STAT2-deficient patients, supports an essential but narrow role for IFN-α/ß in human antiviral immunity.

HIV virological suppression influences response to the AS03-adjuvanted monovalent pandemic influenza A H1N1 vaccine in HIV-infected children.

DESIGN: Children with HIV are especially susceptible to complications from influenza infection, and effective vaccines are central to reducing disease burden in this population. We undertook a prospective, observational study to investigate the safety and immunogenicity of the inactivated split-virion AS03-adjuvanted pandemic H1N1(2009) vaccine in children with HIV. SETTING: National referral centre for Paediatric HIV in Ireland. SAMPLE: Twenty four children with HIV were recruited consecutively and received two doses of the vaccine. The serological response was measured before each vaccine dose (Day 0 and Day 28) and 2 months after the booster dose. Antibody titres were measured using a haemagglutination inhibition (HAI) assay. Seroprotection was defined as a HAI titre ≥ 1:40; seroconversion was defined as a ≥ fourfold increase in antibody titre and a postvaccination titre ≥ 1:40. MAIN OUTCOME MEASURES: The seroconversion rates after prime and booster doses were 75% and 71%, respectively. HIV virological suppression at the time of immunization was associated with a significantly increased seroconversion rate (P = 0·009), magnitude of serological response (P = 0·02) and presence of seroprotective HAI titres (P = 0·017) two months after the booster dose. No other factor was significantly associated with the seroconversion/seroprotection rate. No serious adverse effects were reported. Vaccination had no impact on HIV disease progression. The AS03-adjuvanted pandemic H1N1 vaccine appears to be safe and immunogenic among HIV-infected children. A robust serological response appears to be optimized by adherence to a HAART regimen delivering virological suppression.

Does vaccine dose predict response to the monovalent pandemic H1N1 influenza a vaccine in children with acute lymphoblastic leukemia? A single-centre study.

BACKGROUND: Vaccination against influenza is an important strategy in preventing severe infection among children with acute lymphoblastic leukemia (ALL). Successful vaccination depends on both vaccine and host-related factors. We conducted a study on factors predicting the immunogenicity of the monovalent pandemic H1N1 (pH1N1) influenza A vaccine in children with ALL. METHODS: Children with ALL in our hospital were recruited and received two doses of the inactivated split-virion AS03-adjuvanted vaccine. The serological response was measured before each vaccine dose (Day 0 and 28) and 3 months after the second dose. Antibody titres were measured using a hemagglutination-inhibition assay. Seroconversion was defined as a ≥fourfold increase in antibody titre and a post-vaccination titre ≥1:40. RESULTS: Pre and post-vaccination titres were available from 45 children with ALL after one dose of the vaccine and 39 children after two doses. The seroconversion rate was 11.1% after one dose and 25.6% after the second dose. Univariate analysis demonstrated a significantly higher (P = 0.01) seroconversion rate among children who received the adult dose (0.5 ml) of the vaccine and a trend towards increased seroconversion (P = 0.07) by multivariate analysis. Factors including age, gender, lymphocyte count, treatment phase and regimen did not significantly affect the seroconversion rate. Children who received the adult dose demonstrated a significantly greater magnitude of serological response after both one dose (P = 0.04) and two doses (P = 0.001). CONCLUSIONS: These data suggest that the immunogenicity of the pH1N1 vaccine among children with ALL is improved by repeated and adult doses of the vaccine.

The impact of meningococcal polymerase chain reaction testing on laboratory confirmation of invasive meningococcal disease.

Laboratory methods of diagnosis were examined for 266 children with invasive meningococcal disease. Seventy-five (36%) of 207 cases with bloodstream infection had both positive blood culture and blood meningococcal polymerase chain reaction (PCR), 130 (63%) negative blood culture and positive blood PCR, and 2 (1%) had positive blood culture and negative blood PCR. Sixty-three percent of cases were diagnosed by PCR alone.

Clinical correlation of the CLSI susceptibility breakpoint for piperacillin- tazobactam against extended-spectrum-beta-lactamase-producing Escherichia coli and Klebsiella species.

We assessed infections caused by extended-spectrum-beta-lactamase-producing Escherichia coli or Klebsiella spp. treated with piperacillin-tazobactam to determine if the susceptibility breakpoint predicts outcome. Treatment was successful in 10 of 11 nonurinary infections from susceptible strains and in 2 of 6 infections with MICs of >16/4 mug/ml. All six urinary infections responded to treatment regardless of susceptibility.

Cerebrospinal fluid cytology in seasonal epidemic West Nile virus meningo-encephalitis.

