Enterovirus 75 and aseptic meningitis, Spain, 2005.

Although most human enterovirus (EV) (genus Enterovirus, family Picornaviridae) infections are asymptomatic, they can cause upper respiratory illness, febrile rash, aseptic meningitis, pleurodynia, encephalitis, acute flaccid paralysis, and neonatal sepsislike disease (1). Most EVs have been implicated in aseptic meningitis, most notably echovirus (E) 30, 9, 6, and 11 and coxsackie B virus (CBV) type 5 (2); other serotypes are less frequently associated with neurologic disease.

Specificity of immunoblotting analyses in eosinophilic meningitis

Angiostrongylus cantonensis and Gnathostoma spinigerum are the two most common causative parasites of eosinophilic meningitis (EOM). Serological tests are helpful tools for confirming the identity of the pathogen. Recent reports determined the specificity of such tests by using normal healthy controls. There have been limited studies done to rule out the cross-reactivity between these two causative parasites of EOM. This study aims to assess the specificity of the serological test in EOM by using each condition as a control for the other. Thirty-three patients with a diagnosis of EOM were enrolled. Sera from 22 patients with a positive 29-kDa antigenic diagnostic band of A. cantonensis were tested for the 21 and 24-kDa antigenic bands of G. spinigerum. Similarly, sera of 11 gnathostomiasis patients were tested for the 29-kDa diagnostic band for A. cantonensis. Only one patient in the angiostrongyliasis group had a positive result for the 21 and 24-kDa antigenic bands of G. spinigerum, while no gnathostomiasis patients showed a positive result for the 29-kDa antigenic band of A. cantonensis. The specificity of the 21 and 24-kDa antigenic bands for gnathostomiasis and the 29-kDa antigenic band for A. cantonensis was 95.5% and 100%, respectively. The antigenic bands for the diagnosis of gnathostomiasis and angiostrongyliasis in EOM were highly specific.

Lymphocytic choriomeningitis virus-associated meningitis, southern Spain.

Lymphocytic choriomeningitis virus (LCMV) was detected in 2 patients with acute meningitis in southern Spain within a 3-year period. Although the prevalence of LCMV infection was low (2 [1.3%] of 159 meningitis patients), it represents 2.9% of all pathogens detected. LCMV is a noteworthy agent of neurologic illness in immunocompetent persons.

Molecular diagnosis of eosinophilic meningitis due to Angiostrongylus cantonensis (Nematoda: Metastrongyloidea) by polymerase chain reaction-DNA sequencing of cerebrospinal fluids of patients

Cerebrospinal fluid (CSF) samples from clinically diagnosed patients with detectable Angiostrongylus canto-nensis-specific antibodies (n = 10), patients with clinically suspected cases that tested negative for A. cantonensis-an-tibodies (n = 5) and patients with cerebral gnathostomiasis (n = 2) and neurocysticercosis (n = 2) were examined by a single-step polymerase chain reaction (PCR) method using the AC primers for the 66-kDa native protein gene. The PCR method detected A. cantonensis DNA in CSF samples from four of 10 serologically confirmed angiostrongyliasis cases. The PCR results were negative for the remaining CSF samples. The nucleotide sequences of three positive CSF-PCR samples shared 98.8-99.2% similarity with the reference sequence of A. cantonensis. These results indicate the potential application of this PCR assay with clinical CSF samples for additional support in the confirmation of eosinophilic meningitis due to A. cantonensis.

Eosinophilic meningitis caused by Angiostrongylus cantonensis: an emergent disease in Brazil

Eosinophilic meningitis (EoM) is an acute disease that affects the central nervous system. It is primarily caused by infection with the nematode Angiostrongylus cantonensis. This infection was previously restricted to certain Asian countries and the Pacific Islands, but it was first reported in Brazil in 2007. Since then, intermediate and definitive hosts infected with A. cantonensis have been identified within the urban areas of many states in Brazil, including those in the northern, northeastern, southeastern and southern regions. The goals of this review are to draw the attention of the medical community and health centres to the emergence of EoM in Brazil, to compile information about several aspects of the human infection and mode of transmission and to provide a short protocol of procedures for the diagnosis of this disease.

Utilitat de la Tomografia Computeritzada de crani davant la sospita de meningitis

La meningitis és una malaltia de baixa incidència i una presentació clínica variable. En la pràctica clínica habitual és molt freqüent realitzar una tomografia computeritzada (TC) cranial davant la sospita de meningitis. Les dades del nostre estudi són congruents amb les conclusions de les altres sèries de meningitis: els pacients amb sospita clínica de meningitis que no presenten cap alteració a l’exploració neurològica o factor de risc, són bons candidats per la immediata realització de punció lumbar sense necessitat de fer TC prèvia. En la majoria, la TC de crani no aportarà informació rellevant i demorarà considerablement l’inici de l’antibioteràpia.

Elevated inflammatory markers combined with positive pneumococcal urinary antigen are a good predictor of pneumococcal community-acquired pneumonia in children.

BACKGROUND: Our objective was to evaluate procalcitonin (PCT) and C-reactive protein (CRP) as predictors of a pneumococcal etiology in community-acquired pneumonia (CAP) in hospitalized children. METHODS: Children requiring hospitalization for CAP were prospectively enrolled. The following indices were determined: antibodies against pneumococcal surface proteins (anti-PLY, pneumococcal histidine triad D, pneumococcal histidine triad E, LytB and pneumococcal choline-binding protein A), viral serology, nasopharyngeal cultures and polymerase chain reaction for 13 respiratory viruses, blood pneumococcal polymerase chain reaction, pneumococcal urinary antigen, PCT and CRP. Presumed pneumococcal CAP (P-CAP) was defined as a positive blood culture or polymerase chain reaction for Streptococcus pneumoniae or as a pneumococcal surface protein seroresponse (≥2-fold increase). RESULTS: Seventy-five patients were included from which 37 (49%) met the criteria of P-CAP. Elevated PCT and CRP values were strongly associated with P-CAP with odds ratios of 23 (95% confidence interval: 5-117) for PCT and 19 (95% confidence interval: 5-75) for CRP in multivariate analysis. The sensitivity was 94.4% for PCT (cutoff: 1.5 ng/mL) and 91.9% for CRP (cutoff: 100 mg/L). A value≤0.5 ng/mL of PCT ruled out P-CAP in >90% of cases (negative likelihood ratio: 0.08). Conversely, a PCT value≥1.5 ng/mL associated with a positive pneumococcal urinary antigen had a diagnostic probability for P-CAP of almost 80% (positive likelihood ratio: 4.59). CONCLUSIONS: PCT and CRP are reliable predictors of P-CAP. Low cutoff values of PCT allow identification of children at low risk of P-CAP. The association of elevated PCT or CRP with a positive pneumococcal urinary antigen is a strong predictor of P-CAP.

A qui administrer le vaccin anti-pneumococcique? [We should received and pneumococcal immunization?]

Alors que l'immunisation active contre l'influenza semble être actuellement largement entrée dans la pratique médicale, force est de constater que c'est loin d'être le cas pour les infections à pneumocoque. La vaccination anti-pneumocoque. La vaccination anti-pneumococcique, qui est incluse dans les schémas d'immunisation de nombreux pays, ne fait actuellement pas l'objet de recommendations particulières en Suisse et son utilisation y reste marginale. Compte tenu du nombre élevé d'infections sévères et de décès potentiellement évitables, sa généralisation à tous les groupes à risque doit être encouragée. De plus, cette stratégie pourrait se révéler utile face à la progression inexorable de la proportion de souches résistantes à la pénicilline et aux autres microbes.

Immunity to pneumococcal surface proteins in children with community-acquired pneumonia: a distinct pattern of responses to pneumococcal choline-binding protein A.