The incidence of West Nile Virus (WNV) infection has progressively increased in North America since the first epidemic in 1999. Formal scholarly documentation of cerebrospinal fluid (CSF) cytology changes in patients with WNV infection is limited. We report our experience with CSF cytospins from a population of consecutive patients with documented CSF WNV-specific IgM. Thirty-two patients (12 male, 20 female) with a median age of 52 yr (range, 19-88) diagnosed with WNV meningo-encephalitis were studied. Symptoms were present for a mean of 5 days (range, 1-14) prior to lumbar puncture. CSF proteins were elevated in 94% of patients (30/32) with a mean value of 79 mg/dl (range, 36-185). CSF glucose was normal to elevated in all cases. All cytomorphologically adequate samples demonstrated a pleocytosis with a mean of 156 cells/mm3 (range, 13-683). Nearly, all (26/28) patients showed increased CSF neutrophils--mean 43% (range, 1-83). Mean lymphocyte and monocyte fractions were 44% (range, 8-85) and 14% (range, 2-27), respectively. Three cases showed 1-4% plasma cells. Mean total leukocyte counts (TLC) (197 cells/mm3) and mean neutrophil fractions (50%) were greater in patients sampled within the first 3 days of symptoms than in those sampled beyond day 3 (mean TLC, 126 cells/mm3; mean neutrophil fraction, 37%). Relative lymphocyte proportions increased from a mean of 39 to 48% after 3 days of illness. WNV should be considered as a potential etiology of infectious CSF pleocytosis in the North American late summer and early fall seasons.

Management of outbreaks of methicillin-resistant Staphylococcus aureus infection in the neonatal intensive care unit: a consensus statement.

OBJECTIVE: In 2002, the Chicago Department of Public Health (CDPH; Chicago, Illinois) convened the Chicago-Area Neonatal MRSA Working Group (CANMWG) to discuss and compare approaches aimed at control of methicillin-resistant Staphylococcus aureus (MRSA) in neonatal intensive care units (NICUs). To better understand these issues on a regional level, the CDPH and the Evanston Department of Health and Human Services (EDHHS; Evanston, Illinois) began an investigation. DESIGN: Survey to collect demographic, clinical, microbiologic, and epidemiologic data on individual cases and clusters of MRSA infection; an additional survey collected data on infection control practices. SETTING: Level III NICUs at Chicago-area hospitals. PARTICIPANTS: Neonates and healthcare workers associated with the level III NICUs. METHODS: From June 2001 through September 2002, the participating hospitals reported all clusters of MRSA infection in their respective level III NICUs to the CDPH and the EDHHS. RESULTS: Thirteen clusters of MRSA infection were detected in level III NICUs, and 149 MRSA-positive infants were reported. Infection control surveys showed that hospitals took different approaches for controlling MRSA colonization and infection in NICUs. CONCLUSION: The CANMWG developed recommendations for the prevention and control of MRSA colonization and infection in the NICU and agreed that recommendations should expand to include future data generated by further studies. Continuing partnerships between hospital infection control personnel and public health professionals will be crucial in honing appropriate guidelines for effective approaches to the management and control of MRSA colonization and infection in NICUs.

A laboratory-based, hospital-wide, electronic marker for nosocomial infection: the future of infection control surveillance?

Faced with expectations to improve patient safety and contain costs, the US health care system is under increasing pressure to comprehensively and objectively account for nosocomial infections. Widely accepted nosocomial infection surveillance methods, however, are limited in scope, not sensitive, and applied inconsistently. In 907 inpatient admissions to Evanston Northwestern Healthcare hospitals (Evanston, IL), nosocomial infection identification by the Nosocomial Infection Marker (MedMined, Birmingham, AL), an electronic, laboratory-based marker, was compared with hospital-wide nosocomial infection detection by medical records review and established nosocomial infection detection methods. The sensitivity and specificity of marker analysis were 0.86 (95% confidence interval [CI 95], 0.76-0.96) and 0.984 (CI 95, 0.976, 0.992). Marker analysis also identified 11 intensive care unit-associated nosocomial infections (sensitivity, 1.0; specificity, 0.986). Nosocomial Infection Marker analysis had a comparable sensitivity (P > .3) to and lower specificity (P < .001) than medical records review. It is important to note that marker analysis statistically outperformed widely accepted surveillance methods, including hospital-wide detection by Study on the Efficacy of Nosocomial Infection Control chart review and intensive care unit detection by National Nosocomial Infections Surveillance techniques.

Baylisascariasis.

The raccoon roundworm, Baylisascaris procyonis, is the most common and widespread cause of clinical larva migrans in animals. In addition, it is increasingly recognized as a cause of devastating or fatal neural larva migrans in infants and young children and ocular larva migrans in adults. Humans become infected by accidentally ingesting infective B. procyonis eggs from raccoon latrines or articles contaminated with their feces. Two features distinguish B. procyonis from other helminthes that cause larva migrans: (i) its aggressive somatic migration and invasion of the central nervous system and (ii) the continued growth of larvae to a large size within the central nervous system. Typically, B. procyonis neural larva migrans presents as acute fulminant eosinophilic meningoencephalitis. Once invasion of the central nervous system has occurred, the prognosis is grave with or without treatment. To date, despite anthelmintic treatment of cases of B. procyonis neural larva migrans, there are no documented neurologically intact survivors. Epidemiologic study of human cases of neural larva migrans demonstrate that contact with raccoon feces or an environment contaminated by infective eggs and geophagia or pica are the most important risk factors for infection. In many regions of the United States, increasingly large populations of raccoons, with high rates of B. procyonis infection, live in close proximity to humans. Although documented cases of human baylisascariasis remain relatively uncommon, widespread contamination of the domestic environment by infected raccoons suggests that the risk of exposure and human infection is probably substantial. In the absence of early diagnosis or effective treatment, prevention of infection is the most important public health measure.

Evaluation of performance and potential clinical impact of ProSpecT Shiga toxin Escherichia coli microplate assay for detection of Shiga Toxin-producing E. coli in stool samples.

Shiga toxin-producing Escherichia coli bacteria (STEC) are emerging pathogens capable of producing sporadic and epidemic diarrhea, hemorrhagic colitis, and potentially life-threatening hemolytic-uremic syndrome. Although the presence of E. coli O157 can be readily detected in stool by sorbitol-MacConkey agar culture (SMAC), STEC non-O157 serotypes cannot. In contrast to culture, testing for the presence of Shiga toxins 1 and 2 in stool detects both O157 and non-O157 STEC serotypes capable of causing disease. Over two consecutive summers, we evaluated the performance of the ProSpecT Shiga toxin E. coli Microplate assay (Alexon-Trend, Ramsey, Minn.), an enzyme immunoassay for the detection of Shiga toxins 1 and 2, on all stools submitted for culture of enteric pathogens, and the potential clinical impact of Shiga toxin detection. Twenty-nine stool specimens were STEC positive by ProSpecT assay. Twenty-seven of 29 STEC-positive isolates were confirmed by SMAC and serotyping or by a second enzyme immunoassay and PCR (positive predictive value, 93%). Thirteen of 27 confirmed Shiga toxin-producing strains were serotype O157. The remaining 14 strains represented 8 other serotypes. The ProSpecT assay was 100% sensitive and specific for detection of E. coli O157 in stool (7 of 7) compared to SMAC. In addition, the ProSpecT assay detected twice as many STEC as SMAC. Fifty-two percent of confirmed STEC-positive stools were nonbloody. Thus, in our population, screening strategies that test only visibly bloody stools for STEC would miss a majority of cases. Eleven (41%) STEC-positive patients were hospitalized, and eight (30%) developed severe disease (two developed hemolytic-uremic syndrome, and six developed hemorrhagic colitis). Prior to detection of STEC infection, seven (26%) and eight patients (30%) underwent unnecessary diagnostic procedures or received potentially deleterious empirical treatment, respectively. We propose that establishing a specific diagnosis of STEC may have prevented these potentially harmful interventions. We conclude that the ProSpecT assay is sensitive and specific for the detection of Shiga toxins 1 and 2 in stool and has potentially significant clinical impact for the individual patient and public health. Shiga toxin assays should be considered for routine use in settings where prevalence of STEC disease warrants testing.

Neonatal sepsis caused by Streptococcus bovis variant (biotype II/2): report of a case and review.

Streptococcus bovis is an uncommon cause of infection in neonates. However, S. bovis is capable of causing fulminant neonatal sepsis or meningitis that is indistinguishable clinically from that caused by group B streptococcus. S. bovis and S. bovis variant (sometimes referred to as S. bovis biotypes I and II, respectively) are phenotypically similar but may be differentiated by expanded testing. In adults, specific associations between disease states and different biotypes of S. bovis are apparent. No data exist on possible differences or clinical relevance of neonatal infection caused by different biotypes or newer species of S. bovis. We report a 3-day-old neonate with bacteremia and meningitis caused by S. bovis variant (S. bovis biotype II/2) and review the literature.