Clin Microbiol Infect ABSTRACT: The aetiological diagnosis of community-acquired pneumonia (CAP) is challenging in children, and serological markers would be useful surrogates for epidemiological studies of pneumococcal CAP. We compared the use of anti-pneumolysin (Ply) antibody alone or with four additional pneumococcal surface proteins (PSPs) (pneumococcal histidine triad D (PhtD), pneumococcal histidine triad E (PhtE), LytB, and pneumococcal choline-binding protein A (PcpA)) as serological probes in children hospitalized with CAP. Recent pneumococcal exposure (positive blood culture for Streptococcus pneumoniae, Ply(+) blood PCR finding, and PSP seroresponse) was predefined as supporting the diagnosis of presumed pneumococcal CAP (P-CAP). Twenty-three of 75 (31%) children with CAP (mean age 33.7 months) had a Ply(+) PCR finding and/or a ≥2-fold increase of antibodies. Adding seroresponses to four PSPs identified 12 additional patients (35/75, 45%), increasing the sensitivity of the diagnosis of P-CAP from 0.44 (Ply alone) to 0.94. Convalescent anti-Ply and anti-PhtD antibody titres were significantly higher in P-CAP than in non P-CAP patients (446 vs. 169 ELISA Units (EU)/mL, p 0.031, and 189 vs. 66 EU/mL, p 0.044), confirming recent exposure. Acute anti-PcpA titres were three-fold lower (71 vs. 286 EU/mL, p <0.001) in P-CAP children. Regression analyses confirmed a low level of acute PcpA antibodies as the only independent predictor (p 0.002) of P-CAP. Novel PSPs facilitate the demonstration of recent pneumococcal exposure in CAP children. Low anti-PcpA antibody titres at admission distinguished children with P-CAP from those with CAP with a non-pneumococcal origin.

Is the 23-valent pneumococcal polysaccharide vaccine useful in preventing community-acquired pneumonia?

Although bacteremic pneumococcal pneumonia is the most severe form of pneumonia, non-bacteremic forms are much more frequent. Laboratory methods for the diagnosis of nonbacteremic pneumococcal pneumonia have a low sensitivity and specificity, and therefore all-cause pneumonia has been proposed as a suitable outcome to evaluate vaccination effectiveness. This work reviews the epidemiology of community-acquired pneumonia (CAP) and evaluates the effectiveness of the 3-valent pneumococcal polysaccharide vaccine (PPV-23) in preventing CAP requiring hospitalization in people aged ≥65 years. We performed a case-control study in patients aged ≥65 years admitted through the emergency department who presented with clinical signs and symptoms compatible with pneumonia. Weincluded 489 cases and 1,467 controls and it was obtained a vaccine efectiveness of 23.6 (0.9-41.0). Our results suggest that PPV-23 vaccination is effective and reduces hospital admissions due to pneumonia in the elderly, strengthening the rationale for vaccination programmes in this age group.

Proinflammatory activity of cell-wall constituents from gram-positive bacteria.

Innate immunity reacts to conserved bacterial molecules. The outermost lipopolysaccharide (LPS) of Gram-negative organisms is highly inflammatory. It activates responsive cells via specific CD14 and toll-like receptor-4 (TLR4) surface receptor and co-receptors. Gram-positive bacteria do not contain LPS, but carry surface teichoic acids, lipoteichoic acids and peptidoglycan instead. Among these, the thick peptidoglycan is the most conserved. It also triggers cytokine release via CD14, but uses the TLR2 co-receptor instead of TLR4 used by LPS. Moreover, whole peptidoglycan is 1000-fold less active than LPS in a weight-to-weight ratio. This suggests either that it is not important for inflammation, or that only part of it is reactive while the rest acts as ballast. Biochemical dissection of Staphylococcus aureus and Streptococcus pneumoniae cell walls indicates that the second assumption is correct. Long, soluble peptidoglycan chains (approximately 125 kDa) are poorly active. Hydrolysing these chains to their minimal unit (2 sugars and a stem peptide) completely abrogates inflammation. Enzymatic dissection of the pneumococcal wall generated a mixture of highly active fragments, constituted of trimeric stem peptides, and poorly active fragments, constituted of simple monomers and dimers or highly polymerized structures. Hence, the optimal constraint for activation might be 3 cross-linked stem peptides. The importance of structural constraint was demonstrated in additional studies. For example, replacing the first L-alanine in the stem peptide with a D-alanine totally abrogated inflammation in experimental meningitis. Likewise, modifying the D-alanine decorations of lipoteichoic acids with L-alanine, or deacylating them from their diacylglycerol lipid anchor also decreased the inflammatory response. Thus, although considered as a broad-spectrum pattern-recognizing system, innate immunity can detect very subtle differences in Gram-positive walls. This high specificity underlines the importance of using well-characterized microbial material in investigating the system.

Some pneumococcal serotypes are more frequently associated with relapses of acute exacerbations in COPD patients

Objectives: To analyze the role of the capsular type in pneumococci causing relapse and reinfection episodes of acute exacerbation in COPD patients. Methods: A total of 79 patients with 116 recurrent episodes of acute exacerbations caused by S. pneumoniae were included into this study (1995–2010). A relapse episode was considered when two consecutive episodes were caused by the same strain (identical serotype and genotype); otherwise it was considered reinfection. Antimicrobial susceptibility testing (microdilution), serotyping (PCR, Quellung) and molecular typing (PFGE/MLST) were performed. Results: Among 116 recurrent episodes, 81 (69.8%) were reinfections, caused by the acquisition of a new pneumococcus,and 35 (30.2%) were relapses, caused by a pre-existing strain. Four serotypes (9V, 19F, 15A and 11A) caused the majority (60.0%) of relapses. When serotypes causing relapses and reinfection were compared, only two serotypes were associatedwith relapses: 9V (OR 8.0; 95% CI, 1.34–85.59) and 19F (OR 16.1; 95% CI, 1.84–767.20). Pneumococci isolated from relapses were more resistant to antimicrobials than those isolated from the reinfection episodes: penicillin (74.3% vs. 34.6%, p,0.001), ciprofloxacin (25.7% vs. 9.9%, p,0.027), levofloxacin (22.9% vs. 7.4%, p = 0.029), and co-trimoxazole (54.3% vs. 25.9%, p,0.001). Conclusions: Although the acquisition of a new S. pneumoniae strain was the most frequent cause of recurrences, a third ofthe recurrent episodes were caused by a pre-existing strain. These relapse episodes were mainly caused by serotypes 9V and 19F, suggesting an important role for capsular type

Pneumococcal penumonia presenting with septic shock: host-ant pathogen-related factors and outcomes

BACKGROUND: Host- and pathogen-related factors associated with septic shock in pneumococcal pneumonia are not well defined. The aim of this study was to identify risk factors for septic shock and to ascertain patient outcomes. Serotypes, genotypes and antibiotic resistance of isolated strains were also analysed. METHODS: Observational analysis of a prospective cohort of non-severely immunosuppressed hospitalised adults with pneumococcal pneumonia. Septic shock was defined as a systolic blood pressure of <90 mm Hg and peripheral hypoperfusion with the need for vasopressors for >4 h after fluid replacement. RESULTS: 1041 patients with pneumococcal pneumonia diagnosed by Gram stain and culture of appropriate samples and/or urine antigen test were documented, of whom 114 (10.9%) had septic shock at admission. After adjustment, independent risk factors for shock were current tobacco smoking (OR, 2.11; 95% CI, 1.02 to 4.34; p = 0.044), chronic corticosteroid treatment (OR, 4.45; 95% CI, 1.75 to 11.32; p = 0.002) and serotype 3 (OR, 2.24; 95% CI, 1.12 to 4.475; p = 0.022). No significant differences were found in genotypes and rates of antibiotic resistance. Compared with the remaining patients, patients with septic shock required mechanical ventilation more frequently (37% vs 4%; p<0.001) and had longer length of stay (11 vs 8 days; p<0.001). The early (10% vs 1%; p<0.001) and overall case fatality rates (25% vs 5%; p<0.001) were higher in patients with shock. CONCLUSIONS: Septic shock is a frequent complication of pneumococcal pneumonia and causes high morbidity and mortality. Current tobacco smoking, chronic corticosteroid treatment and infection caused by serotype 3 are independent risk factors for this complication.